Adverse effects Flashcards
What is the total rate of fatal agranular cytosis from Clozapine? (i.e. including countries without monitoring)
1 in 4,250
In monitoring groups is 1 in 8,000
Can Clozapine be re-initiated if there has been a red alert on FBC count
Generally no should avoid - only given if specialist supervision
What are the CNS effects of SS caused by?
5HT2A agonism - therefore 5-HT2A antagonists are given i.e. cyproheptadine, chlorpramizine, methysergide, propanolol
What was the CAITE trial?
Clinical antipsychotic treatment effectiveness - looked at patient or physician discontinuation within 18 months (included Olanzapine, Risperidone, Ziprasidone and Quetiapine)
75% discontinued
Median time to discontinuation was 4.6 months
64% stopped Olanzapine (lowest)
74% risperidone
79% ziprasidone
82% quetiapine
What is the risk of Ebstein’s anomaly in those taking Lithium during preganancy?
2-3 x more than the general population
Risk is dose dependent and highest if taking Lithium in the first trimester (weeks 2-6).
Risk of congential malformations in general population is 1.15% and 2.41% in lithium exposed cohort
Outline the difference between type A and type B adverse drug reactions?
Type A:
- Dose-related
- Generally stop on cessation of the drug
- Pharmacologically related to the action of the drug and can be predicted i.e. ESPEs due to dopamine antagonism
Type B:
- Idiosyncratic
- Often unpredictable - may only be identified after a drug goes on a market
- Not dose related - although higher doses may increase risk
- Not reversible
- Patient factors may helpful to predict risk
- e.g Stevens Johnson post lamotrigine or agranular cytosis post clozapine
What is the management of tardive dyskinesia?
Reduce dose - 50-55% are reversible
Stop anticholinergic
Px:
- Tetrabenazine
- Vitamin E
- BDZ
Exclude anti-NMDA encephalitis - particularly if an early development of TD
What medications may help akasthesia?
5-HT2A antagonist - Cyproheptadine or Mirtazapine
Low dose BDX
What are the most common EPSEs
Akasthesia 25-35% - hours to weeks
Parkinsonism - 20% - hours to days
Dystonia - 10% - minutes to hours
TD - 5% - years
What are the most common EPSEs
Akasthesia 25-35% - hours to weeks
Parkinsonism - 20% - hours to days
Dystonia - 10% - minutes to hours
TD - 5% - years
What antipsychotic is favourable in Parkinson’s disease?
Quetiapine - fast dissociation from D2 receptor
What antipsychotics are associated with most and least anticholinergic side effects?
Most:
- Clozapine
- Quetiapine
- Zuclopenthixol
- Flupenthixol
Least:
- Aripiprazole
- Ami/sulpride
What medications are least affected by sexual dysfunction?
Clozapine
Quetiapine
Aripiprazole
Name some risk factors for agranular cytosis and neutropenia?
0.8% develop agranular cytosis (low neuts, eosinophils, basophils). RF include:
- Asian ethnicity
- Female
- Old age
2.7% develop neutropenia. RF include:
- Black ethnicity
- Female
- Young age
How often if FBC measured in Clozapine
Weekly for first 18 weeks
Every two weeks 18-52 weeks
Every 4 weeks after then
How many given clozapine die of agranular cytosis (from sepsis)
1 in 10,000
How many people on Clozapine develop myocarditis/myopathy?
Between 1 in 10,000 to 20 in 10,000
What percentage of patients given Lithium develop CKD?
20%
- those that develop ESRD is 5.3/1000
Name some SE of semisodium valproate?
Thrombocytopenia
Curly hair regrowth
Weight gain
Hyperammonia
Gastric irritation
Diarrhoea and nausea
If anaemia occurs - macrocytic
Name some SE of carbamazepine
Hyponatraemia, oedema
Diplopia, ataxia, drowsiness, fatigue
Urticaria, dermatitis, skin rash
Leukopenia/blood disorders
Name some SE from Lamotrigine
Rash, arthralgia, back pain
Diplopia, drowsiness, dizziness, aggression, insomnia, agitation, nystagmus, tremor
Dry mouth
Which mood stabilisers can cause LFT derangement?
