yasar kucukardali professor, internal medicine yeditepe university

DRUG İNTERACTİONSYasar Kucukardali Professor , Internal Medicine Yeditepe University

Drug interactions

Definition;

it is the modification of the effect of one drug (the object drug ) by the prior concomitant administration of another (precipitant drug).

Outcomes of drug interactions

1) Loss of therapeutic effect2) Toxicity3) Unexpected increase in pharmacological activity4) Beneficial effects e.g additive & potentiation (intended)

or antagonism (unintended).5) Chemical or physical interaction

e.g I.V incompatibility in fluid or syringes mixture

* Risk factors:

1) High risk drugs; these are the drugs that show a narrow therapeutic index e.g., corticosteroids, rifampin, oral contraceptives, quindine, lidoquine

2) High risk patients; these are the groups of patients that should be treated with caution due to a specific heath condition e.g., pregnant women, malignant cases, diabetic patients, patients with liver or kidney disorders asthmatic patients and cardiac disorders.

Drug-drug interactions (DDIs) are an important subgroup of ADEs which are highly prevalent in patients receiving multiple-drug treatment .

DDIs may lead to severe adverse events which can result in patienthospitalization.

Some studies have estimated that up to 3% of hospital admissions are caused by DDIs .

Estimates about the incidence of DDIs in different countries vary from 6% to 70% due to variability in methodologies and settings .

20% of hospitalized patients were susceptible to DDIs

incidence was higher in patients with heart disease, elderly patients and about one-third of cancer patients

Mechanisms of Drug Interaction• Pharmacokinetic– Reduced rate and/or completeness of absorption– Altered bioavailabilty– Reduced plasma protein binding– Altered tissue distribution– Altered hepatic metabolism– Altered renal excretion– Haemodynamic interactions

• Pharmacodynamic– Potentiation/antagonism at target receptor– Potentiation at non-target receptor– Alteration of fluid/electrolyte environment– Interference with transport mechanisms

In reviewing the patient history, consider the following characteristics in

relation to drug pharmacokinetics:Age: Most drugs were studied in adult patients and recommended dosages may vary in different age groups.Sex: Although data are limited, male and female patients can metabolize and eliminate drugs differently, so the optimal drug dosages may differ.Weight: For patients who are obese or cachectic, changes in drug clearance or volume of distribution often necessitate dosage adjustments.

Disease conditions: Three conditions that must be approached with special caution when prescribing any drug are heart failure (HF), renal disease, and hepatic failure. As HF progresses, bodily organ blood flow declines; the ensuing drug clearance decline necessitates lower dosages for many agents. As kidney or liver function declines, the renal and hepatic elimination of drugs decreases, leading to lower dosage requirements for renally and hepatically cleared agents, respectively.

Genetics: Pharmacogenomics is the study of the relationship of genetics in drug metabolism and ADRs. In a systematic review by Phillips and colleagues, of 27 drugs known to frequently cause ADRs, 59% were known to be influenced by individual patient genetic characteristics.

Drugs with low bioavailability due to high pre-systemic metabolism (First

pass effect

Pharmacodynamic MechanismsWhen drugs with similar pharmacologic effects are administered concurrently, an additive or synergistic response is usually seen.

The two drugs may or may not act on the same receptor to produce such effects.

In theory, drugs acting on the same receptor or process are usually additive, eg, benzodiazepines plus barbiturates.

Drugs acting on different receptors or sequential processes may be synergistic, eg, nitrates plus sildenafil or sulfonamides plus trimethoprim.

Conversely, drugs with opposing pharmacologic effects may reduce the response to one or both drugs.