ADRs and Interactions Flashcards
1
Q
Examples of side effects, beneficical and adverse:
A
- Beneficial:
- sedation with antihistamines when used an OTC sleep medicine (e.g. promethazine)
- Adverse:
- Sedation with antihistamines for allergy.
2
Q
Side-effect frequency descriptors
A
- >1 in 10 people = Very common
- 1:10 to 1:100 = Common
- 1:100 to 1:1,000 = Uncommon
- 1:1,000 to 1:10,000= Rare
- < 1 in 10,000 = Very rare
3
Q
ADR statistics
A
- 5% of hospital admissions are ADR-related
- 10-20% of hospital patients suffer ADR
- 0.1% of medical patient mortality
- Many patients receiving polypharmacy, increases chances of interactions/ADRs
4
Q
Most common ADRs on hospital admission
A
-
NSAIDs 29.6%
- GI bleeding, renal impairment, wheezing
-
Diuretics 27.3%
- Hypotension, electrolyte disturbances
- Warfarin: 10.5%
Ohers: ACEI/ATRAs, ADs and lithium, B-blockers, opioids, digoxin, prednisolone, clopidogrel
5
Q
Define type A ADR
A
- The normal pharmacological response is undesirable
- Dose-related
- Predictable
- Usually managed by dose adjustment
6
Q
Some adverse side effects of B-blockers
A
- Cold extremities
- Bradycardia
- Asthma interactions
7
Q
Some adverse side effects of NSAIDS
A
- Asthma interactions
- Gastric damage
8
Q
ADR with Cimetidine/sprionolactone
A
reduce testosterone synthesis or oestrogenic
9
Q
ADR in opioids/antimuscarinics
A
Constipation
10
Q
ADR associated with antibiotics
A
Diarrhoea
11
Q
ADR associated with digoxin
A
Nausea, vomiting, visual disturbances
12
Q
ADR associated with cytotoxics
A
Myelosurpression
13
Q
Pharmacokinetic mechanisms of ADRs
A
- Absorption
-
Elimination
- Renal+Hepatic
I.E can be adjusted by concentration (Type A)
14
Q
Digoxin in the renally impaired
A
Cuased reased plasma concentrations as 2/3rds of digoxin is renally cleared
- Nausea
- Visual distrubances
- Heart block
- Arrythmias
Adjust concentration (type A)
15
Q
ADRs as a consequence of metabolism
A
- Metabolism: reduced metabolism may lead to increased plasma conc.
- T1/2 diazepam increase by 1hr for each year of age
- Neonates conjugate at a slow rate. Microsomal enzyme activity decreases variably with age
- Genetic differences: 10% of population have defective isoenzyme of cytochrome P450
- Hepatic failure: LFTs poorly predict ability to metabolise.
16
Q
Define type B ADR
A
Bizarre or idiosyncratic
- Unrelated to pharmacology
- Unpredictable
- Rare
- Often Severe
- Often related to genetics or immunology
17
Q
Example of immunological ADRs
A
(Type B)
Penicillins:
- penicillins couple to proteins, forming immunogens
- hypersensitivity reaction
Cephalosporins?
- Recent evidence suggests that cross reactivity is less (0.5-6.5%) than originally thought, some may be used if no alternative is available (see BNF)
18
Q
Examples of of heamatological ADRs
A
Agranulocytosis: absence of neutrophils – mouth ulcers, severe sore throat; infections.
- Clozapine
- Carbimazole
- Carbamazepine
Thrombocytopenia: bruising/bleeding
19
Q
Ulcerogneic NSAID effect
A
(Also for oral steroids)
- Oral NSAIDs (commonly) and corticosteroids (less commonly but especially when co-prescribed with NSAIDs) associated with peptic damage/ulceration.
Very important ADR
- Annually 10,000 hospital admissions and 2,000 deaths.
- (MRSA kills 1,500 pa)
- Risk = 1 in 2,000 for long term users
Use Paracetamol for analgesia instead? Prophylax with PPI
20
Q
NSAIDs and Cardivascular disease interactions
A
- NSAIDs may cause fluid retention
- NSAIDs may exacerbate hypertension / CHF
- Low dose aspirin – ‘less of a problem’
- Increased CV risk with diclofenac
21
Q
NSAIDs and Renal Damage
A
- By inhibiting renal PGs
- Reduced renal blood flow
- Reduced GFR
- Especially in CHF pts
- May lead to acute renal failure (7% of all cases)
22
Q
Beta-blockers and asthma
A
These are contraindicated in asthma as they block bronchial b2 adrenoceptors and may cause bronchospasm
- Caution in COPD
This even applies to ‘selective’ b1-antagonists
- Poor selectivity
23
Q
Statins and myopathy
A
- Myopathy may rarely progress to rhabdomyolysis – may result in renal damage.
