Adverse effects Flashcards by Matthew Cohen

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

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Can Clozapine be re-initiated if there has been a red alert on FBC count

Generally no should avoid - only given if specialist supervision

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What are the CNS effects of SS caused by?

5HT2A agonism - therefore 5-HT2A antagonists are given i.e. cyproheptadine, chlorpramizine, methysergide, propanolol

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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

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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

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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

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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

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What medications may help akasthesia?

5-HT2A antagonist - Cyproheptadine or Mirtazapine

Low dose BDX

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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

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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

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What antipsychotic is favourable in Parkinson’s disease?

Quetiapine - fast dissociation from D2 receptor

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What antipsychotics are associated with most and least anticholinergic side effects?

Most:
- Clozapine
- Quetiapine
- Zuclopenthixol
- Flupenthixol

Least:
- Aripiprazole
- Ami/sulpride

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What medications are least affected by sexual dysfunction?

Clozapine
Quetiapine
Aripiprazole

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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

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How often if FBC measured in Clozapine

Weekly for first 18 weeks
Every two weeks 18-52 weeks
Every 4 weeks after then

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How many given clozapine die of agranular cytosis (from sepsis)

1 in 10,000

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How many people on Clozapine develop myocarditis/myopathy?

Between 1 in 10,000 to 20 in 10,000

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What percentage of patients given Lithium develop CKD?

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20%
- those that develop ESRD is 5.3/1000

Name some SE of semisodium valproate?

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Thrombocytopenia
Curly hair regrowth
Weight gain
Hyperammonia
Gastric irritation
Diarrhoea and nausea

If anaemia occurs - macrocytic

Name some SE of carbamazepine

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Hyponatraemia, oedema

Diplopia, ataxia, drowsiness, fatigue

Urticaria, dermatitis, skin rash

Leukopenia/blood disorders

Name some SE from Lamotrigine

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Rash, arthralgia, back pain

Diplopia, drowsiness, dizziness, aggression, insomnia, agitation, nystagmus, tremor

Dry mouth

Which mood stabilisers can cause LFT derangement?

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Carbamazepine and Sodium Valproate

Generally transient but rarely can present with acute hepatic failure

What skin rashes are associated with mood stabilisers?

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Drug rash with eosinophilia and systemic symptoms (DRESS)

Steven Johnson’s Syndrome (Lamotrigine per PsychMentor)

Toxic epidermal necrolysis

What factors may precipitate Lithium toxicity

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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

Adverse effects Flashcards

(44 cards)