Drug Interactions

Question 1

Common CYP inducers involved in drug interactions

Answer 1

• Phenytoin
• Smoking
• Carbamazepine (also an auto-inducer)
• Rifampin (and rifabutin, rifapentine)
• Oxcarbazepine
• Phenobarbital
• St. John’s wort

PS CROPS

Question 2

Common CYP inhibitors involved in drug interactios

Answer 2

• Grapefruit
• Protease inhibitors
• Azole antifungals
• Cyclosporine, cobicistat
• Macrolides (clarithromycin and erythromycin, not azithromycin)
• Amiodarone (and dronedarone)
• Non-DHP CCBs (diltiazem, and verapamil)

G <3 PACMAN

Question 3

Common P-gp substrates

Answer 3

• Anticoagulants: apixaban, rivaroxaban, edoxaban, dabigatran
• Cardiovascular drugs: digoxin, diltiazem,verapamil, carvedilol, ranolazine
• Imunnosuppressants: tacrolimus, cyclosporinez, sirolimus
• HCV drugs: sofosbuvir
• Others: colchicine, saxagliptin, posaconazole, dolutegravir, raltegravir, atazanavir

Question 4

Common P-gp inducers

Answer 4

• Phenytoin
• Carbamazepine
• Rifampin
• Phenobarbital
• St. John’s wort
• Dexamethasone
• Topranavir

Question 5

Common P-gp inhibitors

Answer 5

• Cardiovascular drugs: amiodarone/dronedarone, quinidine, diltiazem, verapamil, carvedilol, conivaptan
• HIV drugs: cobicistat, ritonavir
• HCV drugs: ledipasvir
• Others: cyclosporine, flibanserin, ticagrelor

Question 6

Serotonergic toxicity

Answer 6

• Antidepressants
• MAO inhibitors
• Opioids
• Triptans
• Natural products: St. John’s wort, L-tryptophan, SAMe
• Others: buspirone, lithium, dextromethorphan (when taken in excess as a drug of abuse)

Question 7

Bleeding

Answer 7

• Anticoagulants
• Antiplatelets
• NSAIDs
• SSRIs, SNRIs
• Natural products: 5G’s, vitamin E, willow bark, fish oils (high dose)

Question 8

Hyperkalemia

Answer 8

• Renin-angiotensin-aldosterone system drugs
• Potassium-sparing diuretics
• Others: salt substitutes (KCl), calcineurin inhibitors (tacrolimus and cyclosporine), SMX/TMP, canagliflozin, drospirenone-containing oral contraceptives

Question 9

QT prolongation

Answer 9

Antiarrhythimics:
* Class 1a, 1c and III

Anti-infectives:
* Antimalarials (e.g., hydroxychloroquine)
* Azole antifungals except isavuconazonium
* Lefamulin
* Macrolides
* Quinolones

Antidepressants:
* SSRIs: highest risk with citalopram and escitalopram
* TCAs
* Others: mirtazapine, trazodone, venlafaxine

Antipsychotics:
* FGAs: thioridazine, haloperidol
* SGAs: highest risk with ziprasidone

Antiemetics:
* 5-HT3 receptor antagonists (e.g., ondansetron)
* Others: droperidol, metoclopramide, promethazine

Oncology medications
* Androgen deprivation therapy (e.g., leuprolide)
* Tyrosine kinase inhibitors (e.g., nilotinib)
* Other: oxaliplatin

Others: cilostazol, donepezil, fingolimod, hydroxyzine, loperamide, ranolazine, solifenacin, methadone, tacrolimus

Question 10

CNS depression

Answer 10

Many drugs/drug classes
* Opioids
* Skeletal muscle relaxants
* Antiepileptic drugs
* Benzodiazepines
* Barbiturates
* Hypnotics
* Antidepressants: mirtazapine, trazodone
* Antihypertensives: propranolol, clonidine
* Cannabis-related drugs: dronabinol, nabilone
* Sedating antihistamines
* Cough syrups with an antihistamine or opioid
* Some NSAIDs

Highest risk for fatality when used in combination:
* Opioids + Benzodiazepines or other CNS depressants

Question 11

Ototoxicity

Answer 11

• Aminoglycosides
• Cisplatin
• Loop diuretics
• Salicylates
• Vancomycin

Question 12

Nephrotoxicity

Answer 12

• Anti-infectives: amioglycosides, amphotericin B, polymyxins, vancomycin
• Cisplatin
• Calcineurin inhibitors
• Loop diuretics
• NSAIDs
• Radiographic-contrast dye

Question 13

Anticholinergic toxicity

Answer 13

• Antidepressants: paroxetine, TCAs
• Antipsychotics: FGAs
• Sedating antihistamines
• Centrally-acting anticholinergics
• Muscle ralaxants
• Antimuscarinics (for urinary incontinence)
• Others: atropine, belladonna, dicyclomine

Question 14

Hypotension/orthostasis

Answer 14

PDE-5 inhibitors
+
CYP3A4 inhibitors
or
Nitrates
or
Alpha-1 blockers