- Often due to drug interactions
24
Q
Cause of green blood
A
- This was an ADR to sumatriptan
- Sumatriptan rarely leads to sulphahaemoglobinaemia: a sulphur atom incorporated in the haem group
- Reversed on stopping to sumatriptan
25
NSAIDS in elderly, consider. Even low dose aspirin isnot without risk
26
Drug interactions with pharmacokinetic mechanisms
* Absorption: 2 drugs may interact to alter rate of uptake e.g. tretracycline + Fe2+ salts or Ca2+ (milk)
* pH: passive absorption of drugs best in uncharged form, governed by pKa value.
* Rises in pH (antacids, H2 antagonists, PPIs) may influence absorption of other drugs.
* Separate by several hours.
27
Inducers of metabolism for ADRs
* Rifampicin
* Phenytoin
* Ethanol
* Carbamazepine-autoinduction
* St John Wort
* Reduce plasma conc of range of drugs *E.g. barbiturates, carbamazepine, rifampicin increase metabolism of OCs*
* May take a week or 2 for effect
* Effect may persist on stopping inducer
28
Enzyme inhibitor Interactions
Cy P450 inhibition
* erythromycin / clarithromycin
* ciclosporin
* Psoralen (from grape fruit juice)
Rapid onset : 1-2 days
Often reverse quickly on stopping
29
Simvastatin drug interactions
Contraindicated with macorlides
Interaction with amlodipine, verapamil, diltiazem
For amlodipine plus statin:
* Pravastatin does not interact
* Use 20mg simvastatin as maximum dose.
30
Renal elimination drug interactions
* Competition for weak acid or base transports:
* Aspirin and Methotrexate compete for elimination and NSAIDs in general may reduce renal perfusion– severe interaction
* Counsel pts taking methotrexate NOT to take OTC ibuprofen or aspirin
* NSAIDs prescribed with care in RA
31
Drug interactions affecting Fluid and Electrolyte interactions
**Diuretics**: lead to volume depletion, when adding an ACEi increased risk of severe _first dose hypotension_
–Stop diuretic?
–Separate in time?
–Take ACEi on retiring to bed?
**Diuretics**: loops and thiazide cause hypokalaemia – so increase toxicity of digoxin
32
K-sparing diuretics Drug interactions
e.g. Sprinolactone, amiloride
* Increase K
* This may be a problem if the pt takes K supplements or ACEIs (which also increase K)
* Risk of hyperkalaemia
33
Salbutamol and B-blocker
34
Beta-blockers and rate-limiting Ca-Channel blockers
Beta blockers and verapamil: risk of bradycardia/asystole
* Potentially fatal
Beta-blockers and diltiazem may interact
* Avoid/extreme caution
Much less of a problem with dihydropyridines
35
Warfarin
Used to prevent thrombosis in:
* Atrial fibrillation
* Artificial heart valves
* PE
* DVT
**Several days to act**¨
* Narrow therapeutic window, Many interactions
* Enzyme inducers _lead tofailure of therapy_
* Enzyme inhibitors _lead to increased bleeding_
*Increased bleeding with aspirin*
36
Monitoring Warfarin
* INR (Prothrombin time)
37
Action of DOACS
eg **Rivaroxaban**
* Direct Oral Anticoagulants
* Factor X inhibitor
* Fewer interactions
* No requirement to monitor
38
St Johns Wort drug interactions
Enzyme indiucer
AVOID with
* OC
* Antiepileptics
* HIV drugs, some
* Ciclosporin
* Warfarin
* Simvastatin
Serotonergic syndrome: Avoid with MAOIs and SSRIs
39
Food drug interaction
* Cranberry juice thought to potentiate warfarin leading to fatalities
* Grapefuit juice interacts with simvastatin and some Ca-antagonists
40
Alcohol Interactions
Labels 2 & 4 (avoid if affected or avoid)
* Mostly CNS depressant / sedating actions enhanced
* E.g. TCAs, sedating antihistamines, benzodiazepines
* Few antibiotics actually interact
* Metronidazole leads to disulfiram-like effect
* Gastric effects
* Avoid aspirin containing products for hangover
