MH- Pharmacology Flashcards
Main side effects of TYPICAL antipsychotics
EPSE - dystonia (acute or tardive), akathisia (acute or tardive), tardive dyskinesia, parkinsonism (acute)
Anticholinergic effects - confusion, dry mouth, constipation, urinary retention, blurred vision
Hyperprolactinaemia - galactorrhoea, amenorrhoea, decreased libido, impotence, osteoporosis (W)
Weight gain but less metabolic syndrome than atypicals
Sedation
Main side effects of ATYPICAL antipsychotics
Metabolic syndrome/CV risk - weight gain, dyslipidaemia, hyperglycaemia, insulin resistance
Alpha-blockade - dizziness, postural hypotension, impotence
Sedation
Less EPSE than typical antipsychotics but can at high enough doses
QTc prolongation
Generally less anticholinergic side effects than typicals
What are some clinical considerations when choosing antipsychotics in older adults?
- Typicals cannot be used in PD or DLB due to increased risk of EPSE
- Atypicals can increase stroke risk in dementia patients
How can neuroleptic malignant syndrome & serotonin syndrome be distinguished?
NMS - SS
Antipsychotic - antidepressants
Muscle rigidity - tremor, myoclonic movements, seizure
Fever, pallor - sweating, flushing
No GIT symptoms - N+V, abdo pain, diarrhoea
What is neuroleptic malignant syndrome & how is it Rx?
Occurs when starting new or sudden increase in dose of antipsychotic -
Can lead to rhabdomyolysis & AKI
Change in mental state - agitation, confusion
Global, severe muscle rigidity
Autonomic dysfunction - labile BP, tachycardia, fever
Pallor
Raised CK & WCC
Rx - stop medication, supportive care (esp. rehydration), often ICU support, can use dopamine agonists & muscle relaxant
What is serotonin syndrome & how is it Rx?
Overstimulation of serotonin pathways - usually by accidental combination of 2+ antidepressants
Change in mental state - agitation, delirium, confusion, disorientation
Sweating, flushing, labile BP
N+V, diarrhoea, abdominal pain
Rx - stop medications, supportive care, sedation with benzo +/- antidote (anticholinergic with serotonin receptor antagonist properties)
What are the 4 EPSE, clinical features & Rx?
- Dystonia (Acute or Tardive) - muscle spasms, abnormal posturing & torsion (i.e. neck movements & tongue protrusion) - particularly eyes and larynx. Benzotropine (anticholinergic)
- Tardive dyskinesia - constant, purposeless movements usually of facial muscles i.e. lip smacking, grimacing. No good Rx, switch drugs, clozapine better for it
- Akathisia (acute or tardive) - restlessness where patient feels need to move but it does not help it (unlike in restless leg syndrome), crawling sensation. Propranolol or diazepam
- Parkinsonism - cogwheel rigidity, bradykinesia, resting tremor, abnormal gait. Benzotropine
What is the effect on positive, negative & cognitive features of psychosis with typical vs. atypical antipsychotics?
Typical - mainly only reduce positive symptoms of psychosis (delusions, hallucinations)
Atypical - reduce positive symptoms but may also affect negative and cognitive features
What are the characteristics (advantages/disadvantages) and any common uses/indications of HALOPERIDOL?
Least sedating antipsychotic - commonly used for delirium
Worst for EPSE - avoid in PD, DLB
Antiemetic effect - commonly used in pal care nausea
What are the characteristics (advantages/disadvantages) and any common uses/indications of OLANZAPINE?
Very efficacious but worst for weight gain and risk of metabolic syndrome
Rapid onset and very sedating - commonly used in ED setting/acute behaviour disturbance
Mood stabilising characteristics
What are the characteristics (advantages/disadvantages) and any common uses/indications of QUETIAPINE?
Most sedating
Most associated with QTc prolongation
Less weight gain
What are the characteristics (advantages/disadvantages) and any common uses/indications of RISPERIDONE?
Less associated weight gain
Not sedating
Most associated with hyperprolactinaemia - monitor prolactin levels
Good choice if view to change from oral to depot injection
Used in BPSD - most effective/evidence, on PBS
What considerations need to be made with antipsychotics and dementia?
