Pharm - Alcohol! Flashcards
Statistics of Alcohol
17 million people DEPENDENT
Alcohol is responsible for 100,000 deaths a year!
Alcohol Content and Proof
14 g ethanol = 1 drink
Percentage of beverage that is that 14 grams = alcohol content
4-6% = beers
10-15% = wine
> 40% = liquor
PROOF is twice this number
8-12 = beer, 20-30 = wine, 80+ proof
BAC
Determined with breathalyzer - analyzes the percentage of ethanol in the blood
Alcohol in the alveolar capillary blood will equilibrate with the alcohol in the air of the alveolar sac
Assuming a constant blood:breath ratio (partition coefficient) of 2000:1, where every 2000 ml of blood contains the same alcohol in 1 mL of breath, ethanol will react with the machine contents
It then extrapolates the content in the blood based on the content of the expired air
Legal limit is 0.08 g/dL or 17 mM
BUT, everybody has slightly different partition coefficients
Gender and Alcohol
Women who weights 70 kg drinks exact same amount as a man who weighs 70 kg, but will have a HIGHER BAC than the man!
Why?
There is less gastric metabolism in women than in men –> lower concentration of alcohol dehydrogenase!!
Lower total body water content - same amount of alcohol in a woman will be at a higher concentration than in men because it is dissolved in a smaller pool!!!!
Metabolism of Alcohol
Readily absorbed from the SMALL INTESTINE, though some is absorbed in the gastric mucosa
On an EMPTY STOMACH, peak absorption takes place 30 minutes AFTER ingestion (food slows gastric emptying and gives alcohol slower release into the duodenum, so it is more GRADUALLY ABSORBED IN THE BLOODSTREAM
As alcohol is absorbed, it experience FIRST PASS METABOLISM by ALCOHOL DEHYDROGENASE which slowly (RATE LIMITING) turns alcohol to ALDEHYDE
Aldehyde is therm RAPIDLY METABOLIZED to acetate by aldehyde dehydrogenase and goes into the circulation as such
1 drink (14 g ethanol) will be completely metabolized in 1 hour (1 drink out of system in an hour)
Number of things like ASPIRIN will affect alcohol dehydrogenase
Alcohol displays ZERO ORDER KINETICS
Metabolism requires the reduction of NAD+ to NADH, limiting the amount of NAD+ in hepatocytes
Limited NAD+ allows the alcohol dehydrogenase mediated metabolism to be QUICKLY SATURATED and this usually occurs at concentrations lower than what the BAC will be even on 1 drink!!!
So, alcohol metabolism is completely dependent on BAC and holds constant with time –> 8 g/hr in a 70 kg person and thus alcohol displays ZERO ORDER KINETICS
Effects of Alcohol
It is obviously a DEPRESSANT and acts in a similar fashion to BENZOS!
Anti-anxiety properties at low concentrations with sedation and even DEATH at very high concentrations –> do not mix with barbiturates/benzos or other sedatives!
Immediate disinhibition effects are because the FRONTAL LOBES ARE VERY SENSITIVE TO ALCOHOL –> in chronic alcoholics, there is a decrease in brain glucose metabolism, and an overall SHRINKAGE of gray and white matter with compensatory ventricular enlargement!!!!
Several effects based on the amount of alcohol ingested (normal ingestion; chronic alcoholics will have enzyme systems induced and will be able to metabolize more than the average person)
Primary activity is GABAergic enhancement –> sleepiness, muscle relaxation and other symptoms similar to benzos
Alcohol can ENHANCE and INHIBIT nicotinic cholinergic receptors, and INHIBIT excitatory glutamate receptors! NMDA (glut) receptors INCREASE during chronic alcohol use to attempt to further sensitize the cells to glutamate
Positive Effects of alcohol?
CARDIOPROTECTIVE!
Protects for coronary heart disease (20-30g/day)
Good at low amounts, but when things get crazy there are BAD CV effects!!! Arrhythmias, cardiomyopathies, hemorrhagic stroke!
Alcohol seems to INCREASE HDL CHOLESTEROL –> reduces atherosclerosis and risk for MI!
Alcohol ALSO REDUCES THE AMOUNT OF BLOOD CLOTTING by increasing tPA, decreasing fibrinogen and inhibiting platelet aggregation (again reduces risk for MI)
FLAVINOIDS in red wine are best (darker the better) –> have an ADDITIONAL anti-atherogenic role! Prevent the oxidation of LDLs and their uptake into macrophages!!! This is critical to forming unstable plaques (foam cells) so this is PREVENTED with FLAVINOIDS
Also inhibits endothelin-1 synthesis, which is a vasoconstrictor!
