Title: Drugs and Nutrition

Key words: Pharmacokinetics, appetite, nausea, taste, absorption, metabolism, excretion,

Date: Nov 1999

Category: 15. Materia Medica

Type: Article

Author: Dr M Draper

 

Drugs and Nutrition

How Drug Administration Can Affect Nutritional Status

Introduction

Pharmacokinetics is defined as the study of the time course of absorption, distribution, metabolism and excretion of drugs and the corresponding pharmacological response. When considering the effect of drugs on nutritional status, it is tempting to use a similar model so that the subject can be approached systematically. However, with nutritional kinetics, we need first to consider the effect of the drugs upon the intake of food. This is especially important in the seriously ill including infants and the elderly (2) who may be on a variety of drugs which can interact and cause adverse effects at lower than expected doses.

Drugs that influence nutritional intake.

There are two main ways that drugs can affect the intake of food, they can increase or decrease the appetite (see Table 1) and they can cause nausea, vomiting or affect the taste (see Table 1). Digoxin, a cardiac glycoside that is commonly prescribed to the elderly for heart failure and atrial fibrillation (1) has been carefully studied, even though the exact way the drug affects the heart is not known. Various factors affect the bioavailability of digoxin. These include its formulation and interactions with other drugs that affect absorption e.g. metoclopramide, which reduces availability by speeding up gut motility. Even though it is protein bound, the main factor that can lead to toxicity is linked to reduced excretion, because 80% of Digoxin is normally excreted unchanged in the urine. The clinical manifestations of digitalis intoxication from 179 patients accidentally given 3 times the prescribed dose include 80% having anorexia and /or nausea. Digoxin has a narrow therapeutic index, so that even normal doses can accumulate and cause similar effects, especially if renal clearance is poor.

Table 1:

DRUGS & APPETITE

Appetite Reducing Drugs

Appetite Increasing Drugs

Drugs Affecting Taste

Amantadine

Cyproheptadine

ACE inhibitors

Digoxin

MAOIS

Allopurinol

Fluoxetine

Tricyclics

Amiodarone

Levodopa

Valproate

Baclofen

Lithium

 

Griseofulvin

Metformin

 

Lithium

Nitrofurantoin

 

Metformin

Penicillamine

 

Metronidazole

Spironolactone

 

Penicillamine

 

 

Terfenadine

 

Drugs that influence the absorption of nutrients.

There are several ways that drugs can influence absorption (see Table 2) and these become particularly important if the drug is chronically administered so that the reduction in absorption of a nutrient or group of nutrients can lead to deficiency symptoms and/or syndromes. Cholestyramine is a basic anion-exchange resin which is not absorbed from the intestine. It binds to bile salts, thus reducing the absorption of fats and increasing their excretion in the faeces, for the therapeutic lowering of blood cholesterol and triglycerides. The main side effects of cholestyramine are bloating, excessive flatus and constipation. However, impaired absorption of vitamins D, K and folic acid can have an influence on calcium metabolism, blood coagulation and synthesis respectively.

Table 2:

How Drugs Can Affect Absorption

Changing GI motility
Changing GI pH
Forming insoluble complexes
Inhibition of mucosal enzymes
Binding of bile acids
Interfering with GI factors (e.g. intrinsic factor)

 

Drugs that affect the metabolism of nutrients.

The way drugs interfere with nutrient metabolism (see Table 3) may be linked to their mechanism of action and therefore this can be a two-way process i.e. the nutrient can affect the drug metabolism. Of the anticonvulsants, Phenytoin has been studied extensively and it appears to work by preventing the propagation of epileptic discharges rather than suppressing the excitability of the primary focus. Phenytoin induces the liver enzymes and therefore increases the metabolism of drugs such as oral contraceptives and anticoagulants as well as the breakdown of active Vitamin D leading to anti-convulsant induced osteomalacia. It also causes a megaloblastic anaemia, which responds to folate supplementation.

Table 3:

DRUGS and NUTRIENT METABOLISM

Drug

Nutrient affected

Frusemide

Thiamine

Tricyclics

Riboflavine

Isoniazid

Pyridoxine

Hydralazine

 

Penicillamine

 

Oral contraceptives (OCs), theophylline

 

Anticonvulsants

Folic Acid

Methotrexate

 

Sulphasalazine

 

Trimethoprim

 

Anticoagulants

Vitamin K

 

 

Drugs that affect the excretion of nutrients

This is an area of growing interest because of the widespread use of diuretics and steroids. (see Table 4) Pharmaceutical companies encourage the co-prescribing of the Bisphosphonates (e.g. Didronel) with long term steroids to prevent and treat steroid induced osteoporosis. Lithium is commonly prescribed for manic-depressive disorders and it has been appreciated for some time that sodium intake can affect urinary excretion of lithium and visa versa. To avoid depletion of sodium it is necessary to find the minimum effective dose of lithium and to monitor salt intake as well as blood levels of lithium and sodium.

Table 4:

DRUGS INFLUENCING NUTRIENT EXCRETION

Drug

Nutrient

Corticosteroids

Na/K

Carbenoxolone

Na/K

Diuretics

Na/K/Mg

 

References.

  1. Rogers, H. J., Spector, R. G., Trounce, J. R. 1981 A Textbook of Clinical Pharmacology p.358-370 - Unibooks.
  2. Lewis, C.W. Drug-Nutrient Interactions in three long-term-care facilities Journal of the American Dietetic Association 1995; 95(3):309-15

General References:1. Ekhard A, Ziegler E, Filer, L.J. Present Knowledge in Nutrition 1996; p.540-546

International Life Sciences Institute.

2. D'arcy, P.F. Nutrient-drug Interactions 1995; 14(4):233-54 - Adverse Drug Reactions &

Toxicological Reviews.

3. Kirk, J.K. American Family Physician 1995; Significant drug-nutrient interactions.

51(5):1175-82, 1185

4. Thomas, J. A. Nutrition Reviews Drug-Nutrient Interactions. 1995; 53(10):271-82