Adverse drug reactions
Do no harm – Hippocrates
“Any response to a drug which is noxious, unintended and occurs at doses in man for
prophylaxis, diagnosis or therapy” – WHO
Predisposing factors
- Genetics
- Age-related
- Sex-related
- Physiological (e.g., pregnancy)
- Exogenous (e.g., drugs, food)
- Disease-related
Classification of ADRs
- There are several ways of classifying adverse reactions, but the simplest is to
separate them into 2 main groups, A and B
- This is the basic system referred to in many textbooks. However, despite the
addition of 4 further groups (C-F) to account for reactions that do not fit neatly into
groups A or B, it is still not fully satisfactory.
A. Dose-related (augmented)
Features
- Common
- Related to pharmacological action of the drug
- Predictable
- Low mortality / high morbidity
Management
- Reduce dose or withhold
- Consider effects of concomitant therapy
Pharmaceutical variation
- Outdated tetracycline
- Break down to produce anhydrotetracycline (toxic) > Fanconi’s syndrome
- An impairment of proximal tubule function
- Substances normally reabsorbed into the blood are lost in the urine e.g., glucose,
amino acid, phosphate, uric acid.
Pharmacokinetic Variation
- Severe hepatitis or advanced cirrhosis can reduce clearance of drugs
- Care must be taken, particularly with:
Drugs with a low therapeutic ratio (phenytoin, theophylline and warfarin)
Drugs that undergo extensive first-pass metabolism
Pharmacodynamics Variation
- If potassium levels are low digoxin can bind more easily to the pump – resulting in a
dangerous increase in its effect
- This can happen with diuretics that promote potassium excretion.
- Hypokalaemia > Reduce available K+ > Reduces binding competition > Increases
digoxin effects > Toxicity
Do no harm – Hippocrates
“Any response to a drug which is noxious, unintended and occurs at doses in man for
prophylaxis, diagnosis or therapy” – WHO
Predisposing factors
- Genetics
- Age-related
- Sex-related
- Physiological (e.g., pregnancy)
- Exogenous (e.g., drugs, food)
- Disease-related
Classification of ADRs
- There are several ways of classifying adverse reactions, but the simplest is to
separate them into 2 main groups, A and B
- This is the basic system referred to in many textbooks. However, despite the
addition of 4 further groups (C-F) to account for reactions that do not fit neatly into
groups A or B, it is still not fully satisfactory.
A. Dose-related (augmented)
Features
- Common
- Related to pharmacological action of the drug
- Predictable
- Low mortality / high morbidity
Management
- Reduce dose or withhold
- Consider effects of concomitant therapy
Pharmaceutical variation
- Outdated tetracycline
- Break down to produce anhydrotetracycline (toxic) > Fanconi’s syndrome
- An impairment of proximal tubule function
- Substances normally reabsorbed into the blood are lost in the urine e.g., glucose,
amino acid, phosphate, uric acid.
Pharmacokinetic Variation
- Severe hepatitis or advanced cirrhosis can reduce clearance of drugs
- Care must be taken, particularly with:
Drugs with a low therapeutic ratio (phenytoin, theophylline and warfarin)
Drugs that undergo extensive first-pass metabolism
Pharmacodynamics Variation
- If potassium levels are low digoxin can bind more easily to the pump – resulting in a
dangerous increase in its effect
- This can happen with diuretics that promote potassium excretion.
- Hypokalaemia > Reduce available K+ > Reduces binding competition > Increases
digoxin effects > Toxicity
