Lecture 5 Alcohol

Depressants (2?)

drugs that depress the nervous system.

ADME

Absorption, Distribution, Metabolism, Excretion.

BAC

Blood Alcohol Concentration

BBB

Blood brain barrier

Enzyme induction (20)

pharmacokinetic tolerance; the body creates more enzymes to metabolize more.

how does alcohol metabolize? (22?)

zero-order kinetics. (approzimately 10mL of pure ethanol/hour).

Liver cirrhosis (23)

death of cells and scaring. Irreversable.

Induction (24)

when alcohol is consumed on a regular base, these liver enzumes increase in number, which increases the rate of metabolism of alcohol and other drugs.

Elimination of alcohol (25)

most is metabolized and filtered through the kidneys, the rest comes out unmetabolized through sweat and the breath.

glutamate

excitatory neurotransmitter

GABA

inhibitory neurotransmitter

What neurotransmitter systems does alcohol act on? (30)

GABA, Glutamate, DA, Opioids.

Specifics effects (31)

directly affect neurotransmitters

nonspecific effects (31)

effects on cell membrane (instead of neurotransmitters)

GABA-A receptor

ionotropic; opens chloride (-) channel; hypoerpolarizes cell. separate binding sites for both alcohol and benzodiazepines.

GABA-B receptor

metabotropic; opens potassium (+) channel; hyperpolarizing;

Alcohol on GABA receptors

positive allosteric modulator; further hyperpolarization.

Alcohol and DA (44)

Alcohol activates DAergic cells in the VTA, causing released of DA int the NAcc, which is involved in positive reinforcement

Alcohol and opioids

Alcohol administration increases opioid production and release; can built tolerance; probably play a role in craving;

Naltrexone (45?)

opioid receptor antagonist used int he treatment of AUD; inconsistently improves abstinence rates; inconsistently reduces alcohol consumption and craving.

(47)

Alcohol and multiple neurotransmitters (48)

alcohol inhibits glutamate, stimulates release of endorphinse, and reduces GABA’s inhibitory effects, thus increasing DA release in the VTA/NAcc

Alcohol Tolerances (58)

acute, metabolic, pharmacodynamic, bahvioural, cross-tolerance

Acute tolerance (59)

happens within a single drink session; (e.g., binge drinker perceive they are less intoxicated when BAC levels are falling);

Metabolic tolerance (60)

increase in P450 liver microsomal enzymes that metabolize alcohol (enzyme induction) so alcohol is metabolized more quickly; happens within days.

pharmacodynamic tolerance (61)

compensatory changes in cell function, such as NMDA receptor upregulation; happens within days to weeks.

Behavioural Tolerance (62)

repeated use in the same environment leads to compensatory response that only occurs in that environment (e.g., always at the same bar vs new bar); operant conditioning where learned behaviour under the influence will improve later proficiency under the influence.

Cross-Tolerance (63)

toleracne to others drugs metabolized by the same enzyme.

Physical dependence on alcohol (64)

intensity and duration of withdrawal signs depend on amount and duration of drug taking; hangovers may be acute withdrawal.

Delerium tremens (DTs; 66)

rapid onset of confusion. may include shaking, shivering, irregular heart rate, and sweating; sometimes hallucinations

Factors increasing risk of Alcohol Use Disorder (69)

anxiety disorders, stress, genetics, [finish[

Treatment of AUD (73)

detoxification, preventing relapse.

Alcohol detoxification (73)

medication may be used to control dnagerous withdrawal sumptoms

preventing alcohol relapse (74)

one pharmacotherapeutic strategy is to make drinking unpleasant by using disulfiram; another strategy is to use an opioid receptor antagonist (naltrexone) to reduce the high; some individuals find individual or group therapy to be helpful in maintaining their abstinence (e.g., AA).