Intentional and Unintentional Presentations Flashcards
What are the most common drugs & ADRS causing hospital admission?
- NSAIDs - GI complications, cerebral haemorrhage, renal impairment, wheezing, rash
- Diuretics - renal impairment, hypotension, electrolyte disturbances, gout
- Warfarin - bleed
- ACE/AII inhibitors - renal impairment, hypotension, electrolyte disturbance (hyperkalaemia)
- beta blockers - bradycardia, heart block, hypotension, wheezing
- opiates - constipation, vomiting, confusing, urinary retention
- digoxin - toxicity
- prednisolone - GI complications, hyperglycaemia, osteoporotic fracture, worsening diabetes
- clopidogrel - GI bleeding
What is an ‘augmented’ ADR?
- dose-related and predictable
- avoidable
- example
- insulin causing hypoglycaemia
- warfarin causing bleeding
- nitrates causing headache
What is a ‘bizarre/idiosyncratic’ ADR?
- not dose-related
- not predictable
- examples
- penicillin: anapylaxis
- halothane: hepatitis
- chloramphenicol: agranulocytosis
- phenytoin: toxic epidermal necrolysis
What is a ‘chronic treatment effect’ ADR?
- variable
- occur with prolonged but short duration treatment
- Examples
- osteoporosis with steroids
- steroid induced Cushing’s syndrome
- phenothiazine-induced tardive dyskinesia
- fenfluramine-induced pulmonary hypertension
What is a ‘delayed effect’ ADR?
- variable
- occurs sometime after discontinuation of treatment
- example
- drug-induced foetal abnormalities
- drug-induced cancers (recipients or offspring)
What is an ‘end-of-treatment’ ADR?
- variable
- effects occur on withdrawal of a drug
- examples
- adrenocortical insufficiency after steroid treatment
- drug withdrawal seizures
- withdrawal reactions following paroxetine
What drugs cause gynaecomastia?
- Spironolactone
- Oestrogens
- Methyldopa
- Digoxin
What drugs cause galactorrhoea?
- Antipsychotics
- Tricyclics
- Metoclopramide
- Oestrogens
- Methyldopa
How do you avoid anaphylaxis in patients?
- 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
How do you avoid adverse drug reactions?
- 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
- Appropriate use of drug
- Common and/or important adverse effects (look up in BNF or Summary of Product Characteristics (SPC)
- Monitor therapy
- Particular care in susceptible patients
What are the objectives of pharmacovigilance?
- Identify previously unrecognised hazards
- Evaluate changes in risks and benefits
- Take action to promote safer use
- Provide optimal information to users
What is the yellow card scheme?
- Means by which suspicions that an ADR has occurred may be collated
- Voluntary - relies on co-operation of healthcare professionals.
- Patients can only report side-effects
- Purpose is early identification of previously unrecognised safety hazards
-
All drugs included - focus on:
- Serious ADRs
- Reactions in children
- New drugs (black triangle)
- Around 18,000 reports per year
- Data from the scheme made available publicity on Yellow Card website as drug analysis prints.
- There is an app available
What are the potential regulatory actions once ADRs have been reported?
- Withdraw drug if risks exceed benefits (rare)
- Make changes to promote safer use
- Remove indication
- Add contraindication
- Add warning or precaution (e.g. monitoring)
- Add drug interaction
- Add ADR
- Inform users
- Drug Safety Update
- Dear Dr/Pharmacist letter
What is meant by an ADR that has been caused by pharmacodynamic mechanism?
- Drugs act on the same target site of clinical effect (receptor or body system)
- Opiates and benzodiazepines causing respiratory depression
What is meant by an ADR that has been caused by a pharmacokinetic mechanism?
- Altered drug concentration at target site of clinical effect
- ADME
- OCP failure with antibiotics
What are the two types of pharmacodynamic interactions?
- synergism/summative - additive effects
- rifamicin + isoniazid at Mycobacterium TB (antimicrobial)
- this example is actually beneficial
- alcohol + benzodiazepines at GABAa causing sedation - harmful
- sildenafil and isosorbide mononitrate - increases hypotensive effects
- rifamicin + isoniazid at Mycobacterium TB (antimicrobial)
- antagonism - opposing effects
- salbutamol +atenolol on b-adrenoceptors (bronchodilation and bronchoconstriction)
- naloxone + morphine on opioid receptor (reverses sedative effects of morphine and may precipitate opiate withdrawal
What are the four types of pharmacokinetic drug interactions?
- Absorption
- Distribution
- Metabolism
- Excretion
What is the effect of absorption interactions?
- Rate
- Faster or slower
- Extent
- Less or more complete
- Mechanisms
- pH
- Gastric emptying and intestinal motility
- Physico-chemical interaction
Describe how pH can effect absorption of a drug:
Antacid –> less acidic stomach contents –> more drug ionisation –> slower absorption
Alcohol –> more acidic stomach contents –> less ionisation –> faster absorption
What are some examples of drugs that decrease rate of gastric emptying?
- Opiate analgesics (e.g. morphine, pethidine) – much slower
- Antimuscarinic drugs (e.g. atropine, propantheline) – slower
- Tricyclic anti-depressants – antimuscarinic side-effects (e.g. imipramine) – slower
What are some examples of drugs that increase gastric emptying?
- Metoclopramide
- Muscarinic agents (e.g. bethanechol)
What is the clinical significance of altered gastric emptying?
For a single dose
- Lower peak concentration
- Prolonged duration
However effect on rate and extent of absorption depends on whether drug absorbed in stomach or small bowel.
How does a physiochemical interaction affect pharmacokinetics?
- Direct chemical interaction reduced absorption
- Antacids form insoluble complexes with tetracyclines, quinolones, iron, bisphosphonates
- Will reduce reduction in antibiotic absorption by as much as 60-70% leading to treatment failure
- Cholestyramine binds non-selectively to acidic drugs e.g digoxin & warfarin
- Activated charcoal binds certain drugs
- Reduces absorption of toxins in the gut by up to 60%
- Adsorbs toxins to surface of charcoal
- Charcoal binds toxins in bowel
- Not absorbed by digestive system so toxins excreted in faeces
- Antacids form insoluble complexes with tetracyclines, quinolones, iron, bisphosphonates
How do distribution interactions cause ADRs?
- Displacement from plasma protein binding increase in free drug concentration
- Involves drugs with high protein-binding
- warfarin, tolbutamide, phenytoin, sulphonamides, statins, amiodarone, NSAIDs, heparin, furosemide
- Usually minor and transient due to compensatory increase in metabolism and excretion
- May become even more significant if 2nd mechanism
- valproate displaces phenytoin + inhibits its metabolism
