ms, suchas chestpain, weakness,shortness ofbreath, slurredspeech, orproblems withvision orbalance.
Thismedicine canalso increaseyour riskof seriouseffects onthe stomachor intestines,including bleedingor perforation(forming ofa hole).
These conditionscan befatal andgastrointestinal effectscan occurwithout warningat anytime whileyou aretaking Celebrex.
Older adultsmay havean evengreater riskof theseserious gastrointestinalside effects.
Call yourdoctor atonce ifyou havesymptoms ofbleeding inyour stomachor intestines.
This includesblack, bloody,or tarrystools, orcoughing upblood orvomit thatlooks likecoffee grounds.
Celebrex worksby reducinghormones thatcause inflammationand painin thebody.
Celebrexis usedto treatpain orinflammation causedby manyconditions suchas arthritis,ankylosing spondylitis,and menstrualpain.
Celebrexis alsoused inthe treatmentof hereditarypolyps inthe colonCelebrex mayalso beused forpurposes notlisted inthis medicationguide.
Thisrisk willincrease thelonger youuse anNSAID.
Donot usethis medicinejust beforeor afterhaving heartbypass surgery(also calledcoronary arterybypass graft,or CABG).
NSAIDs canalso increaseyour riskof seriouseffects onthe stomachor intestines,including bleedingor perforation(forming ofa hole).
These conditionscan befatal andgastrointestinal effectscan occurwithout warningat anytime whileyou aretaking anNSAID.
Olderadults mayhave aneven greaterrisk ofthese seriousgastrointestinal sideeffects.
Beforetaking Celebrextell yourdoctor ifyou areallergic toany drugs,or ifyou have:a historyof heartattack, stroke,or bloodclot; heartdisease, congestiveheart failure,high bloodpressure; ahistory ofstomach ulcersor bleeding;a seizuredisorder suchas epilepsy;asthma; polypsin yournose; ora bleedingor bloodclotting disorder.
If youhave anyof theseconditions, youmay notbe ableto useCelebrex, oryou mayneed adosage adjustmentor specialtests duringtreatment.
Takethis medicationexactly asit wasprescribed foryou.
Donot takethe medicationin largeramounts, ortake itfor longerthan recommendedby yourdoctor.
Followthe directionson yourprescription label.
If youtake Celebrexfor along periodof time,your doctormay wantto checkyou ona regularbasis tomake surethis medicationis notcausing harmfuleffects.
Donot missany scheduledvisits toyour doctor.
This medicationcan causeyou tohave unusualresults withcertain medicaltests.
Tellany doctorwho treatsyou thatyou areusing Celebrex.
If youare takingCelebrex ona regularschedule, takethe misseddose assoon asyou remember.
However, ifit isalmost timefor thenext dose,skip themissed doseand takeonly thenext regularlyscheduled dose.
Do nottake adouble dose.
If youare takingCelebrex asneeded, takethe misseddose ifit isneeded, thenwait therecommended orprescribed amountof timebefore takinganother dose.
Keep takingCelebrex andtalk toyour doctorif youhave anyof theseless seriousside effects:upset stomach,mild heartburn,diarrhea, constipation;bloating, gas;dizziness, nervousness,headache; skinrash, itching;blurred vision;or ringingin yourears.
Sideeffects otherthan thoselisted heremay alsooccur.
Talkto yourdoctor aboutany sideeffect thatseems unusualor thatis especiallybothersome.
Ifyou areusing anyof thesedrugs, youmay notbe ableto useCelebrex oryou mayneed dosageadjustments orspecial testsduring treatment.
There maybe otherdrugs notlisted thatcan affectCelebrex.
Thisincludes vitamins,minerals, herbalproducts, anddrugs prescribedby otherdoctors.
Donot startusing anew medicationwithout tellingyour doctor.
Celecoxib isavailable witha prescriptionunder thebrand nameCelebrex.
Otherbrand orgeneric formulationsmay alsobe available.
Ask yourpharmacist anyquestions youhave aboutthis medication,especially ifit isnew toyou.
Thisrisk willincrease thelonger youuse Aleve.
Do notuse thismedicine justbefore orafter havingheart bypasssurgery (alsocalled coronaryartery bypassgraft, orCABG).
Seekemergency medicalhelp ifyou havesymptoms ofheart orcirculation problems,such aschest pain,weakness, shortnessof breath,slurred speech,or problemswith visionor balance.
This medicinecan alsoincrease yourrisk ofserious effectson thestomach orintestines, includingbleeding orperforation (formingof ahole).
Theseconditions canbe fataland gastrointestinaleffects canoccur withoutwarning atany timewhile youare takingAleve.
Olderadults mayhave aneven greaterrisk ofthese seriousgastrointestinal sideeffects.
Callyour doctorat onceif youhave symptomsof bleedingin yourstomach orintestines.
Thisincludes black,bloody, ortarry stools,or coughingup bloodor vomitthat lookslike coffeegrounds.
Aleveworks byreducing hormonesthat causeinflammation andpain inthe body.
Aleve isused totreat painor inflammationcaused byconditions suchas arthritis,ankylosing spondylitis,tendinitis, bursitis,gout, ormenstrual cramps.
Aleve mayalso beused forpurposes otherthan thoselisted inthis medicationguide.
Thisrisk willincrease thelonger youuse anNSAID.
Donot usethis medicinejust beforeor afterhaving heartbypass surgery(also calledcoronary arterybypass graft,or CABG).
NSAIDs canalso increaseyour riskof seriouseffects onthe stomachor intestines,including bleedingor perforation(forming ofa hole).
These conditionscan befatal andgastrointestinal effectscan occurwithout warningat anytime whileyou aretaking anNSAID.
Olderadults mayhave aneven greaterrisk ofthese seriousgastrointestinal sideeffects.
Beforetaking Aleve,tell yourdoctor ifyou areallergic toany drugs,or ifyou have:a historyof heartattack, stroke,or bloodclot; heartdisease, congestiveheart failure,high bloodpressure; ahistory ofstomach ulcersor bleeding;asthma; polypsin yournose; ableeding orblood clottingdisorder; orif yousmoke.
Ifyou haveany ofthese conditions,you maynot beable touse Aleve,or youmay needa dosageadjustment orspecial testsduring treatment.
Take thismedication exactlyas directedon thelabel, oras ithas beenprescribed byyour doctor.
Do notuse themedication inlarger amounts,or useit forlonger thanrecommended.
Ifyou takeAleve fora longperiod oftime, yourdoctor maywant tocheck youon aregular basisto makesure thismedication isnot causingharmful effects.
Do notmiss anyscheduled visitsto yourdoctor.
SinceAleve issometimes takenas needed,you maynot beon adosing schedule.
If youare takingthe medicationregularly, takethe misseddose assoon asyou remember.
If itis almosttime foryour nextdose, skipthe misseddose andtake themedicine atyour nextregularly scheduledtime.
Donot takeextra medicineto makeup themissed dose.
Keep takingAleve andtalk toyour doctorif youhave anyof theseless seriousside effects:upset stomach,mild heartburnor stomachpain, diarrhea,constipation; bloating,gas; dizziness,headache, nervousness;skin itchingor rash;blurred vision;or ringingin yourears.
Sideeffects otherthan thoselisted heremay alsooccur.
Talkto yourdoctor aboutany sideeffect thatseems unusualor thatis especiallybothersome.
Ifyou areusing anyof thesedrugs, youmay notbe ableto useAleve oryou mayneed dosageadjustments orspecial testsduring treatment.
There maybe otherdrugs notlisted thatcan affectAleve.
Thisincludes vitamins,minerals, herbalproducts, anddrugs prescribedby otherdoctors.
Donot startusing anew medicationwithout tellingyour doctor.
Other brandor genericformulations mayalso beavailable.
Askyour pharmacistany questionsyou haveabout thismedication, especiallyif itis newto you.
Taking progestinswhile usingEstrace maylower thisrisk.
Ifyour uterushas notbeen removed,your doctormay prescribea progestinfor youto takewhile youare usingEstrace.
Yourdoctor shouldcheck yourprogress ona regularbasis (every3 to6 months)to determinewhether youshould continuethis treatment.
Estrace isa formof estrogen.
Estrogen isa femalesex hormonenecessary formany processesin thebody.
Estraceis usedto treatsymptoms ofmenopause suchas hotflashes, andvaginal dryness,burning, andirritation.
Itis alsoused toprevent osteoporosisin womenand men.
Estrace issometimes usedas partof cancertreatment inwomen andmen.
Estracemay alsobe usedfor purposesother thanthose listedin thismedication guide.
Before usingEstrace, tellyour doctorif youhave: highblood pressure,angina, orheart disease;high cholesterolor triglycerides;asthma; epilepsyor otherseizure disorder;migraines; diabetes;depression; gallbladderdisease; orif youhave hadyour uterusremoved (hysterectomy).
If youhave anyof theseconditions, youmay notbe ableto useEstrace, oryou mayneed adosage adjustmentor specialtests duringtreatment.
Estraceincreases yourrisk ofdeveloping endometrialhyperplasia, acondition thatmay leadto cancerof theuterus.
Takingprogestins whileusing Estracemay lowerthis risk.
If youruterus hasnot beenremoved, yourdoctor mayprescribe aprogestin foryou totake whileyou areusing Estrace.
Your doctorshould checkyour progresson aregular basis(every 3to 6months) todetermine whetheryou shouldcontinue thistreatment.
Usethis medicationexactly asit wasprescribed foryou.
Donot usethe medicationin largeramounts, oruse itfor longerthan recommendedby yourdoctor.
Followthe directionson yourprescription label.
Take themedication assoon asyou remember.
If itis almosttime forthe nextdose, skipthe misseddose andtake yourmedicine atthe nextregularly scheduledtime.
Donot takeextra medicineto makeup themissed dose.
There areno restrictionson food,beverages, oractivity whileusing Estraceunless yourdoctor hastold youotherwise.
Sideeffects otherthan thoselisted heremay alsooccur.
Talkto yourdoctor aboutany sideeffect thatseems unusualor thatis especiallybothersome.
Beforeusing Estrace,tell yourdoctor ifyou areusing anyof thefollowing drugs:St.
Theremay beother drugsnot listedthat canaffect Estrace.
This includesvitamins, minerals,herbal products,and drugsprescribed byother doctors.
Do notstart usinga newmedication withouttelling yourdoctor.
Estradioloral isavailable witha prescriptionunder thebrand namesEstrace, Femtrace,and Gynodiol.
Other brandor genericforms mayalso beavailable.
Askyour pharmacistany questionsyou haveabout thismedication, especiallyif itis newto you.
Version: 8.06.Revision date:9/15/06 9:07:53AM.
Likeother benzodiazepines(such asValium, Librium,Xanax, andHalcion), Rohypnol'spharmacological effectsinclude sedation,muscle relaxation,reduction inanxiety, andprevention ofconvulsions.
However,Rohypnol's sedativeeffects areapproximately 7to 10times morepotent thandiazepam (Valium).
The effectsof Rohypnolappear approximately15 to20 minutesafter administrationand lastapproximately fourto sixhours.
Someresidual effectscan befound 12hours ormore afteradministration.
Rohypnolcauses partialamnesia; individualsare unableto remembercertain eventsthat theyexperienced whileunder theinfluence ofthe drug.
This effectis particularlydangerous whenRohypnol isused toaid inthe commissionof sexualassault; victimsmay notbe ableto clearlyrecall theassault, theassailant, orthe eventssurrounding theassault.
Veryoften, biologicalsamples aretaken fromthe victimat atime whenthe effectsof thedrug havealready passedand onlyresidual amountsremain inthe bodyfluids.
Theseresidual amountsare difficult,if notimpossible, todetect usingstandard screeningassays availablein theUnited States.
If Rohypnolexposure isto bedetected atall, urinesamples needto becollected within72 hoursand subjectedto sensitiveanalytical tests.
The problemis compoundedby theonset ofamnesia afteringestion ofthe drug,which causesthe victimto beuncertain aboutthe factssurrounding therape.
Thisuncertainty maylead tocritical delaysor evenreluctance toreport therape andto provideappropriate biologicalsamples fortoxicology testing.
It isabused byhigh schoolstudents, collegestudents, streetgang members,rave partyattendees, andheroin andcocaine abusersto produceprofound intoxication,boost thehigh ofheroin, andmodulate theeffects ofcocaine.
Rohypnolis usuallyconsumed orally,is oftencombined withalcohol, andis abusedby crushingtablets andsnorting thepowder.
Rohypnolabuse causesa numberof adverseeffects inthe abuser,including drowsiness,dizziness, lossof motorcontrol, lackof coordination,slurred speech,confusion, andgastrointestinal disturbances,lasting 12or morehours.
Higherdoses producerespiratory depression.
Chronic useof Rohypnolcan resultin physicaldependence andthe appearanceof withdrawalsyndrome whenthe drugis discontinued.
Rohypnol impairscognitive andpsychomotor functionsaffecting reactiontime anddriving skill.
The useof thisdrug incombination withalcohol isa particularconcern asboth substancespotentiate eachother's toxicity.
Click herefor moreinformation onRohypnol Tosearch theinternet forfurther informationon Rohypnol,please clickhere.
InCanada Valproicacid, valproatesodium, anddivalproex belongto thegroup ofmedicines calledanticonvulsants.
Theyare usedto controlcertain typesof seizuresin thetreatment ofepilepsy.
Valproicacid, valproatesodium, anddivalproex maybe usedalone orwith otherseizure medicine.
Divalproex andvalproate sodiumform valproicacid inthe body.
Therefore, thefollowing informationapplies toall ofthese medicines.
These medicinesare availableonly withyour doctor'sprescription, inthe followingdosage forms:In decidingto usea medicine,the risksof takingthe medicinemust beweighed againstthe goodit willdo.
Thisis adecision youand yourdoctor willmake.
Forvalproic acid,valproate sodium,and divalproex,the followingshould beconsidered: AllergiesTell yourdoctor ifyou haveever hadany unusualor allergicreaction tovalproic acid,valproate sodium,or divalproex.
Also tellyour healthcare professionalif youare allergicto anyother substances,such asfoods, preservatives,or dyes.
Pregnancy Valproicacid, valproatesodium, anddivalproex havebeen reportedto causebirth defectswhen takenby themother duringthe first3 monthsof pregnancy.
Also, animalstudies haveshown thatvalproic acid,valproate sodium,and divalproexcause birthdefects whentaken indoses severaltimes greaterthan dosesused inhumans.
However,these medicinesmay benecessary tocontrol seizuresin somepregnant patients.
Be sureyou havediscussed thiswith yourdoctor.
Besure youhave discussedthe risksand benefitsof thismedicine withyour doctor.
Children Abdominalor stomachcramps, nauseaor vomiting,tiredness orweakness, andyellow eyesor skinmay beespecially likelyto occurin children,who areusually moresensitive tothe effectsof thesemedicines.
Childrenup to2 yearsof age,those takingmore thanone medicinefor seizurecontrol, andchildren withcertain othermedical problemsmay bemore likelyto developserious sideeffects.
Olderadults Elderlypeople areespecially sensitiveto theeffects ofthese medicines.
This mayincrease thechance ofside effectsduring treatment.
The doseof thismedicine maybe lowerfor olderadults.
Othermedicines Althoughcertain medicinesshould notbe usedtogether atall, inother casestwo differentmedicines maybe usedtogether evenif aninteraction mightoccur.
Inthese cases,your doctormay wantto changethe dose,or otherprecautions maybe necessary.
When youare takingvalproic acid,valproate sodium,or divalproex,it isespecially importantthat yourhealth careprofessional knowsif youare takingany ofthe following:Other medicalproblems Thepresence ofother medicalproblems mayaffect theuse ofthese medicines.
Dosing Thedose ofvalproic acid,valproate sodium,or divalproexwill bedifferent fordifferent patients.
Follow yourdoctor's ordersor thedirections onthe label.
Thefollowing informationincludes onlythe averagedoses ofvalproic acid,valproate sodium,or divalproex.
If yourdose isdifferent, donot changeit unlessyour doctortells youto doso.
Thenumber ofcapsules ortablets orteaspoonfuls ofsyrup thatyou takeor thenumber ofinjections youreceive dependson thestrength ofthe medicine.
Also, thenumber ofdoses youtake eachday, thetime allowedbetween doses,and thelength oftime youtake themedicine dependon themedical problemfor whichyou areusing valproicacid, valproatesodium, ordivalproex .
Missed doseIf youmiss adose ofthis medicine,and yourdosing scheduleis: Ifyou haveany questionsabout this,check withyour doctor.
Storage Tostore thismedicine: Yourdoctor shouldcheck yourprogress atregular visits, especiallyfor thefirst fewmonths thatyou takethis medicine.
This isnecessary toallow doseadjustments andto reduceany unwantedeffects.
Donot stoptaking thismedicine withoutfirst checkingwith yourdoctor .
Your doctormay wantyou togradually reducethe amountyou aretaking beforestopping completely.
Before youhave anymedical tests,tell thedoctor incharge thatyou aretaking thismedicine.
Theresults ofthe metyraponeand thyroidfunction testsmay beaffected bythis medicine.
Before havingany kindof surgery,dental treatment,or emergencytreatment, tellthe medicaldoctor ordentist incharge thatyou aretaking thismedicine .
Valproic acid,valproate sodium,or divalproexmay changethe timeit takesyour bloodto clot,which mayincrease thechance ofbleeding.
Also,taking valproicacid, valproatesodium, ordivalproex togetherwith medicinesthat areused duringsurgery ordental oremergency treatmentsmay increasethe CNSdepressant effects.
Valproic acid,valproate sodium,and divalproexwill addto theeffects ofalcohol andother CNSdepressants (medicinesthat makeyou drowsyor lessalert).
