Sedative Hypnotics Flashcards
What are the sedative hypnotics?
alcohols, barbiturates and benzodiazepines
functions of sedative hypnotics
-disinhibition of behavior
-sedation
anticonvulsant
-anesthesia
-respiratory & cardiac depression
common alcohols
- isopropyl alcohol
- methanol
- ethanol
isopropyl alcohol
rubbing alcohol
methanol
-methyl alcohol (wood alcohol)
-antifreeze
toxic to the optic nerve due to the accumulation of formic acid
ethanol
ethyl alcohol
denatured alcohol
acetone/methanol added to ethanol to render it undrinkable
proof
- a measure of alcohol concentration
- twice the percentage of the alcohol content
story behind proof
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)
fermentation
sugar + water + air is invaded by yeast which consume sugar, ethanol & CO2 are produced
distillation
the process of concentrating ethanol after fermentation (remove water)
oral administration
- readily crosses membranes
- 20% alcohol absorbed in stomach, 80% in liver
absorption of alcohol is altered by:
- stomach contents
- carbonation
effects of stomach contents on absorption
- empty stomach: blood levels from 1 drink peak in 20-30min
- carbonation: speeds gastric emptying & absorption
distribution
evenly distributes throughout the water of the body
What is the basis for the breathalyzer test?
- levels of alcohol in blood reflect levels in brain
- ethanol in blood is carried to lungs and vaporized
result of women tending to have higher proportion of body fat to body water
higher blood ethanol concentrations
alcohol metabolism
liver metabolizes 90-95% of the alcohol
- antabuse blocks the metabolism of alcohol
- 50% of Asians lack one of the enzymes to metabolize ethanol
alcohol metabolism pathway
- 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
effects of high acetaldehyde levels
flushing, nausea, headache and increased heart rate
phenotype associated with homozygosity for active form of acetaldehyde dehydrogenase
mild or no flushing
phenotype associated with heterozygosity for acetaldehyde dehydrogenase
flushing
phenotype associated with homozygosity for inactive form of acetaldehyde dehydrogenase
severe flushing
alcohol metabolism in 150lb male
- metabolizes 10g alcohol/hour, or one 12oz beer or 1.25oz whiskey/hour
- consumption over this level results in intoxication
men have more _____ in stomach lining, results of this?
alchohol dehydrogenase; may contribute to lower blood ethanol levels in men than women
enzyme activity ____ with increased exposure, contributing to ____ and _____
increases; tolerance; cross-tolerance
metabolic tolerance
pharmoacokinetic tolerance; rate of elimination
functional tolerance
pharmacodynamic tolerance; can develop tolerance to sedative effects, but not all the effects
high doses of ethanol
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
lower doses
indirect GABA receptor agonist, potentiates the effects of GABA
GABA
most common inhibitory neurotransmitter
GABA receptor recognition sites
alcohol recognition site, benzodiazepine and barbiturate recognition sites
Are GABA receptors metabotropic or ionotropic?
ionotropic
Will ethanol have an effect in the absence of GABA?
no
GABA receptor info:
- forms a chloride channel
- most often contains: 2 alpha subunits, 2 beta subunits and 1 gamma subunit
Why is GABA inhibitory?
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
non-specific actions of GABA
- interacts with polar heads of phospholipids
- alters lipid composition
- disturbs the relationship of protein in membrane
specific actions of GABA
- acts as a neurotransmtter binding site
- modifies gating mechanism inside channel
- direct interaction with channel protein
- stimlates Gs which is linked to adenylyl cyclase
withdrawal after acute intake
- 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
ethanol withdrawal after chronic intake
- life-threatening
- tremors, hallucinations, seizures
- lasts several weeks
- due to massive rebound excitation in nervous system
Why is ethanol withdrawal after chronic intake life threatening?
the nervous system increases excitation in response to GABA potentiation, thus when there is no longer increased inhibition one gets way to much excitation
Alcohol withdrawal, dopamine and nucleus accumbens
since alcohol increases dopamine release, withdrawal decreases dopamine release, linked to rigidity, vocalizations, tremors and depression
Wernicke-Korsakoff’s Syndrome
- 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)
cells of dorsomedial thalamus
- lost in Wernicke-Korsakoff’s syndrome and schizophrenia
- these cells form a wall to lateral ventricles, thus in these illnesses the ventricles are widened
Symptoms of fetal alcohol syndrome
- slowed pre- and post-natal growth
- abnormal facial features (small head, flattened nose, thin upper lip, indistinct philtrum)
- CNS dysfunction
CNS dysfunction in fetal alcohol syndrome
- abnormal behavior, mental retardation
- small brain size
- under-developed brain
Incidence of fetal alcohol syndrome
0.05 - 0.3% in general population
