Drug interaction refers to an adverse drug response produced by the administration of a drug or co exposure of the drug with another substance, which modifies the patient's response to the drug. Any drug, chemical or food element responsible for the interaction is known as precipitant and the drug affected by the interaction is known as object drug.
Drug interaction may occur either pharmacokinetically or pharmacodynamically. Pharmacokinetic interaction occurs, when the absorption, distribution or elimination of the drug is affected by other drug, chemical or food element. It can be antagonistic, synergistic or additive in action. Pharmacodynamic interactions include the concurrent administration of drugs having the same (or opposing) pharmacologic actions and alteration of the sensitivity or the responsiveness of the tissues to one drug by another. They're dependent upon the concentration of the interacting species and on the dose and time. There is another type of interaction that involves physical or chemical incompatibilities. It occurs when two or more drugs are mixed with each other called pharmaceutical interactions.
Naturally drug interaction involves, drug-drug interactions, drug-herbal interactions, drug-food interactions and drug chemical interactions.
Drug interaction involves:-
#.Drug - Drug Interactions
#.Drug - Herbal Interactions
#.Drug - Food Interactions
#.Drug - Chemical Interactions
Drug - drug interactions
Drug - drug interactions is defined as the modulation of the pharmacologic activity of one drug (object drug) by the prior or concomitant administration of another drug (precipitant drug). In these reactions, the therapeutic actions of the object drug or precipitant drug can be either severely enhanced or diminished.
In some cases, predictable drug - drug interactions in the patient are beneficial and clinicians allow them to occur because they result in lower doses of drug being administered, while achieving therapeutic serum - drug levels. For instance, administering penicillin (renally extracted) with the drug probensid will significantly elevate serum levels of penicillin and prolong its half-life.
Some examples of drug - drug interactions that affect the absorption (bioavailability) of the drug from the gastrointestinal tract include:
#.Levofloxacin complexes with divalent cations (Calcium, Magnesium, and Aluminium) causes decrease in the bioavailability,
#.Laxatives & cathartics increase the gastrointestinal motility and lead to decrease the bioavailability for drugs that absorbed slowly
#.H2 blockers and antacids increase the gastric pH, which affects the dissolution of the drug like ketokonazole and omeprazole causing decrease in drug absorption.Some of the interactions are also responsible for displacing the drugs from the plasma protein binding. They are called displacement interactions or tissue and cellular interactions.
#.Valproic acid displaces phenytoin for plasma protein binding sites and reduces hepatic phenytoin clearance by inhibiting the liver's metabolism of phenytoin.
#.Quinidine reduces digoxin clearance and displaces digoxin from tissue binding sites, leads to higher plasma digoxin concentration and a reduced distribution volume.
There are another set of interactions that affect the drug elimination and clearance. Drug metabolism can be affected by enzyme induction, substrate competition for the same enzyme and changes in hepatic blood flow. Many drugs that share the same drug metabolizing enzymes have a potential for drug interactions.
#.Smoking increases the theophylline clearance due to the presence of polycyclic aromatic hydrocarbons is the example of enzyme induction interaction.
#.Cimetidine decreases the theophylline clearance.
Drug - Herbal Interactions
Drug - Herbal interactions are also quite common. Simultaneous usage of medicinal herbs and prescription drugs may lessen the potency of both or even cancel their effects completely. While using prescription drugs and herbs at the same time, everyone should be aware of the possible side effects that might ensue.
Herbal preparations can be either one herb or combinations of herbs. For instance, Hypericum perforatum LINN (St John's wort) comprises of at least six different constituents, including hyperforin, biapigenin, hypericin, quercitin, chlorogenic acid and pseudohypericin. Some herbal preparations may contain unrecognized contaminants such as heavy metals or a similar herb mistakenly harvested.
Drug - herbal interactions are of greatest concern when patients are taking drugs with a narrow therapeutic window. For example, co-enzyme Q10 has the chemical structure related to vit-k. Patient on warfarin therapy will have increased bleeding due to co-enzyme Q10.
The prominent effect or interactions depend upon the relative potency of each constituent in the herb; potency is influenced by a variety of factors.
#.The stage of growth during which the herb was harvested.
#.The drying time
#.The solvent used in extraction of active constituent from herb.
#.The shelf life and storage conditions of herb extract.