Carbamazepine and Sodium Valproate
Generally transient but rarely can present with acute hepatic failure
What skin rashes are associated with mood stabilisers?
Drug rash with eosinophilia and systemic symptoms (DRESS)
Steven Johnson’s Syndrome (Lamotrigine per PsychMentor)
Toxic epidermal necrolysis
What factors may precipitate Lithium toxicity
Dehydration - illness, diarrhoea, sweating
Low salt diets - 3/4 of Lithium is reabsorbed at proximal and distal tubules - if low salt more may get reabsorbed
Drug: loop diuretics, ACEi, NSAIDs - all reduce renal excretion
Outline how the following receptors link to anti-D associated effects:
a) 5-HT1a
b) 5-HT2
c) 5-HT3
d) 5-HT4
e) 5-HT6
f) 5-HT7
a) 5-HT1a - anti-D effect
b) 5-HT2 - sexual dysfunction/vivid dreams
c) 5-HT3 - nausea + increased intestinal motility
d) 5-HT4 chronotropic effects arrhythmias and increased intestinal motility
e) 5-HT6 memory
f) 5-HT7 insomnia
What is the effect of pre-synaptic alpha-2-adrenergic antagonism of Mirtazapine?
Increased serotonin release
Its antagonism of 5-HT2A, 5-HT2c and 5-HT3 make it less likely to cause serotonergic SE
How do BDZ work?
Positive allosteric modulators to GABA on GABA-A channels - make GABA the agonist more likely to bind
Long term Benzodiazepine and Alcohol use leads to downregulation of GABA-A receptor
Name some SE of methadone and buprenorphine
Pruritis, nausea, constipation, headache, resp depression
What are the contraindications of disulfiram?
Cardiac disease, psychosis, personality disorder
What is an iDAP
Interactive drug analysis profile - provides up to date information on the frequency and types of ADRs reported from drugs
How can someone report an ADR
Yellow card scheme through MHRA
OutlWhat is the maximum prescription length for controlled drugs?
NICE advise no more than 30 days
Can be up to 3 months if leaving the country
Outline drug schedules?
I - no medical purpose only research needs exceptional approval from home office i.e. cannabis and LSD
II - handled and stored for safe prescription. Includes cocaine, heroin, pethidine and amphetamines
III - some BDZ (temazepam, midazolam), buprenorphine and barbiturates
IV - pat I includes Z drugs and most BDZ, part II includes gonadotrophins and anabolic steroids.
V - need invoices for 2 years but nothing else
I - III require prescriptions as per controlled drugs advice
Note schedules refers to the benefit / harm provided from a drug and does not relate to the legal ramifications of possessing a drug (class of drug)
Name some drugs that undergo very little hepatic metabolism
Amisulpride, Sulpride
Gabapentin
Topiramate
Lithium
Which medications experience significant first pass effect (not just hepatically metabolised)
Imipramine
Buprenorphine
Morphine
Diazepam
Fluphenazine
Name the SSRI that has the highest concentration in the breast milk?
Fluoxetine
Reboxetine is a noradrenaline reuptake inhibitor due to its peripheral adrenergic effects (constipation, dry mouth, urinary retention) what drugs and examples can be prescribed to manage the side effects?
Alpha-1-antagonists i.e. tamsulosin or doxazosin
Paroxetine is contraindicated in which condition?
Closed angle glaucoma - due to its anticholinergic properties
Which groups are most likely to experience hypothyroidism?
Young females
Apart from topiramate which psychotropic drug may cause weight loss?
Buproprion
What is the incidence of NMS?
0.7 - 2.0%
Why may Linezolid not be prescribed with a certain anti-D?
Can cause serotonin syndrome with MAOI
What is the management of cheese reaction?
BP control:
Alpha-adrenergic antagonist IV - phenolamine or chlorpromazine
Furosemide
HR control:
Beta-blocker to control
Name some side effects associated with acetylcholinesteterase inhibitors
Nausea, vomiting, diarrhoea, muscle cramps, urinary incontinence
