Basics of Pharmacology & Nutrition

Basics of Pharmacology & Nutrition

• Food and drug disposition is a key area of study in pharmacology.
• The objectives of the lecture are to describe effects of nutrition on drug pharmacokinetics and pharmacodynamics, and vice versa.
• Food-drug interactions can alter drug effects, causing either therapeutic failure or increased toxicity.

Objectives

• Students should be able to describe the effect of nutrition on drug pharmacokinetics and list examples.
• Students should be able to describe the effect of nutrition on drug pharmacodynamics and list examples.
• Students should be able to describe the effect of drugs on food pharmacokinetics and list examples.

Food-drug Interactions

• Food-drug interactions can reduce or increase the effect of a drug, leading to therapeutic failure or increased toxicity.
• They can adversely affect patient care, contribute to morbidity, and prolong treatment time or hospitalization.
• Food can affect drug absorption, metabolism, distribution, and excretion.
• Drugs can affect food absorption, metabolism, distribution, and excretion.
• Drug side effects can impact food intake and nutrient absorption.
• Certain foods and drugs can create unhealthy effects when combined.

Types of Food-Drug Interactions

• Food-drug interactions can occur at the pharmacokinetic or pharmacodynamic level.
• Most interactions related to pharmacokinetics happen at the absorption (or the stage of absorption and metabolism) step.
• Few pharmacokinetic interactions happen at the pharmacodynamic level (inhibition/stimulation of enzymes, competition at binding sites).
• A list of examples of drugs and their food recommendations is available.

Effects of Food on Drug Absorption

• Food can affect both the rate and extent of drug absorption from the gastrointestinal tract.
• Absorption interactions can be:
  • Reduced (extent)
  • Delayed (rate)
  • Increased (extent)
  • Accelerated (rate)
  • No effect
• Delayed absorption typically results from slower gastric emptying and/or increased gastric pH. Pharmacokinetically, delayed absorption manifests as decreased Cmax and a longer tmax, but overall extent of absorption (AUC) is usually unaffected.
• Decreased absorption can occur due to certain disease states like diabetes mellitus and inflammatory bowel diseases.
• Examples include aspirin and Isoniazid, where food reduces the rate of absorption.

Absorption interactions:

• Increased or accelerated absorption is seen when absorption is increased from the delayed gastric emptying and increased secretion of bile salts. Example: cyclosporine, halofantrine, griseofulvin. The transport system can also be upregulated by high-protein meals.
• Food-induced malabsorption of drugs: Fatty foods or low fiber foods tend to delay stomach emptying (2hrs), leading to reduced absorption. E.g., Griseofulvin & otlipraz (enhanced absorption & bioavailability after high-fat meal), Ascorbic acid enhances iron absorption. Carbonated drinks or acid juices enhance drug dissolution in the stomach. Tetracyclines can form insoluble complexes with calcium, magnesium, and aluminum.

Factors Alter Absorption

• Characteristics of the drug (e.g., physical and chemical properties, like pKa, molecular weight, etc.). The absorption of Itraconazole is increased by the presence of food but not for fluconazole. The enantiomer(R-to-S) of ibuprofen can be affected by food.
• Characteristics of the meal (e.g., size, composition and fat content, high-fiber content, timing relative to meal). Ex: Bioavailability of lipophilic drugs increase with a high-fat diet, as it results in increased drug solubility or bile secretion.
• Examples: Grapefruit juice can increase bioavailability of felodipine, calcium in milk and milk products reduces the absorption of tetracycline, ascorbic acid in orange juice increases absorption of iron supplements. Drugs should not be consumed with extremely acidic and/or highly carbonated drinks.

Effects of Food on Drug Metabolism

• Various dietary components can influence drug metabolism, including dietary protein, cruciferous vegetables, charcoal-broiled beef (containing polycyclic aromatic hydrocarbons and methylxanthines).
• Malnutrition can alter hepatic metabolism and reduce elimination of conjugates and renally excreted drugs.
• Cytochrome P450 enzymes play a vital role in drug metabolism. Food components can act as inhibitors or inducers of these enzymes, potentially affecting drug metabolism and effectiveness, leading to side effects.
• Examples: Garlic (inhibits CYP2C19, increasing levels and side effects of Omeprazole & Diazepam); Broccoli (induces CYP2C9, affecting drugs like warfarin & tolbutamide).
• Black pepper's active compound, piperine, enhances the bioavailability of certain drugs by inhibiting enzymes.

Food-initiated Alteration of Drug Excretion

• Changes in urine pH due to food can impact the excretion rates of weak acids and bases
• A drug in a unionized state can diffuse from urine back into the bloodstream.
• This is prolonged when the urine is acidic (e.g., prolonged action of acidic drugs).
• Antacid intake with quinidine can cause quinidine toxicity due to the change in urine pH to alkaline.

Pharmacodynamic Interaction

• Vitamin K-rich food intake can directly antagonize the effect of warfarin.
• Avocado intake, potassium-rich foods (bananas, spinach), and food components competing with levodopa (for transporters in Parkinson's disease) can cause pharmacodynamic interactions, potentially resulting in adverse effects.

Effect of Drugs on Food

• Drugs can affect appetite (increase or decrease).
• Drugs can alter nutrient absorption, metabolism or excretion (e.g., laxatives, antacids).
• Some drugs can lead to nausea, vomiting (e.g., cancer drugs), or diarrhea (e.g., antibiotics like amoxicillin).

Summary Examples

• Summary tables are available that detail changes in physiology, potential drug effects, and examples related to drugs commonly involved.

This quiz explores the intersection of pharmacology and nutrition. It focuses on how food affects drug pharmacokinetics and pharmacodynamics, as well as the implications of food-drug interactions. Understand how these interactions can lead to therapeutic failures or enhanced toxicity.