DRUGS USED IN PSYCHIATRY Flashcards
SSRIs:
- Examples
- Indications
- Side-effects
- Contraindications
- Recommendations
- Drug interactions
*Venlafaxine which is a serotonin-noradrenaline reuptake inhibitor has similar but more severe side-effects, promotes hypertension in 10%
- Fluoxetine, Sertraline, Paroxetine, Citalopram
- Depression, Anxiety Disorders, OCD, Bulimia nervosa(fluoxetine)
- a) GI disturbance(early)
- nausea, vomiting, diarrhoea, pain
b) Agitation/anxiety(early)
- increased risk of suicide in adolescents, hence only fluoxetine in <18s
c) Insomnia
d) Appetite loss
e) Weight loss/gain
f) Sweating
g) Sexual dysfunction
h) Bleeding diathesis
i) hyponatraemia(SIADH): fatigue/drowsiness/weakness/confusion/fits
- rare but esp in elderly and can be fatal
* Long QTc with high dose citalopram - Mania
- Patients with cardiac disease(sertraline has best evidence for safe use post MI) , better for patients at risk of overdose compared to TCA
- a) PPI if patient is also taking NSAID
b) warfarin/heparin
- avoid SSRI and consider mirtazapine
c) Triptans
- avoid SSRIs
NORADRENERGIC AND SPECIFIC SEROTONERGIC ANTIDEPRESSANT(NaSSA):
- Example
- Side effects
- Contraindication
- Mirtazapine(tetracyclic antidepressant)
- a) Histamine antagonism leading to increased appetite, weight gain and sedation
b) Headache
c) Dry mouth
d) Less common: Dizziness, postural hypotension, tremor, peripheral oedema - Mania
TRICYCLIC ANTIDEPRESSANTS:
- Mechanism
- Examples
- Side-effects
- Recommendations and Other indications
- Contraindications
- Trazodone(tricyclic-related antidepressant) is a good sedative and is usually used as an adjunct in those receiving non-sedating primary antidepressant
- Lofepramine less potent and shorter half-life
- Presynaptic blockade of noradrenaline and serotonin reuptake pumps. Also blocks muscarinic, histaminergic and alpha-adrenergic receptors
- Amitriptyline, clomipiramine, imipramine, lofepramine
- a) Anticholinergic: constipation, dry mouth, blurred vision(exacerbation of angle-closure glaucoma), urinary retention
b) Histaminergic receptor blockade: Weight gain, sedation
c) Alpha-adrenergic receptor blockade: Postural hypotension leading to dizziness, syncope.
d) Cardiotoxic: QT interval prolongation, arrhythmias - Patients with insomnia, Also used in small doses for treating neuropathic pain(esp amitriptyline) and prophylaxis of headaches(migraine and tension headaches); Anxiety states; OCD(esp clomipramine); ADHD(esp imipramine); noctural eneuresis
- Mania, recent MI, severe liver disease, high risk of overdose, arrhythmias
MONOAMINE OXIDASE INHIBITORS(MAOI)/REVERSIBLE INHIBITOR OF MONOAMINE OXIDASE A(RIMA)
- Examples
- Side-effects
- Contraindications
- Phenelzine, tranylcypromine, isocarboxazid, mocloblemide(RIMA)
- a) Precipitation of hypertensive crisis
- avoid tyramine-containing food and certain drugs
b) Anticholinergic side-effects; Constipation, dry mouth, blurred vision, urinary retention
c) Postural hypotension - Phaeochromocytoma, cerebrovascular disease, hepatic impairment, mania
TYRAMINE-CONTAINING FOODS AND DRUGS TO BE AVOIDED WITH MAOIs
- Cheese
- Pickled herring, smoked chiken, liver
- Chianti wine, beer
- Broad bean pods
- Soya bean extract
- Overripe/unfresh food
- Drugs:
- Adrenaline including local anaesthetics containing adrenaline
- Amfetamines
- Cocaine
- Ephedrine, pseudoephedrine, phenylpropanolamine(cough mixtures, decongestants)
- L-dopa, dopamine
SEROTONIN SYNDROME:
- Precipitants
- Clinical features
- Prevention
- a) When SSRIs/clomipramine/imipramine administered with MAOI
