MRCPsych Flashcards
Name some markers for Clozapine associated myocarditis?
Troponin T and I are the most specific
Other markers to check include LDH, AST, CK and Myoglobin
Which dementia drugs are broken down by hepatic enzymes?
Donepezil (minor) and Galantamine - both mainly by CYP2D6 and CYP3A4
Name some symptoms of discontinuation syndrome?
Anxiety
Vivid dreams
Crying spells
Dizziness
Flu-like symptoms
Electric shock sensations
Irritability
Crying sensations
Which anti-depressants are most likely to cause discontinuation symptoms?
Paroxetine
Venlafaxine
Amitriptyline
Imipramine
Name some factors that would lead to a higher rate of discontinuation symptoms?
Taking for 8 weeks or longer
Higher doses
Receiving other central acting drugs - antihistamines, antipsychotics, anti-hypertensives
Young people
Anxiety symptoms on anti-D initiation
What medications should be avoided when prescribing MAOIs
SSRI
SNRI
TCAs particularly Imipramine and Clomipramine due to risk of serotonin syndrome
Triptan migraine products
St John’s Wart
Cold products - dextromethorphan and chlorpheniramine
Opiods
Which dietary products lead to the cheese reaction?
Dairy:
- All mature/aged cheese
Meat/fish/poultry:
- Fermented meat - salami
- Improperly stored meat
Fruit/veg:
- Fava or broad bean pods
- Banna peel
Drinks:
- Tap beer
Misc:
- Marmite
- Saurkraut
- Soy sauce
- Tyramine containing nutritional supplements
Outline the Gell and Coombs system that classifies immune mediated drug reactions
Type I - IgE mediated - these occurs minutes to hours after drug. Drug IgE complex get detected by mast cells and release histamine - classic urticaria, anaphylaxis, rash, angioedema
Type II - IgG and IgM mediated these occur longer after - neutropenia, thrombocytopenia
Type III - complement mediated reaction, symptoms include rash, fever, vasculitis occur 1-3 weeks after
Type IV - MHC system presents drug complexes to T cells occurs 2-7 days after drug and includes symptoms of dermatitis and rash
Which ADHD drugs are metabolised by CYP450
Atomoxetine - CYP2D6
Guanfanacine - CYP3A4/5
How does sodium valproate work as a mood stabiliser?
GABA agonism and NMDA antagonism
Why does a proportional increase body fat in the elderly matter regarding pharmacokinetics?
Lipid-soluble drugs will be distributed more readily - therefore lipid-soluble drugs half lives decrease
Which anti-depressants have the highest risk on sexual desire, sexual arousal and orgasm?
SSRIs, MAOI, TCAs & Venlafaxine: ++ in all domains
Duloxetine ++ on sexual desire, + on sexual arousal and ++ on orgam
Mirtazapine, Bupropion, Vortioxetine, Moclobemide, Reboxetine and Nefazadone lower effecting
What are the half-lives of the following drugs
Diazepam
Lorazepam
Chlordiazepoxide
Nitrazepam
Temazepam
Zopiclone
Zolpidem
Diazepam 20-100 hrs (36-200 hrs for active metabolite)
Lorazepam 10-20hrs
Chlordiazepoxide 5-30 hrs (36-200 hrs for active metabolite)
Nitrazepam 15-38 hrs
Temazepam 8-22 hrs
Zopiclone 4-6 hrs
Zolpidem 2-6 hrs
What is pethidine?
An opioid - has been associated to the onset of delirium
Name some GABA agonists
BDZ
Z-drugs
Valproate
Topiramate
Which enzyme is encoded for by CYP2D6
Debrisoquine hydroxylase.
Name the active metabolite of Fluoxetine
Norfluoxetine - has a very long half life of up to 14 days
What is the most selective SSRI?
Citalopram and Escitalopram
- Fluoxetine is a weak noradrenaline reuptake inhibitor
- Setraline weakly inhibits noradrenaline and dopamine
- At high doses Paroxetine has anticholinergic effects
Name some interactions with Fluvoxamine?
Reduces the clearance of diazepam - do not generally co-administer both
Inhibits CYP1A2 - can increase level of theophylline therefore 1/3 of the original dose & can increase levels of warfarin
Which SSRIs have non-linear kinetics
Fluoxetine, Fluvoxamine and Paroxetine
What SSRI has the longest half-life?
