Prescribing in Disease

Clive Roberts

So what are drugs good at treating (or preventing)?

• Pain• Inflammation• Infection• Fluid retention• Heart problems• High blood pressure• Epilepsy• Parkinsonism• Asthma / COPD• Peptic ulcer disease

• Diarrhoea/constipation• Depression• Anxiety/sleeplessness• Psychosis• Metabolic /endocrine

diseases• Malignant disease• Degenerative disease• Haematological

problems• Etc Etc

What could happen to this man?

1) Massive fluid overload

2) Hepatic encephalopathy

3) Gross electrolyte abnormality

4) Renal Failure

5) GI or other Haemorrhage

6) Metabolic abnormaility

7) Exacerbation of liver disease

8) Infection

9) Drug accumulation

And so the risks of drug use in decompensated liver disease

• Precipitate encephalopathy– CNS effect

– Electrolyte effect

– GI effect

• Worsen metabolic effect/features of hepatic failure– Fluid retention

– Sodium retention

– Electrolyte abnormality

– Hypoglycaemia

– Clotting abnormalities

Continued:

• Profound pharmacokinetic disturbance leading to drug accumulation and dose related adverse effects– Decreased systemic clearance of lipid soluble drugs– Increased bioavailability of drugs with high extraction ratio– Decreased plasma protein binding– Altered apparent volume of distribution– Associated impairment of renal function– Failure of pro-drugs– Hepatic blood flow reduction

• Worsened hepatic state – Hepatotoxic drugs

Some examples from the BNF table

• Anticoagulants• Antidepressants, anxiolytics and hypnotics• Anti-psychotics• NSAIDs• Diuretics• Phenytoin, Carbamazepine• Glibenclamide• Opioids• Rifampicin

• Co-amoxyclav, clarythromycin, erythromycin, ketoconazole, isoniazid

• Chloramphenicol• Clopidogrel• Cyclophosphamide, methotrexate• Lignocaine• ACE inhibitors• Metformin• Verapamil and some dihydropyridine Ca

blockers

• Statins

• Antacids

• Theophylline

Other risk situations• Renal disease• The Elderly• Need for many drugs• Allergy• Lung disease • Heart disease• Gastrointestinal disease• Inherited diseases• Blood diseases• Bone disease• Skin disease• Pregnancy

The renal patient

• Pharmacokinetic disturbance – Mainly affecting drug clearance– Also protein binding

• Increased sensitivity

• Poor tolerance of adverse effects

• Decreased effectiveness of some drugs

Drugs in the elderly

• Multiple indications leads to polypharmacy

• Pharmacokinetic disturbance of metabolism, excretion, protein binding and drug distribution

• Increased sensitivity to the actions of drugs on CVS, CNS, GIT

• Poor tolerance of adverse effect

Other risk situations• Renal disease• The Elderly• Need for many drugs• Allergy• Lung disease • Heart disease• Gastrointestinal disease• Inherited diseases• Blood diseases• Bone disease• Skin disease• Pregnancy

Remember

• Every disease represents a potential contra-indication to particular drugs

• Prescribing any drug should only follow a decision that potential benefit outweighs potential risk