Adverse drug effects Flashcards
Adverse drug reaction
Response to a drug that is noxious and unintended and that occurs at doses normally used. Includes abuse, medication error, during therapeutic use and overdose. Causes 6.5% of all hospital admissions
Most common ADR 1
- Beta blockers: Bradycardia, heart block, hypotension, wheezing if asthma
- Opiates: Constipation, vomiting, confusion, urinary retention
- Digoxin: toxicity (N+V, arrhythmias)
- Prednisolone: GI complications (worsening of diabetes and ulcers), hyperglycaemia, osteoporotic fracture, bruising
Most common ADR 2
- Clopidogrel: GI bleeding
- NSAIDs: GI complications (pain, ulcers), Cerebral haemorrhage, renal impairment, wheezing, rash
- Diuretics: Renal impairment (AKI), hypotension, electrolyte disturbances (hypokalaemia), gout
- Warfarin: bleeding
- ACE /AII inhibitors: Renal impairment, hypotension, electrolyte disturbances (hyperkalaemia)
Classification of ADR’s A-C
- Augmented: dose related, predictable and avoidable i.e. insulin causing hypoglycaemia
- Bizarre: not dose related and not predictable, tend to be rare but serious i.e. anaphylaxis
- Chronic treatment effects: variable occur with prolonged but not short duration treatment i.e. osteoporosis with steroids
Most common ADR D-E
- Delayed effects: variable, occur some time after discontinuation of treatment. Different to chronic as don’t need to be taken for a long time i.e. drug induced fetal abnormalities
- End of treatment: variable effects occurring on withdrawal of a drug i.e. Addisonian crisis after steroid treatment
Drugs causing gynaecomastia and galactorrhoea
Gynaecomastia: Spironolactone, oestrogens, Methyldopa, Digoxin
Galactorrhoea: Antipsychotics, Tricyclics, Metoclopramide, Oestrogens, Methyldopa. Dopamine antagonists increase prolactin causing galactorrhoea
Common side effects: skin and general appearance
Angioedema: aspirin, ACEI
Skin rashes: antibiotics (Penicillin used in glandular fever)
Steven-John: anticonvulsants
Short stature in puberty: steroid use in childhood
Yellow teeth: tetracyclines in childhood
Squamous cell carcinoma: Immunosuppressants for organ transplant
ADR- criteria for diagnosis
- Timing with drug treatment: not or delayed
- Improvement after drug discontinued (dechallenge) or dose reduced. Ans worsening with increased dose (Type A dose related ADRs)
- Associated with high plasma drug concentrations (Type A dose related ADRs)
- Reaction previously recognised as caused by a drug that the patient is exposed to
- Illness that is commonly the result of an adverse drug reaction (e.g. postural hypotension, confusion)
- Exclusion of other causes
ADR- avoiding anaphylaxis
- Take a careful drug history
- Inform other health professionals
- Record allergies: Hospital and GP notes, Drug charts
- Check with patient before administering drugs
- Inject first dose slowly
- Particular care in atopic subjects
Avoiding ADR
- Only prescribe when there is a clear indication
- Use drug with most favourable risk-benefit
- Check with patient for previous ADRs / Allergy
- Careful patient education
- Monitor therapy: therapeutic range and side effects
- Particular care in susceptible patients
Why can new drugs be unsafe
- Lack of experience in special patient groups: Elderly, children, lactating women, pregnancy, multiple disease, polypharmacy
- Unlikely to detect ADR especially rare ones: only exposed to 1500 people
- Exposed for short duration only: cant detect delayed reactions
Objectives of pharmacovigilance
- Identify previously unrecognised hazards
- Evaluate changes in risks and benefits
- Take action to promote safer use
- Provide optimal information to users
Yellow card scheme
- Used to collate information on suspected ADR important for early detection
- Voluntary- done by healthcare professionals, patients can only report side effects
- Particularly focus’s on: serious ADR’s, ADR’s in children, ADR’s in new drugs (black triangle)
- Can be done electronically, on the app and on paper
Actions from the yellow card scheme
- Withdrawal drug if risks exceed benefits (rare)
- Make changes to promote safer use: remove indication, add contraindication, add warning, add drug interaction, add ADR
- Inform users: drug safety update, send letter
Drug interactions
A clinically meaningful alteration in the effect of one drug (object) due to the co-administration of another drug, food or chemical
Results of drug interactions
- No clinically significant effect
- Clinical harm or benefit
- Increased effect: Summative or synergistic
- Decrease effect: Antagonistic
- Tends to only happen where there is a narrow therapeutic index
- Consequences: increased hospital admission and length of stay, reduction in confidence, lasting morbidity and reduction in functional ability
The two mechanisms of drug interactions
- Pharmacodynamics: drugs act on the same target site of clinical effect (receptor or body site). Example: opiates and benzos causing respiratory depression
- Pharmacokinetics: altered drug concentration at target site of clinical effect. Changes in the processes of absorption, distribution, metabolism and excretion. OCP failure with antibiotics
Pharmacodynamic interactions
- Synergism/summative: additive effects.
- Antagonism: opposing effects
Pharmacodynamic example of additive effect
- Beneficial: rifampicin + isoniazid at Mycobacterium TB (antimicrobial)
- Harmful: alcohol + benzodiazepine at GABAa (sedative- CNS depression)
- Harmful: Sildenafil and Isosorbide Mononitrate: markedly increases hypotensive effect of Isosorbide Mononitrate
Pharmacodynamic examples of antagonism effects
- Harmful: salbutamol + atenolol at ß-adrenoceptors (bronchodilation and bronchoconstriction- reduced effect of salbutamol)
- Beneficial: naloxone + morphine at opioid receptor (reverses sedative effects of morphine and may precipitate opiate withdrawal)