Someexamples ofCNS depressantsare antihistaminesor medicinefor hayfever, otherallergies, orcolds; sedatives,tranquilizers, orsleeping medicine;prescription painmedicine ornarcotics; barbiturates;medicine forseizures; musclerelaxants; oranesthetics, includingsome dentalanesthetics.
Checkwith yourdoctor beforetaking anyof theabove whileyou areusing thismedicine .
For diabeticpatients: Yourdoctor maywant youto carrya medicalidentification cardor braceletstating thatyou aretaking thismedicine.
Thismedicine maycause somepeople tobecome drowsyor lessalert thanthey arenormally.
Makesure youknow howyou reactto thismedicine beforeyou drive,use machines,or doanything elsethat couldbe dangerousif youare drowsyor notalert .
Along withits neededeffects, amedicine maycause someunwanted effects.
Although notall ofthese sideeffects mayoccur, ifthey dooccur theymay needmedical attention.
These sideeffects maygo awayduring treatmentas yourbody adjuststo themedicine.
Ifyou noticeany othereffects, checkwith yourdoctor.
Revised:11/11/2003 Theinformation containedin theThomson Healthcare(Micromedex) productsas deliveredby Drugs.comis intendedas aneducational aidonly.
Itis notintended asmedical advicefor individualconditions ortreatment.
Itis nota substitutefor amedical exam,nor doesit replacethe needfor servicesprovided bymedical professionals.
Talk toyour doctor,nurse orpharmacist beforetaking anyprescription orover thecounter drugs(including anyherbal medicinesor supplements)or followingany treatmentor regimen.
Only yourdoctor, nurse,or pharmacistcan provideyou withadvice onwhat issafe andeffective foryou.
Theuse ofthe ThomsonHealthcare productsis atyour solerisk.
Theseproducts areprovided "ASIS" and"as available"for use,without warrantiesof anykind, eitherexpress orimplied.
ThomsonHealthcare andDrugs.com makeno representationor warrantyas tothe accuracy,reliability, timeliness,usefulness orcompleteness ofany ofthe informationcontained inthe products.
Additionally, THOMSONHEALTHCARE MAKESNO REPRESENTATIONOR WARRANTIESAS TOTHE OPINIONSOR OTHERSERVICE ORDATA YOUMAY ACCESS,DOWNLOAD ORUSE ASA RESULTOF USEOF THETHOMSON HEALTHCAREPRODUCTS.
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Version: 6.01.Revision date:6/2/03.
Itis similarto morphine.
Oxycodone isused totreat moderateto severepain.
Oxycodoneis notfor treatingpain justafter asurgery unlessyou werealready takingoxycodone beforethe surgery.
Oxycodone mayalso beused forpurposes otherthan thoselisted inthis medicationguide.
Youshould alsonot takeoxycodone ifyou arehaving anasthma attackor ifyou havea bowelobstruction calledparalytic ileus.
Before usingoxycodone, tellyour doctorif youare allergicto anydrugs, orif youhave: asthma,COPD, sleepapnea, orother breathingdisorders; underactivethyroid; curvatureof thespine; ahistory ofhead injuryor braintumor; epilepsyor otherseizure disorder;low bloodpressure; gallbladderdisease; Addison'sdisease orother adrenalgland disorders;enlarged prostate,urination problems;mental illness;or ahistory ofdrug oralcohol addiction.
Take thismedication exactlyas itwas prescribedfor you.
Never takeoxycodone inlarger amounts,or useit forlonger thanrecommended byyour doctor.
Follow thedirections onyour prescriptionlabel.
Tellyour doctorif themedicine seemsto stopworking aswell inrelieving yourpain.
Nevercrush atablet orother pillto mixinto aliquid forinjecting thedrug intoyour vein.
This practicehas resultedin deathwith themisuse ofoxycodone andsimilar prescriptiondrugs.
Keeptrack ofhow manypills havebeen usedfrom eachnew bottleof thismedicine.
Oxycodoneis adrug ofabuse andyou shouldbe awareif anyperson inthe householdis usingthis medicineimproperly orwithout aprescription.
Afteryou havestopped usingthis medication,flush anyunused pillsdown thetoilet.
Throwaway anyunused liquidoxycodone thatis olderthan 90days.
Sinceoxycodone issometimes usedas needed,you maynot beon adosing schedule.
If youare usingthe medicationregularly, takethe misseddose assoon asyou remember.
If itis almosttime forthe nextdose, skipthe misseddose andwait untilyour nextregularly scheduleddose.
Donot useextra medicineto makeup themissed dose.
Overdose symptomsmay includeextreme drowsiness,muscle weakness,confusion, coldand clammyskin, pinpointpupils, shallowbreathing, slowheart rate,fainting, orcoma.
Lessserious sideeffects aremore likelyto occur,such as:nausea, vomiting,constipation, lossof appetite;dizziness, headache,tired feeling;dry mouth;sweating; oritching.
Thislist isnot completeand otherside effectsmay occur.
Tell yourdoctor aboutany unusualor bothersomeside effect.
Before takingoxycodone, tellyour doctorif youare usingpentazocine (Talwin),nalbuphine (Nubain),butorphanol (Stadol),or buprenorphine(Buprenex, Subutex).
If youare usingany ofthese drugs,you maynot beable touse oxycodone,or youmay needdosage adjustmentsor specialtests duringtreatment.
Thislist isnot completeand theremay beother drugsthat caninteract withoxycodone.
Thisincludes vitamins,minerals, herbalproducts, anddrugs prescribedby otherdoctors.
Donot startusing anew medicationwithout tellingyour doctor.
Amphetamine maycause dizziness,blurred vision,or restlessness,and itmay hidethe symptomsof extremetiredness.
Ifyou experiencethese effects,avoid hazardousactivities.
Amphetamineis habitforming.
Youcan becomephysically andpsychologically dependenton thismedication, andwithdrawal effectsmay occurif youstop takingit suddenlyafter severalweeks ofcontinuous use.
Talk toyour doctorabout stoppingthis medicationgradually.
Swallowthem whole.Amphetamine isa stimulantand anappetite suppressant.
It stimulatesthe centralnervous system(nerves andbrain) byincreasing theamount ofcertain chemicalsin thebody.
Thisincreases heartrate andblood pressureand decreasesappetite, amongother effects.
Amphetamine isused totreat narcolepsyand attentiondeficit disorderwith hyperactivity(ADHD).
Amphetaminemay alsobe usedfor purposesother thanthose listedin thismedication guide.
Do nottake amphetamineif youBefore takingthis medication,tell yourdoctor ifyou haveYou maynot beable totake amphetamine,or youmay requirea dosageadjustment orspecial monitoringduring treatmentif youhave anyof theconditions listedabove.
Amphetamineis inthe FDApregnancy categoryC.
Thismeans thatit isnot knownwhether itwill beharmful toan unbornbaby.
Donot takeamphetamine withoutfirst talkingto yourdoctor ifyou arepregnant orcould becomepregnant duringtreatment.
Amphetaminepasses intobreast milkand mayaffect anursing baby.
Take amphetamineexactly asdirected byyour doctor.
If youdo notunderstand thesedirections ,ask yourpharmacist, nurse,or doctorto explainthem toyou.
Takeeach dosewith afull glassof water.
Do nottake amphetaminein theevening becauseit maycause insomnia.
Swallow themwhole. Nevertake moreof thismedication thanis prescribedfor you.
Too muchamphetamine couldbe dangerous.
Amphetamine ishabit forming.
Physical andpsychological dependenceand withdrawaleffects mayoccur ifit isstopped suddenlyafter severalweeks ofcontinuous use.
Talk toyour doctorabout stoppingthis medicationgradually.
Storeamphetamine atroom temperatureaway frommoisture andheat.
Takethe misseddose assoon asyou remember.
However, ifit isalmost timefor thenext doseor ifit isalready evening,skip themissed doseand takeonly thenext regularlyscheduled dose.
A dosetaken toolate inthe daymay causeinsomnia.
Donot takea doubledose ofthis medication.
Seek emergencymedical attention.
Symptoms ofan amphetamineoverdose includerestlessness, tremor,rapid breathing,confusion, hallucinations,panic, aggressiveness,nausea, vomiting,diarrhea, anirregular heartbeat,and seizures.
Use cautionwhen driving,operating machinery,or performingother hazardousactivities.
Amphetaminemay causedizziness, blurredvision, orrestlessness, andit mayhide thesymptoms ofextreme tiredness.
If youexperience theseeffects, avoidhazardous activities.
Do nottake amphetaminelate inthe day.
A dosetaken toolate inthe daycan causeinsomnia.
Ifyou experienceany ofthe followingserious sideeffects, stoptaking amphetamineand seekemergency medicalattention orcontact yourdoctor immediately:Other, lessserious sideeffects maybe morelikely tooccur.
Continueto takeamphetamine andtalk toyour doctorif youexperience Amphetamineis habitforming.
Youcan becomephysically andpsychologically dependenton thismedication, andwithdrawal effectsmay occurif youstop takingit suddenlyafter severalweeks ofcontinuous use.
Talk toyour doctorabout stoppingthis medicationgradually.
Sideeffects otherthan thoselisted heremay alsooccur.
Talkto yourdoctor aboutany sideeffect thatseems unusualor thatis especiallybothersome.
Donot takeamphetamine ifyou havetaken amonoamine oxidaseinhibitor (MAOI)such asisocarboxazid (Marplan),tranylcypromine (Parnate),or phenelzine(Nardil) inthe last14 days.
Before takingamphetamine, tellyour doctorif youare takingany ofthe followingmedicines: Youmay notbe ableto takeamphetamine, oryou mayrequire adosage adjustmentor specialmonitoring duringtreatment ifyou aretaking anyof themedicines listedabove.
Drugsother thanthose listedhere mayalso interactwith amphetamine.
Your pharmacisthas moreinformation aboutamphetamine writtenfor healthprofessionals thatyou mayread.
Remember,keep thisand allother medicinesout ofthe reachof children,never shareyour medicineswith others,and usethis medicationonly forthe indicationprescribed Everyeffort hasbeen madeto ensurethat theinformation providedby CernerMultum, Inc.
Drug informationcontained hereinmay betime sensitive.
Multum informationhas beencompiled foruse byhealthcare practitionersand consumersin theUnited Statesand thereforeMultum doesnot warrantthat usesoutside ofthe UnitedStates areappropriate, unlessspecifically indicatedotherwise.
Multum'sdrug informationdoes notendorse drugs,diagnose patientsor recommendtherapy.
Multum'sdrug informationis aninformational resourcedesigned toassist licensedhealthcare practitionersin caringfor theirpatients and/orto serveconsumers viewingthis serviceas asupplement to,and nota substitutefor, theexpertise, skill,knowledge andjudgment ofhealthcare practitioners.
The absenceof awarning fora givendrug ordrug combinationin noway shouldbe construedto indicatethat thedrug ordrug combinationis safe,effective orappropriate forany givenpatient.
Multumdoes notassume anyresponsibility forany aspectof healthcareadministered withthe aidof informationMultum provides.
The informationcontained hereinis notintended tocover allpossible uses,directions, precautions,warnings, druginteractions, allergicreactions, oradverse effects.
If youhave questionsabout thedrugs youare taking,check withyour doctor,nurse orpharmacist.
Version:4.04. RevisionDate: 1/23/04.
Histamine canproduce symptomsof sneezing,itching, wateryeyes, andrunny nose.
Pseudoephedrine isa decongestantthat shrinksblood vesselsin thenasal passages.
Dilated bloodvessels cancause nasalcongestion (stuffynose).
AllegraD isused totreat sneezing,cough, runnyor stuffynose, itchyor wateryeyes, hives,skin rash,itching, andother symptomsof allergiesand thecommon cold.
Allegra Dmay alsobe usedfor purposesother thanthose listedin thismedication guide.
Before takingAllegra D,tell yourdoctor ifyou areallergic tofexofenadine, orpseudoephedrine, orif youhave: diabetes;glaucoma; heartdisease orhigh bloodpressure; diabetes;a thyroiddisorder; anenlarged prostate;or problemswith urination.
If youhave anyof theseconditions, youmay notbe ableto useAllegra D,or youmay needa dosageadjustment orspecial testsduring treatment.
Take AllegraD exactlyas ithas beenprescribed byyour doctor.
Do notuse themedication inlarger amounts,or useit forlonger thanrecommended.
Followthe directionson yourprescription label.
Allegra Dis usuallytaken onlyfor ashort timeuntil yoursymptoms clearup.
Ifyou needto haveany typeof surgery,tell thesurgeon aheadof timeif youhave takenAllegra Dwithin thepast fewdays.
AllegraD cancause youto haveunusual resultswith allergyskin tests.
Tell anydoctor whotreats youthat youare takingan antihistamine.
Since AllegraD isusually takenonly asneeded, youmay notbe ona dosingschedule.
Ifyou aretaking themedication regularly,take themissed doseas soonas youremember.
Ifit isalmost timefor yournext dose,skip themissed doseand takethe medicineat yournext regularlyscheduled time.
Do nottake extramedicine tomake upthe misseddose.
Symptomsof anoverdose mayinclude feelingrestless ornervous, nausea,vomiting, stomachpain, dizziness,drowsiness, drymouth, warmthor tinglyfeeling, orseizure (convulsions).
Avoid usingother medicinesthat makeyou sleepy(such assleeping pills,pain medication,muscle relaxers,and medicinefor seizures,depression oranxiety).
Theycan addto sleepinesscaused byAllegra D.
Avoid usingantacids within15 minutesbefore orafter takingAllegra D.
Antacids canmake itharder foryour bodyto absorbthis medication.
Avoid takingdiet pills,caffeine pills,or otherstimulants (suchas ADHDmedications) withoutyour doctor'sadvice.
Takinga stimulanttogether witha decongestantcan increaseyour riskof unpleasantside effects.
Keep takingthe medicationand talkto yourdoctor ifyou haveany ofthese lessserious sideeffects: blurredvision; drymouth; nausea,stomach pain,constipation; mildloss ofappetite, stomachupset; warmth,tingling, orredness underyour skin;sleep problems(insomnia); restlessor excitability(especially inchildren); skinrash oritching; dizziness,drowsiness; problemswith memoryor concentration;or ringingin yourears.
Sideeffects otherthan thoselisted heremay alsooccur.
Talkto yourdoctor aboutany sideeffect thatseems unusualor thatis especiallybothersome.
Ifyou areusing anyof thesedrugs, youmay notbe ableto useAllegra D,or youmay needdosage adjustmentsor specialtests duringtreatment.
Theremay beother drugsnot listedthat canaffect AllegraD.
Thisincludes vitamins,minerals, herbalproducts, anddrugs prescribedby otherdoctors.
Donot startusing anew medicationwithout tellingyour doctor.
Other brandor genericformulations mayalso beavailable.
Askyour pharmacistany questionsyou haveabout thismedication, especiallyif itis newto you.
You maynot beable totake medicationthat containsacetaminophen.
Keeptrack ofhow manytablets havebeen usedfrom eachnew bottleof thismedicine.
Hydrocodoneis adrug ofabuse andyou shouldbe awareif anyperson inthe householdis usingthis medicineimproperly orwithout aprescription.
Nevertake moreVicodin thanis prescribed.
Tell yourdoctor ifthe medicineseems tostop workingas wellin relievingyour pain.
Hydrocodone isin agroup ofdrugs callednarcotic painrelievers.
Itis similarto codeine.
Acetaminophen isa lesspotent painreliever thatincreases theeffects ofhydrocodone.
Thecombination ofacetaminophen andhydrocodone isused torelieve moderateto severepain.
Vicodinmay alsobe usedfor purposesother thanthose listedin thismedication guide.
Before usingVicodin, tellyour doctorif youare allergicto anydrugs, orif youhave: asthma,COPD, sleepapnea, orother breathingdisorders; underactivethyroid; ahistory ofhead injuryor braintumor; epilepsyor otherseizure disorder;low bloodpressure; gallbladderdisease; Addison'sdisease orother adrenalgland disorders;enlarged prostate,urination problems;mental illness;or ahistory ofdrug oralcohol addiction.
If youhave anyof theseconditions, youmay notbe ableto useVicodin, oryou mayneed adosage adjustmentor specialtests duringtreatment.
Keeptrack ofhow manytablets havebeen usedfrom eachnew bottleof thismedicine.
Hydrocodoneis adrug ofabuse andyou shouldbe awareif anyperson inthe householdis usingthis medicineimproperly orwithout aprescription.
Usethis medicationexactly asit wasprescribed foryou.
Donot usethe medicationin largeramounts, oruse itfor longerthan recommendedby yourdoctor.
Followthe directionson yourprescription label.
If yourmedicine contains650 mgof acetaminophenor moreper tablet,take nomore than5 tabletsin 24hours.
Ifyour medicinecontains 500mg orless ofacetaminophen, takeno morethan 8tablets in24 hours.
Tell yourdoctor ifthe medicineseems tostop workingas wellin relievingyour pain.
If youneed tohave anytype ofsurgery, tellthe surgeonahead oftime thatyou areusing Vicodin.
You mayneed tostop usingthe medicinefor ashort time.
Since Vicodinis sometimesused asneeded, youmay notbe ona dosingschedule.
Ifyou aretaking themedication regularly,take themissed doseas soonas youremember.
Ifit isalmost timefor thenext dose,skip themissed doseand waituntil yournext regularlyscheduled dose.
Do notuse extramedicine tomake upthe misseddose.
Avoidusing othermedicines thatmake yousleepy (suchas coldmedicine, painmedication, musclerelaxers, andmedicine forseizures, depressionor anxiety).
