Lecture 9 Food Drug Interaction Fall 2024 PDF

Basics of Pharmacology & Nutrition Food and Drug Disposition Mohammed Al Zaabi Department of Pharmacology and Clinical Pharmacy  Objectives At the end of this lecture, the student should be able to: Describe the effect of nutrition on drug phar...

Basics of Pharmacology & Nutrition Food and Drug Disposition Mohammed Al Zaabi Department of Pharmacology and Clinical Pharmacy  Objectives At the end of this lecture, the student should be able to: Describe the effect of nutrition on drug pharmacokinetics and list some examples Describe the effect of nutrition on drug pharmacodynamics and list some examples Describe the effect of drug on food pharmacokinetics and list some examples  Food-drugs interactions Food-drugs interactions can: – reduce or increase the effect of the drug – results in therapeutic failure – increased toxicity – adversely affect patient care – contribute to morbidity – prolong treatment time or hospitalisation  Food-drugs interactions Food affects → drug absorption, metabolism, distribution and excretion Drug affects → food absorption, metabolism, distribution and excretion Drug’s side effects affects → food intake and nutrient absorption Drugs + certain food → creates unhealthy effects  Food-drugs interactions Food-drugs interactions can be at: – Pharmacokinetics Majority of interactions Most at the stage of absorption and then metabolism – Pharmacodynamics Few interactions Most at competing sites e.g. transport, receptors bindings  Effects of Food on Drug Absorption Food can affect both the rate and extent of drug absorption from the gastrointestinal tract Absorption drug-food interactions classified into five categories: – reduced (extent) – delayed (rate) – increased (extent) – accelerated (rate) – no effect Cmax and tmax: rate, AUC: extent  Absorption interactions Delayed absorption or decreased rate of absorption usually results from – a slower gastric emptying rate and/or – increased gastric pH resulting from the ingestion of food Pharmacokinetically, this is manifested as a decreased Cmax and a corresponding longer tmax but mostly does not affect overall all extent of absorption (AUC)  Absorption interactions Decreased absorption – decreased extent of gastrointestinal absorption – certain disease states, such as diabetes mellitus and inflammatory bowel diseases (ulcerative colitis and Crohn’s disease), may be associated with the decreased bioavailability of drugs. For instance, in patients with diabetes mellitus the bioavailability of drugs may be decreased by delayed gastric emptying which occurs because of autonomic neuropathy  Absorption interactions Example -Food reduces the rate of absorption of aspirin (acetylsalicylic acid), commonly used to treat fever and pain Aspirin is best taken 2 hours after meals with a full glass of water - Food reduces the absorption of Isoniazid (a drug used for tuberculosis) Therefore, Isoniazid has to be taken 1 hour before or 2 hours after mealsbe taken 1 hour before or 2 hours after meals.  Absorption interactions Increased or Accelerated Absorption – increased intestinal uptake results from the delayed gastric emptying and increased secretion of bile salts which may increase the dissolution rate e.g., cyclosporin, halofantrine, griseofulvin – up-regulation of carrier-mediated transport systems that occurs in response to high-protein meals Food-induced Malabsorption of Drugs - Fatty foods and foods low in fiber delay stomach emptying by 2 h (delaying or reducing drug absorption) - Griseofulvin & oltipraz have enhanced absorption & bioavailability after high-fat meal - Ascorbic acid enhances iron absorption - Carbonated soft drinks or acid juices enhance drug dissolution in stomach than in intestine - Tetracyclines form insoluble complexes in GIT with foods or drugs containing Ca, Mg, Al  Factors Alter Absorption Characteristics of the drug – Physical and chemical characteristics of a drug E.g., antifungals fluconazole (pKa = 1.5) and itraconazole (pKa = 3.7) belong to the same chemical class of triazoles, but differ in molecular weight, lipophilicity and solubility in water and dilute acids. The absorption of itraconazole in the presence of food appears to be increased, the absorption of fluconazole is not affected by food – Enantiomorphic composition of the Drug Meal may induce chiral inversion of the R- to the S enantiomer of ibuprofen and effect – Formulation type  Factors Alter Absorption Characteristics