DRUG INTERRACTIONS, LECTURE NOTES FOR PHARMACY STUDENTS

An altered or modified action or effect of a drug as a result of interaction with one or more other drugs. Do not confuse with:
Adverse drug reaction: an undesirable drug effect that ranges from mild to severe
Drug incompatibility: chemical or physical reaction that occurs among two or more drugs outside the body (in a container, between two drugs in an IV solution, oil and water)
When a person takes 2 drugs at the same time, the rate of absorption of one or both drugs can change – one drug can decrease, increase, or block the absorption rate of another drug
This can occur in 3 ways:
Decrease or increase in GI emptying time
Change in gastric pH
Formation on drug complexes
Drugs that increase the speed of gastric emptying = increased GI motility = decrease in drug absorption = less pharmacological action
Prokinetics (metoclopramide)
Drugs that decrease gastric emptying & decrease GI motility = increase in absorption rate = increase in amount of drug absorbed (especially those absorbed in the stomach)
Antidepressants
Antihypertensives
Low gastric pH and a weak acid drug is more rapidly absorbed, e.g. aspirin
High gastric pH and a weak acid drug suffers a decrease in absorption (antacids raise pH and slow absorption)
A chemical reaction can also occur – some antacids and tertracyclines form a complex, reducing the ability of the tetracyclines to be absorbed
Drug distribution to tissues can be affected by its binding to plasma/serum protein
Remember only unbound (free) drugs can enter body tissues
Two highly bound protein drugs compete for protein = a decrease in binding of one or both drugs = more free drug in circulation = drug toxicity
Many drug interactions of metabolism occur with the induction (stimulation) or inhibition of the hepatic system
A drug can increase the metabolism of another drug by stimulating (inducing) liver enzymes – enzyme inducers
Cytochrome P450
Barbiturates
Increase in metabolism = increase in elimination = decrease in plasma concentration = decrease in drug action
A drug can be an enzyme inhibitor and decrease the metabolism of certain drugs = an increase in plasma concentration = toxicity
Cimetidine + Theophylline
Cigarette smoking increases CYP450 enzyme activity
Chronic alcohol use increases CYP450 enzyme activity
Acute alcohol use decreases CYP450 enzyme activity
Most drugs are excreted in the urine, some through the bile and GI tract
Drugs can increase or decrease renal excretion of other drugs
Cardiac output drugs decrease renal blood flow and delay excretion
Furosemide (diuretic) slows renal filtration and reduces drug clearance = toxicity
Changing urine pH affects drug excretion
Alkaline urine promotes excretion of weak acid drugs (ASA, barbiturates) and promotes reabsorption of weak base drugs
In patients with renal or hepatic disease, there is usually an increase in free drug concentration: MONITOR CLOSELY
Reactions that result in additive, synergistic (potentiation), or antagonistic drug effects
Additive Drug Ef

1. Drug Interactions Dr. Kabiru Abubakar B.Pharm, MSc, PhD American International University West Africa, The Gambia Department of Pharmacy

2. What is a Drug Interaction? An altered or modified action or effect of a drug as a result of interaction with one or more other drugs. Do not confuse with: Adverse drug reaction: an undesirable drug effect that ranges from mild to severe Drug incompatibility: chemical or physical reaction that occurs among two or more drugs outside the body (in a container, between two drugs in an IV solution, oil and water)

3. Pharmacokinetic Interaction: Absorption When a person takes 2 drugs at the same time, the rate of absorption of one or both drugs can change – one drug can decrease, increase, or block the absorption rate of another drug This can occur in 3 ways: Decrease or increase in GI emptying time Change in gastric pH Formation on drug complexes

4. Pharmacokinetic Interaction: Absorption Drugs that increase the speed of gastric emptying = increased GI motility = decrease in drug absorption = less pharmacological action Prokinetics (metoclopramide) Drugs that decrease gastric emptying & decrease GI motility = increase in absorption rate = increase in amount of drug absorbed (especially those absorbed in the stomach) Antidepressants Antihypertensives

