depressants: barbs, benzos and huffing chapter 10

Depressants: Depressants: Barbs, Benzos Barbs, Benzos and Huffingand Huffing

Chapter 10Chapter 10

BarbituratesBarbiturates

Bayer in 1864 combined urea (urine) Bayer in 1864 combined urea (urine) and malonic acid (apples)and malonic acid (apples) barbituric acidbarbituric acid

Origin of the name Origin of the name Barbara contributed the urineBarbara contributed the urine

Barbara was a barmaid where he went to Barbara was a barmaid where he went to celebratecelebrate

St. Barbara - patron saint of artillerySt. Barbara - patron saint of artillery


1903 - 1903 - VeronalVeronal (after Verona, e.g. (after Verona, e.g. Romeo & Juliet- added “al” to end)Romeo & Juliet- added “al” to end)

New barbiturates synthesized New barbiturates synthesized rapidly in early 1900's rapidly in early 1900's

2500 synthesized, about half dozen 2500 synthesized, about half dozen served all clinical applicationsserved all clinical applications

Use increased until 1960’sUse increased until 1960’s


PharmacodynamicsPharmacodynamics Classified by duration of actionClassified by duration of action

determines usedetermines use anesthesia – short actinganesthesia – short acting sleep induction - mediumsleep induction - medium anticonvulsant - long as safely anticonvulsant - long as safely

possiblepossible Administered orally most oftenAdministered orally most often

exceptions - i.v. for convulsant emergenciesexceptions - i.v. for convulsant emergencies anesthetic action & drug abusersanesthetic action & drug abusers


Barb's depress all excitable nervous Barb's depress all excitable nervous tissue - CNS most sensitivetissue - CNS most sensitive

Mechanism thought to be at GABA Mechanism thought to be at GABA synapsesynapse Low doses - increase receptor sensitivity Low doses - increase receptor sensitivity

to GABA to potentiate and prolong its to GABA to potentiate and prolong its effectseffects

Higher dose mimic GABA inhibition Higher dose mimic GABA inhibition possibly by directly activating chloride possibly by directly activating chloride channelschannels


Behavioral effects very similar to Behavioral effects very similar to alcoholalcohol disinhibition, euphoria, sedation, disinhibition, euphoria, sedation,

loss of motor controlloss of motor controlsleep, anesthesia & deathsleep, anesthesia & deathalso tolerance, physical also tolerance, physical dependence, & similar withdrawaldependence, & similar withdrawal

BIG TIME OD PotentialBIG TIME OD Potential


CNS regions affected by Barbs same CNS regions affected by Barbs same as alcoholas alcohol

Low DoseLow Dose Reticular activating system depressionReticular activating system depression Septal projections to amygdala = Septal projections to amygdala =

AnxiolysisAnxiolysis Higher DoseHigher Dose

Global depression of neural activityGlobal depression of neural activity Final symptoms respiratory depression Final symptoms respiratory depression

and spasm of larynxand spasm of larynx


Medical uses for barbs were anxiety, Medical uses for barbs were anxiety, insomnia, and epilepsyinsomnia, and epilepsy most uses replaced by benzodiazepines most uses replaced by benzodiazepines

except epilepsyexcept epilepsy Phenobarbitol most commonly Phenobarbitol most commonly

prescribed anti-epilepticprescribed anti-epileptic cheap, low in toxicity, effective dose well cheap, low in toxicity, effective dose well

below hypnotic levelbelow hypnotic level Side effects all similar to alcoholSide effects all similar to alcohol Used today for general anesthsiaUsed today for general anesthsia


Most commonly abused are short Most commonly abused are short acting Seconal (reds)acting Seconal (reds) Preferred means for suicidePreferred means for suicide Most common barbiturate fatality Most common barbiturate fatality

results from combo of alcohol and results from combo of alcohol and barbituratesbarbiturates Half LD50 of seconal with quarter LD50 of Half LD50 of seconal with quarter LD50 of

alcohol will kill alcohol will kill

BenzodiazepinesBenzodiazepines

Because barbiturates cause problems Because barbiturates cause problems similar to those caused by alcoholsimilar to those caused by alcohol

1.1. suppresses respiration & can lead to deathsuppresses respiration & can lead to death

2.2. not overly safenot overly safe

3.3. high dependence potentialhigh dependence potential

4.4. easily abusedeasily abused

5.5. act synergistically with alcohol to induce act synergistically with alcohol to induce death death

Then we need a better drug --- BenzosThen we need a better drug --- Benzos

Sedatives: Sedatives: BenzodiazepinesBenzodiazepines

Mid 1950's known as "anxious age"-many Mid 1950's known as "anxious age"-many drugs developeddrugs developed 3 main classes3 main classes

Anti-psychoticsAnti-psychotics anti-depressantsanti-depressants MiltownMiltown

Late 1950's accidental discovery of drug Late 1950's accidental discovery of drug with sedative, anti-convulsant and muscle with sedative, anti-convulsant and muscle relaxant propertiesrelaxant properties Very low toxicity Very low toxicity


Drug named Librium & released in Drug named Librium & released in 19601960

Within 3 months #1 prescribed sedativeWithin 3 months #1 prescribed sedative Valium, more potent than librium, Valium, more potent than librium,

introduced 3 yrs laterintroduced 3 yrs later From latin vale - to be strong or well From latin vale - to be strong or well