Some possible medicinal Herb - Drug interactions of mostly used herbs are:
Allium sativum (Garlic)
#.Garlic taken with saquinavir (used to treat HIV infection) makes it less effective.
#.Garlic taken with anticoagulant increases the risk of bleeding.
#.Garlic taken with oral hypoglycemic drugs cause excessive decrease in blood sugar levels.
Panax quinquefolium (Ginseng)
#.Ginseng taken with anticoagulant / aspirin/ NSAIDS increases the risk of bleeding.
#.Ginseng taken with hypoglycemics cause excessive decrease in blood sugar level.
#.Ginseng may intensify the side effects of estrogen.
#.Ginseng may increase the digoxin levels.
#.Ginseng may reduce the effectiveness of opoids.
#.Ginseng can cause headache, tremors and manic episodes when taken with MAO inhibitors.
Glycyrrhiza glabra, (Liquorice)
#.Liquorice may increases salt/water retention leads to increase in blood pressure making anti hypertensive drugs less effective.
#.Liquorice may increase the risk of abnormal heart rhythm, making anti arrhythmic therapy less effective.
#.Liquorice taken with digoxin leads to low K+ levels and increases the risk of digoxin toxicity.
#.Liquorice can cause headache, tremors and manic episodes when taken with MAO inhibitors.
Hypericum perforatum LINN (St John's wort)
#.St John's wort may reduce effectiveness of drugs used in reducing anxiety and may increases drowsiness.
#.St John's wort may reduce blood levels of cyclosporines, making it less effective.
#.St John's wort may reduce blood levels of digoxin, making it less effective.
Food - Drug interactions
Generally, administering oral medications along with food or at a mealtime is a convenient manner of drug dosing. However, there is a risk of food-drug interaction. This interaction may modify the effect of the drug or impair the nutritional benefit of certain foods.
Foods can pharmacodynamically antagonize the effect of some drugs. For instance, spinach and broccoli provides dietary sources of vit - k, which antagonize the effect of warferrin.
Foods can be metabolized by the same liver enzyme that metabolize drugs causing enzyme inhibition or induction. It may result in toxic or subtherapeutic drug levels. For example, grapefruit and valencia oranges inhibit the CYP3A4 isoenzyme systems and leads to increase levels of substrate drugs like saquinavir, indinavir, midazolamand and nimodipine etc.
Some examples of food - drug interactions are:
#.Alprazolam when taken with kawa shows synergistic CNS activity of alprazolam.
#.Amoxicillin and ampicillin taken with catha edulis (Khat) leads to delayed or decrease absorption of both amoxicillin and ampicillin.
Grapefruit Juice
#.Grapefruit taken with astemizole increases the bioavailability of astemizole.
#.Grapefruit taken with buspirone increases the serum levels of buspirone.
#.Grapefruit taken with cyclosporine increases serum drug levels of cyclosporins.
Chemical - Drug Interactions Alcohol
Interactions between drugs and alcohol may lead to a significant increase in risk of illness, injury or even death. Alcohol can increase or decrease activity of hepatic drug metabolizing enzymes.
There is no set formula for what will happen to one if he consumes alcohol and medication at a time. Each person is different and the results vary based on the type and quantity of medication and alcohol ingested, the time involved, individual's tolerance to both alcohol and medication.
#.Alcohol reduces the effectiveness of antibiotics and may leads to nausea/ vomiting and convulsions.
#.Alcohol taken with antipsychotics and antiseizures may leads to decrease protection against seizures and intensified sedation.
#.Alcohol taken with CVS medication may leads to extreme dizziness or fainting.
#.The ingestion of alcohol with sedative and hypnotics is most dangerous, it can lead to severe drowsiness and depressed cardiac and respiratory functions leading to coma and fatality.
Smoking
Nicotine is the primary active ingredient in cigarette. Smoking tobacco leads to mixing of nicotine into blood. Some medicines can interact with nicotine to cause harmful effects.
#.Smoking can lead to increase enzyme induction of drugs as diazepam, theophylline and tricyclic antidepressants.
#.Some drugs used to treat excessive smoking, contains nicotine. It is important not to smoke while using these drugs to avoid interactions.
#.Smoking cigarettes causes blood vessels to narrow and may leads to hypertension. So smoking with antihypertensive drugs can make the situation worse.
(The author is from BIS College of Pharmacy, Punjab).