Pharm 9: Drug-Drug Interactions

Question 1

How can alcohol intoxication affect anticoagulants?

Answer 1

lowers prothrombin levels

REMEMBER: Chronic alcoholism results in enzyme induction. Acute alcoholic intoxication tends to inhibit drug metabolism (whether person is alcoholic or not).

Question 2

How can alcohol intoxication affect insulin?

Answer 2

increases hypoglycemic effect, especially in fasting patients

Question 3

The GI ABSORPTION of drugs may be affected by concurrent use of other agents that: 5 things

Answer 3

(1) have a large surface area upon which the drug can be adsorbed,
(2) bind or chelate,
(3) alter gastric pH,
(4) alter gastrointestinal motility, or
(5) affect transport proteins such as P-glycoprotein and organic anion transporters.

Question 4

The mechanisms by which drug interactions alter drug DISTRIBUTION include:

Answer 4

(1) competition for plasma protein binding,
(2) displacement from tissue binding sites, and
(3) alterations in local tissue barriers, eg, P-glycoprotein inhibition in the blood-brain barrier.

Question 5

What would milk do to tetracyclines?

Answer 5

Milk tends to chelate tetracyclines so they aren’t absorbed. Bad idea to take one with the other

Question 6

What kinds of drugs are CYP inducers? 4 ex. to be aware of.

Answer 6

efavirenz, nevirapine, and rifampin, and St. John’s Wart

Question 7

Is enzyme induction rapid?

Answer 7

Enzyme induction does not take place quickly; maximal effects usually occur after 7–10 days and require an equal or longer time to dissipate after the enzyme inducer is stopped.

Question 8

What is an exception to the rule on the last card?

Answer 8

Rifampin, however, may produce enzyme induction after only a few doses.

Question 9

Is enzyme inhibition rapid?

Answer 9

Inhibition of metabolism generally takes place more quickly than enzyme induction and may begin as soon as sufficient tissue concentration of the inhibitor is achieved.

Question 10

What are some CYP inhibitors?

Answer 10

Atazanavir, chloramphenicol, ciprofloxacin, clarithromycin, cyclosporine, diphenhydramine, erythromycin, fluconazole, furanocoumarins (substances in grapefruit juice), indinavir, isoniazid, itraconazole, ketoconazole, metronidazole, ritonavir, sulfamethoxazole, voriconazole, and zileuton.

AI KIV CE CCMS ZIRCDFF

Question 11

The renal excretion of active drug can also be affected by concurrent drug therapy. How?

Answer 11

The renal excretion of certain drugs that are weak acids or weak bases may be influenced by other drugs that affect urinary pH.

This is due to changes in ionization of the drug

Question 12

What enzyme is important in the renal secretion of drugs into kidney tubules?

Answer 12

P-gp

Question 13

Drugs that are partially eliminated by P-glycoprotein include:

Answer 13

cyclosporine and tacrolimus and digoxin

Question 14

What drugs are inhibitors of P-gp (and thus can increase serum levels of cyclosporine and tacrolimus and digoxin- and others)?

Answer 14

clarithromycin, erythromycin, ketoconazole, ritonavir, among others

KECR

Question 15

T or F. When drugs with similar pharmacologic effects are administered concurrently, an additive or synergistic response is usually seen.

Answer 15

T. Conversely, drugs with opposing pharmacologic effects may reduce the response to one or both drugs

Question 16

What effect does Allopurinol have on metabolism?

Answer 16

Inhibits hepatic drug-metabolizing enzymes.

Question 17

What sorts of drugs would you not want to prescribe with Allopurinol? Why?

Answer 17

Anticoagulants, oral: [NP] Increased hypoprothrombinemic effect. (i.e. more likely to hemorrhage)

Azathioprine: [P] Decreased azathioprine detoxification resulting in increased azathioprine toxicity.

Mercaptopurine: [P] Decreased mercaptopurine metabolism resulting in increased mercaptopurine toxicity.

Question 18

What kinds of drugs would you not want to give while on warfarin or other anticoagulants because they increase the anticoagulant effect of the the drugs?

Answer 18

Acetaminophen: [NE] Impaired synthesis of clotting factors.

Efavirenz, Fluconazole, Metronidazole, Voriconazole: [NP] Decreased warfarin metabolism.

Clopidogrel: [NP] Decreased warfarin metabolism and inhibits platelet function.

Trimethoprim-sulfamethoxazole: [P] Decreased warfarin metabolism.

Question 19

What kinds of drugs would you not want to give while on warfarin or other anticoagulants because they decrease the anticoagulant effect of the the drugs?

Answer 19

St. John’s wort: [NE] Increased elimination of anticoagulant.

Barbiturates: [P] Increased metabolism of anticoagulant.

Rifampin: [P] Increased elimination of anticoagulant.

Nafcillin: [NE] Increased metabolism of anticoagulant