Anxiety & depression Flashcards
example of Tricyclic antidepressants (TCA)
amitriptyline
imipramine
example of SSRI
fluoxetine
citalopram
Example of SNRI
venlafaxine
duloxetine
Example of MAO-I
Selegiline
Name an atypical AD
Buproprion
TCA adverse effects
anti-cholinergic (confusion, urinary retention, blurred vision, dry mouth, constipation, tachycardia); anti-histaminic (sedation, weight gain), and alpha-blocking (postural hypotension) side-effects
Contra-indications for TCA
closed-angle glaucoma (anti-cholinergic properties), BPH (benign prostatic hyperplasia), MI, arrythmia.
Safest TCA in early pregnancy
Amitryptilline
Complications in TCA overdose
Cardiac toxicity – sinus tachycardia (due to anticholinergic effect, worsened by hypotension); refractory hypotension (alpha-1 adrenergic receptor blockade with decreased peripheral resistance, impaired sodium input resulting in impaired myocardial contractility thus contributing to hypotension and decreased cardiac output); cardiac conduction abnormalities (due to inhibition of fast sodium channels, delayed AV conduction, risk of arrythmias).
CNS toxicity – delirium, lethargy, seizures, coma (inhibition of fast sodium channels in the CNS, antagonism of GABA A receptors (seizures), antihistaminic effects)
MOA of SSRI
In addition to serotonin reuptake inhibition, fluoxetine has NE reuptake inhibition (clinically relevant at high doses), CYP450 2D6 and 3A4 inhibition, and serotonin 2C antagonist actions (activating effects).
CYP450 2D6 and 3A4 needed for some metabolizing processes – need to check for drug-drug interactions
Adverse effects SSRI
No cardiac, no anti-cholinergic and no antihistaminic side-effects. Yet, sexual dysfunction (ejaculatory dysfunction, anorgasmia) is a class effect. Nausea and vomiting; energising (not sedation - POTENTIATE SUICIDALITY) and initially anxiogenic (start low, go slow). Can cause weight gain / weight loss.
Age groups of SSRI
In younger age groups, TCAs rather SSRIs. Contra-indicated in adolescents/children – may potentiate suicidality.
Contra-indications of SSRI
Suicidality
Existing sexual dysfunction
Patients of anti-coagulants/warfarin
SSRI in pregnancy
SSRIs relatively safe in early pregnancy (late pregnancy risk of neonatal pulmonary hypertension, apnea, floppy syndrome).
Why not SSRI when on anticoagulants?
5-HT in brain, gut and platelets – SSRIs block serotonin uptake in platelets, thus increased risk of bleeding; warfarin and SSRI’s contra-indicated.
Clinical signs of serotonin syndrome
Neuromuscular hyperactivity:
–tremor, sustained clonus (pathognomonic; mostly if high doses of SSRI’s used, if other serotonergic agents used), hyperreflexia, rigidity
Altered mental state:
–agitation, confusion
Autonomic hyperactivity
–fever, sweating, tachycardia, tachypnoea, diarrhoea
Rx of Serotonin syndrome
Stop drug, benzodiazepine
Factors when choosing AD
Efficacy similar
Advocate monopharmacy
Safety profile and cost determinants
Mianserin - MOA, advantages, side-effect
Mianserin and mirtazepine - tetracyclic antidepressants, alpha 2 antagonists. Not a SSRI, not a TCA. Unlike the tricyclic antidepressants, it does not prevent peripheral reuptake of NE, but releases 5-HT and NE into the synaptic cleft. Free of anticholinergic side-effects (useful in patients with prostatic enlargement; closed-angle glaucoma), not cardiotoxic, no risk of OD. Potentially anti-histaminic side-effect with sedation; and weightgain. Serious risk of neutropenia and agranulocytosis – do baseline and follow-up WCC.
Venlaflaxine - MOA, disadvantages, indications, adverse effects
Venlafaxine – SNRI – at lower doses only has serotonin reuptake inhibition; at higher doses has NE reuptake inhibition (not the case with duloxetine, which has uptake inhibition of both at low and high doses). Thus, at lower doses, acts as SSRI. Problem with venlafaxine – discontinuation/withdrawal syndrome; follows interruption/reduction/discontinuation of drug. Can present with paresthesiae, ataxia/dizzyness, lethargy, insomnia, anxiety, agitation. Consider drug only when patient poorly responsive to others.
