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Chapter 7

Drugs and Behaviour - Chapter 7 (139-153

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Bruce Mc Kay

Drugs and Behaviour - Chapter 7 (139-153)  History and pharmacology of depressants o Depressant drugs share many characteristics with alcohol o Before barbiturates  Number of medications used prior to introduction of barbiturates  Chloral hydrate  1870 – started being used clinically  Has short onset of action and 1-2g will induce sleep in less than an hour  Chloral hydrate abusers grouped with alcohol intempereants and opium eaters  Gastric irritant and can cause considerable stomach upset  Pharldehyde  1882 – started being used clinically  Has noxious taste, but may be of great use as CNS depressant because of wide safety margin  Use discontinued in 2007  Bromides  Used widely to induce sleep  Accumulates in body and cause build up over several days of regular use  Severe toxic effects following repeated hypnotic doses  Dermatitis and constipation, motor disturbance, delirium and psychosis are side effects o Barbiturates  More than 2500 types synthesized  Veronal first clinically used in 1903 o All barbiturates end with –al  Most lipid-soluble drugs have shortest onset time and quickest duration of action  Low dose of long acting barbiturate – calm and relaxed for long period  Higher dose of short acting – sleeping pill  Activates CYP450 enzymes of liver  Some tolerance develops  Psychological and physical depend can develop  Depress respiration o Combined with alcohol, can stop person’s breathing  Barbiturate sleeping pills were chosen above others as suicide pill  Accidental overdoses often occurred too  Great deal of concern about abuse potential and danger of overdose o Meprobamate  Believed to be a unique type of CNS depressant  Marked as an anxiolytic, became popular with drug abusers  Produced barbiturate-like euphoria and pleasure o Prescribing and use gradually decreased  Schedule III drug  Combination product 282-MEP o Used for treatment of pain associated with muscle tightness o Methaqualone  Synthesized in India, found to have sedative properties  Very high rates of overdose  Tolerance develops very quickly, creates euphoric effects  Repeated administration results in physical dependence, severe withdrawal related psychotic symptoms and life threatening seizure activity  Schedule IV drug Brian Kwok 1 Drugs and Behaviour - Chapter 7 (139-153) o Benzodiazepines  First was chlordiazepoxide  First synthesized in 1947  Marketed as more selective anti-anxiety agent, produced less drowsiness and larger safety argin  Physical dependence was almost unheard of and overdose didn’t occur in combination with alcohol  As effective as barbiturates and much safer  Valium (diazepam) replaced in 1970  Xanax (alprazolam) mostly prescribed  As drugs became widely used, physical dependence, psychological dependence and overdose deaths appeared  Over dose deaths o More likely when drug sold in higher doses than prescribed  Psychological dependence o Develops most rapidly when drug hits brain  Physical dependence o Occurs when drug leaves system more rapidly than body can adapt  Chlordiazepoxide  Slow onset of action  Longer duration of action  Produces few problems  Most frequently prescribed psychotropic medication  Variety of psychiatric and medical condition  Anxiety disorders  Sleep disorders  Seizure disorders  Movement disors  Muscle spasticity  Used in anaesthesiology and symptomatic treatment of agitation associated with other disorders  Mechanism of Action of Benziodazepines o Effects of sedative-hypnotic agents found in 1977 o Benzodiazepine receptors always ear receptors for amino acid neurotransmitter GABA  Enhance normally inhibitory effects of GABA on its receptor o Barbiturates act at separate binding site and increase the actions of GABA on its receptors as well o Different subtypes of GABA receptors identified  Structurally different and activated or blocked by different drugs o Benzodiazepines do not independently activate flow of chloride ions into neuron  Facilitate action of primary inhibitory neurotransmitter to increase flux of chloride ions into neuron o Tolerance usually develops among people receiving maintenance therapy with stable dose o Overdoses almost never fatal unless combining with other sedative agents  Beneficial Uses of Depressants o Anxiolytics  Drugs used to reduce anxiety  Used to accept that various types of dysfunctional behaviour resulted from various forms of psychological stress and can be lumped under “anxieties”  Not all conditions can be treated with antianxiety drugs  Most benzodiazepines prescribed for anxiety disorders Brian Kwok 2 Drugs and Behaviour - Chapter 7 (139-153)  Used to treat low-level generalized anxiety disorder  Patients asking to be protected from troubles of daily living  Impossible to determine whether paitent just enjoying the “feel-good pull” or feels better because of a specific antianxiety effect o As sleeping pills  Principle on which hypnotic drug therapy is based: large enough dose is taken to help you get to sleep quickly  Insomnia fairly common symptom  1/3 adults reported some trouble falling asleep, sleeping or both o People underestimate how much they sleep, overestimate how long it takes to fall asleep  Produces a number of adverse psychiatric reactions  Nonbenzodiazepine Hypnotics  Most recent addition does not have chemical structure of benzodiazepines, but similar effects  Better for sleeping o As anticonvulsants  Widely used for epileptic seizure control  Effective in reasonably low doses, combined with other anticonvulsants for better effectiveness  Tolerance tends to develop because they are given chronically
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