Psychopharmacology Flashcards
what is the MOA of SSRIs?
inhibit serotonin reuptake in presynaptic neurone, increasing post-synaptic serotonergic neurone activity
name examples of SSRIs and if they have any particular indications
- CITALOPRAM: 1st line in depression
- FLUOXETINE: 1st line in depression, preferred in younger pts, longets 1/2 life
- SERTRALINE: indicated in cardiac disease
- PAROXETINE: most potent, greater risk of discontinuation syndrome
name the common and/or severe side effects of SSRIs
Common:
- nausea, diarrhoea
- headache
- weight changes
- sexual disturbances
- restlessness
Severe:
- hyponatraemia/SIADH
- arrhythmias/prolonged QT (esp. citalopram/escitalopram)
- serotonin syndrome
- discontinuation syndrome (less with fluoxetine as longer 1/2 life)
- suicidal ideation
- CNS Sx: tremor, EPS
- increased risk bleeding
how long should antidepressants be continued?
6 months post-remission, should be discontinued gradually over 4 weeks
describe the symptoms of discontinuation syndrome. How could you prevent this?
- increased mood changes
- restlessness and insomnia
- GI symptoms: pain, cramping, vomiting, diarrhoea
- unsteadiness
- sweating
- paraesthesia
Decrease dose gradually over 4 weeks, can bridge with fluoxetine as long 1/2 life
can SSRIs be safely used in pregnancy?
Weight up costs and benefits
- can cause congenital cardiac defects in 1st trimester (esp. paroxetine)
- can cause persistent pulmonary HTN of the newborn in 3rd trimester
name an example of a NaSSA. What is its MOA? Main ADRs?
MIRTAZAPINE: presynaptic a2 adrenoR blocker… increases adrenergic and serotonergic neurotransmission.
- sedation
- increased appetite/weight gain
What is the main MOA of antipsychotics?
D2 R antagonists - main therapeutic effect via dopamine blockage in mesolimbic pathway (decrease +ve effects within days/weeks).
Atypicals have lesser dopamine antagonism activity less EPSE.
Name examples of atypical antipsychotics and any features specifically associated
- aripiprazole: often used 1st line as fewer side effects (partial D2 antagonist)
- risperidone
- quetiapine: more sedating
- amisulpiride
- olanzapine
- clozapine: greatest efficacy high risk of agranulocytosis (esp in first 4 mths), hypersalivation
Name examples of typical antipsychotics
- haloperidol
- chlorpromazine
- sulpiride
Compare the side effect profile of typical vs atypical antipsychotics
Typical
- EPSE prominent
- hyperprolactinaemia
Atypical
- metabolic Sx prominent - increased appetite, weight gain, hyperlipidaemia
Both
- neuroleptic malignant syndrome
- prolonged QT interval (can lead to arrhythmias eg torsade de pointes or VF)
Why can antipsychotics cause hyperprolactinaemia? What are the possible effects of this?
Dopamine usually inhibits prolactin release via D2 Rs in tubuloinfundibular pathway so dopamine antagonism results in increased dopamine release.
In males: gynaecomastia, galactorrhoea, hypogonadotropic hypogonaidsm (ED, decreased libido, infertility).
In females: galactorrhoea, hypogonadotropic hypogonadism (amenorrhoea, decreased libido, infertility).
What are EPSE? Describe examples.
Group of movement disorders caused by disruption of dopamine pathways in basal ganglia.
- Acute dystonia
- onset: hours to days
- painful and lasting muscle spasms predominantly of head, neck and tongue
- e.g. torticollis, facial grimacing, oculogyric crisis, tongue protrusion or twisting - Pseudoparkinsonism
- onset: week 1
- bradykinesia, coarse tremor, rigidity - Akathisia
- onset: week 1-8
- restlessness - Tardive dyskinesia
- onset: months to years
- involuntary movements of mouth and tongue, limbs face or respiratory muscles after chronic use of antipsychotics
- e.g. repetitive chewing and lip smacking, choreic movements
- irreversible
explain the pathophysiology of acute dystonias. How would you manage a patient presenting acutely?
Result from an imbalance between dopaminergic and cholinergic neurotransmission - nigrostriatal D2 receptor blockade leads to an excess of striatal cholinergic output.
Management:
- PROCYLCIDINE IM/IV - antimuscarinic
- If Tx with antimuscarinic is ineffective IV DIAZEPAM can be given for life-threatening acute dystonia (e.g. laryngeal dystonia)
what are the risk factors for developing acute dystonias?
- male
- young age (children esp. susceptible)
- previous episode of acute dystonia
- FHx of dystonia
- higher potency D2 R antagonists used at higher doses
- recent cocaine use
how would you manage a patient who has developed tardive dyskinesia?
