ALEKHYA RAVELLA M PHARMACY(PHARMACOLOGY) MALLAREDDY INSTITUTE OF PHARMACEUTICAL SCIENCES

An interaction is said to occur when the effects of one drug are changed by the presence of another drug, food, drink or by some environmental chemical agent.

.For convenience the mechanisms of interactions can be subdivided into those which involve the pharmacokinetics of a drug and those which are pharmacodynamic.

Pharmacokinetic interactions are those which can affect the processes by which drugs are absorbed. distributed. metabolized and excreted (the so-called ADME interactions). .

ALTERATIONS IN ABSORPTION ` Complexation/Chelation: Complexation/Chelation: Example: 1)antacids + tetracycline Impact: tetracycline complexes with divalent cations forming an insoluble complex .

` Effects of changes in gastro intestinal ph: example: ketoconazole + antacids proton pump inhibitors Impact: reduced ketoconazole absorption due to reduced dissolution .

` .may reduce the bioavailability of digoxin.Change in gastrointestinal motility: Example: anticholinergics + acetaminophen Impact: delay in absorption of acetaminophen ` Induction or inhibition of drug transport proteins: Example: Digoxin is a substrate of p glyco protein and drugs induce this such as rifampicin. digoxin.

.the effect is to impair the absorption of no of drugs including digoxin and methotrexate.` Malabsorption caused by drugs: Example: Neomycin causes malabsorption syndrome.

` Protein binding interaction: Example: when patients stabilised on warfarin are given chloral hydrate because its major metabolite. . is a highly bound compound which successfully displaces warfarin. thereby increasing its anticoagulant effects. trichloroacetic acid.

` Changes in first pass metabolism: i)changes in blood flow through liver: Example: Increase in rate of absorption of dofetilide with verapamil.. . ii)Inhibition or induction of first pass metabolism: Example :grape fruit juice induce the cyto chrome p450 isoenzyme cyp3A4 .which increase the metabolism of calcium channel blockers.which has resulted increase of torsade de pointers.

Enzyme induction: Example: phenobarbital + warfarin Impact: phenobarbital increases the metabolism of warfarin. ` Enzyme inhibition: Example: cimetidine + theophylline Impact: cimetidine reduces the clearance of theophylline causing an increase in adverse effects ` . warfarin. resulting in reduced anticoagulation.

whereas moving the pH in the opposite directions will increase their retention. acid for bases) increase the loss of the drug.` Changes in urinary ph: Thus pH changes that increase the amount in the ionised form (alkaline urine for acidic drugs. Example: changes in the excretion of quinidine and salicylate due to alterations in urinary pH caused by antacids .

the renal excretion of lithium is reduced and its serum levels rise as a result. by indometacin). If the synthesis of these prostaglandins is inhibited (e.g.` Changes in active renal tubular excretion: Example: probenecid + penicillin Impact: probenecid prolongs the half-life of penicillin. ` . Changes in kidney blood flow : The flow of blood through the kidney is partially controlled by the production of renal vasodilatory prostaglandins. halfallowing single dose therapy.

etc. tranquillisers. ` Antagonistic or opposing interactions : Example: ` the oral anticoagulants can prolong the blood clotting time by competitively inhibiting the effects of dietary vitamin K.Additive or synergistic interactions and combined toxicity : Example: ` alcohol depresses the CNS and. may cause excessive drowsiness. sedatives. ` .g. if taken in moderate amounts with normal therapeutic doses of any of a large number of drugs (e.).

including antacids. Food-drug interactions can happen with both prescription and over-the-counter medications. vitamins.` ` A food-drug interaction can occur when the food you eat affects the ingredients in a medication you are taking. preventing the medicine from working the way it should. . and iron pills.

grapefruit interactions: Drugs which may exhibit increased serum concentrations based on this interaction ` ` ` ` ` ` ` ` ` ` amiodarone astemizole alprazolam atorvastatin benzodiazepines buspirone carbamazepine carvedilol cerivastatin cilostazol .Drug .

or think you need more information. and interaction precautions printed on all medication labels and package inserts. Read directions. Take medication with a full glass of water. Do not stir medication into your food or take capsules apart (unless directed by your physician). Even over-the-counter medications can cause problems. This may change the way the drug works.What you should remember about food-drug interactions: ` ` ` ` ` Read the prescription label on the container. warnings. If you do not understand something. ask your physician or pharmacist. Do not take vitamin pills at the same time you take medication vitamins and minerals can interact with some drugs .

