Warfarin, Insulin and Digoxin are the most Dangerous drugs in the elderly. Do we believe that?

How dangerous a drug is depends on the skill of the prescriber No Drugs are Dangerous if used properly All Drugs are Dangerous Some drugs have a low therapeutic ratio Some drugs have a low incidence of horrendous effects Some drugs are dangerous in acute poisoning but not when used therapeutically The most dangerous drugs have the greatest potential for benefit GOOD BAD Some adverse effects can be predicted if you know the pharmacology (Type A); some are not (Type B) Some adverse effects occur after a delay or after stopping How dangerous a drug is depends on the skill of the prescriber

The Risk to Benefit Ratio When prescribing drugs a doctor must assess risk to benefit ratio in the individual patient by Choosing an appropriate class of drug then an appropriate individual agent Is it effective ? What are the chances of adverse effect ? Are there features in this patient which affect choice eg other drugs, organ failure, aged Tailoring the dose Considering duration of treatment RISK BENEFIT

The Risks when prescribing drugs with a low therapeutic ratio are greatly increased if Pharmacokinetic process is complicated eg high hepatic extraction, or zero order elimination Wide interindividual variation in kinetics and / or response Pharmacokinetics sensitive to drug interaction, disease or ageing

Adverse drug reactions   An ADR is any unwanted effect resulting from a drug’s use in treatment.  

  Epidemiology 4% of hospital admissions 1 in 1000 deaths in medical wards 10 to 20 % of in-patients 5% of patients in general practice

More frequent in elderly:. erratic drug taking. multiple pathology More frequent in elderly: erratic drug taking multiple pathology altered pharmacokinetics increased sensitivity of CNS and CVS

Drugs - anti-coagulants, NSAIDs,corticosteroids, anti-hypertensives, anti-biotics, diuretics and insulin.  

Occur in circumstances related to drug’s pharmacology, predisposing factors in the patient and care taken in choosing the drug and the dose.

The BNF appendices Drug Interactions Liver disease Renal impairment Pregnancy Breast feeding

BNF chapters of relevance Adverse reactions to drugs Prescribing in the elderly Prescribing for children Emergency treatment of poisoning

Detecting Adverse Effects If a new drug causes a bizarre effect in 1 in 6000 patients it would need 18000 patients to use the drug for it to occur in 3 patients It would take twice as many before there was any suspicion that the effect was due to the drug If the effect also occurs naturally then it would take many times more patients Most early trials involve about 2000 patients

Detecting Adverse Effects MRHA (Medicine and Healthcare products Regulatory Agency) freephone service for reporting and information about suspected ADRs Self reporting by patients and relatives using Yellow cards available at pharmacies Prescription event monitoring New drugs – black triangles and yellow cards Established drugs

Measuring danger MHRA activity through Yellow card reporting and prescription monitoring Huge increase in reports over recent years

Who reports to the MHRA? Under-reporting estimated at 94% in hospital practice (Smith et al 1996) MRHA activity good at detecting adverse effects Not very good at assessing the risk ratio

Prevention of Adverse Drug reactions Never use any drug unless there is good indication. If the patient is pregnant do not use the drug unless the need is imperative. Allergy and idiosyncrasy are important causes of ADRs. Ask if the patient had previous reactions. Ask if the patient is already taking other drugs including self medication

Preventing ADRs cont’d Age, hepatic and renal disease may impair clearance of drugs so smaller doses may be needed. Genetic factors may also predispose to certain ADRs Prescribe as few drugs as possible and give clear instructions Where possible use familiar drugs. With new drugs be particularly alert for ADRs and unexpected event. If serious ADRs are liable to occur warn the patient

Some websites www.yellowcard.gov.uk http://medicines.mhra.gov.uk www.dsru.org http://eis.bris.ac.uk/~pmcjcr/Drug%20Safety.pdf