b) Coadministration of opioids(pethidine and tramadol) with MAOI - Triad of neuromuscular abnormalities, altered consciousness and autonomic instability
- a) Start other antidepressants 2w after stopping MAOI(3w if clomipramine/imipramine)
b) Start MAOI 2w after stopping other antidepressants(3w if clomipramine/imipramine)(5w if fluoxetine)
DISCONTINUATION SYNDROME(SSRI):
- Symptoms
- Prevention
- GI disturbance, dizziness, unsteadiness, agitation, headache, tremor, insomnia, paraesthesia
- When stopping SSRI, gradually taper down over 4w
- not necessary with fluoxetine
- paroxetine has highest incidence of discontinuation symptoms
LITHIUM(Priadel/Camcolit):
- Indications
- Side-effects
- Signs of toxicity
- Drug-interactions
- Starting Lithium
- Contraindications/Cautions
- a) Acute mania
b) Prophylaxis in bipolar affective disorder
c) Augmentation in treatment-resistant depression
d) Adjunct to antipsychotics in schizophrenia, schizoaffective disorder, aggression/impulsivity - Nephrotoxicity(nephrogenic diabetes insipidus): Thirst, polydipsia, polyuria, weight gain, oedema, fine tremor, precipitates/worsens skin problems, concentration and memory problems, hypothyroidism, impaired renal function, cardiac: T-wave flattening/inversion, leucocytosis, teratogenicity, idiopathic intracranial hypertension.
- a)(Toxic) 1.5-2 mmol/L: nausea, vomiting, apathy, coarse tremor, ataxia, muscle weakness
b) (Dangerously toxic) >2 mmol/l: nystagmus, dysarthria, impaired consciousness, hyperactive tendon reflexes, oliguria, hypotension, convulsions, coma
c) Management:
- Fluid resus in mild-moderate toxicity
- Haemodialysis may be needed in severe toxicity
- Sodium bicarbonate(limited evidence) - NSAIDs, Diuretics(especially thiazides), ACE-inhibitors, metronidazole, Antipsychotics(Increase Li-induced neurotoxicity)
- a) Do following investigations prior to initiation:
- FBC, U&E’s, TFT, Pregnancy test, ECG
b) Monitor blood Li levels weekly until therapeutic level stable for 4w
c) Monitor blood Li levels(therapeutic level: 0.4-1.0 mmol/L) every 3/12, measure levels at 12h post-dose; renal function every 6/12; TFT every 6/12; issue patients info booklet, alert card and record book - Pregnancy, breastfeeding, impaired renal function, thyroid disease, cardiac condtions, neurological conditions(eg Parkinson’s/Huntington’s)
OTHER MOOD STABILIZIERS:
- Valproate
a) Indication
b) Side-effects - Carbamazepine
a) Indication
b) Side-effects - Lamotrigine
a) Indication
b) Side-effects
- Check liver and haematological functions prior to initiating
1. a) Epilepsy, Acute mania, Prophylaxis in bipolar affective disorder
b) Increased appetite, weight gain, dizziness, nausea and vomiting, tremor, haematological abnormalities(thrombocytopenia, prolonged bleeding time, leucopenia), raised liver enzymes,
- a) Epilepsy, prophylaxis in bipolar affective disorder
b) Nausea and vomiting, skin rashes, Steven Johnson syndrome, blurred vision/diplopia, dizziness and ataxia, drowsiness, fatigue, hyponatraemia and fluid retention, haematological abn.(leucopenia, thrombocytopenia, eosinophilia), raised liver enzymes, agranulocytosis, SIADH - a) Epilepsy, prophylaxis of depressive episode in bipolar affective disorder
b) Nausea and vomiting, skin rashes(consider withdrawal as risk of Stevens-Johnson syndrome), headache, aggression, irritability, sedation and dizziness, tremor
ANTIPSYCHOTIC EXAMPLES:
- 1st generation
- 2nd generation
- a) Chlorpromazine
b) Sulpiride
c) Haloperidol
d) Flupentixol
e) Zuclopenthixol - a) Clozapine
b) Olanzapine
c) Quetiapine
d) Risperidone
e) Amisulpiride
*Haloperidol, Flupentixol, Zuclopenthixol and Risperidone can be given as long-acting IM
