Non-Medical Drug Use

Question 1

CNS depressants

Answer 1

most augment activity at GABAa receptor complex, increasing Cl- influx, hyperpolarizing the cell, which is an inhibitory action. Alcohol, benzos, barbituates, inhalants

Question 2

alcohol absorption

Answer 2

rapidly absorbed by diffusion through membranes. small molecule, so it crosses membranes easily. most is done in small intestine. rate of absorption depends on if stomach is full/empty, and concentration of alcohol

Question 3

food in stomach does what?

Answer 3

dilutes alcohol. delays stomach emptying. increases effective rate of alcohol metabolism (some enzyme oxidation in the stomach, slower delivery to liver)

Question 4

alcohol distribution

Answer 4

total body water! males 63% body water fraction, females 52% body water fraction

Question 5

alcohol elimination

Answer 5

90-90% oxidized (metabolized). routes of elimination: breath, sweat, urine. metabolism is in stomach and liver.

Question 6

liver metabolism of alcohol

Answer 6

Alcohol dehydrogenase: in liver cytoplasm, uses NAD+ as cofactor. Makes acetaldehyde.

Acetaldehyde dehydrogenase: 1 in liver cytoplasm, 2 in liver mitochondria. Plays greatest role in oxidation. Asians lack functional form of ALDH2, causing alcohol sensitivity

Question 7

what is rate limiting factor for alcohol oxidation?

Answer 7

NAD+ supply. this causes zero order kinetics (saturation kinetics)

Question 8

Cytochrome P-450

Answer 8

mixed function oxidase. primarily CYP2E1. More important factor at high levels of alcohol, and with chronic alcohol consumption. induced by chronic exposure to alcohol and barbituates

Question 9

alcohol mechanism of action

Answer 9

CNS. likely binds GABAa and augments GABA, leading to open chloride channels and inhibition due to hyperpolarization. Alcohol and barbs and benzos have cross tolerance

Question 10

CNS effects of alcohol

Answer 10

weak potency. CNS depressant, from drunk to coma to death. blackouts.

Question 11

Chronic heavy drinking effects

Answer 11

fatty liver –> hepatitis –> necroisis –> fibrosis –> Cirrhosis –> hepatic failure –> death. possibly due to constant exposure to acetaldehyde, damaginc membranes and mitochondria. in the heart, moderate alcohol consumption is protective. increases HDL. GI inflammation –> chronic gastritis. decreased testosterone synth -> feminization. uterine motility suppressed, along with milk ejection suppression

Question 12

fetal alcohol syndrome

Answer 12

growth deficiency. dysmorphic characteristics. CNS manifestation: neurobehavioral effects: microcephaly, tremor, seizures, learning problems, memory problems

Question 13

drug interactions with alcohol

Answer 13

acute: metabolism of other drugs may be inhibited if they undergo oxidative metabolism.
chronic: induces P450, thus metabolism of other drugs may be enhanced.

additive CNS depression with other CNS depressants

Question 14

methyl alcohol

Answer 14

formaldehyde and formic acid. highly toxic, leading to acidosis and blindness. treat with ethyl alcohol

Question 15

ethylene glycol

Answer 15

oxidized to oxalic acid which is very toxic to the kidney. leads to renal insufficiency, acidosis, CNS excitement -> depression. treat with ethyl alcohol or alcohol dehydrogenase inhibitor

Question 16

isopropyl alcohol

Answer 16

gastritis, acidosis, CNS symptoms. no antidote, supportive care