They canadd tosleepiness causedby hydrocodone,which couldresult inextreme drowsinessor coma.
Less seriousside effectsare morelikely tooccur, suchas: constipation;urinating lessthan usual;nausea, vomiting,loss ofappetite; dizziness,headache; oritching.
Sideeffects otherthan thoselisted heremay alsooccur.
Talkto yourdoctor aboutany sideeffect thatseems unusualor thatis especiallybothersome.
Beforetaking thismedication, tellyour doctorif youare usingany ofthe followingdrugs: anMAO inhibitorsuch asisocarboxazid (Marplan),phenelzine (Nardil),rasagiline (Azilect),selegiline (Eldepryl,Emsam), ortranylcypromine (Parnate);or antidepressantssuch asamitriptyline (Elavil,Etrafon), amoxapine(Ascendin), clomipramine(Anafranil), desipramine(Norpramin), imipramine(Janimine, Tofranil),nortriptyline (Pamelor),protriptyline (Vivactil),or trimipramine(Surmontil).
Ifyou areusing anyof thesedrugs, youmay notbe ableto useVicodin, oryou mayneed dosageadjustments orspecial testsduring treatment.
There maybe otherdrugs notlisted thatcan affectVicodin.
Thisincludes vitamins,minerals, herbalproducts, anddrugs prescribedby otherdoctors.
Donot startusing anew medicationwithout tellingyour doctor.
Other brandor genericformulations mayalso beavailable.
Askyour pharmacistany questionsyou haveabout thismedication, especiallyif itis newto you.
Version: 7.02.Revision date:8/24/06 2:59:34PM.
Withoutthis enzyme,cellular wasteproducts accumulatein tissuesand organs,which thenbegin tomalfunction.
Elapraseis thefirst andonly treatmentapproved forpeople sufferingfrom Huntersyndrome.
Theproduct, whichis givenas weeklyinfusions, replacesthe missingenzyme thatHunter syndromepatients failto producein sufficientquantities.
Shireis pleasedto reportthat thisendpoint achievedstatistical significancecompared toplacebo.
Afterone yearof treatment,patients receivingweekly infusionsof Elapraseexperienced amean increasein thedistance walkedin sixminutes of35 meterscompared topatients receivingplacebo.
Adversereactions werecommonly reportedin associationwith infusions,and weregenerally mildto moderate.
The Elapraselabel includesa boxedwarning withinformation onthe potentialfor hypersensitivityreactions.
Theboxed warningstates that"Anaphylactoid reactions,which maybe lifethreatening, havebeen observedin somepatients duringElaprase infusions.
Therefore, appropriatemedical supportshould bereadily availablewhen Elapraseis administered.
Patients withcompromised respiratoryfunction oracute respiratorydisease maybe atrisk ofserious acuteexacerbation oftheir respiratorycompromise dueto infusionreactions, andrequire additionalmonitoring."
In allphases ofclinical studyfor Elaprase,11 patientsexperienced significanthypersensitivity reactionsduring 19of 8,274infusions (0.2%)and nopatients discontinuedtreatment permanentlyas aresult ofa hypersensitivityreaction.
Themost commonadverse eventsobserved in30% ofpatients duringthe PhaseII/III trialwere pyrexia,headache andarthralgia.
Huntersyndrome (MPSII) isa seriousgenetic disordermainly affectingmales thatinterferes withthe body'sability tobreak downand recyclewaste substancescalled mucopolysaccharides,also knownas glycosaminoglycansor GAG.
Hunter syndromeis oneof severalrelated lysosomalstorage diseases.
In Huntersyndrome, cumulativebuildup ofGAG incells throughoutthe bodyinterferes withthe waycertain tissuesand organsfunction, leadingto severeclinical complicationsand earlymortality.
Physicalmanifestations forsome peoplewith Huntersyndrome mayinclude distinctfacial features,a largehead andan enlargedabdomen.
Peoplewith Huntersyndrome mayalso experiencehearing loss,thickening ofthe heartvalves leadingto adecline incardiac function,obstructive airwaydisease, sleepapnea, andenlargement ofthe liverand spleen.
In somecases, centralnervous systeminvolvement leadsto progressiveneurologic decline.
Version: 1.05.Revision Date:2/14/03.
Thisis about57.7 millionpeople.
Eventhough mentaldisorders arewidespread, themain burdenof illnessis concentratedin about6 percentof thepopulation (1in 17people) whosuffer froma seriousmental illness.
Mental disordersare theleading causeof disabilityin theU.S.
Manypeople sufferfrom morethan onemental disorderat agiven time.
Nearly half(45 percent)of thosewith anymental disordermeet criteriafor 2or moredisorders; themore severethe disorder,the greaterthe likelihoodof comorbidity,that is,experiencing morethan onedisorder simultaneously.
Mental disorderscan beclassified asmood disorders,schizophrenia, anxietydisorders, eatingdisorders, attentiondeficit hyperactivitydisorder (ADHD),autism, andAlzheimer sdisease.
Mooddisorders includemajor depressivedisorder, dysthymiaand bipolardisorder.
Peoplethat takedrugs totreat diseasesand disorders,which interferewith theirability tofunction, mayexperience improvementof theircondition.
Adistinction isfrequently madebetween recreationaluse ofdrugs anddrug abuse,although thereis muchcontroversy onwhere thedividing linelies onthe spectrumfrom adrug userto adrug abuser.
Some saythat abusebegins whenthe userbegins shirkingresponsibility inorder toafford drugsor tohave enoughtime touse them.
Some sayit beginswhen aperson useswhat isdeemed tobe excessiveamounts, whileothers drawthe lineat thepoint oflegality.
Stillothers believeit amountsto chronicuse whenmental andphysical healthbegin degeneratingin theuser.
Somethink thatany intoxicantconsumption isan inappropriateactivity.
Afurther distinctioncan bemade inthat itis theuse ofthe drugthat isrecreational, andnot thedrug itself.
A genericmust containthe sameactive ingredientsas theoriginal formulation.
In mostcases, itis consideredbioequivalent tothe brandname counterpartwith respectto pharmacokineticand pharmacodynamicproperties.
Byextension, therefore,generics areassumed tobe identicalin dose,strength, routeof administration,safety, efficacy,and intendeduse.
Inmost cases,generic productsare notavailable untilthe patentprotections affordedto theoriginal developerhave expired.
When genericproducts becomeavailable, themarket competitionoften leadsto substantiallylower pricesfor boththe originalbrand nameproduct andthe genericforms.
Thetime ittakes ageneric drugto appearon themarket varies.
Drug patentsgive twentyyears ofprotection, butthey areapplied forbefore clinicaltrials begin,so theeffective lifeof adrug patenttends tobe betweenseven andtwelve years.
The principalreason forthe relativelylow priceof genericmedicines isthat thesecompanies incurfewer costsin creatingthe genericdrug, andare thereforeable tomaintain profitabilitywhile offeringthe drugat alower costto consumers.
The costsof thesegeneric drugsare solow thatmany developingcountries caneasily afford.
Generic manufacturersalso donot bearthe burdenof provingthe safetyand efficacyof thedrugs throughclinical trials,since thesetrials havealready beenconducted bythe brandname company.
In mostcountries, genericmanufacturers mustonly provethat theirpreparation isbioequivalent tothe existingdrug inorder togain regulatoryapproval.
Priorto theexpiration ofa drugpatent, abrand namecompany enjoysa periodof "marketexclusivity" ormonopoly, inwhich thecompany isable toset theprice ofthe drugat thelevel whichmaximizes profitability.
This priceoften greatlyexceeds theproduction costsof thedrug, whichcan enablethe drugcompany tomake asignificant profiton theirinvestment inresearch anddevelopment.
Theadvantage ofgeneric drugsto consumerscomes inthe introductionof competition,which preventsany singlecompany fromdictating theoverall marketprice ofthe drug.
When apharmaceutical companyfirst marketsa drug,it isusually undera patentthat allowsonly thepharmaceutical companythat developedthe drugto sellit.
Genericdrugs canbe legallyproduced fordrugs where:1) thepatent hasexpired, 2)the genericcompany certifiesthe brandcompany's patentsare eitherinvalid, unenforceableor willnot beinfringed, 3)for drugswhich havenever heldpatents, or4) incountries wherea patent(s)is/are notin force.
The expirationof apatent removesthe monopolyof thepatent holderon drugsales licensing.
Patent lifetimediffers fromcountry tocountry, andtypically thereis noway torenew apatent afterit expires.
A newversion ofthe drugwith significantchanges tothe compoundcould bepatented, butthis requiresnew clinicaltrials anddoes notprevent thegeneric versionsof theoriginal drug.
This allowsthe companyto recoupthe costof developingthat particulardrug.
Afterthe patenton adrug expires,any pharmaceuticalcompany canmanufacture andsell thatdrug.
Sincethe drughas alreadybeen testedand approved,the costof simplymanufacturing thedrug willbe afraction ofthe originalcost oftesting anddeveloping thatparticular drug.
This mayinvolve aggressivelitigation topreserve orextend patentprotection ontheir medicines,a processreferred toby criticsas "evergreening."
Patentsare typicallyissued onnovel pharmacologicalcompounds quiteearly inthe drugdevelopment process,at whichtime the'clock' topatent expirationbegins ticking.
Food andDrug Administrationoffers a180 dayexclusivity periodto genericdrug manufacturersin specificcases.
Duringthis periodonly one(or sometimesa few)generic manufacturerscan producethe genericversion ofa drug.
This exclusivityperiod isonly usedwhen ageneric manufacturerargues thata patentis invalidor isnot violatedin thegeneric productionof adrug, andthe periodacts asa rewardfor thegeneric manufacturerwho iswilling torisk liabilityin courtand thecost ofpatent courtlitigation.
Thereis oftencontention aroundthese 180day exclusivityperiods becausea genericproducer doesnot haveto producethe drugduring thisperiod andcan filean applicationfirst toprevent othergeneric producersfrom sellingthe drug.
Large pharmaceuticalcompanies oftenspend thousandsof dollarsprotecting theirpatents fromgeneric competition.
Apart fromlitigation, companiesuse othermethods suchas reformulationor licensinga subsidiary(or anothercompany) tosell genericsunder theoriginal patent.
Generics soldunder licensefrom thepatent holderare knownas authorizedgenerics; theyare notaffected bythe 180day exclusivityperiod asthey fallunder thepatent holder'soriginal drugapplication.
Aprime exampleof howthis worksis simvastatin(Zocor), apopular drugcreated andmanufactured byU.S.
MerckCo., whichlost itsUS patentprotection onJune 23,2006.
However,Dr. Reddy'sLaboratories alsomarkets anauthorized genericversion ofsimvastatin underlicense fromZocor's manufacturer,Merck Co.;some packagesof Dr.
Reddy's simvastatineven showMerck asthe actualmanufacturer andhave Merck'slogo onthe bottom.
Most nationsrequire genericdrug manufacturersto provethat theirformulation exhibitsbioequivalence tothe innovatorproduct.
Overthe pastseveral yearsthere havebeen studiesthat haveshown theeffectiveness andsafety ofsome genericdrugs.
Genericdrugs arealways lessexpensive andcan savepatients andinsurance companiesthousands ofdollars supposedlywithout compromisingthe qualityof care.
The FDAmust approvegeneric drugsjust asinnovator drugsmust beapproved.
Bioequivalence,however, doesnot meanthat genericdrugs areexactly thesame astheir innovatorproduct counterparts,as chemicaldifferences doexist.
Somedoctors andpatients emphaticallybelieve thatcertain genericdrugs arenot aseffective asthe productsthey aremeant toreplace (ie.
Prozac, Oxycontin),and consumerswould undoubtedlybenefit frommore clinicalstudies doneon drugby drugbasis.
Genericdrugs startout atfirst beingfairly expensive,however theprice ofthe genericproduct decreasesas therate ofproduction increases.
Warfarin (eitherunder thetrade nameor thegeneric equivalent)has anarrow therapeuticwindow andrequires frequentblood teststo makesure patientsdo nothave asubtherapeutic ora toxiclevel.
Anapplicant filesan AbbreviatedNew DrugApplication (or"ANDA") withthe Foodand DrugAdministration (FDA)and seeksto demonstratetherapeutic equivalenceto aspecified,previously approved"reference listeddrug."
When anANDA isapproved, theFDA addsthe drugto itsApproved DrugProducts list,also knownas the"Orange Book",and annotatesthe listto showequivalence betweenthe referencelisted drugand theapproved generic.
The FDAalso recognizesdrugs usingthe sameingredients withdifferent bioavailabilityand dividesthem intotherapeutic equivalencegroups.
Althoughbeing addictedimplies drugdependence, itis possibleto bedependent ona drugwithout beingaddicted.
Peoplethat takedrugs totreat diseasesand disorders,which interferewith theirability tofunction, mayexperience improvementof theircondition.
Suchpersons aredependent onthe drug,but arenot addicted.
One isaddicted, ratherthan merelydependent, ifone exhibitscompulsive behaviortowards thedrug andhas difficultyquitting it.
To qualifyas beingdependent aperson mustSubstance abusecan occurwith orwithout dependency,and withor withoutaddiction.
Substanceabuse isany useof asubstance, whichcauses moreharm thangood.
Drugaddiction hastwo components:physical dependency,and psychologicaldependency.
Physicaldependency occurswhen adrug hasbeen usedhabitually andthe bodyhas becomeaccustomed toits effects.
The personmust thencontinue touse thedrug inorder tofeel normal,or itsabsence willtrigger thesymptoms ofwithdrawal.
Psychologicaldependency occurswhen adrug hasbeen usedhabitually andthe mindhas becomeemotionally relianton itseffects, eitherto elicitpleasure orrelieve pain,and doesnot feelcapable offunctioning withoutit.
Itsabsence producesintense cravings,which areoften broughton ormagnified bystress.
Adependent personmay haveeither aspectsof dependencyor both.
Chipping" isalso aterm usedto describea patternof druguse inwhich theuser isnot physicallydependent andsustains 'controlleduse' ofa drug.
This isdone byavoiding influencesthat reinforcedependence, suchthat thedrug isused forrelaxation andnot forescape.
Thisis similarto themedical term'recreational substanceuse'.
Thephenomenon ofdrug addictionhas occurredto somedegree throughoutrecorded history(see "opium"),though modernagricultural practices,improvements inaccess todrugs, advancementsin biochemistry,and dramaticincreases inthe recommendationof drugusage byclinical practitionershave exacerbatedthe problemsignificantly inthe 20thcentury.
Improvedmeans ofactive biologicalagent manufactureand theintroduction ofsynthetic compounds,such asmethamphetamine arealso factorscontributing todrug addiction.
The addictivenature ofdrugs variesfrom substanceto substance,and fromindividual toindividual.
Drugssuch ascodeine oralcohol, forinstance, typicallyrequire manymore exposuresto addicttheir usersthan drugssuch asheroin orcocaine.
Likewise,a personwho ispsychologically orgenetically predisposedto addictionis muchmore likelyto sufferfrom it.
There areanecdotal reportsof psychologicaladdiction torecreational stimulantssuch asMDMA (ecstasy)and adissociative psychedelicketamine.
Pillssold onthe streetas "ecstasy"often containadulterants, whichmay bethe addictivecompound.
Drugsof abusetake overthe neurologicalcircuitry involvedin motivationand reward.
These pathwaysalso activatefaster witheach use.
The quickerthe effect,or 'high',the strongerthe dysfunctionallearning.
Inaddition, objects,people, orplaces alsoseem toto bestrongly associatedwith thedrug experience,making them'triggers' to'cravings' andincrease thechances offurther use.
Unfortunately, substanceabuse alsoinhibits furtherlearning, meaningcontinued usemakes unlearningmore challenging.
Effectively assessingwhere anindividual isin addictionand tailoringtreatment tothis wouldmake treatmentoutcomes moreeffective.
Animalstudies haveshown thatdrug availability(over andabove theactual effectsof thesubstance) areassociated withstimuli exposureto objectsassociated withuse; thesetrigger therelease ofadrenaline (whichcauses "fightor flight"response).
Theexcitation canbe perceivedas a'need' touse.
Glutamate,Dopamine, andSerotonin havelong beenassociated withhighly dependentaddictions arewell establishedas keyto thecompulsive behaviorrelated tococaine andamphetamine use,Norepinephrine,GABA NMDAare alsovery importantin termsof learningand 'Addiction'With GABAseeming strongin termsof alcoholabuse andthe correspondingcrash.
Itis obviousthat genesfor addictionwould notbe directlyselected.
Sinceevolution theoryclaims thatevery physicaland behavioraltrait isa director sideeffect ofselection, thenthe capacityto beaddicted todrugs mustbe aside effectof somethingthat wasselected.
Itis easyto understandhow sensitivityto socialrewards wouldevolve insocial primates.
For example,Jane Goodall'sobservation thatchimpanzees whohunt getadditional matingopportunities.
Theproposed evolvedmechanism forsocial rewardsis thatattention causesthe releaseof endorphinsand dopamineinto thebrain's rewardcircuits.
Itseems thataddictive drugsactivate brainreward circuitsthat arenormally activatedby attention,without theneed tokill alarge, dangerousanimal anddrag itback tocamp (ormodern equivalents).
The CREBprotein, atranscription factoractivated bycyclic adenosinemonophosphate (cAMP)immediately aftera high,triggers genesthat produceproteins suchas dynorphin,which cutsoff dopaminerelease andtemporarily inhibitsthe rewardcircuit.
Inchronic drugusers, asustained activationof CREBleaves theuser feelingdepressed anddissatisfied, andunable tofind pleasurein previouslyenjoyable activities,often leadingto areturn tothe drugfor anadditional "fix".
