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Pharm Block 3 > 5 - Alcohol > Flashcards

5 - Alcohol Flashcards

1
Q

What pharmacological property differentiates alcohol from other drugs?

A

Alcohol is NOT a potent drug.

1 drink (12 oz beer, 5 oz wine, 1.5 oz 80 poof liquor) = 14 grams of alcohol

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2
Q

In a 70 kg person, what effect does one drink (14 grams) of alcohol have on their blood alcohol concentration?

A

Results in ~30 mg/dL blood alcohol concentration, which is 0.03 w/v and ~7 mM BAC.

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3
Q

What clinical effects occur in nontolerant individuals at 50-100, 100-200, 200-300, 300-400, and >400 mg/dl of alcohol?

A

50-100: Sedation, subjective “high”, slow rxn times

100-200: Impaired motor function, slurred speech, ataxia

200-300: Emesis, stupor, unwanted falling asleep

300-400: coma

> 400: Respiratory depression, death

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4
Q

Describe the effects of tolerance in terms of what amount of alcohol (mg/dl) people with tolerance can have and still appear sober? What is the legal driving limit in most states?

A

Tolerant individuals may appear sober even at 300-400 mg/dl.

Driving limit is 80 mg/dl (~17 mM) in most states

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5
Q

What words describe the pharmacokinetics of alcohol?

A

Absorption
Distribution
Metabolism
Excretion

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6
Q

What is the absorption of alcohol? What can increase or decrease the absorption?

A

Primarily oral route, rapid absorption in the proximal small intestine (mainly) and some absorbed throughout GI tract.

Increased with gastric emptying - enhanced with carbonated beverages and decreased by food.

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7
Q

What is the distribution of alcohol?

A

Vol of distribution approximates total body water (~1 L/kg)

Small molecule, water soluble/very hydrophilic

Crosses membranes freely, including alveoli from lung capillaries (breathalyzer test)

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8
Q

90-98% of ethanol is metabolized to ________. What happens to the rest? What other aspect of alcohol metabolism is important?

A

Acetaldehyde.

This occurs by 2 major enzymatic routes. The remained is eliminated unchanged in the breath, sweat, and saliva.

Significant 1st pass effect by both gastric and liver alcohol dehydrogenase.

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9
Q

What are the 2 major pathways of metabolism of alcohol? What cofactor does each use?

A
  1. Alcohol dehydrogenase (ADH) - lower stomach ADH in women. Uses lots of NAD+ to convert ethanol into acetaldehyde.
  2. Microsomal ethanol-oxidizing System (MEOS): cytP450s: 2E1, 1A2, 3A4. Uses NADPH+ to convert ethanol into acetaldehyde
  3. Catalase is a minor metabolic pathway of alcohol that also yields acetaldehyde
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10
Q

In the microsomal Ethanol-oxidizing system, what is induced with chronic alcohol use? What is the result of this?

A

CYP2E1 induced in alcoholics and can result in an increase in the clearance of other drugs.

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11
Q

What occurs with the acetaldehyde made via alcohol dehydrogenase (ADH) and the Microsomal ethanol-oxidizing system (MEOS)?

A

Aldehyde dehydrogenase converts it to acetate.

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12
Q

Mitochondrial genetic polymorphisms affect the activity of which alcohol metabolizing enzyme?

A

Aldehyde dehydrogenase (which normally converts acetaldehyde to acetate in ethanol metabolism.)

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13
Q

What can be used to treat methanol poisoning? Why does this work?

A

Fomepizole or Ethanol can block alcohol dehydrogenase to prevent the metabolism of methanol to the toxic metabolites formaldehyde and formate.

The result is that the methanol is excreted unchanged instead of metabolized.

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14
Q

What drug has a similar metabolism to ethanol and methanol and is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase? What can be used to treat poisonings of this?

A

Ethylene glycol

Alcohol dehydrogenase can be blocked by fomepizole or ethanol.

Aldehyde dehydrogenase can be blocked by disulfiram.

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15
Q

What limits alcohol metabolism? What is the speed of alcohol metabolism?

A

NAD+ availability
-saturation results in zero-order kinetics

7-10 g/hour in a 70 kg adult, which is ~1 drink every 90-120 minutes.

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16
Q

What are the major metabolic consequences of alcohol metabolism?

A
  1. Increased NADH/NAD+ ratio inhibits TCA cycle: accumulation of AcetylcoA, lactic acidosis, accumulation of ketones.
  2. Increased NADP+/NADPH ratio: causes limited regeneration of GSH
  3. Increased acetaldehyde: generates adducts and inhibits mts.
17
Q

What do the metabolic changes associated with alcohol metabolism result in?

A

Fatty liver
Hepatic inflammation
Induction of CYP2E3 - can cause the metabolism of xenobiotics to carcinogenic agents

Ie bad news for the liver

18
Q

What is the Mellanby effect?

A

Acute functional tolerance - symptoms associated with a dose during the ascending limb of the curve are greater than the symptoms associated with the same dose in the descending limb.

19
Q

What are the CNS effects of ethanol?

A
  1. Potentiates GABA-A receptor-ligand Cl- channels: suppreses neuronal transmission
  2. NMDA receptor antagonist: cognitive function, learning and memory

Alcohol disturbs balance between excitatory and inhibitory transmission in the brain and promotes inhibition.

