Drug-Drug Interactions Flashcards
Properties of Acid-reducing agents (Antacids)
- 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
Example of drugs affected by DDI properties of Antacids
Antacids decrease GI absorption of Quinolones: (Ciprofloxacin, Norfloxacin, …)
DDI Properties of Alcohol
- 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
Example of drugs affected by DDI properties of alcohol
Cefotetan and Moxalactam induce Disulfiram-like reactions
DDI properties of Allopurinol
Inhibiting liver metabolic enzymes
Example of drugs affected by DDI properties of Allopurinol
Allopurinol will decrease Azathioprine detoxification (metabolism), resulting in increased azathioprine toxicity
DDI properties of oral anticoagulants (eg. Warfarin)
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
Example of drugs affected by DDI properties of anticoagulants
- 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
DDI properties of Antidepressants (eg. Tricyclics/Heterocyclics)
- inhibition of serotonin and NE reuptake
- additive antimuscarinic effects with antimuscarinic drugs
- susceptible to induction and inhibition of CYT P450 family:
(3A4 and 2D6)
Example of drugs affected by DDI properties of antidepressants
- Amiodarone decreases antidepressant metabolism
- Barbiturates increase antidepressant metabolism
- Sympathomimetics increase vasoconstriction response of Epinephrine and Phenylephrine
State the Azole antifungals
F: Fluconazole
K: Ketoconazole
V: Voriconazole
I: Itraconazole
P: Posaconazole
(FucK VIP)
DDI properties of Azole antifungals
- 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
Example of drugs affected by DDI properties of azole antifungals
Azoles will decrease the metabolism of Alprazolam, Midazolam, Triazolam
DDI properties of Barbiturates
- induction of CYT P450
- induction of P-glycoprotein activity
Example of drugs affected by DDI properties of Barbiturates
Barbiturates increase the metabolism of beta blockers; reducing their effects
DDI properties of beta blockers
- Beta blockade, especially the non-specific Propranolol
- decrease the response of beta agonists; they are blockers
Example of drug affected by DDI properties of beta blockers
Amiodarone decreases the metabolism of beta blockers; increasing their effects
DDI properties of Bile acid binding resins
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
Example of drug affected by DDI properties of bile acid binding resins
Bile acid resins decrease GI absorption of Furosemide
DDI properties of estrogen
Enterohepatic circulation of estrogen may be interrupted by alteration in bowel normal flora
Example of drug affected by DDI properties of estrogen
Rifampin and St. John’s Wort increases estrogen metabolism; reducing oral contraceptive efficacy
DDI properties of iron
Iron binds with drugs in GIT, reducing their absorption
Example of drug affected by DDI properties of iron
- Quinolones: absorption is decreased in the presence of iron
- Iron absorption is decreased in the presence of tetracyclines
DDI properties of Probenecid
- 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
Example of drug affected by DDI properties of Probenecid
Probenecid decreases Penicillin excretion
Most common reported adverse effect of warfarin in DDIs
GI bleeding
Cerebral hemorrhage
Liver enzyme inducers
Barbiturates
Carbamazepine
Rifampin
St. John’s wort (Herbal medicine)
Liver enzymes inhibitors
Amiodarone
Clarithromycin
Erythromycin
Ketoconazole
Drugs that inhibit P-glycoprotein excretion activity
Amiodarone
Clarithromycin
Erythromycin
Ketoconazole
Drugs that get partially eliminated by P-glycoprotein
Digoxin
Cyclosporine
Tacrolimus
Example of additive drugs
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