Fluoxetine 1.9 days
Shortest half life is Paroxetine (10hr), Fluvoxamine and then Sertraline (26hr)
How does Buspirone work?
5HT-1A agonism - inhibits release of serotonin presynaptically reducing anxiety
Post-synaptic agonism leads to anti-D properties
What is the half-life of Mirtazapine?
20-40hrs
Paroxetine/Fluoxetine can increase levels but no clinical consequences
Carbamezepine can reduce levels
Mirtazapine does not inhibited CYP enzymes.
It undergoes extensive 1st pass metabolism producing a bioavailability of 50%
Why is it important to maintain a steady sodium intake with lithium?
Sodium is excreted in the proximal tubules and as a compensatory mechanism Lithium is reabsorbed. Increasing sodium intake can lead to toxicity.
What is the half life of Lithium
Initially 18hrs then increases to 36hrs
- Lithium takes 4-5 days to reach a steady state
What agents may increase Lithium levels?
ACEi, loop diuretics, thiazide diuretics, Fluoxetine and NSAIDs
Name some agents that may decrease Lithium levels?
Osmotic diuretics
Caffeine
Carbonic anhydrase inhibitors
Aminophylline and Theophylline
Divide benzodiazepines into long, intermediate/short and very short acting:
Long acting
- Diazepam: 30-hr half life, metabolite desmethyldiazepam
- Clonazepam
- Chlordiazepoxide
Intermediate or short acting (less daytime impairment, rebound insomnia and anterograde amnesia)
- Lorzepam - 15 hrs half life
- Oxazepam
- Temezepam - 10hrs
- Alprazolam
Very short acting:
- Triazolam
How do the Z drugs differ with regards to effect on sleep onset or maintenance?
Zopiclone - for maintenance. Onset within 45 minutes, half life of 4-5hrs. Acts up to 8hrs
Zolpidem - for sleep onset problems. Onset within 30 mins, half life of 1-4hrs. Acts up to 6hrs
Zaleplon - for sleep onset problems. Onset within 30 mins, half life 1-2hrs, acts up to 4hrs
How does Agomelatine work?
5HT2C antagonism - DA and NAA release in frontal cortex
M1 and M2 melatnonin receptor agonism
Name two anti-D licensed for PTSD
Sertraline and Paroxetine
How long does Olanzapine take to reach a steady state?
7 days
Moclobemide has a minimum effective dose of what for depression?
300mg a day
What are biogenic amines?
Compounds derived from amino acids they include
HANDS
Histamine
Adrenaline
Noradrenaline
Dopamine
Serotonin
What are biogenic amines?
Compounds derived from amino acids they include
HANDS
Histamine
Adrenaline
Noradrenaline
Dopamine
Serotonin
What is zopiclone contraindicated in?
Unstable myasthenia gravis
Sleep apnoea
Respiratory failure
Neuromuscular respiratory weakness
Which antipsychotics are least likely to result in EEG changes?
Quetiapine
- Clozapine most likely to cause EEG changes
5% of patients per year taking a typical antipsychotic develop…
Tardive Dyskinesia
- More commonly seen in elderly patients, those with an affective illness, those with EPSE’s earlier on
- Switch to atypical (Clozapine/Quetiapine) if develop
- Takes months to years to develop
- Can also prescribe Tetrabenazine, Ginkgo biloba
5% of patients per year taking a typical antipsychotic develop…
Tardive Dyskinesia
- More commonly seen in elderly patients, those with an affective illness, those with EPSE’s earlier on
- Switch to atypical (Clozapine/Quetiapine) if develop
- Takes months to years to develop
- Can also prescribe Tetrabenazine, Ginkgo biloba
Outline the treatments for
a) Dystonia
b) Akasthesia
c) Parkinsonism
d) Tardive dyskinesia
a) Botulism toxim, anticholinergic drugs (trihexyphenidyl, procyclidine,, orphenadrine, benztropine. Note diphenhydramine (an antihistamine is also used due to its anticholinergic properties)
b) Beta-blockers, BDZs, Cryprohepadine, Clonidine, Mirtazapine or Mianserin (low dose)
c) Tetrabenazine, Ginko Biloba
Note for all reducing the dose and alternative atypical options should be considered
How does Disulfiram put individuals off alcohol?
Bind irreversibly to aldehyde dehydrogenase - this leads to a build up of acetaldehyde that causes facial flushing, N&V, hypertension, respiratory distress.
