Unit 3 - Non-Medicinal Drug Use Flashcards Preview

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Flashcards in Unit 3 - Non-Medicinal Drug Use Deck (35):

what are the CNS depressants and how do they work?

augment activity at GABA-A receptor complex, increasing Cl- influx, hyperpolarizing cell (inhibitory)
-include alcohol, barbiturates, benzodiazepines, and inhalants


alcohol absorption?

very rapidly absorbed by diffusion through membranes
-very small molecule that easily crosses membranes
--mouth mucus membrane, stomach, small intestine (most here)
--lungs absorb alcohol vapor


what does the rate of alcohol absorption depend on?

1. concentration of alcoholic beverage
2. stomach (empty has higher and faster peak, slower drop; full has lower and slower peak)


what does food in the stomach do to alcohol?

1. dilutes alcohol
2. delays stomach emptying
3. increases effective rate of alcohol metabolism
-some enzyme oxidation in stomach
-slower delivery to liver through portal circulation > liver oxidation


what are blood alcohol units?

BAC (blood alcohol concentration)
-based on plasma or serum in hospital, or whole blood legally
-100 mg% = 100 mg/dL = 1 mg/mL = 0.10% (wt/vol) = 22 nM


explain alcohol distribution?

total body water, as small molecule can easily cross all membranes


how is alcohol eliminated?

90-98% metabolized (oxidized)
-routes are urine, breath, and sweat


how is alcohol metabolized?

mostly in liver, some stomach
-small intestines > portal circulation > liver
-alcohol dehydrogenase, acetaldehyde dehydrogenase, and microsomal ethanol oxidizing system


what is alcohol dehydrogenase?

ADH - dimeric Zn-containing metallo-enzyme in liver cytoplasm, and a bit in gastric mucosa
-ethyl alcohol + NAD+ --> acetaldehyde + NADH + H+


what is acetaldehyde dehydrogenase?

ALDH - 1 in liver cytoplasm, 2 in liver mitochondria
-acetaldehyde + NAD+ + H2O --> acetate + NADH + H+


what is the "Asian flush" due to?

1. "atypical" B2 allele with enhanced rate of hepatic ADH (increases metabolism to acetaldehyde)
2. lack of functional ALDH2 causes build-up


what happens if there is a high magnitude of alcohol consumed?

tremendous load for liver, causing dramatic change in redox state
-all NAD-dependent reactions in liver are affected by alcohol
--impaired gluconeogenesis leads to hypoglycemia
--increased lactic acid and ketone body production
--inhibits uric acid excretion (hyperuricemia)
--decreases fatty acid oxidation and increases TG and FA synthesis


what is the rate-limiting factor in alcohol oxidation?

supply of NAD+; causes saturation (zero-order) kinetics results


what is microsomal ethanol oxidizing system?

MEOS P450 (esp. CYP2E1)
-smooth ER mixed function oxidase
-more important factor at high levels of alcohol, and with chronic alcohol consumption
-induced by chronic exposure to alcohol and barbiturates


what three drugs have cross-tolerance and what is it for?

alcohol, barbiturates, and benzodiazepines have X-tolerance for inhibitory neurotransmitter GABA-A and intrinsic Cl- channel
-opens Cl- channel --> hyperpolarizatin --> inhibition


effects of alcohol on CNS

1. potency as a drug is very weak
2. CNS depressant - dose-related graded effects
-mild mood alteration --> intoxication --> coma --> death
3. acute intoxication (mild or moderate)


what is "mild intoxication" from alcohol?

"impairment"; 25-100 mg% BAC
-loss of inhibitions, altered mood, impaired cognition, incoordination, sedation
-due to preferential involvement of polysynaptic neuronal pathways in reticular formation (cerebral cortex, brain stem, cerebellum)


what is "intoxication" from alcohol?

