Adverse reactions, interactions and safe-medication principles

A safe drug, a new antibiotic, a bleed

• A patient stable on warfarin for years is given a common antibiotic. A week later the INR has doubled and the gums are bleeding.
• Neither drug was wrong alone. Safety comes from knowing reaction types, interactions and the habits that catch errors.

Two types of reaction

• Type A reactions A型反应 are dose-related and predictable from the drug's action: a β-blocker slowing the heart too much, bleeding on an anticoagulant.
• Type B reactions B型反应 are not dose-related and hard to predict: allergy or a rare idiosyncratic toxicity. They are rare but often serious.

Enzyme induction

• Enzyme induction 酶诱导 (rifampicin, phenytoin, carbamazepine) makes the liver build more CYP enzyme, so another drug's level falls.
• Building enzyme takes days, and so does losing it: the effect starts late and lasts after the inducer is stopped.

Enzyme inhibition

• Enzyme inhibition 酶抑制 (clarithromycin, grapefruit juice at CYP3A4) blocks existing enzyme, so another drug's level rises.
• It starts with the first doses. Narrow-TI drugs such as warfarin, digoxin and lithium are where this matters most.

Finding rare reactions

• Trials of a few thousand people cannot find a 1-in-10,000 reaction. By the rule of three, you need about 3 × 10,000 = 30,000 patients to have a good (95%) chance of seeing one case.
• So rare type B reactions are found after approval, by reporting: the UK MHRA Yellow Card scheme and the US FDA MedWatch.

The five rights

• Right patient, right drug, right dose, right route, right time: the bedside checks that catch most errors before they reach the patient.
• Report near-misses too. They show where the system lets errors through.

Worked example: the warfarin INR

Worked example: how big a study?

Three common slips

Recap