These effects start within 15-30 minutes of starting and can last several hours
Name the secondary amines?
Nortryptiline
Desipramine
Protriptyline
Amoxapine
What does the Amdisen scale assess for?
Lithium toxicty:
- 0 = no clinical signs
- 1 = mild, nausea + vomiting, coarse tremor, hyperreflexia, agitation
- 2 = moderate. stupor, rigidity, hypertonia and hypotension
- 3 = severe toxicity (myoclonus, coma)
Name some notable contraindications for Carbamazepine?
Bone marrow suppression
MAOIs
What are the indications of Carbamazepine?
Neuropathic pain
Partial focal epilepsy
Maintenance bipolar disorder
Name some very common side effects with Carbamazepine?
Leucopenia
Ataxia, Dizziness, Somnolence
Nausea and vomiting
Urticaria
Fatigue
Name some very common side effects with Carbamazepine?
Leucopenia
Ataxia, Dizziness, Somnolence
Nausea and vomiting
Urticaria
Fatigue
Does Diazepam or Clonazepam have longer half lives?
Diazepam (20-100hrs) > Clonazepam (18-50hrs)
How does Flumazenil work?
GABA-A receptor antagonism to stop BDZ binding to receptor and reverses effects of substances bound
Given IV
Short half life of 60 mins
Reverses other agents like Zopiclone
How is a diagnosis of SIADH confirmed?
Low serum osmolality < 275 mOsm/kg
Increased urine osmolality > 100 mOsm/kg
Euvolaemic
Raised urinary sodium > 20ml/L
No other caused of hyponatraemia
Name some psychotropic drugs that can cause SIADH
Carbamazepine, oxcarbazepine, chlorpropamide, cyclophosphamide, and selective serotonin reuptake inhibitors (SSRI).
How is SIADH treated?
Fluid restriction or demeclocycline
Which antipsychotics have a low propensity for elevating prolactin?
Aripiprazole
Quetiapine
Clozapine
Asenapine
Low - moderate risk:
- Olanzapine
- Lurasidone
- Ziprasidone
High risk:
- All typicals
- Palpileridone/Rispeidone
- Amisulpride/Sulpride
Name the side effects of Topiramate
Weight loss, nephrolithiasis and metabollic acidosis - it does this as it inhibits carbonic anhydrase - calcium phosphate stones can develop
Used epilepsy and as a mood stabiliser in BPAD - inhibits voltage gated sodium channels suppressing action potentials, it also increases GABA
Name the minimum effective doses of Agomelatine, Trazadone, Duloxetine, Fluvoxamine, Moclobemide
Agomelatine - 25mg/day
Fluvoxamine - 50mg/day
Trazadone - 150mg/day
Moclobemide - 300mg/day
Duloxetine - 60mg/day
What medications can be added to Olanzapine or Clozapine to reduce weight gain
Aripiprazole
- Orlistat
- Liraglutide
- Metformin
Name some non-psychiatric drugs that can increase QTc?
Antimalarials - chloroquinine and quinine
Antibiotics - Erythromycin and Ampicilin
Anti-arrhythmics - sotalol and amiodarone
Methadone
Tamoxifen
Amantadine
What percentage of D2 receptors need to be blocked for a therapeutic effect and for ESPE’s to occur?
65-80% is the therapeutic window
> 80% EPSE’s likely
Which anti-D is least likely to associate with withdrawal syndrome?
Agomelatine
Outline the triad of symptom clusters for serotonin syndrome?
Confusion/altered mental state, neuromuscular abnormalities and autonomic dysfunction
Neuromuscular abnormalities are more prominent in the lower limbs and include:
- Clonus - nearly always present - contraction on stretching of the muscle
- Hyperreflexia
- Rigidity
- Tremor
A temperature indicates immediate action
What tool is helpful in diagnosis of serotonin syndrome?
Hunter’s tool
What pharmacological changes may induce serotonin syndrome?
Over dose of a serotonergic drug - 16% of SSRI overdoses may lead to serotonin syndrome
Increasing the dose of a serotonergic drug
Combination of two serotonergic drugs
Administration of drugs that inhibit the P450 enzyme system
- typically symptoms begin within 24hrs however subacute presentations ma occur
How do you treat serotonin syndrome?
