Term
| What separates EtOH from other drugs? |
|
Definition
| Large doses required for desired effects |
|
|
Term
|
Definition
|
|
Term
| what are serving sizes for beer, wine, and liquor? |
|
Definition
| 12 oz bottle of beer = 5 oz glass of wine = 1.5 oz shot of hard liquor |
|
|
Term
|
Definition
Legal limit 80-100 mg/dL in most states
>10mg/dL for people under 21 years of age
Measured in expired air
High diffusion coefficient of alcohol |
|
|
Term
| Why does a breathlizer work? |
|
Definition
Measured in expired air
High diffusion coefficient of alcohol |
|
|
Term
| Is EtOH soluable in lipid or in air? |
|
Definition
| backbone = lipid soluable, OH group = water soluable. |
|
|
Term
| What do the dual properties of EtOH explain? |
|
Definition
| the pharmacokinetic properties of EtOH? |
|
|
Term
| What are the 4 pillars of Pharmacokinetics? |
|
Definition
Absorption;
Distribution;
Metabolism;
Excretion |
|
|
Term
| when do you achieve an average peak blood level? |
|
Definition
| 30 min (in fasting state) |
|
|
Term
| Do you absorb in SI or in stomach? |
|
Definition
|
|
Term
| Is SI or stomach faster at absorbing? |
|
Definition
|
|
Term
| What facilitates absorbption? |
|
Definition
|
|
Term
| What type of diffusion process? |
|
Definition
|
|
Term
|
Definition
| No--it's passive diffusion--(not facilitated)--keep drinking, keep absorbing. |
|
|
Term
| What does the rate of absorption depend upon? |
|
Definition
Rate depends on:
Concentration: shot ? wine ? beer;
Food in stomach delays absorption;
Type: Fat ? CHO ? Prot;
Pattern: Habitual ? occasional |
|
|
Term
| What predicts the BAL achieved? |
|
Definition
|
|
Term
| Where does EtOH get distrobuted to in the body? |
|
Definition
| througout. both water and fat soluable. The volume of distribution closely approximates the total body water |
|
|
Term
| Does EtOH selectively get stored in any one tissue? |
|
Definition
|
|
Term
| Does EtOH enter fat fast or slowly? |
|
Definition
|
|
Term
| Why do women achieve a higher BAL for a given dose than men? |
|
Definition
| greater fat content (so smaller volume of distribution), and lower total body water content. |
|
|
Term
|
Definition
|
|
Term
| what does the Vol of Dist depend upon? |
|
Definition
Will depend on:
Total dose;
Strength of solution (affects rate of absn);
Time over which its ingested (affects rate of absn);
Food (presence, absence and type affects rate of absn);
Gender;
Pattern of consumption |
|
|
Term
| What does max BAL depend upon? |
|
Definition
Maximum BAL depends on
the volume of distribution ;
the rate of absorption;
the rate of metabolism |
|
|
Term
| What % of EtOH is secreted? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| oxidative pathways in the liver (microcrosmal EtOH oxidizing system (MEOS)) |
|
|
Term
| What are 3 key metabolic enxymes? |
|
Definition
| ADH, MEOS (CYP 2E1, 3A4), ALDH |
|
|
Term
|
Definition
| converts EtOH--acetaldehyde |
|
|
Term
|
Definition
| mainly in the liver, but it exists partout. Also in the brain and stomach |
|
|
Term
| who has higher stomach ADH activity, men or women? |
|
Definition
|
|
Term
| what is an ADH polymorphism? |
|
Definition
| A polymorphism in ADH (with lower ADH levels) that exists in Asian populations is associated with a increased risk of alcoholism |
|
|
Term
| what does MEOS stand for? |
|
Definition
| Microsomal ethanol oxidizing system (MEOS) |
|
|
Term
|
Definition
| converts EtOH to acetaldehyde |
|
|
Term
|
Definition
| Kicks in when ADH is saturated (depletion of NAD) |
|
|
Term
|
Definition
| Inducible CYPs in response to increased exposure |
|
|
Term
| why does your tolerance increase when you drink more? |
|
Definition
| because the more you drink the more CYPs are induced |
|
|
Term
|
Definition
| Byproducts (H2O2, Toxins, free radicals, etc) |
|
|
Term
|
Definition
| Converts acetaldehyde to acetate and then to CO2 and H2O |
|
|
Term
|
Definition
| Enzyme is inhibited by disulfuram |
|
|
Term
| Who has a deficiency of ALDH? |
|
Definition
| People of Asian descent have deficiency of this enzyme |
|
|
Term
| What are the side effects of disulfuram? |
|
Definition
| Both disulfuram and some Asians when they drink alcohol experience flushing, vomiting, dizziness |
|
|
Term
| Does EtOH have first order kinetics? |
|
Definition
yes--but only First order kinetics to BAL of 10 – 100 mg/dl
enzymatic (ADH) elimination becomes saturated |
|
|
Term
| When do Zero order kinetics apply? |
|
Definition
Zero order kinetics then apply
with increasing concentrations the elimination rate stays steady at 8 grams / hour