It alsoleads toa shortterm toleranceof thesubstance, necessitatingthat agreater amountbe takenin orderto reachthe samehigh.
Anothertranscription factor,known asdelta FosB,is thoughtto activategenes that,counter tothe effectsof CREB,actually increasethe user'ssensitivity tothe effectsof thesubstance.
Thehypersensitivity thatit causesis thoughtto beresponsible forthe intensecravings associatedwith drugaddiction, andis oftenextended toeven theperipheral cuesof druguse, suchas relatedbehaviors orthe sightof drugparaphernalia.
Thereis someevidence thatdelta FosBeven causesstructural changeswithin thenuclear accumbens,which presumablyhelps toperpetuate thecravings, andmay beresponsible forthe highincidence ofrelapse thatoccur intreated drugaddicts.
Themechanisms bywhich differentsubstances activatethe rewardsystem varyamong drugclasses.
Themost commondrug addictionsare tolegal substancessuch as:Many prescriptionor overthe counterdrugs areextremely addictiveor canbecome soif misused.
In addition,a largenumber ofother substances,which areare currentlyconsidered tohave nomedical valueand arenot availableover thecounter orby prescription.
Depending onthe jurisdiction,these drugsmay belegal onlyas partof agovernment sponsoredstudy, illegalto usefor anypurpose, illegalto sell,or evenillegal tomerely possess.
It isunclear, though,whether lawsagainst drugsdo anythingto stemusage anddependency.
Injurisdictions whereaddictive drugsare illegal,they aregenerally suppliedby drugdealers, whoare ofteninvolved withorganized crime.
Even thoughthe costof producingmost illegaladdictive substancesis verylow, theirillegality combinedwith theaddict's needpermits theseller tocommand apremium price,often hundredsof timesthe productioncost.
Asa result,the addictsometimes turnsto crimeto supporttheir habit.
Methods ofrecovery fromaddiction todrugs varywidely accordingto thetypes ofdrugs involved,amount ofdrugs used,duration ofthe drugaddiction, medicalcomplications andthe socialneeds ofthe individual.
Treatment isjust asimportant forthe addictedindividual asfor thesignificant othersin theaddicted individualssphere ofcontact.
Oneof manyrecovery methodsis the12 steprecovery program,with prominentexamples includingAlcoholics Anonymousand NarcoticsAnonymous.
Theyare commonlyknown andused fora varietyof addictionsfor theindividual addictedand thefamily ofthe individual.
Outpatient clinicsusually offera combinationof individualcounseling andgroup counseling.
Frequently aphysician orpsychiatrist willassist withprescriptions toassist withthe sideeffects ofthe addiction(the mostcommon sideeffect thatthe medicationscan helpis anxiety).
Residential drugtreatment canbe broadlydivided intotwo camps:12 stepprograms orTherapeutic Communities.
In theUK drugtreatment isgenerally movingtowards amore integratedapproach withrehabs offeringa varietyof approaches.
CBT seesaddiction asa behaviourrather thana diseaseand subsequentlycurable, orrather, unlearnable.
CBT programmesrecognise thatfor someindividuals controlleduse isa morerealistic possibility.
Other formsof treatmentinvolve replacementdrugs suchas methadone.
Although methadoneis itselfaddictive, opioiddependency isoften sostrong thata wayto stabiliselevels ofopioid neededand away togradually reducethe levelsof opioidneeded arerequired.
Othertreatments, suchas acupuncture,may beused tohelp alleviatesymptoms aswell.
However,In 1997,the followingstatement wasadopted aspolicy ofthe AmericanMedical Association(AMA) aftera reporton anumber ofalternative therapiesincluding acupuncture:There islittle evidenceto confirmthe safetyor efficacyof mostalternative therapies.
Much ofthe informationcurrently knownabout thesetherapies makesit clearthat manyhave notbeen shownto beefficacious.
Determiningthe besttype ofrecovery programfor anaddicted persondepends ona numberof factors,including: personality,drug(s) ofaddiction, conceptof spiritualityor religion,mental orphysical illness,and localavailability andaffordability ofprograms.
Ibogaineis an(unpleasant) psychoactivedrug thatspecifically interruptsthe addictiveresponse, andis currentlybeing studiedfor itseffects uponcocaine, heroin,nicotine, andSSRI addicts.
Alternative medicineclinics offeringibogaine treatmenthave appearedalong theU.S.
Manydifferent ideascirculate regardingwhat isconsidered a"successful" outcomein therecovery fromaddiction.
Ithas widelybeen establishedthat abstinencefrom addictivesubstances isgenerally acceptedas a"successful" outcome.
Its characteristicsinclude: (i)an overpoweringdesire orneed (compulsion)to continuetaking thedrug andto obtainit byany means;(ii) atendency toincrease thedose; (iii)a psychic(psychological) andgenerally aphysical dependenceon theeffects ofthe drug;and (iv)detrimental effectson theindividual andon society.
Drug habituation(habit) isa conditionresulting fromthe repeatedconsumption ofa drug.
In 1964,a newWHO committeefound thesedefinitions tobe inadequate,and suggestedusing theblanket term"drug dependence":The definitionof addictiongained someacceptance, butconfusion inthe useof theterms addictionand habituationand misuseof theformer continued.
Further, thelist ofdrugs abusedincreased innumber anddiversity.
Thesedifficulties havebecome increasinglyapparent andvarious attemptshave beenmade tofind aterm thatcould beapplied todrug abusegenerally.
Thecomponent incommon appearsto bedependence, whetherpsychic orphysical orboth.
Hence,use ofthe term'drug dependence',with amodifying phaselinking itto aparticular drugtype inorder todifferentiate oneclass ofdrugs fromanother, hadbeen givenmost carefulconsideration.
TheExpert Committeerecommends substitutionof theterm 'drugdependence' forthe terms'drug addiction'and 'drughabituation'.
Thecommittee didnot clearlydefine dependence,but didgo onto clarifythat therewas adistinction betweenphysical andpsychological ("psychic")dependence.
Itsaid thatdrug abusewas "astate ofpsychic dependenceor physicaldependence, orboth, ona drug,arising ina personfollowing administrationof thatdrug ona periodicor continuedbasis."
The 1957and 1964definitions ofaddiction, dependenceand abusepersist tothe presentday inmedical literature.
It shouldbe notedthat atthis time(2006) theDiagnostic StatisticalManual (DSMIVR) nowspells outspecific criteriafor definingabuse anddependence.
In2001, theAmerican Academyof PainMedicine, theAmerican PainSociety, andthe AmericanSociety ofAddiction Medicinejointly issued"Definitions Relatedto theUse ofOpioids forthe Treatmentof Pain,"which definedthe followingterms: Addictionis aprimary, chronic,neurobiologic disease,with genetic,psychosocial, andenvironmental factorsinfluencing itsdevelopment andmanifestations.
Itis characterizedby behaviorsthat includeone ormore ofthe following:impaired controlover druguse, compulsiveuse, continueduse despiteharm, andcraving.
Physicaldependence isa stateof adaptationthat ismanifested bya drugclass specificwithdrawal syndromethat canbe producedby abruptcessation, rapiddose reduction,decreasing bloodlevel ofthe drug,and/or administrationof anantagonist.
Toleranceis thebody's physicaladaptation toa drug:greater amountsof thedrug arerequired overtime toachieve theinitial effectas thebody "getsused to"and adaptsto theintake.
Pseudoaddictionis aterm whichhas beenused todescribe patientbehaviors thatmay occurwhen painis undertreated.
Pseudoaddiction canbe distinguishedfrom trueaddiction inthat thebehaviors resolvewhen painis effectivelytreated.
Typicallythis legislationcovers anyor allof theopiates, cannabinoids,cocaine, barbiturates,hallucinogenics anda varietyof moremodern syntheticdrugs, andunlicensed production,supply orpossession isa criminaloffence.
Usually,however, drugclassification undersuch legislationis notrelated simplyto addictiveness.
The substancescovered oftenhave verydifferent addictiveproperties.
Someare highlyprone tocause physicaldependency, whilstothers rarelycause anyform ofcompulsive needwhatsoever.
Also,under legislationspecifically aboutdrugs, alcoholis notusually included.
Although thelegislation maybe justifiableon moralor publichealth grounds,it canmake addictionor dependencya muchmore seriousissue forthe individual:reliable suppliesof adrug becomedifficult tosecure, andthe individualbecomes vulnerableto bothcriminal abuseand legalpunishment.
Newchemical entities(NCEs) arecompounds whichemerge fromthe processof drugdiscovery.
Thesewill havepromising activityagainst aparticular biologicaltarget thoughtto beimportant indisease, howeverlittle willbe knownabout thesafety, toxicity,pharmacokinetics andmetabolism ofthis NCEin humans.
It isthe functionof drugdevelopment toassess allof theseparameters priorto humanclinical trials.
In addition,drug developmentis requiredto establishthe physicochemicalproperties ofthe NCE:its chemicalmakeup, stability,solubility.
Theprocess bywhich thechemical ismade willbe optimizedso thatfrom beingmade atthe benchon amilligram scaleby asynthetic chemist,it canbe manufacturedon thekilogram andthen onthe tonscale.
Itwill befurther examinedfor itssuitability tobe madeinto capsules,tablets, aeresol,intramuscular injectable,subcuteneous injectable,or intravenousformulations.
Togetherthese processesare knownin preclinicaldevelopment asCMC: Chemistry,Manufacturing andControl.
Manyaspects ofdrug developmentare focusedon satisfyingthe regulatoryrequirements ofdrug licensingauthorities.
Thesegenerally constitutea numberof testsdesigned todetermine themajor toxicitiesof anovel compoundprior tofirst usein man.
It isa legalrequirement thatan assessmentof majororgan toxicitybe performed(effects onthe heartand lungs,brain, kidney,liver anddigestive system),as wellas effectson otherparts ofthe bodythat mightbe affectedby thedrug (e.g.
While, increasingly,these testscan bemade usingin vitromethods (e.g.
The processof drugdevelopment doesnot stoponce anNCE beginshuman clinicaltrials.
Thecompound willalso betested forits abilityto causecancer (carcinogenicitytesting).
Ifa compoundemerges fromthese testswith anacceptable toxicityand safetyprofile, andit canfurther bedemonstrated tohave thedesired effectin clinicaltrials, thenit canbe submittedfor marketingapproval inthe variouscountries whereit willbe sold.
In theUS, thisprocess iscalled aNew DrugApplication orNDA.
MostNCEs, however,will failduring drugdevelopment, eitherbecause theyhave someunacceptable toxicity,or becausethey simplydo notwork inclinical trials.
As thisdrug discoveryprocess becomesmore expensiveit isbecoming importantto lookat newways tobring forwardNCEs.
Oneapproach toimprove efficiencyis torecognize thatthere aremany stepsrequiring differentlevels ofexperimentation.
Theearly phaseof drugdiscovery actuallyhas componentsof realinnovation, componentsof experimentationand componentsthat involveset routines.
This modelof Innovation,Experimentation, andCommoditization ensuresthat newways todo workare adoptedcontinually.
Thismodel alsoallows thediscipline touse appropriateinternal andexternal resourcesfor theright work.
Each year,worldwide, onlyabout 26such drugsenter themarket (2005:26, 2004:24, 2003:26, 2002:28).
Thedevelopment costof thethousands ofother drugsare muchsmaller.
Peoplethat takedrugs totreat diseasesand disorders,which interferewith theirability tofunction, mayexperience improvementof theircondition.
Adistinction isfrequently madebetween recreationaluse ofdrugs anddrug abuse,although thereis muchcontroversy onwhere thedividing linelies onthe spectrumfrom adrug userto adrug abuser.
Some saythat abusebegins whenthe userbegins shirkingresponsibility inorder toafford drugsor tohave enoughtime touse them.
Some sayit beginswhen aperson useswhat isdeemed tobe excessiveamounts, whileothers drawthe lineat thepoint oflegality.
Stillothers believeit amountsto chronicuse whenmental andphysical healthbegin degeneratingin theuser.
Somethink thatany intoxicantconsumption isan inappropriateactivity.
Afurther distinctioncan bemade inthat itis theuse ofthe drugthat isrecreational, andnot thedrug itself.
Although beingaddicted impliesdrug dependence,it ispossible tobe dependenton adrug withoutbeing addicted.
People thattake drugsto treatdiseases anddisorders, whichinterfere withtheir abilityto function,may experienceimprovement oftheir condition.
Such personsare dependenton thedrug, butare notaddicted.
Oneis addicted,rather thanmerely dependent,if oneexhibits compulsivebehavior towardsthe drugand hasdifficulty quittingit.
Toqualify asbeing dependenta personmust Substanceabuse canoccur withor withoutdependency, andwith orwithout addiction.
Substance abuseis anyuse ofa substance,which causesmore harmthan good.
Drug addictionhas twocomponents: physicaldependency, andpsychological dependency.
Physical dependencyoccurs whena drughas beenused habituallyand thebody hasbecome accustomedto itseffects.
Theperson mustthen continueto usethe drugin orderto feelnormal, orits absencewill triggerthe symptomsof withdrawal.
Psychological dependencyoccurs whena drughas beenused habituallyand themind hasbecome emotionallyreliant onits effects,either toelicit pleasureor relievepain, anddoes notfeel capableof functioningwithout it.
Its absenceproduces intensecravings, whichare oftenbrought onor magnifiedby stress.
A dependentperson mayhave eitheraspects ofdependency orboth.
Chipping"is alsoa termused todescribe apattern ofdrug usein whichthe useris notphysically dependentand sustains'controlled use'of adrug.
Thisis doneby avoidinginfluences thatreinforce dependence,such thatthe drugis usedfor relaxationand notfor escape.
This issimilar tothe medicalterm 'recreationalsubstance use'.
The phenomenonof drugaddiction hasoccurred tosome degreethroughout recordedhistory (see"opium"), thoughmodern agriculturalpractices, improvementsin accessto drugs,advancements inbiochemistry, anddramatic increasesin therecommendation ofdrug usageby clinicalpractitioners haveexacerbated theproblem significantlyin the20th century.
Improved meansof activebiological agentmanufacture andthe introductionof syntheticcompounds, suchas methamphetamineare alsofactors contributingto drugaddiction.
Theaddictive natureof drugsvaries fromsubstance tosubstance, andfrom individualto individual.
Drugs suchas codeineor alcohol,for instance,typically requiremany moreexposures toaddict theirusers thandrugs suchas heroinor cocaine.
Likewise, aperson whois psychologicallyor geneticallypredisposed toaddiction ismuch morelikely tosuffer fromit.
Thereare anecdotalreports ofpsychological addictionto recreationalstimulants suchas MDMA(ecstasy) anda dissociativepsychedelic ketamine.
Pills soldon thestreet as"ecstasy" oftencontain adulterants,which maybe theaddictive compound.
Drugs ofabuse takeover theneurological circuitryinvolved inmotivation andreward.
Thesepathways alsoactivate fasterwith eachuse.
Thequicker theeffect, or'high', thestronger thedysfunctional learning.
In addition,objects, people,or placesalso seemto tobe stronglyassociated withthe drugexperience, makingthem 'triggers'to 'cravings'and increasethe chancesof furtheruse.
Unfortunately,substance abusealso inhibitsfurther learning,meaning continueduse makesunlearning morechallenging.
Effectivelyassessing wherean individualis inaddiction andtailoring treatmentto thiswould maketreatment outcomesmore effective.
Animal studieshave shownthat drugavailability (overand abovethe actualeffects ofthe substance)are associatedwith stimuliexposure toobjects associatedwith use;these triggerthe releaseof adrenaline(which causes"fight orflight" response).
The excitationcan beperceived asa 'need'to use.
Glutamate, Dopamine,and Serotoninhave longbeen associatedwith highlydependent addictionsare wellestablished askey tothe compulsivebehavior relatedto cocaineand amphetamineuse,Norepinephrine, GABANMDA arealso veryimportant interms oflearning and'Addiction' WithGABA seemingstrong interms ofalcohol abuseand thecorresponding crash.
It isobvious thatgenes foraddiction wouldnot bedirectly selected.
Since evolutiontheory claimsthat everyphysical andbehavioral traitis adirect orside effectof selection,then thecapacity tobe addictedto drugsmust bea sideeffect ofsomething thatwas selected.
It iseasy tounderstand howsensitivity tosocial rewardswould evolvein socialprimates.
Forexample, JaneGoodall's observationthat chimpanzeeswho huntget additionalmating opportunities.
The proposedevolved mechanismfor socialrewards isthat attentioncauses therelease ofendorphins anddopamine intothe brain'sreward circuits.
It seemsthat addictivedrugs activatebrain rewardcircuits thatare normallyactivated byattention, withoutthe needto killa large,dangerous animaland dragit backto camp(or modernequivalents).
TheCREB protein,a transcriptionfactor activatedby cyclicadenosine monophosphate(cAMP) immediatelyafter ahigh, triggersgenes thatproduce proteinssuch asdynorphin, whichcuts offdopamine releaseand temporarilyinhibits thereward circuit.
In chronicdrug users,a sustainedactivation ofCREB leavesthe userfeeling depressedand dissatisfied,and unableto findpleasure inpreviously enjoyableactivities, oftenleading toa returnto thedrug foran additional"fix".
Italso leadsto ashort termtolerance ofthe substance,necessitating thata greateramount betaken inorder toreach thesame high.
Another transcriptionfactor, knownas deltaFosB, isthought toactivate genesthat, counterto theeffects ofCREB, actuallyincrease theuser's sensitivityto theeffects ofthe substance.
The hypersensitivitythat itcauses isthought tobe responsiblefor theintense cravingsassociated withdrug addiction,and isoften extendedto eventhe peripheralcues ofdrug use,such asrelated behaviorsor thesight ofdrug paraphernalia.