Remove serotonergic agent
BDZ and fluids if mild case
May administer 5HT2A antagonist - cyproheptadine
How may one differentiate between NMS and Serotonin syndrome?
NMS - develops slower and remits slower 9-14 days of appropriate treatment. Often associated with bradykinesia and leadpiping rigidity (uniform) and hyporeflexia. Pupils will be normal
SS - faster onset and rapid improvement with treatment. Pupillary dilatation. Hyperactive bowel sounds. Hyperreflexia
Which antipsychotic has the longest half life (75hrs)?
Aripiprazole
Name some features of hydrophilic drugs?
Poorly absorbed
Rapidly excreted
Little 1st pass metabolism
Little protein binding
Experience tubular reabsorption
Name the features of NMS
- Mental state changes
- Muscular rigidity (also hyporeflexia)
- Autonomic instability - especially tachycardia
Fever
Diaphoresis
Rigidity
Confusion
Flutuating consciousness
Fluctuating blood pressure
Tachycardia
Elevated CK
Leukocytosis
Altered LFTs
What is the treatment of NMS
- Stop antipsychotic + BDZ in psychiatric unit
- Bromocriptine + Dantrolene in medical unit
- When re-starting choose low dose monitoring temp, BP and HR
- Choose structurally different or that with low D2 affinity (Quetiapine/Clozapine)
- Avoid depot
- Avoid FGA
Is anti-depressant induced hyponatraemia dose related?
No
- Often begins within 30 days of initiation
What diuretics are safer with a patient on Lithium?
Loop diuretics and K+ sparing diuretics
Name the teratogenic effects of Carbamazepine?
Fingernail hypoplasia and craniofacial defects
Name some anti-D that undergo little metabolism via the Liver and therefore would be suitable if hepatic impairment is present?
Citalopram
Sertraline
Paroxetine
Vortioxetine
Avoid TCAs and MAOI
What heart rate is optimum for Bazzett’s formula?
60-100 BPM
At < 60 bpm it under-corrects
At > 100 bpm it over corrects
Name some of the side effects of alpha 1 blockade?
Orthostatic hypotension
Sexual dysfunction
Sedation
Priapism
What are the side effects of Varencicline?
Nasopharyngitis
Headaches
Nausea
Abnormal dreams
Name some medications associated with priapism?
Tazadone
Chlorpromazine
Thioridazine
What are the risk factors for prolonged QT interval?
Cardiac:
- Bru
What are the risk factors for prolonged QT interval?
Cardiac:
- Bradycardia
- Long QT syndrome
- IHD
- Myopathy
- LVH
Electrolyte:
- Hypomagnesia
- Hypokalaemia
- Hypocalcaemia
Other:
- Female
- Anorexia Nervosa
- Stress/Shock
- Extremities of age
Which antipsychotics are/are not associated with postural hypotension
Are associated with postural hypotension:
- Risperidone
- Olanzapine
- Quetiapine
- Clozapine
- Ziprasidone
Are not:
- Aripiprazole
- Amisulpride
- Sulpride
- Haloperidol
- Trifluperozine
Severe liver damage and Pancreatitis are the severe/rare complications of which AED?
Sodium Valproate
Name some drugs that should not be included in dosette boxes due to poor drug stability?
Sodium valproate
Zopiclone
Venlafaxine
Topiramate
Methylphenidate
Mirtazapine
Olanzapine
Amisulpride
Aripiprazole
What anti-depressant is licenced for Bullimia?
Fluoxetine
What are the contraindications for first generation anti-histamines?
Acute angle closure glaucoma
Pyloric stenosis
BPH
1st generation anti-histamines include:
Diphenhydramine
Promethazine
Hydroxyzine
Chlorpheniramine
Cyproheptadine
Cyclizine
Ketotifen
Acamprosate is a positive allosteric modulator of what?
GABA-A
Acamprosate is also an NMDA antagonist
Which is the least cardiotoxic TCA?
Lofepramine
Is teratogenicity in valproate dose dependent?
Yes
Valproate is a GABA agonist and NMDA antagonist
Vitamin involved in Carbohydrate catabolism?
Thiamine
Is Duloxetine allowed in hepatic impairment?
No
Which SSRI has been linked to ESPE?
Fluoxetine
Which SSRI has been linked to ESPE?
Fluoxetine
Is Reboxetine associated with sexual dysfunction?
No
Do depot or oral antipsychotics carry a higher risk for NMS?
The risk is the same!