Therefore as the BAL increases the t1/2 increases |
|
|
Term
| What is the general metabolic rule? |
|
Definition
| As the BAL increases the t1/2 increases |
|
|
Term
|
Definition
No--But in reality Zero order kinetics applies once ADH is saturated
therefore the t1/2 is not steady...This is the most important example of zero order kinetics in human pharmacology |
|
|
Term
| In habitual drinkers, what is upregulated? |
|
Definition
|
|
Term
| What is tolerance of EtOH? |
|
Definition
| Lower BAL for a given dose of EtOH |
|
|
Term
|
Definition
Loss of white and grey matter (frontal lobe);
Reduced brain metabolism;
Wernickes / Korsakoff (amnestic) syndrome;
Neuropathy – central vs. peripheral(
Saturday night palsy) |
|
|
Term
| Name the 2 CNS ETOH disorders |
|
Definition
Wernickes / Korsakoff (amnestic) syndrome
and
Saturday night palsy |
|
|
Term
| What is Saturday night palsy? |
|
Definition
| compression of brachial plexus (ulnar, radial, medial nerves) |
|
|
Term
What is
Wernickes / Korsakoff (amnestic) syndrome? |
|
Definition
|
|
Term
| What are acute CV effects? |
|
Definition
Acute effects:
Vasodilatation;
Reduced myocardial contractility;
Atrial and ventricular arrhythmias ;(enhanced release of catecholamines) |
|
|
Term
| What are chronic CV effects? |
|
Definition
Chronic Effects:
Increased blood pressure;
Dilated cardiomyopathy;
Increased triglyceride levels |
|
|
Term
| What is the French paradox? |
|
Definition
Moderate ingestion (<30g/d) may be cardioprotective (The French Paradox):::
Raises HDL cholesterol levels;
Antioxidant content of alcoholic beverages;
Increases in tissue plasminogen activator |
|
|
Term
| What are effects on the kidney? |
|
Definition
Increasing BAL decreases ADH secretion
Diuresis and kaluriesis;
Alcohol is vasodilatory - diuresis;
Alcohol decreases uric acid excretion |
|
|
Term
|
Definition
Stimulates secretion of gastrin, pepsin, histamine and gastric acid;
Increased incidence of PUD ;
An emetic agent;
Pancreatitis;
Gastric and esophageal cancers
Alcohol itself not a carcinogen but acetaldehyde probably is. |
|
|
Term
| What gastric juices does it stimulate? |
|
Definition
| gastrin, pepsin, histamine, and gastric acid |
|
|
Term
|
Definition
|
|
Term
| Where does EtOH cause cancer? |
|
Definition
Mouth;
Larynx;
Pharynx;
Breast ;
Esophagus
;
Gastric;
Liver |
|
|
Term
| What does EtOH do to the liver? |
|
Definition
Directly hepatotoxic;
Fatty infiltration – fibrosis – cirrhosis;
Liver failure;
Hepatorenal syndrome – acute ingestion;
Mechanism – unclear;
Neoantigens, free radicals, collagen synthesis |
|
|
Term
| What does EtOH do to hematopoesis and immuno functioning? |
|
Definition
Think reduction and poor function:::
Reduced platelet count – marrow suppression;
Macrocytosis;
Folate metabolism – reduced stores + absorption;
Reduced neutrophil function (infection);
Reduced T-cell function (infection);
TB, HIV, Pneumonia |
|
|
Term
| What does EtOH do to the respiratory system? |
|
Definition
Increased # of respiratory tract cancers;
Increased BAL decreases the ventilatory response to increasing CO2 levels |
|
|
Term
| What are the nighttime effects of EtOH ingestion? |
|
Definition
Nighttime effects of ETOH ingestion:
Reduces initial sleep latency;
Reduces latency to REM sleep;
Increases wake time;
Increases # of apneic episodes |
|
|
Term
| What does EtOH do to Endocrine functioning |
|
Definition
Testicular atrophy;
Gynecomastia;
Hypoglycemia (
Reduced hepatic gluconeogenisis)
Hyperkalemia
(Vomiting, diarrhea, secondary aldosteronism) |
|
|
Term
| What does EtOH do acutely for sex? |
|
Definition
“…provokes desire, takes away performance”;
Increased libido – disinhibition |
|
|
Term
| What does EtOH do chronically for sex? |
|
Definition
Chronic ingestion :
Reduces performance in both sexes;
Impotence reported in 50% of males;
Gonadal atrophy occurs over time;
Feminization syndrome |
|
|
Term
|
Definition
Alcohol freely crosses the placenta and enters breast milk;
Metabolic pathway not developed in fetus and neonate;
(30 mg twice a week – increased incidence of abortion);
(30 mg/day decreased birth weight);
(90 mg/d fetal alcohol syndrome) |
|
|
Term
| What is fetal alcohol syndrome? |
|
Definition
Fetal alcohol syndrome:
Microcephaly ;
IUGR;
Hypotonia;
Irritability;
Mental retardation;
Malformations –facial, skeletal, cardiac |
|
|
Term
|
Definition
Mechanism involved is unclear:
ETOH crosses placenta readily to reach concentrations similar to maternal levels;
Fetal live has no ADH so relies on maternal and placental enzymes |
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|