. which together can have additive and possibly synergistic effects. Alcohol may also continue to interact the next day if the barbiturate has hangover effects. Activities requiring alertness and good co-ordination. such as driving a car or handling other potentially dangerous machinery.` Alcohol + Barbiturates Alcohol and the barbiturates are CNS depressants. will be made more difficult and more hazardous.

and simple additive CNS depression provides part of the effects. 9 Acute alcohol ingestion may inhibit the liver enzymes concerned with the metabolism of the barbiturates.5-g/kg dose of alcohol. 1 Mechanisms ` Both alcohol and the barbiturates are CNS depressants. 10 .Clinical evidence ` A study in man of the effects of a single 0. taken in the morning after a dose of amobarbital 100 mg every night for 2 weeks showed that the performance of co-ordination skills was much more impaired than with either drug alone.

triglyceride levels and blood pressure.Garlic is used for lowering blood cholesterol. especially in patients already taking certain anti-clotting medications. Garlic may increase bleeding. .

. vomiting and vertigo ` Ginger may increase bleeding. especially in patients already taking certain anti-clotting medications.Ginger ` Ginger is used for reducing nausea.

John's Wort is used for mild to moderate depression or anxiety and sleep disorders. . John's Wort may prolong the effect of certain anesthetic agents. St.` St.

it can enhance the effects of alcohol. Kava-kava may increase the effects of certain anti-seizure medications and/or prolong the effects of certain anesthetics. anxiety or restlessness. ` .` Kava-kava is used for nervousness. it is also a muscle relaxant. It may increase the risk of suicide for people with certain types of depression.

` ` ` ` ` ` ` ` ` ` ` ` DRUG Astemizole CATEGORY antihistamine Bromfenac analgesic Dexfenfluramine anorectic Felbamate anticonvulsant Flosequinan vasodilator Grepafloxacin antibiotic Mibefradil Ca channel blocker Temafloxacin antibiotic Terfenadine antihistamine Travafloxacin antibiotic REASON serious metabolic drug intxns hepatotoxicity cardiovascular tox aplastic anemia increased mortality proarrhythmic serious drug intxns severe ADR serious drug intxn hepatotoxicity .

anticoagulants.` ` ` ` Be on the alert with any drugs which have a narrow therapeutic window or where it is necessary to keep serum levels at or above a suitable level (e. immunosuppressants. cytotoxics. .g. barbiturates. phenytoin. Think about the basic pharmacology of the drugs under consideration so that obvious problems (additive CNS depression for example) are not overlooked. digitalis glycosides. antiinfectives. Keep in mind that the elderly are most at risk because of reduced liver and kidney function on which drug clearance depends. rifampicin. etc. cimetidine). antihypertensives. hypoglycaemic agents. etc) or enzyme inhibiting agents (e. And don¶t forget that many drugs affect more than one type of receptor which results in side-effects. Remember those drugs which are enzyme inducing agents (e.g.). and try to think what might happen if drugs which affect the same receptors are used together. anticonvulsants.g.

D. 1998. Journal of Clinical Pharmacology and Therapeutics 2002. . Herb-drug interactions: review and assessment of report reliability. J. 46: p.D. Clin. Abebe W. Br. Malcolm. Pharmacol. British Journal of Clinical Pharmacology 2001.` ` ` Fugh-Berman A..Bailey. J.. J. Grapefruit Juice-Drug Interactions.G. Ernst E. Arnold. O. Herbal medication: potential for adverse interactions with analgesic drugs. 27(6): 391-401 . 101-110. 52(5): 587595. and Spence.

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