Drug-Drug Interactions

Question 1

Properties of Acid-reducing agents (Antacids)

Answer 1

• decrease absorption:
  → adsorb to the GI lumen
  → decrease stomach acidity (like PPIs & H2 antagonists); some drugs require certain pH to dissolve
• alkalize urine:
  → drugs like (Al3OH, Mg2OH) alter urine pH and decrease the excretion of basic drugs

Question 2

Example of drugs affected by DDI properties of Antacids

Answer 2

Antacids decrease GI absorption of Quinolones: (Ciprofloxacin, Norfloxacin, …)

Question 3

DDI Properties of Alcohol

Answer 3

• chronic alcoholism
  → results in stimulating liver metabolic enzymes
• acute alcoholic
  → causes alcohol-induced hepatic dysfunction, resulting in
  inhibiting liver metabolic enzymes
• Disulfiram-like reaction
  → severe NVD when administering drugs with alcohol
• Additive & Synergistic CNS depression
  → increasing CNS depression on top of any existing one

Question 4

Example of drugs affected by DDI properties of alcohol

Answer 4

Cefotetan and Moxalactam induce Disulfiram-like reactions

Question 5

DDI properties of Allopurinol

Answer 5

Inhibiting liver metabolic enzymes

Question 6

Example of drugs affected by DDI properties of Allopurinol

Answer 6

Allopurinol will decrease Azathioprine detoxification (metabolism), resulting in increased azathioprine toxicity

Question 7

DDI properties of oral anticoagulants (eg. Warfarin)

Answer 7

Warfarin’s effect can change with:
- CYT P450 2C9, both stimulation and inhibition
- drugs that displace it from albumin
- drugs that alter clotting factor breakdown

Question 8

Example of drugs affected by DDI properties of anticoagulants

Answer 8

• Amiodarone inhibits anticoagulant elimination (metabolism & excretion)
• PPIs increase warfarin activity and increase the risk of bleeding
• the most fatal reports were seen when giving antidepressants with warfarin

Question 9

DDI properties of Antidepressants (eg. Tricyclics/Heterocyclics)

Answer 9

• inhibition of serotonin and NE reuptake
• additive antimuscarinic effects with antimuscarinic drugs
• susceptible to induction and inhibition of CYT P450 family:
  (3A4 and 2D6)

Question 10

Example of drugs affected by DDI properties of antidepressants

Answer 10

• Amiodarone decreases antidepressant metabolism
• Barbiturates increase antidepressant metabolism
• Sympathomimetics increase vasoconstriction response of Epinephrine and Phenylephrine

Question 11

State the Azole antifungals

Answer 11

F: Fluconazole
K: Ketoconazole

V: Voriconazole
I: Itraconazole
P: Posaconazole

(FucK VIP)

Question 12

DDI properties of Azole antifungals

Answer 12

• inhibition of CYT P450 family: (3A4 and 2C9) → F, V
• inhibition of P glycoprotein → P, I, K (PIcK)
• susceptible to enzyme inducers → V, I, K

Question 13

Example of drugs affected by DDI properties of azole antifungals

Answer 13

Azoles will decrease the metabolism of Alprazolam, Midazolam, Triazolam

Question 14

DDI properties of Barbiturates

Answer 14

• induction of CYT P450
• induction of P-glycoprotein activity

Question 15

Example of drugs affected by DDI properties of Barbiturates

Answer 15

Barbiturates increase the metabolism of beta blockers; reducing their effects

Question 16

DDI properties of beta blockers

Answer 16

• Beta blockade, especially the non-specific Propranolol
• decrease the response of beta agonists; they are blockers

Question 17

Example of drug affected by DDI properties of beta blockers

Answer 17

Amiodarone decreases the metabolism of beta blockers; increasing their effects

Question 18

DDI properties of Bile acid binding resins

Answer 18

These drugs can bind with other drugs, which will:
A. decrease absorption, by binding with oral drugs
B. decrease distribution, by binding with parenteral drugs

Question 19

Example of drug affected by DDI properties of bile acid binding resins

Answer 19

Bile acid resins decrease GI absorption of Furosemide

Question 20

DDI properties of estrogen

Answer 20

Enterohepatic circulation of estrogen may be interrupted by alteration in bowel normal flora

Question 21

Example of drug affected by DDI properties of estrogen

Answer 21

Rifampin and St. John’s Wort increases estrogen metabolism; reducing oral contraceptive efficacy

Question 22

DDI properties of iron

Answer 22

Iron binds with drugs in GIT, reducing their absorption

Question 23

Example of drug affected by DDI properties of iron

Answer 23

• Quinolones: absorption is decreased in the presence of iron
• Iron absorption is decreased in the presence of tetracyclines

Question 24

DDI properties of Probenecid

Answer 24

• decrease excretion:
  → Probenecid interferes with the excretion of weak acidic
  drugs that undergo active tubular secretion
• decrease Phase II metabolism:
  → Probenecid inhibits glucuronide reaction of other drugs

Question 25

Example of drug affected by DDI properties of Probenecid

Answer 25

Probenecid decreases Penicillin excretion

Question 26

Most common reported adverse effect of warfarin in DDIs

Answer 26

GI bleeding Cerebral hemorrhage

Question 27

Liver enzyme inducers

Answer 27

Barbiturates Carbamazepine Rifampin St. John’s wort (Herbal medicine)

Question 28

Liver enzymes inhibitors

Answer 28

Amiodarone Clarithromycin Erythromycin Ketoconazole

Question 29

Drugs that inhibit P-glycoprotein excretion activity

Answer 29

Amiodarone Clarithromycin Erythromycin Ketoconazole

Question 30

Drugs that get partially eliminated by P-glycoprotein

Answer 30

Digoxin Cyclosporine Tacrolimus

Question 31

Example of additive drugs

Answer 31

Benzodiazepine and Barbiturate (sedative drugs): both act on GABA receptors in CNS, once all receptors are occupied by either drugs → Emax is achieved for this type of receptors