Pharm - Psych - Alcohol

Front 1

NT affects of alcohol

Back 1

INDUCES DA RELEASE

Releases endogenous opioids

Inhibits glutamate

Activates GABA

Activates cannabinoids.

Front 2

Alcohol - DA effects

Back 2

Explains the cravings and reinforcement.

It disinhibits (so it increases) DA neurons and VTA and DA release in N.A.

Front 3

Alcohol effects on NMDA receptor

Back 3

Allosterically inhibits glutamte from binding NMDA receptor and this explains the hypnotic/sedative effects as well as neuroadaptation (glutamate plays big role in brain plasticity)

Also inhibits glutamate release presynaptically by binding presynaptic receptors and calcium channels.

SO IT WORKS PRE AND POST-SYNAPTICALLY.

Front 4

Alcohol - activation of GABAergic system.

Back 4

Facilitates GABA-A receptor at different site than GABA or benzos. This results in activation of DA neurons in mesolimbic system.

This further explains sedative and anxiolytic effects.

Front 5

Alcohol - Cannabinoid system.

Back 5

Agonist for presynaptic CB1 receptors.

Front 6

Rimonabant

Back 6

CB1 receptor antagonist. Reduces alcohol consumption/cravings.

***think the rim of your bowl/bong.

Front 7

Alcohol absorption

Back 7

Food (fat in stomach results in slower gastric emptying and thus longer time of absorption). This also means more time for alcohol dehydrogenase to work on it.

This is first-pass metabolism.

Front 8

Women or men more susc to alcoholic liver disease, heart muscle damage and brain damage?

Back 8

Women

Front 9

Where can ethanol not cross?

Back 9

Skin and urinary bladder.

Front 10

CNS ethanol [] rises quickly or slowly?

Back 10

quickly.

Front 11

What % of alcohol is oxidized?

Back 11

90% (mostly in liver).

Other 10% is excreted unchanged (basis of DUI test)

Front 12

What is the main factor for BAC level?

Back 12

Early metabolism in the stomach.

Front 13

Order rate of plasma disappearance of ethanol?

Back 13

0-order. Rate of rxn doesn't depend on [] because there is saturation of degradative enzymes by ethanol.

Front 14

Only known way to hasten ethanol elimination

Back 14

hemodialysis.

Front 15

Alcohol dehydrogenase

Back 15

Mostly in the liver - small amt in brain and stomach.

Converts alcohol to acetaldehyde.

This increases the NADH/NAD+ ratio.

Front 16

Low grade alcohol tolerance due to...

Back 16

modest induction of ADH

Front 17

Result of increasing NADH/NAD+ ratio after alcohol dehydrogenase works...(5)

Back 17

Lactic acidemia --> hyperuricemia

Increased production of ketone bodies to produce ketonemia.

Increased triglyc synth --> fatty liver

NE-stimulated lipolysis further leading to fatty liver.

Decreased gluconeogenesis and liver glycogen causing hypoglycemia.

MAIN THINGS WITH ACUTE ALCOHOL POISOINING ARE LACTIC ACIDOSIS AND HYPOGLYCEMIA

Front 18

Microsomal ethanol oxidizing system

Back 18

Works at BAC > 0.1% (100mg/dl), when NAD+ is depleted.

Results in clearance of other drugs eliminated by cytochrome P450s. This produces byproducts--toxins, free radicals, H2O2.

Converts ethanol to acetaldehyde as well.

Highly upregulated in chronic drinkers.

Front 19

Aldehyde dehydrogenase

Back 19

Converts acetaldehyde to acetate.

Acetate is then oxidized by body organs.

Disulfiram inhibits it. So does metronidazole, cefotetan and trimethoprim.

Deficiency (Asians) or inhibition leads to the asian flush, nausea, vomiting, dizziness, HA.

Front 20

Disulfiram

Back 20

Inhibits aldehyde dehydrogenase

This leads to increased acetaldehyde, and thus you get the asian flush, nausea, vomiting, dizziness, HA.

Causes extreme discomfort, but poor pt compliance.

Can result in vasogenic shock.

Front 21

BAC levels (2 imp ones)

Back 21

50% people obviously drunk at 150mg/dl (BAC=0.15%)

Lethal BAC is around 0.5%.

Front 22

Why can't alcohol be used as an anesthetic

Back 22

The level needed is very close to the threshold for respiratory depression.

Front 23

Acute Alcohol effects on stomach

Back 23

Irritant of stomach lining leading to gastric secretions and vomiting.

Front 24

Acute Alcohol effects on kidneys

Back 24

Diuresis results from suppression of ADH release by pituitary.

Front 25

Acute Alcohol effects on circulatory system

Back 25

Minor effects only after resp depression.

Sweating, increased skin blood flow leading to more heat loss.

Front 26

Acute Alcohol effects on aspirin

Back 26

Increases antiplatelet activity.

Front 27

Chronic alcohol effects on nervous system

Back 27

Neurotoxicity - symm parasthesis of hands/feet

Dementia

Demyelinating disease

Wernicke-Korsakoff syndrom

Front 28

Wernicke-Korsakoff syndrome

Back 28

Effect on chronic ethanol consumption.