20
Q

What receptor does alcohol act on? What other drugs does alcohol interact with?

A

The GABA-A receptor.

Alcohol potentiates GABA and sedative hypnotics. Chronic alcohol use results in cross-tolerance to sedative hypnotics.

21
Q

What effect does alcohol have when combined with CNA depressants? What are drugs that can have additive effects when combined with alcohol?

A

Effects are additive, whether or not they bind to GABA-A receptor.

Barbiturates, benzodiazepines, opioids, neuroleptics, volatile anesthetics, and propofol

22
Q

What affect does alcohol have on drug metabolism?

A

Acute- high doses can inhibit CYP-mediated metabolism.

Chronic-induces CYP2E1 and therefore accelerates metabolism of some drugs

Acetaminophen toxicity worse in alcoholics when intoxicated due to glutathione depletion.

23
Q

Describe the caloric burden of ethanol?

A

7.1 cal/gram (~100 Cal/drink from alcohol alone).

Heavy ethanol load can produce transient hypoglycemia (due to insulin secretion).

Alcohol induced ketoacidosis (increase in serum ketones).

24
Q

Top 1-% of Americans drink an average of ____ drinks per day.

A

10+ drinks/day

25
Q

What are the liver and GI effects of chronic ethanol use?

A

Steatosis: fatty liver
Hepatitis C: often co-morbid
Cirrhosis: due to liver necrosis and chronic inflammation

Gastritis, pancreatitis, malabsorption of vitamins, chronic diarrhea, cancers of the esophagus, liver, and bladder.

26
Q

Describe the tolerance that occurs with chronic ethanol use?

A

Combo of:

Adaptive neuronal changes: chronic ethanol use causes DNA depression which results in up-regulation of excitatory transmission to compensate (this can cause seizures from withdrawal of CNS depression that the brain has become accustomed to)

Metabolic tolerance: up-regulation of CYP2E1

27
Q

Besides tolerance, what other CNS effects occur with chronic ethanol use?

A

Psychological (craving) and physical dependence occurs: withdrawal can be dangerous and cause seizure if metabolic imbalance occurs as well.

Alcohol addiction (alcoholism) occurs in 5-10% of men and 3-5% of women.

28
Q

What are symptoms of withdrawal after chronic ethanol use in the order they occur?

A

Anxiety, insomnia, tremor, palpitations, nausea, anorexia.

Withdrawal seizures, alcohol hallucinations.

Delirium tremens: tachy, HTN, low-grade fever, tremor, diaphoresis, delirium, and agitation.

29
Q

What is the mortality of untreated delirium tremens? What about with treatment?

A

Untreated: 30% mortality

With treatment: <5% mortality

30
Q

What is the neurotoxicity that occurs in alcoholism?

A

Neuralgias and peripheral nerve injury Memory impairment; blackouts Cerebral/cerebellar atrophy.

31
Q

What can Thiamine deficiency associated with chronic alcohol use produce? What are symptoms?

A

Dry beriberi:
-peripheral neuropathy, wernicke’s encephalopathy, and korsakoff’s psychosis.

Thiamine deficiency also associated with wet beriberi which has more of a cardiovascular presentation.

32
Q

What are the teratogenic effects of alcohol?

A

Associated with chronic maternal alcohol abuse.

Triad of symptoms:

  • Pre or postnatal growth deficiencies
  • facial abnormalities
  • CNS dysfunction

Ethanol and/or acetaldehyde affect embryonic cell proliferation.

33
Q

How would you determine if someone has acute alcohol intoxication? What else can present like acute alcohol intox? What amount of alcohol in the body is lethal?

A

Measure blood ethanol concentration for diagnosis.

Similar presentation: Diabetic coma, drug intoxication, CV accidents, brain injury.

Generally 400 mg/dl is lethal (~12 drinks).

34
Q

How do you treat acute alcohol intoxication?

A

Based on severity of respiratory and CNS depression: commonly observe for 4-6 hours while its metabolized and support respiration and prevent aspiration.

Correct problems such as: dehydration, hypoglycemia, ketosis, electrolyte imbalance.

35
Q

What are signs of acute alcohol withdrawal? What is the goal of treatment?

A

Alcohol craving, agitation, anxiety, insomnia, seizures, mood swings, sweating, and tachycardia.

Goal: prevent seizures, delirium, and arrhythmias.

36
Q

How should you treat acute alcohol withdrawal?

A

Benxodiazepines: diazepam and chlordiazepoxide

These can substitute alcohol and allow gradual tapering. Remember that the brain has increased excitatory transmission in response to chronic alcohol.

Atenolol can prevent cardiac arrest.

37
Q

How can naltrexone be used to treat alcoholism?

A

Mu opioid receptor antagonist that can reduce craving and increase self-control.

Best when used in combination with psychosocial therapy.

38
Q

What drug is a GABA-A agonist that decreases drinking freq and relapse in abstinent individuals but may not be effective in those still drinking? How does this drug work?

A

Acamprosate; thought to normalize dysregulated neurotransmission (un-opposed excitation when ethanol is removed)

Can cause diarrhea

39
Q

What FDA approved drug to treat alcoholism works by inhibiting aldehyde dehydrogenase and results in an accumulation of acetaldehyde?

A

Disulfiram

Aversion therapy. Not very effective.

Pharm Block 3 (15 decks)

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