of the meal – size of the meal – composition of a meal bioavailability of lipophilic drugs is often increased by a high fat content, either because of increased drug solubility (e.g., albendazole and isotretinoin) or stimulation of bile secretion (e.g., griseofulvin and halofantrine) a high fibre content may reduce the bioavailability of certain drugs (e.g., digoxin and lovastatin) because of binding to the fibre – timing of drug intake in relation to a meal Grapefruit juice at 1, 4, 10 or 24 hours before drug administration resulted in a 32 to 99% increase in the mean Cmax of felodipine relative to concomitant intake of water and felodipine  Factors Alter Absorption - The calcium in milk and milk products decreases the absorption of certain antibiotics, including tetracycline. These foods should not be taken at the same time this drug is taken. - Ascorbic acid-containing juices such as orange juice enhance absorption of iron supplements. It is recommended that an iron supplement should be taken it with this type of beverage, if possible.  Factors Alter Absorption - Drugs should not be taken with soda or high acid fruit or vegetable juices, because these can cause excess stomach acidity which can dissolve some drugs before they reach the intestine. Since drugs are mostly absorbed into the body in the intestines, this will decrease the amount of drug that can get into your body. - Sometimes certain foods can speed up absorption of a drug. For example, fatty foods increase absorption of the antifungal drug griseofulvin. Effects of Food on Drug Metabolism Various dietary components are known to influence drug metabolism examples include: – dietary protein – cruciferous vegetables – charcoal-broiled beef containing polycyclic aromatic hydrocarbons, and methylxanthines Malnutrition can be associated with altered hepatic metabolism and reduced elimination of conjugates and renally excreted drugs GFJ: grapefruit juice Effects of Food on Drug Metabolism Cytochrome P450 enzyme plays a crucial role in the metabolism of various drugs in the human body. Inhibitors or stimulators (inducers) of these enzymes can affect the metabolism of drugs that are substrates for these enzyme, leading to changes in their effectiveness and potential side effects. Effects of Food on Drug Metabolism Garlic contains compounds that can inhibit the activity of the CYP2C19 enzyme, which can lead to increased levels and side effects of Omeprazole (proton pump inhibitor) and Diazepam (anticonvulsant) Broccoli contains compounds that can induce the activity of the CYP2C9 enzyme. Examples of drugs that are affected by broccoli include: warfarin (blood thinner) and tolbutamide (diabetes medication).  Black Pepper and Drug Bioavailability - Active principle piperine enhances the bioavailability of a number of drugs as well as phytochemicals by inhibiting hepatic and intestinal aryl hydrocarbon hydroxylase and UDP- glucuronyl transferase - Piperine's bioavailability enhancing property is also partly attributed to increased absorption as a result of its effect on the ultrastructure of intestinal brush border - Piperine enhanced the oral bioavailability of phenytoin in normal & epileptic patients Food-initiated Alteration of Drug Excretion - pH affects ionization of weak acids & bases - Changes in urine pH caused by food (making urine acidic or alkaline) can have significant effects on excretion rates of some drugs - A drug in unionized state can diffuse more easily from urine back in the blood, thus prolong drug action. Action of acidic drug is prolonged when urine is acidic - Antacid intake with quinidine causes quinidine toxicity because it changes urine pH to alkaline  Pharmacodynamic Interaction The effect of warfarin may be directly antagonised by the ingestion of foodstuffs rich in vitamin K such as cabbage, broccoli, liver and certain dietary supplements. Avocado intake has been reported to cause warfarin antagonism. Potassium-rich foodstuffs such as bananas and spinach may result in hyperkalaemia with some diuretic drugs. Some food components competes with levodopa (used in Parkinson disease) for transporters.  Effect of Drugs on Food Examples for effect of drugs on food: – Appetite Increase e.g., corticosteroid Decrease e.g., antidepressant – Change nutrient absorption, metabolism, or excretion Laxatives cause loss of nutrients Antacids – Nausea and vomiting e.g., cancer drugs – Diarrhoea e.g., some antibiotics e.g., amoxicillin Summary examples