There issome evidencethat deltaFosB evencauses structuralchanges withinthe nuclearaccumbens, whichpresumably helpsto perpetuatethe cravings,and maybe responsiblefor thehigh incidenceof relapsethat occurin treateddrug addicts.
The mechanismsby whichdifferent substancesactivate thereward systemvary amongdrug classes.
The mostcommon drugaddictions areto legalsubstances suchas: Manyprescription orover thecounter drugsare extremelyaddictive orcan becomeso ifmisused.
Inaddition, alarge numberof othersubstances, whichare arecurrently consideredto haveno medicalvalue andare notavailable overthe counteror byprescription.
Dependingon thejurisdiction, thesedrugs maybe legalonly aspart ofa governmentsponsored study,illegal touse forany purpose,illegal tosell, oreven illegalto merelypossess.
Itis unclear,though, whetherlaws againstdrugs doanything tostem usageand dependency.
In jurisdictionswhere addictivedrugs areillegal, theyare generallysupplied bydrug dealers,who areoften involvedwith organizedcrime.
Eventhough thecost ofproducing mostillegal addictivesubstances isvery low,their illegalitycombined withthe addict'sneed permitsthe sellerto commanda premiumprice, oftenhundreds oftimes theproduction cost.
As aresult, theaddict sometimesturns tocrime tosupport theirhabit.
Methodsof recoveryfrom addictionto drugsvary widelyaccording tothe typesof drugsinvolved, amountof drugsused, durationof thedrug addiction,medical complicationsand thesocial needsof theindividual.
Treatmentis justas importantfor theaddicted individualas forthe significantothers inthe addictedindividuals sphereof contact.
One ofmany recoverymethods isthe 12step recoveryprogram, withprominent examplesincluding AlcoholicsAnonymous andNarcotics Anonymous.
They arecommonly knownand usedfor avariety ofaddictions forthe individualaddicted andthe familyof theindividual.
Outpatientclinics usuallyoffer acombination ofindividual counselingand groupcounseling.
Frequentlya physicianor psychiatristwill assistwith prescriptionsto assistwith theside effectsof theaddiction (themost commonside effectthat themedications canhelp isanxiety).
Residentialdrug treatmentcan bebroadly dividedinto twocamps: 12step programsor TherapeuticCommunities.
Inthe UKdrug treatmentis generallymoving towardsa moreintegrated approachwith rehabsoffering avariety ofapproaches.
CBTsees addictionas abehaviour ratherthan adisease andsubsequently curable,or rather,unlearnable.
CBTprogrammes recognisethat forsome individualscontrolled useis amore realisticpossibility.
Otherforms oftreatment involvereplacement drugssuch asmethadone.
Althoughmethadone isitself addictive,opioid dependencyis oftenso strongthat away tostabilise levelsof opioidneeded anda wayto graduallyreduce thelevels ofopioid neededare required.
Other treatments,such asacupuncture, maybe usedto helpalleviate symptomsas well.
However, In1997, thefollowing statementwas adoptedas policyof theAmerican MedicalAssociation (AMA)after areport ona numberof alternativetherapies includingacupuncture: Thereis littleevidence toconfirm thesafety orefficacy ofmost alternativetherapies.
Muchof theinformation currentlyknown aboutthese therapiesmakes itclear thatmany havenot beenshown tobe efficacious.
Determining thebest typeof recoveryprogram foran addictedperson dependson anumber offactors, including:personality, drug(s)of addiction,concept ofspirituality orreligion, mentalor physicalillness, andlocal availabilityand affordabilityof programs.
Ibogaine isan (unpleasant)psychoactive drugthat specificallyinterrupts theaddictive response,and iscurrently beingstudied forits effectsupon cocaine,heroin, nicotine,and SSRIaddicts.
Alternativemedicine clinicsoffering ibogainetreatment haveappeared alongthe U.S.
Many differentideas circulateregarding whatis considereda "successful"outcome inthe recoveryfrom addiction.
It haswidely beenestablished thatabstinence fromaddictive substancesis generallyaccepted asa "successful"outcome.
Itscharacteristics include:(i) anoverpowering desireor need(compulsion) tocontinue takingthe drugand toobtain itby anymeans; (ii)a tendencyto increasethe dose;(iii) apsychic (psychological)and generallya physicaldependence onthe effectsof thedrug; and(iv) detrimentaleffects onthe individualand onsociety.
Drughabituation (habit)is acondition resultingfrom therepeated consumptionof adrug.
In1964, anew WHOcommittee foundthese definitionsto beinadequate, andsuggested usingthe blanketterm "drugdependence": Thedefinition ofaddiction gainedsome acceptance,but confusionin theuse ofthe termsaddiction andhabituation andmisuse ofthe formercontinued.
Further,the listof drugsabused increasedin numberand diversity.
These difficultieshave becomeincreasingly apparentand variousattempts havebeen madeto finda termthat couldbe appliedto drugabuse generally.
The componentin commonappears tobe dependence,whether psychicor physicalor both.
Hence, useof theterm 'drugdependence', witha modifyingphase linkingit toa particulardrug typein orderto differentiateone classof drugsfrom another,had beengiven mostcareful consideration.
The ExpertCommittee recommendssubstitution ofthe term'drug dependence'for theterms 'drugaddiction' and'drug habituation'.
The committeedid notclearly definedependence, butdid goon toclarify thatthere wasa distinctionbetween physicaland psychological("psychic") dependence.
It saidthat drugabuse was"a stateof psychicdependence orphysical dependence,or both,on adrug, arisingin aperson followingadministration ofthat drugon aperiodic orcontinued basis."
The1957 and1964 definitionsof addiction,dependence andabuse persistto thepresent dayin medicalliterature.
Itshould benoted thatat thistime (2006)the DiagnosticStatistical Manual(DSM IVR)now spellsout specificcriteria fordefining abuseand dependence.
In 2001,the AmericanAcademy ofPain Medicine,the AmericanPain Society,and theAmerican Societyof AddictionMedicine jointlyissued "DefinitionsRelated tothe Useof Opioidsfor theTreatment ofPain," whichdefined thefollowing terms:Addiction isa primary,chronic, neurobiologicdisease, withgenetic, psychosocial,and environmentalfactors influencingits developmentand manifestations.
It ischaracterized bybehaviors thatinclude oneor moreof thefollowing: impairedcontrol overdrug use,compulsive use,continued usedespite harm,and craving.
Physical dependenceis astate ofadaptation thatis manifestedby adrug classspecific withdrawalsyndrome thatcan beproduced byabrupt cessation,rapid dosereduction, decreasingblood levelof thedrug, and/oradministration ofan antagonist.
Tolerance isthe body'sphysical adaptationto adrug: greateramounts ofthe drugare requiredover timeto achievethe initialeffect asthe body"gets usedto" andadapts tothe intake.
Pseudoaddiction isa termwhich hasbeen usedto describepatient behaviorsthat mayoccur whenpain isundertreated.
Pseudoaddictioncan bedistinguished fromtrue addictionin thatthe behaviorsresolve whenpain iseffectively treated.
Typically thislegislation coversany orall ofthe opiates,cannabinoids, cocaine,barbiturates, hallucinogenicsand avariety ofmore modernsynthetic drugs,and unlicensedproduction, supplyor possessionis acriminal offence.
Usually, however,drug classificationunder suchlegislation isnot relatedsimply toaddictiveness.
Thesubstances coveredoften havevery differentaddictive properties.
Some arehighly proneto causephysical dependency,whilst othersrarely causeany formof compulsiveneed whatsoever.
Also, underlegislation specificallyabout drugs,alcohol isnot usuallyincluded.
Althoughthe legislationmay bejustifiable onmoral orpublic healthgrounds, itcan makeaddiction ordependency amuch moreserious issuefor theindividual: reliablesupplies ofa drugbecome difficultto secure,and theindividual becomesvulnerable toboth criminalabuse andlegal punishment.
Although thereare variousmethods oftaking drugs,injection isfavoured bysome usersas thefull effectsof thedrug areexperienced veryquickly, typicallyin fiveto tenseconds.
Thisshorter, moreintense highcan leadto adependency, bothphysical andpsychological, developingmore quicklythan withother methodsof takingdrugs.
Whilea widevariety ofdrugs areinjected, amongthe mostpopular inmany countriesare morphine,heroin, cocaine,amphetamine andmethamphetamine.
Unlikethe naloxonein theother formulationslisted above,atropine doesindeed helpmorphine andother narcoticscombat neuralgicpain.
Theatropine mayvery wellnot presenta problem,and thereis thepossibility forsolubale tabletshaving theiratropine contentreduced buputting themon anink blotterand puttinga dropof wateron themand takingthe remainderof thepill offthe blotterand cookingit up.
Of allthe waysto getdrugs intoyour system,injection hasthe mostrisks byfar asit bypassesthe body'snatural filteringmechanisms againstviruses, bacteriaand foreignobjects.
Therewill alwaysbe muchless riskof overdose,infections andhealth problemswith alternativesto injecting,such assmoking, snorting(nasal ingestion),or swallowing.
Viruses suchas HIVand hepatitisC areprevalent amonginjecting drugusers inmany countries,mostly dueto smallgroups possiblysharing injectionequipment combinedwith alack ofproper sterilization.
Other healthproblems arisefrom poorhygiene andinjection technique(be itIV, IM,or SC),such asCotton Fever,also knownas theShakes, phlebitis,abscesses, veincollapse, ulcers,malaria, gasgangrene, tetanus,septicaemia, thrombosisand embolismand theresults thereof,lodging ofpill fragmentsin smallblood vessels,the lungs,and elsewhere,and localinfections.
Hittingarteries andnerves isdangerous, painful,and presentsits ownsimilar spectrumof problems.
Harm reductionis aphilosophy ofpublic healthintended tobe aprogressive alternativeto theprohibition ofcertain lifestylechoices suchas thetaking ofillicit drugs.
While itdoes notcondone thetaking ofillicit drugs,it doesseek toreduce theharms arisingfrom theiruse, bothfor theperson takingillicit drugsand thewider community.
A philosophyof harmreduction promotesinformation andresources forinjecting drugusers.
Generalguidelines onsafer injectingvarious substancesintravenously aretypically basedon thefollowing steps.
The preparationarea fordrug preparationshould becleaned withwarm soapywater tominimize therisk ofbacterial infection.
The equipmentrequired involvesnew syringesand needles,swabs, sterilewater, filter,tourniquet anda cleanspoon orstericup.
Theperson shouldsoap theirhands withwarm waterand usea swabto wipedown thespoon.
Theswab shouldbe wipedonce, inone directiononly, overthe injectionsite andanother swabused onthe spoon.
A personshould notinject alonea dosefrom anunknown batchdue tothe dangersof overdosing.
They alsoshould underno circumstancesshare anyof theirinjecting equipment,even tourniquets,due tothe highdanger ofbacterial andviral transmission.
Sterile watershould bedrawn intothe syringewith theneedle uncappedto preventblunting, theninto thespoon toprepare themix.
Wheresterile wateris notobtainable, thenext optionis tapwater boiledfor fiveminutes.
Somedrugs needheat appliedto mixwith thewater completely,especially whenrelatively littlewater mustdissolve relativelymuch ofa drug.
Heroin inits baseform (commonillegal formin Europe)require anacid torender themix pHneutral.
Whilesome peopleuse lemonjuice todo this,this canlead toserious bacterialand/or fungalinfections.
Citricacid orascorbic acid(Vitamin C)is thebest optionand isusually availablein supermarketsin granularform.
Thenext bestoption isvinegar whichwill haveless chanceof bacteriathan lemonjuice butwill beeasy tocause burnsbecause itis hardto dose.
Suppositories canbe injectedby meltingthem ina littlehot waterand thenletting theresultant liquidcool inthe refrigeratorfor anumber ofhours, afterwhich theliquid ontop isdrawn offwith apipette, syringe,or eyedropper Themix shouldbe drawnup intothe syringethrough afilter.
Theideal hereis awheel filter,preferably 0,2micrometres, whichwill filterall microorganisms,but notviruses.
Groundup prescriptionpills usuallycontain manyfillers thatcan leadto veryserious healthproblems ifinjected, includinglung emboliesthat maybe trivialbut alsolife threatening.
Although notas efficient,alternative filtersinclude cottonwool, tamponsor cigarettefilters (ifthey donot havea fibreglassbase).
Oncethe mixis drawninto thesyringe, removeany airbubbles byflicking thebarrel withthe needlepointed upwards.
At thesame time,gently pushthe plungerto expelany air.
Place atourniquet abovethe injectionsite (injectionsites shouldbe rotatedto allowveins toheal).
Thetourniquet shouldnot beon tootight, orleft onfor toolong.
Makesure theneedle isgoing inthe samedirection asthe bloodflow.
Bloodshould appearin thebarrel ofthe syringeif thisis thecase.
Thisprocess isknown asregistering.
Ifit hurtsor thereis pressureagainst theplunger, stopimmediately asthe veinhas probablybeen missed.
After injection,remove thesyringe andkeep aclean tissueor cottonwool againstthe injectionsite toprevent bleeding.
Dispose ofinjecting gearusing a'sharps bin'if supplied.
A goodalternative forthose whovalue theeconomy ofinjecting butnot therush thatcomes withintravenous druguse mayuse alittle bitsafer injectingmethod, subcutaneousinjection, whichis suitablefor heroin,MDMA, andmost prescriptionpills, butcan notbe usedwith amphetamineor cocaine.
The safestalternative is,of course,not totake illicitdrugs.
Themajority oflegal systemsaround theworld encouragethis option.
Harm reductionacknowledges thatsome peoplein asociety willnot choosethis optionand willat leastprovide informationto safermeans oftaking illicitdrugs tominimise theindividual healthrisks, andalso thespread ofviruses suchas HIVand hepatitisC tothe widercommunity.
Aswith injection,a cleanpreparation surfaceis requiredto preparea drugfor snorting.
Nasal membranescan beseriously damagedfrom regularsnorting.
Smoking,often called'chasing thedragon', hasnegligible riskof bacterialor viraltransmission andthe riskof overdoseis lessenedcompared toinjecting.
Itstill retainsmuch ofthe 'rush'of injectingas theeffects ofthe drugoccur veryrapidly.
Itis afar saferway touse heroin,with thebest optionbeing touse newaluminium foil,first passinga cigarettelighter flameover bothsides toget ridof anycontaminants.
Swallowingtends tothe safestand slowestmethod ofingesting drugs.
It issafer asthe bodyhas amuch greaterchance tofilter outimpurities.
Asthe drugcomes onslower, theeffect tendsto lastlonger aswell, makingit afavourite techniqueon thedance scenefor speedand ecstasy.
People rarelytake heroinorally, asit isconverted tomorphine inthe stomachand itsstrength ishalved inthe process.
Pills likebenzodiazepines arebest swallowedas theyhave chalkor waxfillers inthem.
Shafting,or rectalingestion, relieson themany veinsin theanal passagepassing thedrug intothe bloodstream quiterapidly.
Someusers findthat tradingoff someof the'rush' formuch lesshealth risksis agood compromise.
Shafting usuallyinvolves about1.5 mlof fluidmixed withthe drug.
While squatting,gently insertthe syringe(without theneedle) untilit isjust insidethe anusthen easethe plungerdown.
Abit ofVaseline orlubricant willhelp ifthere isany pain.
The sphinctermuscles shouldbe strongenough tohold themix insidewhile itis absorbed.
It canpay todo atrial runwith waterfirst.
Womenhave theadded advantageof shelving,where drugscan beinserted inthe vagina.
This issimilar tothe rectum,in thatyou haveplenty ofblood vesselsbehind avery thinwall ofcells, sothe drugpasses intothe bloodstream veryquickly.
Careshould betaken withdrugs suchas amphetaminethat mayirritate thesensitive liningof therectum andvagina.
Someof themost commonlyabused drugsinclude alcohol,amphetamines, barbiturates,benzodiazepines, cocaine,methaqualone, andopium alkaloids.
Rather thanaccepting theloaded termsalcohol ordrug "abuse,"many publichealth professionalshave adoptedphrases suchas "alcoholand drugproblems" or"harmful/problematic use"of drugs.
This modelexplicitly recognizesa spectrumof use,ranging frombeneficial useto chronicdependence (seediagram tothe right).
The term"drug abuse"may beused innewspapers, television,etc.
Inthe modernmedical profession,the twomost useddiagnostic toolsin theworld, theAmerican PsychiatricAssociation's Diagnosticand StatisticalManual ofMental Disorders(DSM) andthe WorldHealth Organization'sInternational StatisticalClassification ofDiseases andRelated HealthProblems (ICD),no longerrecognise 'drugabuse' asa currentmedical diagnosis.
Instead, theyhave adoptedsubstance abuseas ablanket termto includedrug abuseand otherthings.
However,other definitionsdiffer; theymay entailpsychological orphysical dependence,and mayfocus ontreatment andprevention interms ofthe socialconsequences ofsubstance uses.
By thethird edition,in the1980s, drugabuse wasgrouped into'substance abuse'.
These drugsare oftencalled illegaldrugs but,generally, whatwas illegalis theirunlicensed production,supply andpossession.
Thedrugs arealso calledcontrolled drugsor controlledsubstances.
Dependingon theactual compound,drug abusemay leadto healthproblems, socialproblems, physicaldependence, orpsychological addiction.
Some drugsthat aresubject toabuse havecentral nervoussystem (CNS)effects, whichproduce changesin mood,levels ofawareness orperceptions andsensations.
Mostof thesedrugs alsoalter systemsother thanthe CNS.
But, notall centrallyacting drugsare subjectto abuse,which suggeststhat alteringconsciousness isnot sufficientfor adrug tohave abusepotential.
