Depressants Barbs Benzos and Huffing Chapter 10 Barbiturates

Depressants: Barbs, Benzos and Huffing Chapter 10

Barbiturates n Bayer in 1864 combined urea (urine) and malonic acid (apples) n n barbituric acid Origin of the name n Barbara contributed the urine n Barbara was a barmaid where he went to celebrate n St. Barbara - patron saint of artillery

Barbiturates 1903 - Veronal (after Verona, e. g. Romeo & Juliet- added “al” to end) n New barbiturates synthesized rapidly in early 1900's n 2500 synthesized, about half dozen served all clinical applications n Use increased until 1960’s n

Barbiturates n n Pharmacodynamics n Classified by duration of action n determines use n anesthesia – short acting n sleep induction - medium n anticonvulsant - long as safely possible Administered orally most often n n exceptions - i. v. for convulsant emergencies anesthetic action & drug abusers

Barbiturates Barb's depress all excitable nervous tissue CNS most sensitive n Mechanism thought to be at GABA synapse n Low doses - increase receptor sensitivity to GABA to potentiate and prolong its effects n Higher dose mimic GABA inhibition possibly by directly activating chloride channels n

Barbiturates n Behavioral effects very similar to alcohol n disinhibition, euphoria, sedation, loss of motor control n sleep, anesthesia & death n also tolerance, physical dependence, & similar withdrawal n BIG TIME OD Potential

Barbiturates CNS regions affected by Barbs same as alcohol n Low Dose n Reticular activating system depression n Septal projections to amygdala = Anxiolysis n n Higher Dose Global depression of neural activity n Final symptoms respiratory depression and spasm of larynx n

Barbiturates n Medical uses for barbs were anxiety, insomnia, and epilepsy most uses replaced by benzodiazepines except epilepsy n Phenobarbitol most commonly prescribed antiepileptic n n cheap, low in toxicity, effective dose well below hypnotic level Side effects all similar to alcohol n Used today for general anesthsia n

Barbiturates n Most commonly abused are short acting Seconal (reds) Preferred means for suicide n Most common barbiturate fatality results from combo of alcohol and barbiturates n n Half LD 50 kill of seconal with quarter LD 50 of alcohol will

Benzodiazepines n Because barbiturates cause problems similar to those caused by alcohol 1. 2. 3. 4. 5. n suppresses respiration & can lead to death not overly safe high dependence potential easily abused act synergistically with alcohol to induce death Then we need a better drug --- Benzos

Sedatives: Benzodiazepines n Mid 1950's known as "anxious age"-many drugs developed n 3 main classes n n Anti-psychotics anti-depressants Miltown Late 1950's accidental discovery of drug with sedative, anti-convulsant and muscle relaxant properties n Very low toxicity

Benzodiazepines Drug named Librium & released in 1960 n Within 3 months #1 prescribed sedative n Valium, more potent than librium, introduced 3 yrs later n From latin vale - to be strong or well (diazepam) n Went on to become most prescribed drug of any kind n Replaced barbs as hypnotics (sleeping pills) in 1970's with introduction of Dalmane n

Benzodiazepines Went on to sell like hotcakes - 1975 104. 5 million prescriptions n 1977 decreased to 54 mill but 8000 tons still consumed that year n that's 2, 415, 000 individuals at 2 -3 doses per day n Common description of user n middle age to elderly n residing in Western U. S. n female n

Benzodiazepines n n Benzodiazepines 1. Librium 2. Valium 3. Dalmane 4. Xanax 5. Halcion 6. Clonopin Chlordiazepoxide Diazepam Flurazepam Alprazolam Triazolam Clonazepam Primary Uses (based upon duration of action) 1) Muscle Relaxant 2) Sleeping aids n favorites are triazolam and flurazepam 3) Anxiety (Generalized anxiety disorder) 4) Epilepsy - Clonazepam (Clonipin)5) Panic attacks - Xanax (alprazolam) n anti-depressant action in some situations

Benzodiazepines Pharmacokinetics n Administration n most taken orally - completely absorbed via G. I. Tract. Absorbed slowly n Can be given by IV (seizure or pre-surgery) n

Benzodiazepines n Agonist at GABA receptor benzodiazepine site present at GABA receptor n GABA tightly coupled to Cl- channel (opens Clchannel) n get full effect if both GABA and benzodiazepines are present n Cl- enters cell which inhibits firing n

Benzodiazepines have active metabolites via biotransformation n Breakdown by liver n Tolerance does not appear to develop for anxiolytic action n Does fairly rapidly for effects on sleep n

Benzodiazepines n Location of binding sites n Primary sites n cortex n limbic system Secondary sites n thalamus n cerebellum n locus coeruleus n

Benzodiazepines n Actions anticonvulsant n hypnotic n n anxiolytic cortex and locus coeruleus limbic system and locus coeruleus

Benzodiazepines n Problems with benzodiazepines n over prescribed n n n treat the anxiety but not the source of problem memory impairments n n especially when used as hypnotic agent-have amnesia for events while individual is receiving the drug can provide a sense of euphoria n n often given on request from patient abused in combination w/alcohol for greater sense of euphoria ataxia-incordination Benzodiazepines have a fairly safe therapeutic index Rohypnol – Powerful benzo that is an amnestic. One of the unfortunately many date rape drugs.

Inhalants Adhesives - Glue n Aerosols – Spray paint n Anesthetics - NO n Cleaning Agents – Degreaser n Solvents - Nail polish remover, gas n Gases - Butane n Nitrites - Poppers n

Inhalants Not all are true depressants n NO is a true deprssant n Most produce a dizzy “euphoric” rush n Effects are complex and not well understood n

Inhalants Abused by children and adolescents n Certain subcultures as well n n n Popper and gay men A particular problem in homeless and runaway populations