Sedative Hypnotics

Question 1

What are the sedative hypnotics?

Answer 1

alcohols, barbiturates and benzodiazepines

Question 2

functions of sedative hypnotics

Answer 2

-disinhibition of behavior
-sedation
anticonvulsant
-anesthesia
-respiratory & cardiac depression

Question 3

common alcohols

Answer 3

• isopropyl alcohol
• methanol
• ethanol

Question 4

isopropyl alcohol

Answer 4

rubbing alcohol

Question 5

methanol

Answer 5

-methyl alcohol (wood alcohol)
-antifreeze
toxic to the optic nerve due to the accumulation of formic acid

Question 6

ethanol

Answer 6

ethyl alcohol

Question 7

denatured alcohol

Answer 7

acetone/methanol added to ethanol to render it undrinkable

Question 8

proof

Answer 8

• a measure of alcohol concentration

- twice the percentage of the alcohol content

Question 9

story behind proof

Answer 9

British soldiers poured liquor on gunpowder and lit it, if the power popped in despite it being wet, it was proof that the liquor was 50% alcohol or better (ie 100 proof)

Question 10

fermentation

Answer 10

sugar + water + air is invaded by yeast which consume sugar, ethanol & CO2 are produced

Question 11

distillation

Answer 11

the process of concentrating ethanol after fermentation (remove water)

Question 12

oral administration

Answer 12

• readily crosses membranes

- 20% alcohol absorbed in stomach, 80% in liver

Question 13

absorption of alcohol is altered by:

Answer 13

• stomach contents

- carbonation

Question 14

effects of stomach contents on absorption

Answer 14

• empty stomach: blood levels from 1 drink peak in 20-30min

- carbonation: speeds gastric emptying & absorption

Question 15

distribution

Answer 15

evenly distributes throughout the water of the body

Question 16

What is the basis for the breathalyzer test?

Answer 16

• levels of alcohol in blood reflect levels in brain

- ethanol in blood is carried to lungs and vaporized

Question 17

result of women tending to have higher proportion of body fat to body water

Answer 17

higher blood ethanol concentrations

Question 18

alcohol metabolism

Answer 18

liver metabolizes 90-95% of the alcohol

• antabuse blocks the metabolism of alcohol
• 50% of Asians lack one of the enzymes to metabolize ethanol

Question 19

alcohol metabolism pathway

Answer 19

• alcohol broken down into acetaldehyde by alcohol dehydrogenase
• acetaldehyde dehydrogenase breaks acetaldehyde into acetic acid
• acetic acid broken down into carbon dioxide by an oxidation reaction

Question 20

effects of high acetaldehyde levels

Answer 20

flushing, nausea, headache and increased heart rate

Question 21

phenotype associated with homozygosity for active form of acetaldehyde dehydrogenase

Answer 21

mild or no flushing

Question 22

phenotype associated with heterozygosity for acetaldehyde dehydrogenase

Answer 22

flushing

Question 23

phenotype associated with homozygosity for inactive form of acetaldehyde dehydrogenase

Answer 23

severe flushing

Question 24

alcohol metabolism in 150lb male

Answer 24

• metabolizes 10g alcohol/hour, or one 12oz beer or 1.25oz whiskey/hour
• consumption over this level results in intoxication

Question 25

men have more _____ in stomach lining, results of this?

Answer 25

alchohol dehydrogenase; may contribute to lower blood ethanol levels in men than women

Question 26

enzyme activity ____ with increased exposure, contributing to ____ and _____

Answer 26

increases; tolerance; cross-tolerance

Question 27

metabolic tolerance

Answer 27

pharmoacokinetic tolerance; rate of elimination

Question 28

functional tolerance

Answer 28

pharmacodynamic tolerance; can develop tolerance to sedative effects, but not all the effects

Question 29

high doses of ethanol

Answer 29

increases membrane fluidity: - disrupts lipid matrix of membranes - non-specific disruption in neuronal function - failures in axonal conduction and transmitter release - relevant to blackouts and anesthetic properties

Question 30

lower doses

Answer 30

indirect GABA receptor agonist, potentiates the effects of GABA

Question 31

GABA

Answer 31

most common inhibitory neurotransmitter

Question 32

GABA receptor recognition sites

Answer 32

alcohol recognition site, benzodiazepine and barbiturate recognition sites

Question 33

Are GABA receptors metabotropic or ionotropic?

Answer 33

ionotropic

Question 34

Will ethanol have an effect in the absence of GABA?

Answer 34

no

Question 35

GABA receptor info:

Answer 35

- forms a chloride channel | - most often contains: 2 alpha subunits, 2 beta subunits and 1 gamma subunit

Question 36

Why is GABA inhibitory?

Answer 36

the docking of GABA at GABA receptor opens chloride channel, when Cl- flows into cell, it hyperpolarizes the cell making it less likely to fire

Question 37

non-specific actions of GABA

Answer 37

- interacts with polar heads of phospholipids - alters lipid composition - disturbs the relationship of protein in membrane

Question 38

specific actions of GABA

Answer 38

- acts as a neurotransmtter binding site - modifies gating mechanism inside channel - direct interaction with channel protein - stimlates Gs which is linked to adenylyl cyclase

Question 39

withdrawal after acute intake

Answer 39

- headache, upset stomach, depression, anxiety, thirst - severity related to amount consumed and type of beverage - partly due to dehydration and alterations in blood sugar levels

Question 40

ethanol withdrawal after chronic intake

Answer 40

- life-threatening - tremors, hallucinations, seizures - lasts several weeks - due to massive rebound excitation in nervous system

Question 41

Why is ethanol withdrawal after chronic intake life threatening?

Answer 41

the nervous system increases excitation in response to GABA potentiation, thus when there is no longer increased inhibition one gets way to much excitation

Question 42

Alcohol withdrawal, dopamine and nucleus accumbens

Answer 42

since alcohol increases dopamine release, withdrawal decreases dopamine release, linked to rigidity, vocalizations, tremors and depression

Question 43

Wernicke-Korsakoff's Syndrome

Answer 43

- confusion and memory loss - due to deficits in vitamin B1 (thiamine) intake - loss of cells in dorsomedial thalamus (not diagnostic criteria, found in other illnesses)

Question 44

cells of dorsomedial thalamus

Answer 44

- lost in Wernicke-Korsakoff's syndrome and schizophrenia | - these cells form a wall to lateral ventricles, thus in these illnesses the ventricles are widened

Question 45

Symptoms of fetal alcohol syndrome

Answer 45

- slowed pre- and post-natal growth - abnormal facial features (small head, flattened nose, thin upper lip, indistinct philtrum) - CNS dysfunction

Question 46

CNS dysfunction in fetal alcohol syndrome

Answer 46

- abnormal behavior, mental retardation - small brain size - under-developed brain

Question 47

Incidence of fetal alcohol syndrome

Answer 47

0.05 - 0.3% in general population