Paralysis of external eye muscles.
Ataxia
Confused state that can progress to coma/death.
Associated with thiamin deficiency.

Front 29

Any pt in ED with altered consciousness, sz or both should receive...

Back 29

THIAMINE.

Front 30

Physical dependence of alcohol

Back 30

Withdrawal leads to hyperexcitability, sz, toxic psychosis, delirium tremens.

Front 31

Psychological dependence of alcohol

Back 31

Produces DA release in nuc accumbens.

Enhances local [] of serotonin, opioids and DA (brain reward)

Front 32

Naltrexone

Back 32

Long acting Opioid antagonist

Helps pts abstain from drinking.

This suggests common reward system shared btwn v. different drugs.

Front 33

Chronic alcohol on liver

Back 33

Fatty liver (reversible)

Alcoholic hepatitis

Cirrhosis

Liver failure (tx is liver transplantation)

Front 34

Pathogenesis of liver disease

Back 34

Ethanol oxidation, dysregulation of FA metabolism, activation of innate immune system by ethanol metabolites, bacterial endotoxins able to access liver.

TNF APPEARS TO PLAY MAJOR ROLE IN LIVER DISEASE.

Front 35

Chronic ethanol on digestive system

Back 35

Pancreatitis, inc suscep to gastritis, anemia, protein malnutrition, malabsorption to water-sol vitamins.

Front 36

Chronic alcohol on CV system

Back 36

Cardiomyopathy, heart failure, HTN, coronary heart disease, anemia (folic acid deficiency).

Front 37

Chronic ethanol on immune system

Back 37

Inc risk of mouth, pharynx, larynx, esoph and liver CA

Reduced immune function in lung and enhanced in the liver and pacreas.

Front 38

FAS - appearance in children

Back 38

It is bc fetus has no alcohol dehydrogenase

Epicanthal folds, flat nasal bridge, small palpebral fissures, railroad track ears, upturned nose, smooth philtrum, thin upper lip.

Front 39

Acute alcohol tx

Back 39

Glucose for hypoglycemia
Phosphate (it can be aggravated by glucose admin)
Thiamine for Wernicke...
Naloxone for possible opioid ingestion.
Potassium if vomiting is severe

Front 40

Tx of alcohol withdrawal

Back 40

Glucose (hypoglycemia)
Thiamine (Wernicke...
Naloxone (opioid antag to stop cravings)
Benzos (anticonvulsant)
Butyrophenones

Front 41

Benzos used in alcohol withdrawal syndrome

Back 41

Lorazepam or Oxazepam (short 1/2 life)
**lorazepam 1/2 life increases a little with liver failure.

Chlordiazepoxide or diazepam (long-acting)
**chlordiazepoxide 1/2 life increases A TON with liver failure.

Front 42

Butyrophenones used in alcohol withdrawal syndrome

Back 42

Haloperidol - DA antagonist - when benzos aren't working and the pt is in delirium tremens.

Front 43

Tx of alcoholism

Back 43

Depression/anxiety tx
Naltrexone
acamprosate
disulfiram

Front 44

Never rx naltrexone with...

Back 44

DISULFIRAM!

Front 45

Acamprosate

Back 45

Used in tx of alcohol dependence

NMDA antagonist and GABAA receptor activator.

Acts on serotonin, noradrenergic and dopaminergic receptors.

Front 46

Mechanism of disulfiram and vasogenic shock

Back 46

Acetaldehyde normally releases NE AND has a vasodilatory effect.

However, in pts with disulfiram, NE in depleted via inhibition of dopamine beta-hydroxylase (the enzyme that converts DA to NE) - disulfiram does this.

Therefore, there is strong dilatation and no NE to counteract it. So BP falls drastically.

Front 47

Other drugs to maintain abstinence in pts with ethanol dependence (non-FDA approved)

Back 47

Ondansetron (5-HT3 receptor antag)

Topiramate (anticonvulsant)

Baclofen (GABAb receptor antagonist)

Rimonabant (CB1 receptor antagonist)

Front 48

Methanol metabolism

Back 48

Via alcohol dehydrogenase, which forms formaldehyde and then formate (which is toxic)

Front 49

Methanol SE

Back 49

Visual disturbances and acidosis.

Front 50

Methanol/ethylene glycol Tx

Back 50

Bicarbonate to counter acidosis
Hemodialysis (remove toxic metabolites)
Ethanol (to take up the ADH sites)
Fomepizol (inhibit ADH)

**DL: How many methanol bottles did you drink?
Huang: Fo'!

Front 51

Fomepizol

Back 51

Inhibits alcohol dehydrogenase (good for methanol poisoining and ethylene glycol poisoining)

Front 52

Ethylene glycol

Back 52

Antifreeze

Metabolized by alcohol dehydrogenase

Leads to metabolic acidosis.

CHARACTERISTIC SIGN IS CALCIUM OXALATE CRYSTALLURIA.

Nephrotoxic effect results in late acute renal failure.

Tx same as methanol

Front 53

Isopropanol (rubbing alcohol)

Back 53

May produce deep coma with vascular collapse.

Difficult in ddx with regard to diabetic ketoacidosis

Tx - symptomatic and supportive.