>100 mg%
-diplopia, nystagmus, dysarthria, ataxia
-vestibular and cerebellar dysfunction --> stupor --> death
-blackouts are dangerous outcome
-temporal correlation between peak BAC and peak bheavioral effects, thus behavioral effects correlate with BAC


between males and females, which have higher BAC?

women have higher BAC due to gastric metabolism and less body H2O


what happens to the liver if chronic heavy drinking?

fatty liver, although uncertain pathology
-progression: lipid metabolism alteration --> fatty liver --> hepatitis --> necrosis --> fibrosis --> cirrhosis --> hepatic failure --> death


what happens if there is constant exposure to acetaldehyde?

increase lipid peroxidation and damage to membranes and mitochondria
-depletion of glutathione and some vitamins
-alteration in protein transport


wwhat are cardiovascular effects of alcohol?

most studies show moderate alcohol consumption is protective
-increases HDL to decrease CDH
-but all-cause mortality has U-shaped relationship (as other causes of mortality, caused by actions while intoxicated)


effect of alcohol on dementia?

decreased dementia with 1-6 drinks/week compaired to abstaining


what are GI and endocrine effects of alcohol?

1. GI irritation --> inflammation --> chronic gastritis
2. well-known diuretic effect from decreased secretion of antidiuretic hormone
3. stressor to stimulate adrenal cortex
4. decreased testosterone synthesis
-male alcoholics --> hypogonadism and feminization, gynecomastia
5. suppresses uterine motlity and milk ejection


explain what fetal alcohol syndrome causes

1. growth deficiency (pre- and postnatal body length and weight below mean)
2. dysmorphic characteristics (facial features, limb abnormalities)
3. CNS manifestations (neurobehavioral effects)
-microcephaly, tremor, seizures, slow development, hyperactivity, learning problems, memory problems


what are drug interactions with alcohol

1. pharmacokinetic interactions with many drugs
-acute (while alcohol is on board): metabolism of other drugs will be inhibited if they undergo oxidative metabolism
-chronic (induces P450, thuus metabolism of some other drugs may be enhanced, which also contributes to tolerance of alcohol)
2. pharmacodynamic interactions
-additive CNS depression with other CNS depressants


what is methyl alcohol and treatment?

windshield washer antifreeze
-formaldehyde and formic acid are highly toxic metabolites --> severe acidosis
-visual disturbances --> blindness
-treatment = ethyl alcohol (to tie up alcohol dehydrogenase) + bicarbonate (to decrease acidosis state)


what is ethylene glycol and treatment?

autommotive antifreeze
-oxidized to oxalic acid, which is very toxic to kidney
--renal insufficiency
--CNS excitement --> depression


what does disulfiram do?

inhibit acetaldehyde dehydrogenase, so that acetaldehyde cannot be converted into acetic acid
-worsens their toxic effects, so used as alcoholism treatment


what is treatment for both methanol and ethylene glycol poisoning?

1. ethyl alcohol (vodka; maintain 100 mg/dL)
2. alcohol dehydrogenase inhibitor (4-methylpyrazole)


what is isopropyl alcohol and treatment?

rubbing alcohol
-causes gastritis, acidosis, and CNS symptoms
-no antidote, so must use symptomatic and supportive treatment


what are barbiturates?

multi-use, generally replaced by benzodiazepines
-augment activity at GABA-A receptor complex to produce CNS inhibition
-cause drowsiness, confusion, impaired judgement, slurred speech


what are phenobarbital and thiopental?

barbiturates still in use today
-phenobarbital: anti-seizure
-thiopental: induce anesthesia


what are benzodiazepines?

augment activity at GABA-A receptor complex to produce CNS inhibition
-many benzos, and widely used to induce anesthesia, treat anxiety, sleep aids, and for recreation
-cause alcohol-like drunkenness with relaxation, loss of inhibition, impaired judgement, and loss of short-term memory


what are CNS stimulants?

amphetamine and cocaine
-increase CNS catecholamine, especially dopamine, directly or indirectly by several mechanism