NEGATIVE CV EFFECTS
Heavy use increases BP –> HTN
Alcohol can cause ARRHYTHMIAS because it is associated with prolongation of the QT interval (Torsades!!)
Alcohol can also STIMULATE THE SNS and should be considered as a cause of arrhythmias resistant to cardioversion, digitalis or calcium channel blockers
Can DEPRESS CONTRACTILITY just by direct tissue toxicity and thus cause cardiomyopathy! –> 50% of cardiomyopathy patients are alcohol dependent!!!!! They better stop or they die within a few years!
People who drink 40-60 g per day (3+ drinks) will have a higher incidence of hemorrhagic and ischemic stroke! Usually due to HTN or the arrhythmia risk
Low Mg2+ predisposes to stroke, and alcoholics have less Mg2+
Also HEAD TRAUMA from being drunk and falling!!!
Negative blood vessel effects
Decreased hematopoiesis, anemia (secondary to folic acid depletion), reversible thrombocytopenia, suppression of lymphocytes/granulocytosis
Other Negative effects 1 – musculoskeletal, body temp, renal
Musculoskeletal!!! Heavy alcohol consumption can lead to IRREVERSIBLE muscle damage; also, with liver damage seen in alcoholics, vitamin D hydroxylation is INTERRUPTED and can result in WEAKER Ca2+ regulation and osteoporosis
Temperature –> increases cutaneous and gastric blood flow that results in a LOSS OF BODY HEAT –> long term use can compromise the hypothalamic regulating mechanism and cause hypothermic death!
RENAL – alcohol decreases the release of ADH so drinkers have increased urine production (less water retained) –> over time alcoholics develop a TOLERANCE TO THIS –> if they go through withdrawal there is a large compensatory increase in ADH release!!! Lots of retention –> DANGEROUS HTN!
Other Negative effects 2 – GI
GI –> causes ESOPHAGEAL dysfunction because it decreases peristalsis and lower esophageal sphincter pressure –> causes eophageal REFLUX and potential BARRET’S ESOPHAGUS which predisposes to esophageal cancer!
Also, forceful vomiting with prolonged alcohol use could cause MALLORY-WEISS TEARS and traumatic RUPTURE of the esophagus
Also increases gastric secretions –> disrupts the mucosal barrier –> acute and chronic gastritis
WIth malabsorption in the small intestine it can lead to chronic diarrhea!
Direct effect on PANCREATIC ACINAR CELLS and is directly responsible for the MAJORITY OF ACUTE AND CHRONIC PANCREATITIS CASES IN THE COUNTRY
Other Negative effects 3 – Hepatic
Metabolism of alcohol through ADH and ALDH causes a buildup of EXCESS NADH (and depletion of NAD+)
Excess NADH acts as a NEGATIVE FEEDBACK SIGNAL onto the Kreb’s cycle and beta oxidation of fatty acids –> PREVENTS BREAKDOWN OF FAT and causes FATTY INFILTRATION OF THE LIVER (fatty liver!) or HEPATITIS
As the alcohol DIRECTLY DAMAGES the liver, it will REPLACE normal tissue with FIBROUS TISSUE and lead to CIRRHOSIS (Mallory Bodies in cirrhotic hepatocytes)
Cirrhosis and direct liver damage can be expedited through ACETAMINOPHEN INGESTION –> as it is metabolized, it has a reactive intermediate NAPQI, which is DIRECTLY HEPATOTOXIC
Normally NAPQI is rapidly conjugated to glutathione and excreted, but EXCESS ALDEHYDE from alcohol breakdown STEALS THE GLUTHIANONE –> NAPQI has more time to hang out and damage hepatocytes
Other Negative Effects 4 – CNS and Sexual
CNS –> alcoholics have prolonged NUTRIENT DEFICIENCIES particularly with B complex vitamins!
Thiamine (vit B1) causes an acute neuropsyche reaction called WERNICKE’S ENCEPHALOPATHY –> mental disturbance, eye movement paralysis, ataxia –> can go on to develop KORSAKOFF’S PSYCHOSIS –> retrograde and anterograde amnesia with confabulation (invention of memories that occurred during blackout episodes)
Sexual –> disruption of normal sexual function!
Disinhibition –> more likely to want or attempt sex –> but had low function!
Reproductive/sexual health problems (cycle abnormalities, testicular atrophy, decreased arousal, latency on ejaculation, loss of libido, etc)
Chronic alcoholism can lead to IMPOTENCE
FAS!!! CNS dysfunction, growth retardation, learning deficits, craniofacial abnormalities
Dealing with ETHANOL intoxication
1 drink is completely metabolized within 90 minutes
Acute intoxication –> comatose and respiratory depressed patients should be INTUBATED, given STOMACH LAVAGE, and HEMODIALYZED
Non-comatose –> observe for 4-6 hours!
