Adverse reactions, interactions and safe-medication principles
Đã giới thiệu| English | Ý nghĩa |
|---|---|
| type A reactions | type A reactions |
| type B reactions | type B reactions |
| enzyme induction | enzyme induction |
| enzyme inhibition | enzyme inhibition |
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.
A patient on a drug starts rifampicin. What happens to the first drug's level?
Độ khó 1/5 · 100 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
Rifampicin induces enzymes, which takes days to build.
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.
Match each event to what lies behind it.
Độ khó 2/5 · 140 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
Two reaction types and two interaction mechanisms.
Enzyme inhibition begins with the first doses, but enzyme induction takes days.
Độ khó 1/5 · 100 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
Inhibition blocks existing enzyme; induction must build new enzyme.
Which group of drugs is most affected by interactions?
Độ khó 1/5 · 100 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
A small change in level crosses from effective to toxic.
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.
A reaction occurs in 1 in 5,000 patients. Using the rule of three, about how many patients are needed for a 95% chance of seeing at least one case?
Độ khó 2/5 · 140 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
3 × 5,000 = 15,000.
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.
Put the five rights in the order they are usually listed.
Độ khó 3/5 · 200 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
Patient, drug, dose, route, time.
Worked example: the warfarin INR
- (Fictional) Warfarin + clarithromycin (an inhibitor): warfarin clearance falls, the INR rises within days, and bleeding risk climbs.
- Warfarin + rifampicin (an inducer): the INR falls over a week or more, and stays low for weeks after rifampicin stops.
A patient stable on warfarin starts clarithromycin. What should you expect?
Độ khó 1/5 · 100 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
Clarithromycin inhibits CYP3A4 and slows warfarin clearance.
Worked example: how big a study?
- (Illustrative) A reaction occurs in 1 in 2,000 patients. Rule of three: 3 × 2,000 = 6,000 patients for a 95% chance of at least one case.
- A 1,500-patient trial would probably miss it, and seeing one case does not tell you the rate.
Three common slips
- Blaming type B reactions on dose. Dose neither predicts nor prevents them.
- Forgetting the inducer's tail. Its effect lasts after it is stopped, so doses must be re-checked then too.
- Thinking a clean trial means a safe drug. Rare reactions appear only in large populations.
Recap
- Type A = dose-related, predictable; type B = idiosyncratic, rare, serious.
- Induction lowers levels (slow on, slow off); inhibition raises levels (fast on); narrow-TI drugs suffer most.
- Rule of three: about 3n patients to see a 1-in-n reaction; report through Yellow Card (UK) or MedWatch (US); check the five rights.