Increase risk of stroke in dementia patients - esp. if they have other stroke risk factors
Only use if they have intractable aggression/psychosis that is not manageable with environmental/psychosocial methods
Only use if low-moderate risk of stroke
What are the side effects/toxicity of CLOZAPINE?
Decreases seizure threshold - increased risk of seizure
Agranulocytosis - increased risk of infection, esp. encapsulated bacteria, often present with sore throat
Non-specific resp symptoms - difficulty breathing, cough
Cardiac - tachycardia, myocarditis (usually first 4 weeks), can lead to cardiomyopathy, metabolic syndrome
Anticholinergic, metabolic syndrome, sedation, postural hypotention +++
What should be monitored when starting CLOZAPINE?
- Agranulocytosis - FBE (neutrophil count early, eosinophils later), weekly initially, then monthly
- Myocarditis - baseline ECG and/or ECHO, ongoing monitoring of CRP, troponins, vitals
- Metabolic syndrome - BMI, waist circumference, lipids, BGL/HbA1c
How does smoking affect CLOZAPINE?
Smoking increases hepatic clearance of clozapine, therefore run on lower serum levels
If suddenly stop smoking levels can rapidly increase, leading to toxicity
Which antipsychotics have been shown to have some benefit on negative symptoms of schizophrenia?
Clozapine and olanzapine
Describe the onset of effect of ANTIPSYCHOTICS
More immediate affect on calming/reducing agitation, however there is a delay in effect on disease/symptoms (disorder response) of ~2-4 weeks
Describe the onset of effect of DEPRESSANTS
Delayed onset of disorder response - takes ~4-8 weeks
How long should antidepressants be used in Rx of depression?
If first episode - continue for 6-12 months after stabilised/recovered
If 2 - 3+ episodes within 5 years should have 3-5 year maintenance therapy
If severe, psychotic features may require longer maintenance course
How long should antipsychotics be used in Rx of schizophrenia?
First episode psychosis can begin to withdraw after 12 months if good effect
Relapse is common however, so need to monitor for early signs and reintroduce medication
If negative signs often require ongoing Rx
What antidepressants are used 1st line and 2nd line in depression Rx?
1st = SSRI, SNRI, Mirtazipine
2nd = TCA, MAOI
What are examples of, mechanism of action, S/E and uses of SSRIs?
- Sertraline, escitalopram, citalopram, fluoxetine, paroxetine
- Inhibits pre-synaptic reuptake of serotonin
- GIT upset and sexual dysfunction (common/prominent), weight gain (less so than others), dizziness, headache, sweating, insomnia, hyponatraemia
- Used first line for depression and can be beneficial in anxiety disorder Rx. Generally well tolerated
What are common side effects generally of antidepressants?
Weight gain Insomnia GIT upset Anticholinergic effects Alpha-blockade effects Sexual dysfunction
What are examples of, mechanism of action, S/E and uses of SNRIs?
- Venlafaxine, duloxitine
- Inhibits serotonin and NA reuptake
- Same as SSRIs + constipation, HTN, hypercholesterolaemia
- Can be used 1st line in depression, Venlafaxine 1st line in treatment resistant, particularly useful in melancholic or severe depression
What is the mechanism of action, S/E and uses of Mirtazipine?
- Inhibits H1 receptors and presynaptic alpha2 and 5HT2 & 3 receptors
- Weight gain, increased appetite and sedation prominent. Also oedema and postural hypotension common
Less sexual and GIT S/Es than SSRIs and SNRIs - Commonly used to exploit side-effects - depression with weight loss and insomnia
What are examples of, mechanism of action, S/E and uses of TCA?
- Amitriptyline, imipramine
- Blocks muscarinic, alpha and histamine receptors and some also block reuptake of NA and serotonin
- Usual (wt gain, insomnia, GIT upset, sexual dysfunction) + tachycardia, postural hypotension, anticholinergic side-effects and confusion/increased risk of delirium
- Efficacious but less well tolerated and toxic in overdose so used 2nd line
What are examples of, mechanism of action, S/E and uses of MAOIs?
- Phenelzine
- Inhibits mitochondrial enzymes MAO-B and -A which metabolise NA, serotonin and dopamine
- Generally well tolerated and less side effects but risk of hypertensive crisis (requires dietary restriction and monitoring) so less commonly used
- Treatment resistant, melancholic and atypical depression
