Drug Interactions Flashcards by Dylan Null

What drug classes are most commonly involved in Drug to Drug Interactions?

NSAIDs
Anticoagulants
Antiplatelets
Cardiovascular drugs

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What are some of the main risks for Drug to Drug Interactions?

Age
Narrow Therapeutic Index
Self-Prescribing

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Medications or substances that increase the rate of metabolic activity of a specific CYP450 enzyme?

Inducers

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Medications or substances that decrease the rate of metabolic activity of a specific CYP450 enzyme?

Inhibitors

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Medications or substances that use CYP450 enzymes to be metabolized in the liver?

Substrates

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What two mechanisms are responsible for the majority of drug interactions?

Induction and Inhibition

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Efflux transporters found in the gut and other organs.
Pump drugs back into the gut (out of the bloodstream)

P-Glycoproteins

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Inducers (CORRPPSESN)

Carbamazepine
Oxcarbazepine
Rifampin
Ritonavir
Phenytoin
Phenobarbital & Primidone
Smoking
Efavirenz
St. John’s Wort
Nafcillin

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How long would it take to see a drug to drug interaction when administering an inducer?

2 - 3 weeks

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2C9 Inhibitors

Bactrim
Metronidazole

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2D6 Inhibitors

Tricyclic Antidepressants
Fluoxetine
Paroxetine

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3A4 Inhibitors

Haloperidol
Azoles (anti-fungals)
Protease Inhibitors
NNRTIs
Diltiazem
Verapamil
Erythromycin

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How long would it take to see a drug to drug interaction when administering an inhibitor?

2 - 3 days

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Inhibitors (G-PACMAN)

Grapefruit
Protease Inhibitors
Azole (anti-fungals)
Cimetidine
Macrolides
Amiodarone
Non-Dihydropyridine Calcium Channel Blockers
(Diltiazem and Verapamil)

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Serious adverse drug reactions?

Steven Johnson Syndrome
Toxic Epidermal Necrolysis (TEN)
Anaphylaxis

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Medication that is pharmacologically inactive in the body.

Prodrugs

Amiodarone

Inhibitor: 2C9, 2D6, 3A4
Decrease dose of Digoxin and Warfarin by 30-50%
Do not use grapefruit juice

Azole Anti-fungals

Require low pH (acidic) for absorption
Avoid with drugs that increase pH
(antacids, H2 blockers, proton pump inhibitors)

Digoxin

Narrow therapeutic index medication
Hypokalemia = ↑ Digoxin Toxicity
85% Renally Cleared. ↓ Renal Function = ↓ Digoxin Dose

Statins

Substrates of 3A4 = ↑ levels with 3A4 inhibitors
Clinical outcome of higher risk for muscle toxicity

What mechanism increases the level of the drug in the blood causing increased toxicity?

Inhibitors

Lithium

100% Renally Cleared
Increased Lithium with:
NSAIDs
ACE-inhibitors
Angiotensin Receptor Blockers
Dehydration
Diuretics

MAO Inhibitors

Tranylcypromine, Isocarboxazid, Phenelzine, Selegline

Metabolism is decresed in the presence of:
Norepinephrine & Epinephrine
Serotonin
Tyramine (aged, fermented, pickled, smoked)

Serotonin Syndrome or Hypertensive Crisis:
Antidepressants
Triptans
Dextromethorphan

NSAIDs

COX Inhibitors block prostaglandin synthesis
Increased Risk of:
- Bleeding
- Kidney Injury
- Cardiovascular Toxicity

Oral Contraceptives

CYP450 Enzyme Inducers can decrease effectiveness Examples: Anticonvulsants: barbiturates, phenytoin, carbamazepine St. John's Wort ABX: Ampicillin, Sulfonamides, Rifampin, Tetracycline Some Anti-Retrovirals Smoking (more likely to form blood clots)

Rifampin

GOLD STANDARD INDUCER Strong Inducer of: CYP 2C9, 2C19, and 3A4 Will decrease the concentration of any drug that is a substrate listed above. Used to treat TB and Leprosy

Phenytoin

Induces CYP 2C8, 9 & 19, 3A4, and P-Glycoprotein Highly protein bound (albumin) Can displace medications from albumin CAUTION with other CNS Depressants (additive effects)

Carbamazepine

Strong 3A4 inducer and induces its own metabolism 3A4 Substrate 3A4 inhibitors will increase carbamazepine levels 3A4 inducers will decreases carbamazepine levels

Tetracycline and Quinolone ABX

Ciprofloxacin, Levofloxacin, Moxifloxacin Bind or Chelate with: Aluminum, Magnesium, Calcium, Iron, and Zinc Decreased absorption of ABX

Separate administration of what and for how long when prescribing Tetracyclines or Quinolones?

Vitamins Iron Supplements Antacids Dairy Sucralfate Coated aspirin

Warfarin (Pharmacokinetics)

Substrate of 2C9 Induction of 2C9 = ↓ Effectiveness Inhibition of 2C9 = ↑ Effectiveness Effectives is measured by INR

Warfarin (Pharmacodynamics)

Combined toxicity of bleeding risks Additive bleeding risk with NSAIDs & anti-platelets - no change in INR

What herbal drugs will increase the risk of bleeding while on Warfarin?

Garlic Ginkgo

What supplements decrease the effectiveness of Warfarin?

Ginseng Vitamin K (reversal agent)

What classes of medications can cause hyperkalemia?

ACE Inhibitors ARBs Trimethoprim Aldosterone Antagonists NSAIDs Digoxin

What can hyperkalemia lead to?

Cardiac arrhythmias and sudden cardiac death

CNS depressants that when used together cause additive effects

Alcohol Opiates Muscle Relaxers Benzodiazepines Hypnotics Barbiturates

Risk factors for Torsades de Pointes (Polymorphic Ventricular Tachycardia)

Medications QT interval > 500 msec Bradycardia Electrolyte abnormalities Females Congenital QT prolongation

Red flag medications for long QT syndrome

Warfarin Highly Active Anti-retroviral Therapy (HAART) Amiodarone Tricyclic Antidepressants Quinolones Antipsychotics Antibiotics Anti-aryhtmics Anti-convulsants Statins