Pharmacokinetics II

Question 1

Understand the role of phase 1 and phase 2 reactions in the disposition of drugs

Answer 1

Drugs usually are lipophilic before Phase 1 and by the end of phase 2 they are fully hydrophilic.

Question 2

What are phase 0 and phase 3 in drug metabolism?

Question 3

What are some of the common agents that induce and inhibit CYP450?

Answer 3

Inducers:	
* Rifampin	
* Chronic alcohol	
* Saint John's wort
Inhibitors:	
* Acute alcohol	
* Grapefruit juice	
* Valproic acid

Question 4

Know drugs recommended by FDA for pharmacogenomic tests

Question 5

Understand how drugs are eliminated by renal clearance.Know how urinary pH affects renal excretion of drugs.

Answer 5

• Drugs less than 5000 MWs are completely filtered, between 5000 and 10,000 MWs are partially filtered.
• Drugs present freely in the plasma (not protein bound) are filtered at 125 ml/min, same rate as creatinine.
• Drugs that are weak acids or bases have enhanced clearence in basic and acidic urine respectively.

Question 6

Understand processes for drugs eliminated by biliary clearance.Explain the enterohepatic cycle.

Answer 6

• Drugs secreted into the bile often go through the enterhepatic cycle
• These drugs often go through the process of glucouronidation.
• Smaller glucuronide conjugates are excreted via urinary secretion, larger via biliary secretion.

Question 7

Understand how the enterohepatic cycling of drugs affects half-life, clearance and volume of distribution

Answer 7

A drug that participates in the enterhepatocycle has an increased volume of distribution, lower clearence and hence increased half life.

Question 8

Explain how does alcohol increases acetaminophen liver toxicity?

Answer 8

Chronic alcohol or isoniazid use induced CYP2E1 which causes increased amounts of NAPQI, treatment is to give N-acetylcysteine.