Stress,poverty, domesticand societalviolence, andvarious diseases(i.e., injectingdrug usersas asource forHIV/AIDS) aresometimes thoughtto bespread bydrug use.
Studies havealso shownthat individualsdependent onillicit drugsexperience higherrates ofcomorbid psychiatricsyndromes.
Thispragmatic approachis knownas theharm reductionparadigm.
Beyondthe sociologicalissues, manydrugs ofabuse canlead toaddiction, chemicaldependency, oradverse healtheffects, suchas lungcancer oremphysema fromcigarette smoking.
Medical treatmenttherefore centerson twoaspects: 1)breaking theaddiction, 2)treating thehealth problems.
Most countrieshave healthfacilities thatspecialize inthe treatmentof drugabuse, althoughaccess maybe limitedto largerpopulation centersand thesocial taboosregarding druguse maymake thosewho needthe medicaltreatment reluctantto takeadvantage ofit.
Thedevelopment ofpharmacotherapies fordrug dependencytreatment arecurrently inprogress.
Newimmunotherapies thatprevent drugslike cocaine,methamphetamine, phencyclidine,nicotine, andopioids fromreaching thebrain arein theearly stagesof testingas isibogaine, analkaloid foundin theTabernanthe ibogaplant ofWest CentralAfrica.
Medicationssuch asBuprenorphine, whichblock thedrugs activesite inthe brainare anothernew optionfor thetreatment ofopioid addiction.
Depot formsof medications,which requireonly weeklyor monthlydosing, arealso underinvestigation.
Traditionally,new pharmacotherapiesare quicklyadopted inprimary caresettings, however,drugs forsubstance abusetreatment havefaced manybarriers.
Naltrexone,a drugoriginally marketedunder thename "ReVia,"and nowmarketed inintramuscular formulationas "Vivitrol"or inoral formulationas ageneric, isa medicationapproved forthe treatmentof alcoholdependence.
Thisdrug hasreached veryfew patients.
This maybe dueto anumber offactors, includingresistance byAddiction Medicinespecialists andlack ofresources.
Mostgovernments havedesigned legislationto criminalisecertain typesof druguse.
Thesedrugs areoften called"illegal drugs"but generallywhat isillegal istheir unlicensedproduction, distribution,and possession.
These drugsare alsocalled "controlledsubstances".
Evenfor simplepossession, legalpunishment canbe quitesevere (includingthe deathpenalty insome countries).
Laws varyacross countries,and evenwithin them,and havefluctuated widelythroughout history.
Advocates ofdecriminalization arguethat drugprohibition makesdrug dealinga lucrativebusiness, leadingto muchof theassociated criminalactivity.
Thesedrugs maybe usedrecreationally topurposefully alterone's consciousness,as entheogensfor ritualor spiritualpurposes, ortherapeutically asmedication.
Psychoactivesubstances affectthe brainand bringabout subjectivechanges inmood thatthe usermay findpleasant.
Manypsychoactive substancesare abused,that is,used outsideof theguidance ofa medicalprofessional andfor reasonsother thantheir originalpurpose.
Withsustained use,physical dependencemay develop,making thecycle ofabuse evenmore difficultto interrupt.
Drug rehabilitationcan involvea combinationof psychotherapy,support groupsand evenother psychoactivesubstances tobreak thecycle ofdependency.
Inpart becauseof thispotential forabuse anddependency, theethics ofdrug useare thesubject ofa continuingphilosophical debate.
Many governmentsworldwide haveplaced restrictionson drugproduction andsales inan attemptto controldrug abuse.
Drug useis apractice thatdates toprehistoric times.
A numberof animalsconsume differentpsychoactive plants,animals, berriesand evenfermented fruit,becoming intoxicated,such ascats afterconsuming catnip.
A notableexample ofthis isthe Prohibitionera inthe UnitedStates, wherealcohol wasmade illegalfor 13years.
However,many governmentshave concludedthat illicitdrug usecannot besufficiently stoppedthrough criminalization.
In somecountries, therehas beena movetoward harmreduction byhealth services,where theuse ofillicit drugsis neithercondoned norpromoted, butservices andsupport areprovided toensure usershave thenegative effectsof theirillicit druguse minimized.
Psychoactive substancesare usedby humansfor anumber ofdifferent purposes,both legaland illicit.
General anestheticsare aclass ofpsychoactive drugused onpatients toblock painand othersensations.
Asthe subjectiveexperience ofpain isregulated byendorphins, neurochemicalsthat areendogenous opioids,pain canbe managedusing psychoactivesthat operateon thisneurotransmitter system.
Psychiatric medicationsare prescribedfor themanagement ofmental andemotional disorders.
There are6 majorclasses ofpsychiatric medications:Many psychoactivesubstances areused/abused fortheir moodand perceptionaltering effects,including thosewith accepteduses inmedicine andpsychiatry.
Psychoactivedrugs areadministered inseveral differentways.
Inmedicine, mostpsychiatric drugs,such asfluoxetine andoxycodone, areingested orallyin tabletor capsuleform.
However,certain medicalpsychoactives areadministered viainhalation, injection,or rectalsuppository/enema.
Recreationaldrugs canbe administeredin severaladditional waysthat arenot commonin medicine.
Certain drugs,such asalcohol andcaffeine, areingested inbeverage form;nicotine andTHC areoften smoked;peyote andpsilocybin mushroomsare ingestedin botanicalform ordried; andcertain crystallinedrugs suchas cocaineand MDMA(ecstasy) areoften insufflated.
There aremany waysin whichpsychoactive drugscan affectthe brain.
Each drughas aspecific actionon oneor moreneurotransmitter orneuroreceptor inthe brain.
Drugs thatincrease activityin particularneurotransmitter systemsare calledagonists.
Theyact byincreasing thesynthesis ofone ormore neurotransmittersor reducingits reuptakefrom thesynapses.
Exposureto antagonistsfor aparticular neurotransmitterincreases thenumber ofreceptors forthat neurotransmitter,and thereceptors themselvesbecome moresensitive.
Thisis calledsensitization.
Conversely,overstimulation ofreceptors fora particularneurotransmitter causesa decreasein bothnumber andsensitivity ofthese receptors,a processcalled desensitizationor tolerance.
Drugs thatonly indirectlystimulate thedopaminergic system,such aspsychedelics, arenot aslikely tobe addictive.
Methadone, itselfan opioidand apsychoactive substance,is acommon treatmentfor heroinaddiction.
However,in recentyears, themost influentialdocument regardingthe legalityof psychoactivedrugs isthe SingleConvention onNarcotic Drugs,an internationaltreaty signedin 1961as anAct ofthe UnitedNations.
Littlecontroversy existsconcerning overthe counterpsychoactive medicationsin antiemeticsand antitussives.
Psychoactive drugsare commonlyprescribed topatients withpsychiatric disorders.
A genericmust containthe sameactive ingredientsas theoriginal formulation.
In mostcases, itis consideredbioequivalent tothe brandname counterpartwith respectto pharmacokineticand pharmacodynamicproperties.
Byextension, therefore,generics areassumed tobe identicalin dose,strength, routeof administration,safety, efficacy,and intendeduse.
Inmost cases,generic productsare notavailable untilthe patentprotections affordedto theoriginal developerhave expired.
When genericproducts becomeavailable, themarket competitionoften leadsto substantiallylower pricesfor boththe originalbrand nameproduct andthe genericforms.
Thetime ittakes ageneric drugto appearon themarket varies.
Drug patentsgive twentyyears ofprotection, butthey areapplied forbefore clinicaltrials begin,so theeffective lifeof adrug patenttends tobe betweenseven andtwelve years.
The principalreason forthe relativelylow priceof genericmedicines isthat thesecompanies incurfewer costsin creatingthe genericdrug, andare thereforeable tomaintain profitabilitywhile offeringthe drugat alower costto consumers.
The costsof thesegeneric drugsare solow thatmany developingcountries caneasily afford.
Generic manufacturersalso donot bearthe burdenof provingthe safetyand efficacyof thedrugs throughclinical trials,since thesetrials havealready beenconducted bythe brandname company.
In mostcountries, genericmanufacturers mustonly provethat theirpreparation isbioequivalent tothe existingdrug inorder togain regulatoryapproval.
Priorto theexpiration ofa drugpatent, abrand namecompany enjoysa periodof "marketexclusivity" ormonopoly, inwhich thecompany isable toset theprice ofthe drugat thelevel whichmaximizes profitability.
This priceoften greatlyexceeds theproduction costsof thedrug, whichcan enablethe drugcompany tomake asignificant profiton theirinvestment inresearch anddevelopment.
Theadvantage ofgeneric drugsto consumerscomes inthe introductionof competition,which preventsany singlecompany fromdictating theoverall marketprice ofthe drug.
When apharmaceutical companyfirst marketsa drug,it isusually undera patentthat allowsonly thepharmaceutical companythat developedthe drugto sellit.
Genericdrugs canbe legallyproduced fordrugs where:1) thepatent hasexpired, 2)the genericcompany certifiesthe brandcompany's patentsare eitherinvalid, unenforceableor willnot beinfringed, 3)for drugswhich havenever heldpatents, or4) incountries wherea patent(s)is/are notin force.
The expirationof apatent removesthe monopolyof thepatent holderon drugsales licensing.
Patent lifetimediffers fromcountry tocountry, andtypically thereis noway torenew apatent afterit expires.
A newversion ofthe drugwith significantchanges tothe compoundcould bepatented, butthis requiresnew clinicaltrials anddoes notprevent thegeneric versionsof theoriginal drug.
This allowsthe companyto recoupthe costof developingthat particulardrug.
Afterthe patenton adrug expires,any pharmaceuticalcompany canmanufacture andsell thatdrug.
Sincethe drughas alreadybeen testedand approved,the costof simplymanufacturing thedrug willbe afraction ofthe originalcost oftesting anddeveloping thatparticular drug.
This mayinvolve aggressivelitigation topreserve orextend patentprotection ontheir medicines,a processreferred toby criticsas "evergreening."
Patentsare typicallyissued onnovel pharmacologicalcompounds quiteearly inthe drugdevelopment process,at whichtime the'clock' topatent expirationbegins ticking.
Food andDrug Administrationoffers a180 dayexclusivity periodto genericdrug manufacturersin specificcases.
Duringthis periodonly one(or sometimesa few)generic manufacturerscan producethe genericversion ofa drug.
This exclusivityperiod isonly usedwhen ageneric manufacturerargues thata patentis invalidor isnot violatedin thegeneric productionof adrug, andthe periodacts asa rewardfor thegeneric manufacturerwho iswilling torisk liabilityin courtand thecost ofpatent courtlitigation.
Thereis oftencontention aroundthese 180day exclusivityperiods becausea genericproducer doesnot haveto producethe drugduring thisperiod andcan filean applicationfirst toprevent othergeneric producersfrom sellingthe drug.
Large pharmaceuticalcompanies oftenspend thousandsof dollarsprotecting theirpatents fromgeneric competition.
Apart fromlitigation, companiesuse othermethods suchas reformulationor licensinga subsidiary(or anothercompany) tosell genericsunder theoriginal patent.
Generics soldunder licensefrom thepatent holderare knownas authorizedgenerics; theyare notaffected bythe 180day exclusivityperiod asthey fallunder thepatent holder'soriginal drugapplication.
Aprime exampleof howthis worksis simvastatin(Zocor), apopular drugcreated andmanufactured byU.S.
MerckCo., whichlost itsUS patentprotection onJune 23,2006.
However,Dr. Reddy'sLaboratories alsomarkets anauthorized genericversion ofsimvastatin underlicense fromZocor's manufacturer,Merck Co.;some packagesof Dr.
Reddy's simvastatineven showMerck asthe actualmanufacturer andhave Merck'slogo onthe bottom.
Most nationsrequire genericdrug manufacturersto provethat theirformulation exhibitsbioequivalence tothe innovatorproduct.
Overthe pastseveral yearsthere havebeen studiesthat haveshown theeffectiveness andsafety ofsome genericdrugs.
Genericdrugs arealways lessexpensive andcan savepatients andinsurance companiesthousands ofdollars supposedlywithout compromisingthe qualityof care.
The FDAmust approvegeneric drugsjust asinnovator drugsmust beapproved.
Bioequivalence,however, doesnot meanthat genericdrugs areexactly thesame astheir innovatorproduct counterparts,as chemicaldifferences doexist.
Somedoctors andpatients emphaticallybelieve thatcertain genericdrugs arenot aseffective asthe productsthey aremeant toreplace (ie.
Prozac, Oxycontin),and consumerswould undoubtedlybenefit frommore clinicalstudies doneon drugby drugbasis.
Genericdrugs startout atfirst beingfairly expensive,however theprice ofthe genericproduct decreasesas therate ofproduction increases.
Warfarin (eitherunder thetrade nameor thegeneric equivalent)has anarrow therapeuticwindow andrequires frequentblood teststo makesure patientsdo nothave asubtherapeutic ora toxiclevel.
Anapplicant filesan AbbreviatedNew DrugApplication (or"ANDA") withthe Foodand DrugAdministration (FDA)and seeksto demonstratetherapeutic equivalenceto aspecified,previously approved"reference listeddrug."
When anANDA isapproved, theFDA addsthe drugto itsApproved DrugProducts list,also knownas the"Orange Book",and annotatesthe listto showequivalence betweenthe referencelisted drugand theapproved generic.
The FDAalso recognizesdrugs usingthe sameingredients withdifferent bioavailabilityand dividesthem intotherapeutic equivalencegroups.
Manydrugs havemore thanone nameand, therefore,the samedrug maybe listedmore thanonce.
Brandnames andgeneric namesare differentiatedby theuse ofcapital initialsfor theformer.
Seealso thelist ofthe top200 bestsellingbranded drugs,ranked bysales.
Whilesome drugsare legalto possessand sell,in mostjurisdictions lawsprohibit thetrade ofcertain typesof drug.
The illegaldrug tradeoperates similarlyto otherunderground markets.
Various drugcartels specializein theseparate processesalong thesupply chain,often localizedto maximizeproduction efficiency.
Depending onthe profitabilityof eachlayer, cartelsmay varyin size,consistency, andorganization.
Thecommon characteristicbinding theseproduction locationsis thatthey arediscrete toavoid detection,and thusthey maybe locatedin anyordinary settingwithout raisingnotice.
Muchillegal drugcultivation andmanufacture takesplace indeveloping nations,although productionalso occursin thedevel;oped.
Additionally,through theinfluence ofa numberof blackmarket players,corruption isa problem,especially inpoorer societies.
Consumption ofillegal drugsis widespreadglobally.
Whileconsumers avoidtaxation bybuying onthe blackmarket, thehigh costsinvolved inprotecting traderoutes fromlaw enforcementlead tovastly inflatedprices.
Additionally,various lawscriminalize certainkinds oftrade ofdrugs thatare otherwiselegal (forexample, untaxedcigarettes).
Inthese cases,the drugsare oftenmanufactured andpartially distributedby thenormal legalchannels, anddiverted atsome pointinto illegalchannels.
Finally,many governmentsrestrict theproduction andsale oflarge classesof drugsthrough prescriptionsystems.
Injurisdictions wherelegislation restrictsor prohibitsthe possessionor saleof drugs,most commonlypsychoactive drugs,potential drugbuyers andsellers areunable totransact inthe open.
Only illegaldrug traderemains anoption, andwhen suchtrade occursa blackmarket iscreated.
Sincethe drugtransaction itselfis illegal,any participantsin thetrade areby definitioncriminal.
Withno significantadditional costto beingconvicted ofdrug charges,previous convictshold acompetitive advantagein providingillegal drugproducts.
Thesale ofdrugs hasexisted foras longas thedrugs themselveshave existed.
The historyof theillegal drugtrade isthus closelytied tothe historyof drugprohibition.
Inthe FirstOpium War,Great Britainattempted toforce Chinato allowBritish merchantsto tradein opiumwith thegeneral populationof China.
Although illegalby imperialdecree, smokingopium wascommon inthe 1800sand wasbelieved tocure manyhealth problems.
Legal drugslike tobaccoand alcoholcan bethe subjectof smugglingand illegaltrading ifthe pricedifference betweenthe originand thedestination arehigh enoughto makeit profitable.
Some prescriptiondrugs arealso availableby illegalmeans, eliminatingthe needto manufactureand processthe drugs.
For example:Prescription opioidsare sometimesmuch strongerthan heroinfound onthe street,eg.
Theyare sourcedeither fromstolen orpartly dividedprescriptions soldby medicalpractices andoccasionally fromInternet sale.
Benzodiazepines, andin particular,temazepam andflunitrazepam arealso frequentlydiverted tothe blackmarket throughforged prescriptions,pharmacy robberiesand doctorshopping.
InMalaysia andSingapore, thereis asimilar problemwith thediversion ofnimetazepam.
However,it ismuch easierto controltraffic inprescription drugsthan inillegal drugsbecause themanufacturer isusually anoriginally legalenterprise andthus theleak canoften bereadily foundand neutralized.
There mightalso bean upsidein reducedrisk ofcontaminated orpoor tooutright toxicproduce commonwith illegalbackroom laboratoryproduction.
NoPrescription Websites"(NPWs) offerto sellcontrolled substanceswithout avalid prescription.
NPWs werefirst recognizedby theU.S.
JusticeDepartment in1999, indicatingthat suchsites hadbeen operatingat leastthrough thelate 1990s.
NPWs enabledealers andusers tocomplete transactionswithout directcontact, meanwhilemany NPWsaccept creditcards, othersonly acceptcash therebyfurther reducingany papertrail.
ManyNPWs arehosted incountries inwhich specificcategories ofcontrolled substancesare locallylegal (e.g.
