A Brief Note on Drug-drug Interactions

Drug-drug interactions are very common and many thousands are described in standard prescribing reference books. However, there are few clinically relevant or significant drug–drug reactions. This is extremely important. Three types of drug–drug interactions need to be discussed with respect to clinical situations:

The good: therapeutically useful (agonist–antagonist) interactions. In many clinical situations drugs interacting with each other are used for the benefit of the patient, such as antidotes administered after overdoses, drugs used to combat heart effects when reversing neuromuscular blockade by atropine after anaesthesia, leucovorin rescue given after a high methotrexate dose, etc.

The awful: potentially harmful interactions which should be remembered and identified at an early stage.

The only ugly: interactions of no or little clinical significance which constitute the vast majority and should be identified as being low risk.

It is not possible to remember all relevant drug-drug interactions or to look them up in reference manuals or computer databases due to time constraints in the clinical situation. However, one should memorize the more common and harmful drug-drug interactions, particularly those where one component has a small therapeutic window, as with warfarin, digoxin, tricyclic antidepressants, aminoglycosides, antiepileptic drugs such as phenytoin and carbamazepine, anti-arrhythmics, AIDS drugs and ciclosporin.

Patients with co-morbidities, the elderly and those with impaired cardiac, liver or renal function should be assessed before a drug is prescribed or administered. If the pharmacist has time, a trustworthy reference source or medicine information centre can be consulted. Otherwise and in an emergency, pharmacokinetic reasoning can help. Knowledge of the chemical properties of similar drugs from the same class may allow some insight into absorption from or transport through the gastrointestinal tract, and whether metabolism might include enzyme induction or inhibition as well as competition for excretion via the kidneys. However, the conclusions drawn must be verified as soon as possible. Finally you must always ask yourself whether the effect could be caused by the drug itself for example, a side effect, and insufficient effect of the drug or disease breakthrough.

Pharmacologists, pharmacists, and other drug experts have been at the forefront during the COVID‐19 outbreak. Pharmacological expertise was required in various areas such as the daily health care of patients admitted to our hospitals, the implementation of pharmacokinetic and pharmacokinetic‐pharmacodynamic studies in clinical trials of repurposed drugs , and even in providing up‐to‐date information to the general population.

Assessment of drug-drug interactions is one of the areas of pharmacological expertise that directly contributes to patient health care through the effective and safe management of pharmacotherapy. Indeed, drug-drug interactions are an under recognized source of medical errors, which have major health consequences and significantly increase health costs. This has been thoroughly demonstrated in the aging population presenting with increasing multi-morbidity and polypharmacy. Thereby, assessing drug–drug interactions is of primary importance in the context of COVID‐19 therapy where older patients and those presenting with co‐morbidities (hypertension, diabetes, chronic kidney disease, etc.) are those particularly at risk for severe illness. It is also of primary importance for the COVID‐19 patients admitted in intensive care units and receiving treatments for critical care and complications.

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