5. Pharmacokinetic Interaction: Absorption Low gastric pH and a weak acid drug is more rapidly absorbed, e.g. aspirin High gastric pH and a weak acid drug suffers a decrease in absorption (antacids raise pH and slow absorption) A chemical reaction can also occur – some antacids and tertracyclines form a complex, reducing the ability of the tetracyclines to be absorbed

6. Pharmacokinetic Interaction: Distribution Drug distribution to tissues can be affected by its binding to plasma/serum protein Remember only unbound (free) drugs can enter body tissues Two highly bound protein drugs compete for protein = a decrease in binding of one or both drugs = more free drug in circulation = drug toxicity

7. Pharmacokinetic Interaction: Distribution Many drug interactions of metabolism occur with the induction (stimulation) or inhibition of the hepatic system A drug can increase the metabolism of another drug by stimulating (inducing) liver enzymes – enzyme inducers Cytochrome P450 Barbiturates Increase in metabolism = increase in elimination = decrease in plasma concentration = decrease in drug action

8. SCRAP GP S ulfonylureas C arbamazepine R ifampin A lcohol P henytoin G riseofulvin P henobarbital

9. Pharmacokinetic Interaction: Distribution A drug can be an enzyme inhibitor and decrease the metabolism of certain drugs = an increase in plasma concentration = toxicity Cimetidine + Theophylline Cigarette smoking increases CYP450 enzyme activity Chronic alcohol use increases CYP450 enzyme activity Acute alcohol use decreases CYP450 enzyme activity

10. SICKFACES.COM S odium valproate I soniazid C imetidine K etoconazole F luconazole A lcohol C hloramphenicol E rythromycin S ulfonamides C iprofloxacin O meprazole M etronidazole

11. Pharmacokinetic Interaction: Excretion Most drugs are excreted in the urine, some through the bile and GI tract Drugs can increase or decrease renal excretion of other drugs Cardiac output drugs decrease renal blood flow and delay excretion Furosemide (diuretic) slows renal filtration and reduces drug clearance = toxicity

12. Pharmacokinetic Interaction: Excretion Changing urine pH affects drug excretion Alkaline urine promotes excretion of weak acid drugs (ASA, barbiturates) and promotes reabsorption of weak base drugs In patients with renal or hepatic disease, there is usually an increase in free drug concentration: MONITOR CLOSELY

13. Pharmacodynamic Interactions Reactions that result in additive, synergistic (potentiation), or antagonistic drug effects Additive Drug Effect – when 2 drugs with similar action in the same drug category/class are administered together The sum of the effects of the two drugs Desirable or undesirable

14. Pharmacodynamic Interactions Desirable = 2 analgesics; Tylenol and Codeine – together increase pain relief Undesirable = Alcohol and Aspirin – can increase bleeding time and cause gastric bleeding

15. Pharmacodynamic Interactions Synergistic Drug Effect – when 1 drug potentiates or enhances the effect of the other drug Greater than the effect of each alone Can be desirable or undesirable Desirable - Tramadol (analgesic) + Promethazine (antihistamine) = promethazine potentiates the effect of tramadol Undesirable – Alcohol + Diazepam (sedative) = increase in CNS depression Some antimicrobials have enzymes added to potentiate the effect of the drug (e.g. Amoxicillin + Clavulanate)

16. Pharmacodynamic Interactions Antagonistic Drug Effect – 2 drugs combined that have opposite effects and cancel each other out – Undesirable Naloxone (opioid antagonist) given after a morphine overdose to reverse the effect – Desirable

17. Drug-Food Interactions Food can increase, decrease or delay drug absorption Decrease when food binds to drug, ex. Statins (cholesterol) and grapefruit = less plasma concentration of statins Separate by 1 to 2 hours, or if possible, avoid completely during therapy Only a few cases where food increases absorption Nitrofurantoin with food Iron tablets with vitamin C rich foods (oranges)

18. Drug-Food Interactions A classic interaction is when an antidepressant of the MAO (monoamine oxidase) inhibitor class is taken with foods rich in tyramine – cheese, wine, beer, yogurt, bananas Result is hypertensive crisis Another is when warfarin is taken with foods high in Vitamin K – dark, green leafy vegetables Result is decreased drug action Patient must be educated to avoid these foods in these types of situations