Adverse Drug Reactions Flashcards
What is the key difference between ADRs and Side Effects?
difficult to distinguish
SEs may be good or bad
ADRs are bad
What is a key safety concept for prescribing?
benefits must outweigh drawbacks
What is the beneficial SE of old anti-histamines (give eg.)?
sedation, OTC sleep medication
promethazine
What is the adverse effect of old anti-histamines (give eg.)?
sedation for allergy
promethazine
What must you do when prescribing to patients?
indicate 2-3 common or key SEs
What is the most important ADR?
NSAIDs: GI bleeding, renal impairment, wheezing
What is the second most important ADR?
Diuretics: hypotension (incl. postural: falls - encourage not too give up too rapidly), electrolyte imbalances (thiazide-like: hypokalaemia)
What is the third most important ADR?
Warfarin (bleeding + drug interactions)
What are the last 4-10 ADRs?
ACEIs/ATRAs (renal disfunction, measure eGFR during)
Antidepressants + lithium -in bipolar, narrow TW
Beta-blockers (avoid in asthma as risk of bronchospasm)
Opioids
Digoxin
Prednisolone
Clopidogrel (GI bleeding)
What are type A ADRs?
Augmented response
dose-related
predictable
usually managed by dose adjustment
How can u predict a dry mouth?
inhibition of saliva such as in anti-muscarinic drugs, blurred vision, constipation due to slower GI, urinary retention
How can you predict oesophageal erosion?
bisphosnates
osteeoporisis
corrosive
What is the most ADR of NSAIDs?
ulcerogenic effects
what else alongside NSAIDs can be associated with peptic damage/ulceration?
corticosteroids, esp. when co-prescribed with NSAIDs
low-dose aspirin also carries 3-fold risk
What anti-platelet drug may also cause GI bleeding?
clopidogrel
What NSAID has the lowest incidence of GI SEs?
ibuprofen
How do NSAIDs work?
inhibit production of prostaglandins (which contribute to inflammatory response, fever and pain)
prostaglandins are synthesized from arachnoid acid by COX action
COX1: always expressed in most cells, COX2 induced in inflammed tissues
different isoforms have diff fucntions in diff tissues
levels normally low but go up drastically in acute inflammation
What is the difference between selective and non-selective NSAIDs?
non-selective, inhibit both COX-1 and COX-2
COX-2 selective
what do all non-selective NSAIDs, except aspirin act as?
reversible COX inhibitors, compete with AA for binding to the enzyme
aspirin covalently modifies and permanently destroys COX enzymes
Where is the irreversible action of aspirin most notable?
blood platelets
cannot synthesize new COX enzymes as have no nucleus
enzyme inactivated = no production of Thromboxane A2 and hence no platelet aggregation for lifespan of platetels
aspirin is therefoe a potent anti-thrombotic agent
Can aspirin be taken with other non-selective NSAIDs?
no or at least 2 hours after aspirin as will compete with aspirin for common binding site on platelets COX-1
What are the contraindications of aspirin?
being anti-thrombotic, aspirin prolongs bleeding and is contra-indicated in patients with bleeding risks or hemorrhagic disorders
Why do NSAIDs cause GI irritation
COX-1-dependent prostaglandins suppress gastric acid secretion and help maintain gastric mucosal barrier, providing protection to the stomach lining because non-selective NSAIDs inhibit COX-1, they may cause gastric irritation, peptic ulcer disease and GI bleeding
How can GI damage be reduced?
- paracetamol for analgesia
- identify patients at risk eg. 65+, ulcer history, H.Pylori infection
- prophylaxis with PPI
- give in combo with misoprostol
How does misoprostol minimise GI damage?
It is a stable PGE1 analogue, acts on prostanoid receptors to inhibit gastric H+ secretion
What are Antibiotics associated with?
- diarrhoea
- bacteria levels in the gut can unbalance causing diarrhoea
- mild is fine but if severe and bloody: urgent
What is the key side effect of PPIs?
very safe and used to manage peptic ulcer disease
prevent acid secretion -> stomach no longer has an acidic pH -> acid no longer sterilises the food -> incr. risk of food poisoning whilst on PPIs
what do antimuscarinic drugs tend to do to the patient?
- constipation
- opioids, codeine, morphine
- reduce contractility of the lower GI tract
- ## consider the need for laxatives when prescribing opioids
Why is the liver important in ADRs?
- many drugs metabolised there
- many drugs can cause significant liver damage
- LFT monitoring during treatment
- eg. statins, anti epileptic drugs
What are signs of liver damage?
derangements of liver enzymes
signs of jaundice
signs of hyperbilirubinemia
What is the key adverse effect of beta-blockers?
-bronchospasm
- as they take out beta2 mediated bronchodilation
- b1 blockers can still affect b2adrenoreceptors
- contraindicated in asthma as block bronchial b2 adrenoreceptors and may cuase
- can worsen COPD, use with caution monitoring resp
When are beta-blockers contraindicated?
