ch 9 pharm pt.1

alcohol

types of alcohol

safe to consume: ethyl (ethical) alcohol - A CNS depressant, consumed as a bev

not same to consume: Isopropyl alc- rubbing alcohol/disinfectant

methyl alcohol- industrial solvent in antifreeze metabolite formaldehyde

toxic to the optic nerve → causes blindness can be made from moonshine (M methyl Moonshine)

alcohol use and abuse

81.5% age 12+ use alcohol at some point more than 50% are current consumers and 11.5% of consumers are 12-17

Where does alcohol come from?

ethyl alcohol is created by fermentation of yeast present in the air and sugars

fermentation continues until alcohol reaches 15% which kills the yeast that’s making it

higher % alcohol content requires distillation (whiskey)

in-between are the fortified wines (wine + added alc)

a standard drink

servings of different drinks will level off to 0.48-.5 per serving in ounces

alcohol content and a standard drink

proof: double the percent of alc purpose to have proof it has enuf alc under 50% wont light anything 100% proof lights

US legal history

18th amendment prohibition era didn’t ban alc consumption only the sale and distribution of it

21st amendment repealed the 18th

absorption and distribution

alcohol is very lipid soluble → absorb in intestine BAC is # grams of alc per 100ml of blood

absorption is affected by: food consumption + food composition

food (any) slows absorption, fatty food slow absorption carbonation speeds it

body size + composition smaller body= more alcohol by volume more fat= more lipid to dissolve into

metabolism

once alc reaches bloodstream

95% is metabolized by liver→ excreted in urine

5% is excreted intact by lungs (breathalyzer test)

metabolsim is mostly zero-order kinetics (constant rate)

rate is 1 standard drink/hour

if you get ahead of your metabolism = intoxication

metabolism- enzymes

alcohol (enzyme: alcohol dehydrogenase) → acetaldehyde (enzyme: acetaldehyde dehydrogenase)→ (chemical reaction:oxidation reaction)→ carbon dioxide + energy

Gender & Absorption

gender

women are smaller (more alc per body weight)

women have higher fat to water ratio

digestive enzyme alcohol dehydrogenase is 60% less active in women than men!

Alc passes palcental barrier easily→ fetal alc syndrome

BAC and Gender

BAC = 0.08 legal limit in CA

what role does expectation have?

act drunker and drunker bc were given alcohol and didnt know alc feels like flu 

race and alcohol metabolism

10% of Asian descent have genes that code for a completely inactive form of enzyme Acetaldehyde dehydrogenase

leads to a build-up of toxic metabolite acetaldehyde

red face, heart flutters= asian flush

alcohol + other drug interactions

interfere with metabolism

aspirin inhibits alcohol dehydrogenase, slowing metabolism

antibiotics kill gut bacteria that metabolize alcohol

acetaminophen shares CYP 2E1 enzyme slowing metabolism

enhance effects: cocaine results in stronger active metabolite cocaethylene

benzodiazepines synergistic effect: magnifying alcohol’s sedative-hypnotic effects

GABA A

depressants work by increasing activity of inhibitory neurotransmitter GABA

via GABA A receptors: ionotropic

open Cl- channels

this lets Cl- into neuron… making it more negative inside and less likely to fire

GABA A in the brain

The sedation spreads by dose:

cortex- alertness

limbic system- anxiety relief

brain stem - respiratory depression

GABA and reward

alcohol is rewarding via GABA in 3 ways:

1. activates GABA A in Nucleus Accumbens (the end of the mesolimbic DA pathway) which turns down GABA release (turn off breaks) DA release there, feel good

2. It activates GABA A in VTA (the start of the mesolimbic DA pathway) which turns down GABA release (turn off breaks) freeing it to release DA at the nucleus accumbens, which feels good

3. It increases release of endogenous opiate b-endorphin in the VTA which also turns down GABA release (same as 2)

GABA and chronic use

1. The brain reduces number and sensitivity of GABA A receptors… which then inhibit GABA less… which comes back online as a brake for the mesolimbic DA reward system

2. The b-endorphin receptors also get sensitive to alcohol which makes them inhibit GABA less which comes back online as a brake for the mesolimbic DA reward system

alcohol and glutamate

alcohol inhibits glutamate→ more depressant effects

NMDA receptors (learning/memory) are glutamate receptors

inhibition of glutamate inhibits NMDA double-hits

explains memory problems in drinkers

chronic administration makes brain increase number of NMDA receptors to compensate

withdrawal: body rebounds with up glutamate release user’s neurons are now extra sensitive… can lead to dangerous excitotoxic cascade

Alcohol and Calcium

voltage-gated (electricity activated) calcium is needed for exocytosis alc interferes w/ exocytosis in neurons

many organs have these channels too, including heart, muscle, kidneys, pancreas (6 known calcium channel subtypes, alc inhibits functioning of L-type calcium channels

vasopressin (a hormone) is not released: urination and aggression up, cognition, blood pressure altered circadian rhythms

Alcohol and Serotonin

Alcohol increases serotonin release in the NA (end of DRP)

this enhances the reward felt by drugs

serotonin appears important in connecting alcohol to DA release in mesolimbic DA pathway

evidence: giving 5-HT blocker prevented alcohol from increasing DA release in NA

alcohol and endocannabinoids

alcohol increases endocannabinoid (endogenous cannabis) release in brain

this enhances the reward felt by drugs

endocannabinoids are important in connecting alcohol to DA release in mesolimbic pathway

CB1 is a sub-receptor of the endocannabinoid system. In CB1 gene-knockout rats, alcohol doesn’t increase DA. Release in nucleus accumbens as much as in normal rats