ANTIPSYCHOTIC MECHANISM OF ACTION:
- D2-receptor antagonism in mesolimbic pathway
- most antipsychotics other than clozapine - 5-HT2 receptor blockade
- Clozapine
- 5-HT2 and D4 receptors antagonism
ANTIPSYCHOTIC SIDE-EFFECTS:
- Worsening of negative and cognitive symptoms of schizophrenia
- Extrapyramidal side-effects:
- Parkinsonian symptoms
- Acute dystonia
- Akathisia
- Tardive dyskinesia(40% of patients)(increased risk in elderly)
- Neuroleptic malignant syndrome - Hyperprolactinaemia
- Galactorrhoea
- Amenorrhoea and infertility
- Impaired glucose tolerance
- Sexual dysfunction - Anticholinergic
- Dry mouth
- Constipation
- Urinary retention
- Blurred vision - Antihistaminergic
- Sedation
- Weight Gain - Cardiac effects
- QT prolongation(especially haloperidol)
- Arrhythmias
- Myocarditis
- Sudden death - Increased risk of metabolic syndrome
- esp olanzapine, clozapine - Lowers seizure threshold
- greater risk with 2nd gen - Hepatotoxicity
- Cholestatic jaundice
- Increased risk of stroke(especially olanzapine and risperidone) and VTE in elderly patients
- Postural hypotension
- Sexual dysfunction
- Allergic rx
- exp to phenothiazines(eg chlorpromazine) and clozapine
CLOZAPINE:
- Important side-effects
- Contraindications/Cautions
- Monitoring
- a) Increased risk of metabolic syndrome
- obesity, hypertension, dyslipidaemia, diabetes
- increases cardiovascular mortality
b) Agranulocytosis(0.8%), neutropaenia(3%)
c) Myocarditis
d) Cardiomyopathy
e) constipation
- large bowel hypostasis - a) Severely reduced conscious level
b) Phaeochromocytoma
c) Parkinson’s disease
d) Epilepsy
- reduces seizure threshold, induces seizures in up to 3% of patients
e) Cardiac disease
f) Metabolic syndrome - a) FBC prior to starting
b) Weekly FBC for several weeks then monthly throughout treatment
- reduces risk of agranulocytosis to <1 in 5000
MANAGING ANTIPSYCHOTIC-INDUCED EXTRAPYRAMIDAL SIDE-EFFECTS:
- Acute dystonia(days)
- Parkinsonian motor symptoms(days-weeks)
- Akathisia(days-weeks)
- Tardive dyskinesia(months-years)
- Neuroleptic malignant syndrome
- a) Anticholinergics eg procyclidine(IV/IM/ORAL)
b) Dose reduction
c) Switch antipsychotic - Same as 1
- a) Propanolol/short-term benzodiazepine
b) Dose reduction
c) Switch antipsychotic - a) Withdraw antipsychotic if possible
b) Consider clozapine
c) Consider benzodiazepines
* Avoid anticholinergics
NEUROLEPTIC MALIGNANT SYNDROME VS SEROTONIN SYNDROME:
- Defining features
- Neuromuscular abnormalities
- Onset
- Medication History
- Typical blood results
- Treatment
- Mortality
- Triad of neuromuscular abnormalities, altered consciousness level and autonomic dysfunction(sweating, hyperthermia, tachycardia, unstable BP)
- Reduced activity: severe rigidity, dysphagia, dyspnoea, bradyreflexia vs increased activity: myoclonus/clonus, hyperreflexia, tremor, less severe muscular rigidity
- Insidious vs Acute
- Usually within 4-11d of initiation/dose increase of dopamine antagonist OR stopping/reducing dose of levodopa vs usually after 1-2 doses of new serotonergic medication
- Elevated CK, WCC, hepatic transaminases, metabolic acidosis
- a) Discontinue offending drugs
b) Cool patient
c) Monitor and manage hydration and haemodynamics. IV fluids to prevent renal failure. Consider ITU
d) Monitor for complications ie pneumonia and renal failure
e) Benzodiazepines for sedation if agitated
f) i) in neuroleptic malignant syndrome
- Bromocriptine to reverse dopamine blockade
- Dantrolene to reduce muscle spasm
- ECT
ii) in serotonin syndrome
- Cyproheptadine(5HT-2A antagonist) - 20% if untreated vs Low