- asthma
- as they block bronchial b2 adrenoreceptors and may cause bronchospasm
- caution in COPD
- also applies to ‘selective’ b1-antagonists - poor selectivity
Give an example of a drug which may induce fibrosis?
- amiodarone
- antiarrhythmic
- be cautious for cough or change in resp function
- chest XRay if suspecting damage
What is the medical emergency ADR?
- anaphylaxis
- severe allergic response
how is anaphylaxis managed?
- with adrenaline and histamine one receptor antagonists and steroids
What is the penicillin hypersensitivity response?
- penicillins couple to proteins
- forming immunogens or haptan
- hypersensitivity reaction
What drugs have cross-recativity with pencillin
- cephalosporins
- similar structure
What should you always check on a patients drug chart?
aleergy secrion
always confirm if there is NKA
What can some drugs do to the heart electrically?
- cardiac arrythmias
- QT prolongation
- older antipsychotics
What is another cardiac ADR?
- cardiotoxicity
- some cytotoxic anti-cancer drugs
What drugs can cause congestive HF?
- worse by fluid retaining drugs (NSAIDs, corticosteroids)
- rate limiting CCIs contraindicated in HF
- High dose beta-blockers
- Glitazones
How are NSAIDs linked to CVD?
- some incr. CV events
- eg. diclofenac, rofecoxib
- may cause fluid retention
- may exercerbate hypertension and chronic HF
- low dose aspirin not as bad
What drugs can cause postural hypotension?
- some antihypertensives
- diuretics
- difficult to maintain blood pressure when changing posture
- falls partic. in elderly
What drugs can cause hypertension?
- antidepressant venlafaxine/venofacine
- shouldn’t be used in patients with hypertension
- measure BP
- NSAIDs could also worsen hypertension due to fluid retention
What is a site of very severe ADRs?
bone marrow
What is neutropenia?
- drug kills off production of white cells
- incr. infections
- eg. atypical antipsychotic closopene, end line, WBC monitoring
What is thrombocytopenia?
- kills off production of platelets
- incr. bleeding and bruising
What is myelosuppression?
- overall suppression of BM
- consequence of most cytotoxic anticancer chemotherapies
- carried out in cycles to let BM recover
What is aplastic anaemia?
- failure of BM
How do certain drugs cause bleeding problems?
- affect coagulation system
anti-coagulants - can cause cerebral haemorrhage, haemorrhagic stroke
What is agranulocytosis?
- another term for neutropenia
- absence of neutrophils
- mouth ulcers, severe sore throat
- eg. clozapine, carbimazole, carbamazepine
What is the usual response when there is haematological affects?
stop drug
What drugs can cause renal damage?
- NSAIDs
- Aminoglycosides (gentamycin: cancer)
- ACEis/ATRAs (but protective of kidney in diabetes, prevent diabetic methopety)
if there is a significant drop in eGFR using ACEi or ATRA what should u do?
drop dose or stop drug
What drugs can cause fluid retention?
- NSAIDs
- steroids
What drugs can cause potassium issues?
hypokalaemia
-thiazide and loop diabetics
hyperkalaemia
- ACEi
how can NSAIDs lead to renal failure?
- inhibit renal PGs
- reduce renal blood flow
- reduce GFR
- esp. in CHF pts
may lead to acute renal failure
may also cause acute interstitial nephritis
What can drugs acting on the central nervous system cause?
- sedation (prescribe at night)
- parkinsonism (dopamine receptor antagonists, stop the drug, sometimes give antimuscarninic to manage those symptoms)
- depression
- addiction (opiods)
- nausea (use anti emetics)
How can skin be affected by drugs?
- most commonly affected
- urticaria (nettle rash)
- erythematous eruptions (reddening, may resemble measles or maculopapular)
- toxic epidermal necrolysis: rare but often fatal with blistering and skin peels off
- stevens-johnson syndrome: fever, rash, blisters
how are skin reactions managed?
- stop drugs
- relieve with anti-histamines and creams
What drugs can induce stevens-johnsons syndrome in pateints with a speicifc allele.
- carbamazepine and phenytoin
- screen patients from chinese + thai origin before use
What drugs can result in myopathy?
- statins
- myopathy may rarely progress to rhabdomyolysis, may result in renal damage
- often due to drug interactions
What should you look out for?
Changes in renal & liver functions
Blood counts (associated symptoms)
Rashes
Allergy/anaphylaxis
CNS effects
Visual disturbances
Muscle pain (e.g. statins + fibrates)
What are some alarm bells?
- NSAIDs in elderly (even low dose aspirin)
- NSAIDs with ulcers (consider protecting with PPI)
- beta-blockers in COPD/asthma
- corticosteroids