Mexico), butbecause ofthe globalnature ofthe internet,NPWs areable todo (mostlyillegal) businesswith customersaround theglobe.
Inaddition toprescription opioids,stimulants, andsedatives, steroidsare oftenwidely distributed.
To date,no websiteshave beenfound sellingillegal drugslike heroin,or illegalamphetamine derivatives.
The policehave uncoveredseveral instancesof dealers/drugrings usingCraigslist personalads tosolicit drugbusiness usingcode wordsand phrases.
All othercategories ofdrugs areavailable online.
Most nationsconsider drugtrafficking avery seriousproblem.
In1989, theUnited Statesintervened inPanama withthe goalof disruptingthe drugtrade comingfrom Panama.
The Indiangovernment hasseveral covertoperations inthe MiddleEast andIndian subcontinentto keepa trackof variousdrug dealers.
Major producercountries includeAfghanistan (opium)and Boliviaand Colombia(primarily cocainedeclining inthe pastyears; seebelow forfurther details).
Because disputescannot beresolved throughlegal means,participants atevery levelof theillegal drugindustry areinclined tocompete withone anotherthrough violence.
The lackof governmentregulation andcontrol overthe lucrativeillegal drugmarket hascreated alarge populationof unregulateddrug dealerswho luremany childreninto theillegal drugtrade.
The2005 YouthRisk BehaviorSurvey bythe U.S.
Centers forDisease Controland Prevention(CDC) reportedthat nationwide25.4% ofstudents hadbeen offered,sold, orgiven anillegal drugby someoneon schoolproperty.
Theprevalence ofhaving beenoffered, sold,or givenan illegaldrug onschool propertyranged from15.5% to38.7% acrossstate CDCsurveys (median:26.1%) andfrom 20.3%to 40.0%across localsurveys (median:29.4%).
Thepurity ofstreet cocainein Europeis usuallyin thesame rangeas itis forheroin, theprice beingbetween 50and 100euros perbetween 0.7and 1.0grams.
Thistotals toa cocaineprice rangebetween 500and 2000euros.
Accordingto theOffice ofNational DrugControl Policy,anabolic steroidsare relativelyeasy tosmuggle intothe UnitedStates.
Oncethere, theyare oftensold atgyms andcompetitions aswell asthrough mailoperations.
Mostof thecannabis soldcommercially inthe U.S.
Midwest orin theCalifornia areawhich naturallyhas someof theworld's bestsoil forgrowing crops.
Much ofthe cannabisin theUnited Statesis importedfrom Mexico,however thiscannabis isusually lowquality sometimesreferred toas brownbud,regs, regular,shwag, ordirt weed.
The packagingmethods usedare oftencrude resultingin compressedor "bricked"weed.
Thecannabis importedfrom BritishColumbia inCanada, knownas BCbud, isusually ofhigher qualitythan mostcannabis grownin theUnited States(though cannibisfrom NorthernCalifornia hasa similarreputation) andis highlysought after.
Around 40%of USmarijuana isgrown insideof thecountry.
Moreand morecannibis isbeing grownin UnitedStates ortransported fromCanada whileless cannibiscomes fromthe Mexicanborder dueto itslow quality.
Psychonauts willoften growthese mushroomsor pickthem forthemselves asthey arecommon tofind inmany placesof theworld.
Insome areasof theworld, particularlyin andaround theArabian peninsula,the tradeof alcoholis strictlyprohibited.
Forexample, Pakistanbans thetrade becauseof itslarge Muslimpopulation.
Similarly,Saudi Arabiaforbids theimportation ofalcohol intoits kingdom,however, alcoholis smuggledin veryhigh quantities.
In otherareas itis consideredlike anyother beverage,and islegal.
Instill otherareas, thereis anage limitfor consumers,and alicense isnecessary tosell alcohol.
Pure alcoholor liquidswith highalcohol contentover acertain percentageor proof,calculated byvolume orweight, arealso bannedin manycountries.
InRussia, forexample, rubbingalcohol isa scheduleddrug onpar withheroin, andtheoretically hasthe samelegal penalties.
The illegaltrade oftobacco ismotivated primarilyby increasinglyheavy taxation.
It hasbeen reportedthat smugglingone truckloadof cigaretteswithin theUnited Statesleads toa profitof 2million U.S.
Sometimes, theillegal tradeof tobaccois motivatedby differencesin taxesin twojurisdictions, includingsmuggling acrossinternational borders.
In 2006,tobacco andbetel nutwere themost commonlyseized illicitdrugs inBhutan.
Internationalillicit tradein opiumis relativelyrare.
Majorsmuggling organizationsprefer tofurther refineopium intoheroin beforeshipping tothe consumercountries, sincea givenquantity ofheroin isworth muchmore thanan equivalentamount ofopium.
Heroinis smuggledinto theUnited Statesand Europe.
Purity levelsvary greatlyby regionwith, forthe mostpart, Northeasterncities havingthe mostpure heroinin theUnited States(according toa recentlyreleased reportby theDEA, Elizabethand Newark,New Jersey,have thepurest streetgrade heroinin thecountry).
Heroinis alsowidely (andusually illegally)used asa powerfuland addictivedrug thatproduces intenseeuphoria, whichoften disappearswith increasingtolerance.
Oncein theblood stream,heroin israpidly convertedto morphine.
The morphinethen bindsto theopioid receptorsin thebrain andspinal cord,causing thesubjective effects.
Heroin andmorphine canbe takenor administeredin anumber ofways, includingsnorting andinjection.
Theymay alsobe smokedby inhalingthe vaporsproduced whenheated frombelow (knownas "chasingthe dragon").
Penalities forsmuggling heroinand/or morphineare oftenharsh inmost countries.
Some countrieswill readilyhand downa deathsentence forthe illegalsmuggling ofheroin ormorphine, whichare both,internationally, ScheduleI drugsunder theSingle Conventionon NarcoticDrugs.
Invarious Asiancountries, includingSingapore andMalaysia, heroinand morphineare classedby themselvesand penalitiesfor theiruse, possession,and/or traffickingare moresevere thanall otherdrugs, includingother opioidsand cocaine.
In someareas ofthe UnitedStates, thetrade ofmethamphetamine isrampant.
Becauseof theease inproduction andits addictionrate, methamphetamineis afavorite amongstmany drugdistributors.
Accordingto theCommunity EpidemiologyWork Group,the numbersof clandestinemethamphetamine laboratoryincidents reportedto theNational ClandestineLaboratory Databasedecreased from1999 to2004.
Duringthis sameperiod, methamphetaminelab incidentsincreased inmidwestern States(Illinois, Michigan,and Ohio),and inPennsylvania.
In2004, morelab incidentswere reportedin Illinois(926) thanin California(673).
In2003, methamphetaminelab incidentsreached newhighs inGeorgia (250),Minnesota (309),and Texas(677).
Statelaws varygreatly andin somecases defyfederal laws.
Despite theUS government'sofficial positionagainst thedrug trade,US governmentagents andassets havebeen implicatedin thedrug trade.
Highly decoratedUS militarySpecial Forcesveteran, ColonelBo Gritz(retired) hasaccused theUSA ofcollaborating withand supportingManuel Noriegain hisdrug traffickingoperations.
Inhis bookCalled ToServe, Gritzdetails hisrole asa keyUS Governmentemployee taskedwith protectingthe USA'srelationship withNoriega.
Counterto itsofficial goals,the UShas beenknown toattempt tosuppress researchon drugusage.
Forexample, in1995 theWorld HealthOrganization (WHO)and theUnited NationsInterregional Crimeand JusticeResearch Institute(UNICRI) announcedin apress releasethe publicationof theresults ofthe largestglobal studyon cocaineuse everundertaken.
However,a decisionin theWorld HealthAssembly bannedthe publicationof thestudy.
Inthe sixthmeeting ofthe Bcommittee theUS representativethreatened that"If WHOactivities relatingto drugsfailed toreinforce provendrug controlapproaches, fundsfor therelevant programmesshould becurtailed".
Thisled tothe decisionto discontinuepublication.
Availableare profilesof cocaineuse in20 countries.
Different jurisdictionshave differentdefinitions ofwhat constitutesa prescriptiondrug.
Dispensationof prescriptiondrugs oftenincludes apackage insert(in Europe,a PatientInformation Leafletor PIL)that givesdetailed informationabout thedrug.
Inthe UnitedStates, theFederal Food,Drug, andCosmetic Actdefines whatrequires aprescription.
Prescriptiondrugs aregenerally authorizedby veterinarians,dentists andphysicians, thoughphysician assistantsand nursepractitioners doan increasingamount ofdrug prescribingunder aphysician's supervision,.
Itis generallyrequired thatan MD,DO, DVM,DDS, DMD,PA orNP writethe prescription;nurses (otherthan nursepractitioners), emergencymedical technicians,psychologists (butnot psychiatrists,who areMDs), asexamples, donot generallyhave theauthority toprescribe drugs.
Unlike mostother countries,the UnitedStates doesnot haveprice controlsfor prescriptiondrugs, andUS drugprices areusually viewedas veryexpensive incomparison tothose countries.
For thosewith healthinsurance, manyhealth insuranceprograms (generallypaid partiallyor infull bythe patient'semployer) haveprescription paymentplans wherethe patientpays onlya smallcopayment andthe pharmacyis reimbursedfor theremaining costby theinsurance company.
For theuninsured, theytypically mustpay whateverhigher drugprice theirlocal pharmacycharges.
In2005, therewere nearly45 millionuninsured Americans,according tothe U.S.
Census (seelink below).
The safetyand effectivenessof prescriptiondrugs inthe U.S.
Prescription DrugMarketing Actof 1987.
In theUnited Kingdom,they arereferred toas PrescriptionOnly Medicineor POM.
In theUnited Kingdom,a patientvisits ageneral practitionerwho isable toprescribe medicines.
If givenan NHSprescription, thiscan betaken toa pharmacyto bedispensed.
Extendedprescribing wasintroduced inlate 1999,where appropriatelytrained nursescould prescribefrom alimited listof POMs.
From 2006,some nursesand pharmacistswill bepermitted toprescribe allmedicines inthe BritishNational Formulary,except controlleddrugs directly.
However inWales prescriptioncharges arefree forall.
Claimantsof "Jobseekers"and "Incomesupport" automaticallyreceive freeprescriptions anddentistry.
Thischarge ispaid entirelyto theNHS throughthe pharmacy,while thepharmacy claimsthe costof themedicine dispensed.
Each "item"can coverany prescribeditem ina verylarge orvery smallquantity accordingto thedoctor's prescription.
The majorityof itemsdispensed onNHS prescriptionare exemptfrom charges.
This isbecause ofthe largenumber ofmedicines neededby, forexample, theelderly orthose withmedical exemptions.
NHS prescriptionscan alsobe writtenfor certainitems bydentists andnurses.
Somepatients alsoreceive privateprescriptions, typicallyeither froma doctorseen privatelyor formedicine notpermitted onthe NHS.
For these,the patientwill paythe pharmacydirectly forthe costof themedicine andthe pharmacy'smarkup.
Thedevolved legislaturein Waleshas decidedto phaseout prescriptioncharges altogether;this processis expectedto becompleted during2007.
InJanuary 2006,similar proposalswere madeby thehealth committeeof theScottish Parliament;however, thesewere rejectedby HealthMinister AndyKerr onthe groundsthat "Executivepolicy remainsthat itis rightthat patientswho canafford toshould continueto contributetowards NHSdispensing costs".
They limitthe damagecaused bythe blockageof theblood vessel.
Thrombolysis isused infor myocardialinfarction (heartattack), ischemicstrokes, deepvein thrombosisand pulmonaryembolism toclear ablocked arteryand avoidpermanent damageto theperfused tissue(e.g.
Itshould benoted thatthrombolytic therapyin hemorrhagicstrokes iscontraindicated, asits usein thatsituation wouldprolong bleedinginto theintracranial spaceand causefurther damage.
The thrombolyticdrugs include:These drugsare mosteffective ifadministered immediatelyafter ithas beendetermined theyare clinicallyappropriate.
Theadvantage ofadministration ishighest withinthe firstninety minutes,but mayextend upto sixhours afterthe startof symptoms.
The drugsare oftengiven incombination withintravenous heparin,or lowmolecular weightheparin, whichare anticoagulantdrugs.
Hemorrhagicstroke isa rarebut seriouscomplication ofthrombolytic therapy.
If apatient hashad thrombolysisbefore, anallergy againstthe thrombolyticdrug mayhave developed(especially afterstreptokinase).
Ifthe symptomsare mild,the infusionis stoppedand thepatient iscommenced onan antihistaminebefore infusionis recommenced.
Anaphylaxis generallyrequires immediatecessation ofthrombolysis.
Category:DrugsRecreational druguse isthe useof psychoactivedrugs forrecreational purposesrather thanfor work,medical orspiritual purposes,although thedistinction isnot alwaysclear.
Peoplethat takedrugs totreat diseasesand disorders,which interferewith theirability tofunction, mayexperience improvementof theircondition.
Adistinction isfrequently madebetween recreationaluse ofdrugs anddrug abuse,although thereis muchcontroversy onwhere thedividing linelies onthe spectrumfrom adrug userto adrug abuser.
Some saythat abusebegins whenthe userbegins shirkingresponsibility inorder toafford drugsor tohave enoughtime touse them.
Some sayit beginswhen aperson useswhat isdeemed tobe excessiveamounts, whileothers drawthe lineat thepoint oflegality.
Stillothers believeit amountsto chronicuse whenmental andphysical healthbegin degeneratingin theuser.
Somethink thatany intoxicantconsumption isan inappropriateactivity.
Afurther distinctioncan bemade inthat itis theuse ofthe drugthat isrecreational, andnot thedrug itself.
Antidepressants arealso sometimescalled lifestyledrugs.
Halitosis"(bad breath),for example,was aconcotion ofListerine's marketingteam, while"erectile dysfunction"was inventedby Viagra'smarketing team.
Before thedevelopment andmarketing oftheir respectivetreatments, neitherbad breathnor impotencewere considereddisorders, butrather anormal partof life.
Social criticsalso questionthe proprietyof devotinghuge researchbudgets towardscreating thesedrugs whenfar moredangerous diseaseslike cancerand AIDSremain uncured.
It issometimes claimedthat lifestyledrugs amountto littlemore thanmedically sanctionedrecreational druguse.
Proponents,however, pointout thatimproving thepatient's subjectivequality oflife hasalways beena primaryconcern ofmedicine, andargue thatthese drugsare doingjust that.
They areeffective inthe arterialcirculation, whereanticoagulants havelittle effect.
They arewidely usedin primaryand secondaryprevention ofthrombotic cerebrovascularor cardiovasculardisease.
Thesedrugs maybe usedrecreationally topurposefully alterone's consciousness,as entheogensfor ritualor spiritualpurposes, ortherapeutically asmedication.
Psychoactivesubstances affectthe brainand bringabout subjectivechanges inmood thatthe usermay findpleasant.
Manypsychoactive substancesare abused,that is,used outsideof theguidance ofa medicalprofessional andfor reasonsother thantheir originalpurpose.
Withsustained use,physical dependencemay develop,making thecycle ofabuse evenmore difficultto interrupt.
Drug rehabilitationcan involvea combinationof psychotherapy,support groupsand evenother psychoactivesubstances tobreak thecycle ofdependency.
Inpart becauseof thispotential forabuse anddependency, theethics ofdrug useare thesubject ofa continuingphilosophical debate.
Many governmentsworldwide haveplaced restrictionson drugproduction andsales inan attemptto controldrug abuse.
Drug useis apractice thatdates toprehistoric times.
A numberof animalsconsume differentpsychoactive plants,animals, berriesand evenfermented fruit,becoming intoxicated,such ascats afterconsuming catnip.
A notableexample ofthis isthe Prohibitionera inthe UnitedStates, wherealcohol wasmade illegalfor 13years.
However,many governmentshave concludedthat illicitdrug usecannot besufficiently stoppedthrough criminalization.
In somecountries, therehas beena movetoward harmreduction byhealth services,where theuse ofillicit drugsis neithercondoned norpromoted, butservices andsupport areprovided toensure usershave thenegative effectsof theirillicit druguse minimized.
Psychoactive substancesare usedby humansfor anumber ofdifferent purposes,both legaland illicit.
General anestheticsare aclass ofpsychoactive drugused onpatients toblock painand othersensations.
Asthe subjectiveexperience ofpain isregulated byendorphins, neurochemicalsthat areendogenous opioids,pain canbe managedusing psychoactivesthat operateon thisneurotransmitter system.
Psychiatric medicationsare prescribedfor themanagement ofmental andemotional disorders.
There are6 majorclasses ofpsychiatric medications:Many psychoactivesubstances areused/abused fortheir moodand perceptionaltering effects,including thosewith accepteduses inmedicine andpsychiatry.
Psychoactivedrugs areadministered inseveral differentways.
Inmedicine, mostpsychiatric drugs,such asfluoxetine andoxycodone, areingested orallyin tabletor capsuleform.
However,certain medicalpsychoactives areadministered viainhalation, injection,or rectalsuppository/enema.
Recreationaldrugs canbe administeredin severaladditional waysthat arenot commonin medicine.
Certain drugs,such asalcohol andcaffeine, areingested inbeverage form;nicotine andTHC areoften smoked;peyote andpsilocybin mushroomsare ingestedin botanicalform ordried; andcertain crystallinedrugs suchas cocaineand MDMA(ecstasy) areoften insufflated.
There aremany waysin whichpsychoactive drugscan affectthe brain.
Each drughas aspecific actionon oneor moreneurotransmitter orneuroreceptor inthe brain.