- discontinuation of antipsychotic drug
- switch to atypical
- dose reduction may initially worsen condition - possible medications:
- TETRABENAZINE - most common s/e is depression
- CLONAZEPAM (benzodiazepine)
TD Sx do improve in about 1/2 pts who stop antipsychotics. May resolve completely if signs caught early but may be irreversible.
what are the risk factors for the development of tardive dyskinesia?
- typical antipsychotics at high dose
- longer duration of Tx
- age >50 yrs
- African descent
how would you manage a patient on antipsychotics who presents with akathisia?
- dose reduction or switch to an atypical antipsychotic
2. PROPRANOLOL
how would you manage a patient on antipsychotics who presents with pseudoparkisnoism?
- dose reduction or switch to an atypical antipsychotic
- medication
- anticholinergic agent e.g. PROCYCLIDINE
- AMANTADINE (weak dopamine agonist with modest antiparkinsonian effects)
describe the clinical features of neuroleptic malignant syndrome
Usually occur within 2 weeks of 1st dose.
- tetrad of: fever + muscle rigidity + autonomic instability (eg tachycardia, labile BP, diaphoresis) + mental status changes (eg confusion, delirium)
- rhabdomyolysis
- elevated creatine kinase + leucocytosis
(FALTER: Fever + Autonomic instability + Leucocytosis + Tremor + Elevated enzymes (CK, transaminases) + Rigor)
how would you manage a patient presenting with neuroleptic malignant syndrome?
- discontinuation of antipsychotic drug (usually lasts 5-7 days after discontinuation)
- supportive measures e.g. ICU care
- pharmacotherapy (no proven effective treatment)
- DANTROLENE (ryanodine R antagonist): prevents release of Ca2+ from sarcoplasmic reticulum of striated muscle… reduced muscle rigidity and hyperthermia
- BROMOCRIPTINE: D2 R agonist
what are the main s/e of lithium?
- fine tremor (one of most common, can be treated with propranolol if persistent)
- polyuria, polydipsia, nephrogenic DI
- nausea, vomiting and diarrhea (is a salt so affects fluid balance)
- weight gain
- metallic taste, dry mouth
- muscle weakness
- ECG changes e.g. T wave depressions, U waves, sinus bradycardia
- hypothyroidism, goitre
- hyperparathyroidism + hypercalcaemia
- leucocytosis
which tests would you perform before prescribing lithium?
- weight/BMI
- U&Es inc. calcium
- eGFR
- TFTs
- FBC
- ECG - if CVD or risk factors for it
what is the pathophysiology of lithium-induced DI? How would it present? How would you manage?
- Lithium interferes with ADH signaling… reduces aquaporins on collecting duct cell’s surface… fewer water molecules reabsorbed and kidneys unable to concentrate urine… increased free water excretion.
- Clinical features: polyuria, nocturia, polydipsia (increased risk of dehydration and subsequent Li toxicity).
- Management: amiloride
Is lithium safe in pregnancy?
No, esp. in 1st trimester. Associated with cardiac defects, e.g. Ebstein’s anomaly.
how would a patient with lithium toxicity present?
- vomiting and diarrhoea
- coarse tremor, ataxia, dysarthria, fasiculations
- drowsiness, coma, seizures
describe possible complications of lithium toxicity
- seizures and coma
- ventricular tachycardia
- renal failure
- SILENT (syndrome of irreversible lithium-effectuated neurotoxicity) - after cessation of lithium >2 mths: truncal ataxia, ataxic gait, scanning speech, incoordination
how would you manage a patient presenting with lithium toxicity?
Mild:
- stop lithium and check level
- encourage fluids, stop diuretics, monitor U&Es and renal function
Moderate-sever:
- consider whole bowel irrigation for severe, acute ingestions
- IV fluids
- benzodiazepines if seizures
- haemodialysis if seizures, coma, renal insufficiency + [Li+] >4
describe the MOA of benzodiazepines
Act on GABA Rs to enhance inhibitory effects of GABA - post-synaptic inhibition causes hypnotic and anxiolytic effect
name examples of benzodiazepines and the typical doses used to treat anxiety
lorazepam: 0.5 - 4 mg
diazepam: 6 - 30 mg
suggest possible side effects of benzodiazepines
- CNS depression: confusion, drowsiness, depression
- respiratory depression
- tremor, vertigo, ataxia
- paradoxical increase in aggression, suicidal ideation
- dependence
- withdrawal syndrome (seizure trigger if abrupt)
name a contraindication for benzodiazepines
pregnancy - neonatal withdrawal symptoms or resp. depression, cleft lip/palate
