How long does it take for tricyclic antidepressants (TCA) to work?
only after 2 - 3 weeks of chronic dosing will a therapeutic benefit emerge
What is thought to be the mechanism of action of TCAs?
- inhibition of norepinephrine neuronal reuptake
- time dependent changes in beta adrenergic function parallel the delayed onset of clinical efficacy
- mild effect on 5-HT central serotonin receptor sensitivity
What is the half life range of TCAs?
8 - 89 hours or redonkulously long either answer will be accepted
TCAs undergo metabolism where?
the liver (through oxidative metabolism)
TCAs cause an antimuscarinic effect. What are antimuscarinic effects?
tachycardia blurred vision constipation dry mouth
Other adverse effects seen with TCAs.
neuroleptic malignant syndrome
All TCAs are weak _____ adrenergic antagonists.
(most common CV effects are orthostatic hypotension and tachycardia)
How is sedation thought to be mediated with TCAs?
through antagonist properties at the alpha 1-adrenoceptor and H1-histaminergic receptor sites in the brain
Overdose of TCA are frequently fatal with unresolvable __________.
Selective serotonin reuptake inhibitors (SSRI) produce therapeutic action through an ability to do what?
modulate serotonin neurotransmission in the brain
Biggest clinical difference with TCAs and SSRIs, in my opinion.
- the side effect profile is much different between the two and better tolerated with SSRI
(ie. the anticholinergic and CV side effects were not present in the SSRI group)
Common side effects of SSRIs?
GI: nausea and diarrhea, weight loss
CNS: insomnia and anxiety
Sexual: aorgasmia and delayed ejaculation
Caution must be used when SSRIs are used in combination with other antidepressants, benzodiazepines, neuroleptics, and carbamepazine. Why?
because the blood levels of SSRIs will increase
What is the half life of SSRIs?
2 - 3 days
(not bad, compared to TCAs of 8 - 89 days)
Monoamine oxidase inhibitors (MAOI) are reserved for what conditions?
- atypical depression
- depression unresponsive to TCAs or SSRIs
- depression resistant to electo-convulsive therapy (ECT)
MAOI mechanism of action?
- monoamine oxidase exists on the body as type A and type B
- transmitter amines, such as norepi, are preferentially metabolized by MAO-A in brain tissue
- MAO-B is involved in the catabolism of dopamine
- drugs inhibit both A and B, but A is where the therapeutic effect occurs (so, norepi and dopamine don't get broken down)
What is a toxicity that can occur with MAOI use?
(occasionally seen with long term therapy, particularly for those identified as slow acetylators)
What are some side effects of MAOIs? (5)
- CV effects (can occur with ingestion of certain foods, such as cheese, beer, or wine; these people need to be on a low tyrosine diet)
- ejaculatory delay
- orthostatic hypotension
- hyperpyrexia with meperidine, dextromethorphan, and TCAs
Trazadone. What is it used for and what are some side effects?
- antidepressant (in the "miscellaneous" category)
- anxiolytic properties act at both serotonin and norepi sites in the brain
- side effects: marked sedation, dizziness, hypotension, and nausea
Bupropion. What is it used for and what are some side effects?
- antidepressant (in the "miscellaneous" category)
- mechanism of action unknown
- free of muscarinic side effects
- side effects: CNS stimulation with insomnia and nervousness
Which medication is effective in 60-80% of bipolar disorder patients?
(it's a mood stabilizing agent)
What are some anesthetic considerations with lithium carbonate use? (4)
- adverse reactions associated directly with therapeutic levels
- narrow therapeutic window (0.5-1.5 mEq/L) necessitates frequent monitoring
- toxicity presents as nausea, diarrhea, vomiting, abdominal pain, polyuria, sedation, and mild tremor
- many become hypothyroid after long term use
How do antipsychotic drugs, like lithium, work?
mechanism of action:
- block synaptic actions of dopamine in the brain
- the antagonism of dopamine in the mesolimbic-mesocortical system is thought to be the basis of the therapeutic actions of the antipsychotic drugs, while antagonism of the nigrostriatal system is the major factor in the extrapyramidal side effects seen with antipsycotics
(really simple stuff)
What are some side effects of antipsychotics? (7)
- extrapyramidal reactions
- alpha adrenergic antagonism
- cholinergic antagonism
- postural hypotension
- hyperprolactinemia (amenorrhea, galactorrhea, infertility in women, impotence in men)
What types of extrapyramidal reactions are seen with antipsychotics?
- acute dystonia (sustained muscle contractions cause twisting and repetitive movements or abnormal postures) (in 5% of cases, treated with centrally acting muscarinic agent)
- akathisia (inner restlessness that manifests itself with an inability to sit still or remain motionless) (treated with benzos or beta blockers)
- tardive dyskinesia (involuntary, repetitive body movements) (typically a late occurance, hence "tardive" and usually irreversible)
- neuroleptic malignant syndrome (fever, diffuse muscle rigidity, severe EPS, autonomic dysfunction such as elevated BP and HR)
Some fun facts about neuroleptic malignant syndome. (5)
- more common in men than women
- 80% of cases occur under age 40
- can be misdiagnosed as MH*
- treated with cooling and hydration (dantrium has been used to lessen muscle rigidity and fever)
- discontinue the antipsychotic drug ASAP
What are 4 contraindications to antipsychotic use?
- parkinson's disease
- hepatic failure
- bone marrow depression
- use of other sedatives
Hypotension related to antipsychotics responds better to epinephrine or norepinephrine?
What is the cause of extrapyramidal side effects?
D2 receptor blockage