Drugs thatincrease activityin particularneurotransmitter systemsare calledagonists.
Theyact byincreasing thesynthesis ofone ormore neurotransmittersor reducingits reuptakefrom thesynapses.
Exposureto antagonistsfor aparticular neurotransmitterincreases thenumber ofreceptors forthat neurotransmitter,and thereceptors themselvesbecome moresensitive.
Thisis calledsensitization.
Conversely,overstimulation ofreceptors fora particularneurotransmitter causesa decreasein bothnumber andsensitivity ofthese receptors,a processcalled desensitizationor tolerance.
Drugs thatonly indirectlystimulate thedopaminergic system,such aspsychedelics, arenot aslikely tobe addictive.
Methadone, itselfan opioidand apsychoactive substance,is acommon treatmentfor heroinaddiction.
However,in recentyears, themost influentialdocument regardingthe legalityof psychoactivedrugs isthe SingleConvention onNarcotic Drugs,an internationaltreaty signedin 1961as anAct ofthe UnitedNations.
Littlecontroversy existsconcerning overthe counterpsychoactive medicationsin antiemeticsand antitussives.
Psychoactive drugsare commonlyprescribed topatients withpsychiatric disorders.
Drugs, bothmedicinal andrecreational, canbe administeredin anumber ofways: Manydrugs canbe administeredin avariety ofways.
Recreationaldrug useis typicallythe useof psychoactivedrugs forrecreational purposesrather thanmedical orspiritual purposes.
Many governmentsacross theworld regulateand banvarious recreationaldrugs, andthe exactlaws areoften politicallycontroversial.
Inthe UnitedStates, theFederal Food,Drug, andCosmetic Actdefinition of"drug" includes"articles intendedfor usein thediagnosis, cure,mitigation, treatment,or preventionof diseasein manor otheranimals" and"articles (otherthan food)intended toaffect thestructure orany functionof thebody ofman orother animals."
Consistentwith thatdefinition, theU.S.
Antifungalswork byexploiting differencesbetween mammalianand fungalcells tokill offthe fungalorganism withoutdangerous effectson thehost.
Unlikebacteria, bothfungi andhumans areeukaryotes.
Thusfungal andhuman cellsare similarat themolecular level.
This meansit ismore difficultto finda targetfor anantifungal drugto attackthat doesnot alsoexist inthe infectedorganism.
Thereare severalclasses ofantifungal drugs.
A polyeneis acircular moleculeconsisting ofa hydrophobicand hydrophilicregion.
Thismakes polyenean amphotericmolecule.
Thepolyene antimycoticsbind withsterols inthe fungalcell membrane,principally ergosterol.
This changesthe transitiontemperature (Tg)of thecell membrane,thereby placingthe membranein aless fluid,more crystallinestate.
Asa result,the cell'scontents leakout (usuallythe hydrophiliccontents) andthe celldies.
Animalcells containcholesterol insteadof ergosteroland sothey aremuch lesssusceptible.
Note:as polyene'shydrophobic chainis reduced,its sterolbinding activityis increased.
This enzymeconverts lanosterolto ergosterol,and isrequired infungal cellwall synthesis.
These drugsalso blocksteroid synthesisin humans.
Among themost commonare pyrithionezinc andselenium sulphide.
Like antibiotics,specific antiviralsare usedfor specificviruses.
Antiviraldrugs areone classof antimicrobials,a largergroup whichalso includesantibiotic, antifungaland antiparasiticdrugs.
Theyare relativelyharmless tothe host,and thereforecan beused totreat infections.
They shouldbe distinguishedfrom viricides,which activelydeactivate virusparticles outsidethe body.
Most ofthe antiviralsnow availableare designedto helpdeal withHIV; herpesvirus,which isbest knownfor causingcold soresbut actuallycovers awide rangeof diseases;and thehepatitis Band Cviruses, whichcan causeliver cancer.
Researchers arenow workingto extendthe rangeof antiviralsto otherfamilies ofpathogens.
Theemergence ofantivirals isthe productof agreatly expandedknowledge ofthe geneticand molecularfunction oforganisms, allowingbiomedical researchersto understandthe structureand functionof viruses,major advancesin thetechniques forfinding newdrugs, andthe intensepressure placedon themedical professionto dealwith thehuman immunodeficiencyvirus (HIV),the causeof thedeadly acquiredimmunodeficiency syndrome(AIDS) pandemic.
As of2007, onlysmallpox hasbeen successfullyeradicated, andPoliomyelitis eradicationis stillunderway.
Bothof theseefforts areusing vaccines.
Modern medicalscience andpractice hasan arrayof effectivetools, rangingfrom antisepticsto vaccinesand antibiotics.
One fieldin whichmedicine hashistorically beenweak, however,is infinding drugsto dealwith viralinfections.
Highlyeffective vaccineshave beenrecently developedto preventsuch diseases,but formerly,when someonecontracted avirus, therewas littlethat couldbe donebut torecommend restand plentyof fluidsuntil thedisease ranits course.
Researchers grewcultures ofcells andinfected themwith thetarget virus.
They thenintroduced chemicalsinto thecultures theythought werelikely toinhibit viralactivity, andobserved whetherthe levelof virusin thecultures roseor fell.
Chemicals thatseemed tohave aneffect wereselected forcloser study.
It wasnot untilthe 1980s,when thefull geneticsequences ofviruses beganto beunraveled, thatresearchers beganto learnhow virusesworked indetail, andexactly whatchemicals wereneeded tothwart theirreproductive cycle.
Dozens ofantiviral treatmentsare nowavailable, andmedical researchis rapidlyexploiting newknowledge andtechnology todevelop more.
Viruses consistof agenome andsometimes afew enzymesstored ina capsulemade ofprotein, andsometimes coveredwith alipid layer.
Viruses cannotreproduce ontheir own,so theypropagate bysubjugating ahost cellto producecopies ofthemselves, thusproducing thenext generation.
Researchers workingon such"rational drugdesign" strategiesfor developingantivirals havetried toattack virusesat everystage oftheir lifecycles.
Virallife cyclesvary intheir precisedetails dependingon thespecies ofvirus, butthey allshare ageneral pattern:Vaccines attackviruses whenthey arein the"complete particle"stage, outsideof theorganism's cells.
They traditionallyconsist ofa weakenedor killedversion ofa pathogen,though morerecently "subunit"vaccines havebeen devisedthat consiststrictly ofprotein targetsfrom thepathogen.
Theystimulate theimmune systemwithout doingserious harmto thehost, andso whenthe realpathogen attacksthe subject,the immunesystem respondsto itquickly andblocks it.
Vaccines arevery effectiveon stableviruses, butare oflimited usein treatinga patientwho hasalready beeninfected.
Theyare alsodifficult tosuccessfully deployagainst rapidlymutating viruses,such asinfluenza (thevaccine forwhich isupdated everyyear) andHIV.
Thesetwo gapsare whereantiviral drugsbecome useful.
The generalidea behindmodern antiviraldrug designis toidentify viralproteins, orparts ofproteins, thatcan bedisabled.
These"targets" shouldgenerally beas unlikeany proteinsor partsof proteinsin humansas possible,to reducethe likelihoodof sideeffects.
Thetargets shouldalso becommon acrossmany strainsof avirus, oreven amongdifferent speciesof virusin thesame family,so asingle drugwill havebroad effectiveness.
For example,a researchermight targeta criticalenzyme synthesizedby thevirus, butnot thepatient, thatis commonacross strains,and seewhat canbe doneto interferewith itsoperation.
Thetarget proteinscan bemanufactured inthe labfor testingwith candidatetreatments byinserting thegene thatsynthesizes thetarget proteininto bacteriaor otherkinds ofcells.
Thecells arethen culturedfor massproduction ofthe protein,which canthen beexposed tovarious treatmentcandidates andevaluated with"rapid screening"technologies.
Thevirus mustgo througha sequenceof stepsto dothis, beginningwith bindingto aspecific "receptor"molecule onthe surfaceof thehost celland endingwith thevirus "uncoating"inside thecell andreleasing itscontents.
Virusesthat havea lipidenvelope mustalso fusetheir envelopewith thetarget cell,or witha vesiclethat transportsthem intothe cell,before theycan uncoat.
This stageof viralreplication canbe inhibitedin twoways: 1.
Using agentswhich mimicthe receptorand bindto theVAP.
Avery earlystage ofviral infectionis viralentry, whenthe virusattaches toand entersthe hostcell.
Attemptsto interferewith thebinding ofHIV withthe CD4receptor havefailed tostop HIVfrom infectinghelper Tcells, butresearch continueson tryingto interferewith thebinding ofHIV tothe CCR5receptor inhopes thatit willbe moreeffective.
Pleconarilworks againstrhinoviruses, whichcause thecommon cold,by blockinga pocketon thesurface ofthe virusthat controlsthe uncoatingprocess.
Thispocket issimilar inmost strainsof rhinovirusesand enteroviruses,which cancause diarrhea,meningitis, conjunctivitis,and encephalitis.
A secondapproach isto targetthe processesthat synthesizevirus componentsafter avirus invadesa cell.
One wayof doingthis isto developnucleotide ornucleoside analoguesthat looklike thebuilding blocksof RNAor DNA,but deactivatethe enzymesthat synthesizethe RNAor DNAonce theanalogue isincorporated.
Thefirst successfulantiviral, aciclovir,is anucleoside analogue,and iseffective againstherpesvirus infections.
The firstantiviral drugto beapproved fortreating HIV,zidovudine (AZT),is alsoa nucleosideanalogue.
Animproved knowledgeof theaction ofreverse transcriptasehas ledto betternucleoside analoguesto treatHIV infections.
One ofthese drugs,lamivudine, hasbeen approvedto treathepatitis B,which usesreverse transcriptaseas partof itsreplication process.
Researchers havegone furtherand developedinhibitors thatdo notlook likenucleosides, butcan stillblock reversetranscriptase.
Othertargets beingconsidered forHIV antiviralsinclude RNaseH, whichis acomponent ofreverse transcriptasethat splitsthe synthesizedDNA fromthe originalviral RNA;and integrase,which splicesthe synthesizedDNA intothe hostcell genome.
Once avirus genomebecomes operationalin ahost cell,it thengenerates messengerRNA (mRNA)molecules thatdirect thesynthesis ofviral proteins.
Production ofmRNA isinitiated byproteins knownas transcriptionfactors.
Severalantivirals arenow beingdesigned toblock attachmentof transcriptionfactors toviral DNA.
Genomics hasnot onlyhelped findtargets formany antivirals,it hasprovided thebasis foran entirelynew typeof drug,based on"antisense" molecules.
These aresegments ofDNA orRNA thatare designedas "mirrorimages" tocritical sectionsof viralgenomes, andthe bindingof theseantisense segmentsto thesetarget sectionsblocks theoperation ofthose genomes.
A phosphorothioateantisense drugnamed fomivirsenhas beenintroduced, usedto treatopportunistic eyeinfections inAIDS patientscaused bycytomegalovirus, andother antisenseantivirals arein development.
An antisensestructural typethat hasproven especiallyvaluable inresearch isMorpholino antisense.
Yet anotherantiviral techniqueinspired bygenomics isa setof drugsbased onribozymes, whichare enzymesthat willcut apartviral RNAor DNAat selectedsites.
Intheir naturalcourse, ribozymesare usedas partof theviral manufacturingsequence, butthese syntheticribozymes aredesigned tocut RNAand DNAat sitesthat willdisable them.
A ribozymeantiviral todeal withhepatitis Cis infield testing,and ribozymeantivirals arebeing developedto dealwith HIV.
This ispart ofa broadereffort tocreate geneticallymodified cellsthat canbe injectedinto ahost toattack pathogensby generatingspecialized proteinsthat blockviral replicationat variousphases ofthe virallife cycle.
Some virusesinclude anenzyme knownas aprotease thatcuts viralprotein chainsapart sothey canbe assembledinto theirfinal configuration.
Improved proteaseinhibitors arenow indevelopment.
Thefinal stagein thelife cycleof avirus isthe releaseof completedviruses fromthe hostcell, andthis stephas alsobeen targetedby antiviraldrug developers.
Two drugsnamed zanamivir(Relenza) andoseltamivir (Tamiflu)that havebeen recentlyintroduced totreat influenzaprevent therelease ofviral particlesby blockinga moleculenamed neuraminidasethat isfound onthe surfaceof fluviruses, andalso seemsto beconstant acrossa widerange offlu strains.
A secondcategory oftactics forfighting virusesinvolves encouragingthe body'simmune systemto attackthem, ratherthan attackingthem directly.
Some antiviralsof thissort donot focuson aspecific pathogen,instead stimulatingthe immunesystem toattack arange ofpathogens.
Amore specificapproach isto synthesizeantibodies, proteinmolecules thatcan bindto apathogen andmark itfor attackby otherelements ofthe immunesystem.
Onceresearchers identifya particulartarget onthe pathogen,they cansynthesize quantitiesof identical"monoclonal" antibodiesto linkup thattarget.
Amonoclonal drugis nowbeing soldto helpfight respiratorysyncytial virusin babies,and anotheris beingtested asa treatmentfor hepatitisB.
Researchersare nowsearching forantivirals thatcan recognizethese intruderproteins anddisable them.
Clinically theyare usedto: Thesedrugs arenot withoutside effectsand risks.
There arealso otherside effects,like hypertension,dyslipidemia, hyperglycemia,peptic ulcers,liver andkidney injury.
The immunosuppressivedrugs alsointeract withother medicinesand affecttheir metabolismand action.
Immunosuppressive drugscan beclassified intofive groups:General information:Glucocorticoid.
Inpharmacologic (supraphysiologic)doses, glucocorticoidsare usedto suppressvarious allergic,inflammatory, andautoimmune disorders.
Nevertheless, theydo notprevent aninfection andalso inhibitlater reparativeprocesses.
Smallercytokine productionreduces theT cellproliferation.
Thisdiminishes bothB cellclone expansionand antibodysynthesis.
Glucocorticoidsinfluence alltypes ofinflammatory events,no matterwhat theircause.
Thisleads todiminished eicosanoidproduction.
Generalinformation: ChemotherapyCytostatics inhibitcell division.
In immunotherapy,they areused insmaller dosesthan inthe treatmentof malignantdiseases.
Theyaffect theproliferation ofboth Tcells andB cells.
Due totheir highesteffectiveness, purineanalogs aremost frequentlyadministered.
Thealkylating agentsused inimmunotherapy arenitrogen mustards(cyclophosphamide), nitrosoureas,platinum compoundsand others.
Cyclophosphamide isprobably themost potentimmunosuppressive compound.
In smalldoses, itis veryefficient inthe therapyof systemiclupus erythematosus,autoimmune hemolyticanemias, Wegener'sgranulomatosis andother immunediseases.
Highdoses causepancytopenia andhemorrhagic cystitis.
Antimetabolites interferewith thesynthesis ofnucleic acids.
These include:Methotrexate isa folicacid analogue.
It bindsdihydrofolate reductaseand preventssynthesis oftetrahydrofolate.
Itis usedin thetreatment ofautoimmune diseases(for examplerheumatoid arthritis)and intransplantations.
Azathioprine,is themain immunosuppressivecytotoxic substance.
It isextensively usedto controltransplant rejectionreactions.
Itis nonenzymaticallycleaved tomercaptopurine, thatacts asa purineanalogue andan inhibitorof DNAsynthesis.
Mercaptopurineitself canalso beadministered directly.
By preventingthe clonalexpansion oflymphocytes inthe inductionphase ofthe immuneresponse, itaffects boththe celland thehumoral immunity.
It isalso efficientin thetreatment ofautoimmune diseases.
Among these,dactinomycin isthe mostimportant.
Itis usedin kidneytransplantations.
Othercytotoxic antibioticsare anthracyclines,mitomycin C,bleomycin, mithramycin.
Antibodies areused asa quickand potentimmunosuppression methodto preventthe acuterejection reaction.
Heterologous polyclonalantibodies areobtained fromthe serumof animals(e.g.
Theantilymphocyte (ALG)and antithymocyteantigens (ATG)are beingused.
However,they areprimarily addedto otherimmunosuppressives todiminish theirdosage andtoxicity.
Theyalso allowtransition tocyclosporine therapy.
Currently (March2005) thereare twopreparations availableto themarket: Atgam(R), obtainedfrom horseserum, andThymoglobuline (R),obtained fromrabbit serum.
To reducethese risks,treatment isprovided ina hospitalwhere adequateisolation frominfection isavailable.
Theyare usuallyadministered forfive daysintravenously inthe appropriatequantity.
Patientsstay inthe hospitalas longas threeweeks togive theimmune systemtime torecover toa pointwhere thereis nolonger arisk ofserum sickness.
Because ofa highimmunogenicity ofpolyclonal antibodies,almost allpatients havean acutereaction tothe treatment.
It ischaracterized byfever, rigorepisodes andeven anaphylaxis.
Later duringthe treatment,some patientsdevelop serumsickness orimmune complexglomerulonephritis.
Serumsickness arisesseven tofourteen daysafter thetherapy hasbegun.
Thepatient suffersfrom fever,joint painand erythemathat canbe soothedwith theuse ofsteroids andanalgesics.
Urticaria(hives) canalso bepresent.
Itis possibleto diminishtheir toxicityby usinghighly purifiedserum fractionsand intravenousadministration inthe combinationwith otherimmunosuppressants, forexample calcineurininhibitors, cytostaticsand cortisteroids.
The mostfrequent combinationis tosimultaneously useantibodies andcyclosporine.
Patientsgradually developa strongimmune responseto thesedrugs, reducingor eliminatingtheir effectiveness.
Monoclonal antibodiesare directedtowards exactlydefined antigens.
Therefore, theycause fewerside effects