(diazepam)(diazepam) Went on to become most prescribed drug Went on to become most prescribed drug

of any kindof any kind Replaced barbs as hypnotics (sleeping pills) Replaced barbs as hypnotics (sleeping pills)

in 1970's with introduction of Dalmane in 1970's with introduction of Dalmane


Went on to sell like hotcakes - 1975 Went on to sell like hotcakes - 1975 104.5 million prescriptions104.5 million prescriptions

1977 decreased to 54 mill but 8000 1977 decreased to 54 mill but 8000 tons still consumed that yeartons still consumed that year

that's 2,415,000 individuals at 2-3 that's 2,415,000 individuals at 2-3 doses per daydoses per day

Common description of user Common description of user middle age to elderlymiddle age to elderly residing in Western U.S.residing in Western U.S. femalefemale

BenzodiazepinesBenzodiazepines BenzodiazepinesBenzodiazepines

1. Librium1. Librium ChlordiazepoxideChlordiazepoxide2. Valium2. Valium DiazepamDiazepam3. Dalmane3. Dalmane FlurazepamFlurazepam4. Xanax4. Xanax AlprazolamAlprazolam5. Halcion5. Halcion TriazolamTriazolam6. Clonopin6. Clonopin ClonazepamClonazepam

Primary Uses (based upon duration of action)Primary Uses (based upon duration of action)1) Muscle Relaxant1) Muscle Relaxant2) Sleeping aids 2) Sleeping aids favorites are triazolam and flurazepamfavorites are triazolam and flurazepam

3) Anxiety (Generalized anxiety disorder)3) Anxiety (Generalized anxiety disorder)4) Epilepsy - Clonazepam (Clonipin)-4) Epilepsy - Clonazepam (Clonipin)-5) Panic attacks - Xanax (alprazolam)5) Panic attacks - Xanax (alprazolam) anti-depressant action in some situationsanti-depressant action in some situations

BenzodiazepinesBenzodiazepines PharmacokineticsPharmacokinetics AdministrationAdministration

most taken orally - completely most taken orally - completely absorbed via G.I. Tract. Absorbed absorbed via G.I. Tract. Absorbed slowlyslowly

Can be given by IV (seizure or pre-Can be given by IV (seizure or pre-surgery)surgery)


Agonist at GABA receptor Agonist at GABA receptor benzodiazepine site present at GABA benzodiazepine site present at GABA

receptorreceptor GABA tightly coupled to Cl- channel GABA tightly coupled to Cl- channel

(opens Cl- channel)(opens Cl- channel) get full effect if both GABA and get full effect if both GABA and

benzodiazepines are presentbenzodiazepines are present Cl- enters cell which inhibits firingCl- enters cell which inhibits firing


Benzodiazepines have active Benzodiazepines have active metabolites via biotransformationmetabolites via biotransformation

Breakdown by liverBreakdown by liver Tolerance does not appear to Tolerance does not appear to

develop for anxiolytic actiondevelop for anxiolytic action Does fairly rapidly for effects on Does fairly rapidly for effects on

sleepsleep


Location of binding sitesLocation of binding sites Primary sitesPrimary sites

cortex cortex limbic systemlimbic system

Secondary sitesSecondary sites thalamusthalamus cerebellumcerebellum locus coeruleuslocus coeruleus


ActionsActions anticonvulsantanticonvulsant cortexcortex hypnotichypnotic cortex and locus cortex and locus

coeruleuscoeruleus anxiolyticanxiolytic limbic system and limbic system and

locus locus coeruleuscoeruleus

BenzodiazepinesBenzodiazepines Problems with benzodiazepinesProblems with benzodiazepines

over prescribedover prescribed often given on request from patientoften given on request from patient

treat the anxiety but not the source of problemtreat the anxiety but not the source of problem memory impairmentsmemory impairments

especially when used as hypnotic agent-have amnesia for especially when used as hypnotic agent-have amnesia for events while individual is receiving the drugevents while individual is receiving the drug

can provide a sense of euphoriacan provide a sense of euphoria abused in combination w/alcohol for greater sense of abused in combination w/alcohol for greater sense of

euphoriaeuphoria ataxia-incordinationataxia-incordination

Benzodiazepines have a fairly safe therapeutic Benzodiazepines have a fairly safe therapeutic indexindex

Rohypnol – Powerful benzo that is an amnestic. Rohypnol – Powerful benzo that is an amnestic. One of the unfortunately many date rape drugs.One of the unfortunately many date rape drugs.

InhalantsInhalants

Adhesives - GlueAdhesives - Glue Aerosols – Spray paintAerosols – Spray paint Anesthetics - NOAnesthetics - NO Cleaning Agents – DegreaserCleaning Agents – Degreaser Solvents - Nail polish remover, gasSolvents - Nail polish remover, gas Gases - ButaneGases - Butane Nitrites - PoppersNitrites - Poppers

InhalantsInhalants

Not all are true depressantsNot all are true depressants NO is a true deprssantNO is a true deprssant Most produce a dizzy “euphoric” Most produce a dizzy “euphoric”

rushrush Effects are complex and not well Effects are complex and not well

understoodunderstood

InhalantsInhalants

Abused by children and adolescentsAbused by children and adolescents Certain subcultures as wellCertain subcultures as well

Popper and gay menPopper and gay men A particular problem in homeless A particular problem in homeless

and runaway populationsand runaway populations

depressants: barbs, benzos and huffing chapter 10

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