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Lecture

Pharmacology 2060A/B Lecture Notes - Sauerkraut, Warfarin, Tachycardia


Department
Pharmacology
Course Code
PHARM 2060A/B
Professor
Angela Nissen

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Module 11
Drug Interactions
11.1 Introduction
Drugs can interact with each other or diet to complicate response
Drug-drug interactions can occur whenever patient takes 2 or more drugs
Drug-food interactions can occur even if patient only has one drug
Risk of drug interactions increases (almost linearly) with number of medications taken
Important in elderly – average 65 yr old takes 7 medications
Most common are those affecting pharmacokinetics (ADME)
11.2 Consequences of Drug Interactions
When 2+ drugs interact – 3 possible outcomes
1. Increased Effects
2. Decreased Effects
3. Generation of new effect
Increased Effects
oDrug interactions can increase drug effects by either increased therapeutic effect or increased
adverse effect
oIncreased Therapeutic Effect
Ampicillin – antibiotic rapidly inactivated by bacterial enzymes
Poor therapeutic response
Sulbactam – inhibitor of bacterial enzyme that inactivates ampicillin
oIncreased Adverse Effect
Warfarin – anticoagulant used to thin blood
Aspirin – analgesic that also thins blood
Warfarin + Aspirin = bleeding (potentially life threatening side effect)

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Decreased Effects
oDrug interactions can reduce drug effects by either reducing therapeutic effects or reducing
adverse effects
oReduced Therapeutic Effects
Clopidogrel – anticoagulant, prodrug that requires metabolic activation by CYP2C19
Omeprazole – drug used to treat stomach ulcers – inhibits CYP2C19
When given together  active metabolite of clopidogrel not formed
Insufficient anticoagulation
oReduced Adverse Effects
Morphine – analgesic used to treat pain
Overdose  produces coma, respiratory depression and even death
Treating morphine overdose  naloxone (antagonist)
Generation of New Effect
oUnusual
oDisulfiram – helps treat chronic alcoholism
oAlcohol – normally metabolized to acetaldehyde and then to acetic acid
Acetaldehyde makes you feel hung over (headache, nausea, vomiting, etc.)
Disulfiram inhibits metabolism of acetaldehyde
Patient will have severe hangover symptoms
oOccurs within 10 mins after alcohol intake
11.3 Types of Drug Interactions
Direct Physical Interaction
oDirect chemical or physical interaction of two drugs
oMost common when two or more IV solutions mixed together
Often precipitate to form
If precipitate forms, mixture should be discarded – not administered
oDrug solutions should never be mixed together without consulting a compatibility chart
oBenzodiazepine drug diazepam – should never be mixed with another drug

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oMay occur following administration too
oEx. If given Sodium Bicarbonate, followed by Calcium Gluconate – precipitate may form in
blood
Pharmacokinetic Interaction
oInteractions affecting Absorption, Distribution, Metabolism or Excretion (ADME)
oAbsorption
Altered pH
Affects ionization of many drugs
Drugs that effect gastric or intestinal pH can alter drug absorption
Antacids
oIncrease gastric pH – increase the absorption of drugs that are weak bases
Decreases absorption of weak acid drugs
oAlso dramatically affect absorption of enteric coated drugs
Designed to pass through acidic stomach without dissolution
Once they reach alkaline intestine, dissolution begins
After antacid, the increased pH promotes premature dissolution of
enteric coated drugs
Chelation/Binding
Some drugs bind other drugs in intestine
oCausing formation of insoluble complexes that cant be absorbed
Bile Acid Sequestrants
oDesigned to bind bile acids and prevent absorption from intestine
Cholestyramine-bile acid complex is excreted in feces
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