DDIs

Question 1

Concurrent use of ALPHA-1 ADRENERGIC BLOCKERS and BETA-ADRENERGIC BLOCKERS (two drugs that are antagonists acting on separate receptors in the sympathetic nervous system to prevent hypertension) might result in what effect?

Answer 1

Exaggerated hypotensive response due to additive effect

Question 2

What is a possible DDI between an ACE inhibitor (that acts on prostaglandins to decrease BP) and an NSIAD?

Answer 2

NSAIDs act by decreasing prostaglandins, so they remove the targets for ACE inhibitors–leading to decreased effectiveness in preventing hypertension

Question 3

Combining aspirin with clopidogrel (anti-platelet) may have what effect?

Answer 3

aspirin irreversibly binds to platelets to inhibit them, so there would be an increased risk of bleeding due to an additive effect.

Question 4

Oral contraceptives commonly have DDIs with what agents?

Answer 4

antibiotics (ex. amoxicillin) will decrease the effectiveness of OCs

Question 5

Mixing potassium tablets with some anti-hypertensives may lead to what effect?

Answer 5

hyperkalemia (may lead to arrhythmia via electrical activity)

Question 6

Why is digoxin a very tricky drug?

Answer 6

it has a very small therapeutic window, and when it is mixed with other drugs, this window can be altered, increasing its serum concentration and is LIFE THREATENING

Question 7

What are the 4 main areas of concern with DDIs?

Answer 7

• Patient coagulation Status
• Drugs that relate to heart
• Drugs that affect the CNS
• Hepatic Toxicity

Question 8

What anticoagulant has a narrow therapeutic window?

Answer 8

warfarin (hemorrhage or thrombosis)

Question 9

What antidepressant has a narrow therapeutic window?

Answer 9

doxepin (excessive sedation, tachyarrhythmias)

Question 10

What bronchodilator has a narrow therapeutic window?

Answer 10

theophylline (CNS toxicity)

Question 11

What immunosuppressives have narrow therapeutic windows?

Answer 11

Cyclosporine (nephrotoxicity, HTN, hyperlipidemia)

Methotrexate (pancytopenia, hepatotoxicity)

Question 12

What inotropic agent has a narrow therapeutic window?

Answer 12

Digoxin (cardiac tachyarrhythmias, AV block)

Question 13

List mechanisms of PHARMACOKINETIC chemical interactions.

Answer 13

Biotransformation
Distribution
Absorption
Excretion

Question 14

List mechanisms of PHARMACODYNAMIC chemical interactions.

Answer 14

Receptor

Non-receptor

Question 15

Explain how a drug induces CYP metabolism.

Answer 15

When a drug enters the cell, it binds to the PXR which forms a complex with RXR. This complex binds to DNA upstream of target genes and recruits a coactivator to bind to TATA box binding protein and activates transcription by RNA polymerase II. Target genes for PXR include CYP3A4.

Question 16

Name a drug that induces its own metabolism by inducing CYP.

Answer 16

atorvastatin

Question 17

Name a CYP3A4 inducer that can interfere with OCs and warfarin.

Answer 17

Rifampin

Question 18

How does ranitidine affect absorption?

Answer 18

(H2 receptor antagonist, raises GI pH) leads to increase in absorption of basic drugs (ex. tirazolam) in the stomach

Question 19

How does cholestyramine affect absorption? What drug?

Answer 19

bile-acid sequestrants ike cholestyramine leads to significantly reduced serum concentrations of propranolol and may diminish its effect for a given dose.

Question 20

What leads to toxicity in drugs that are highly protein-bound in plasma?

Answer 20

In overdose, these drugs have enhanced toxicity if protein binding sites become saturated, if patient has physiological state that leads to hypo-albuminemia, or if the drug is displaced from the plasma protein by another drug

Question 21

What chemotherapy drugs have the same target and will form a complex that enhances binding?

Answer 21

methotrexate and fluorouracil

Question 22

What chemotherapy drugs bind to two different binding sites of the same target protein, enhancing the interactions of each other?

Answer 22

cisplatin and cyclophosphamide