Psychopharmacology Flashcards
What is the mechanism of action of commonly used antidepressants?
- Inhibition of serotonin re-uptake
- Inhibition of the re-uptake of both serotonin and norepinephrine
- Stimulation of nor-adrenergic and dopaminergic activity
- Alpha 2 antagonism of nor-adrenergic and serotonergic neurons.
What are the adverse effects of commonly used antidepressants-SSRIs vs. the TCAs?
● SSRI ADRs: Insomnia, Sedation, Appetite Change, Nausea, Dry mouth, Headache, Sexual Dysfunction
● TCA ADRs:
○ Anticholinergic: dry eye, mouth, constipation, urinary retention, blurred vision, AMS
○ Histaminic – sedation, weight gain
○ Alpha -1 adrenergic blockade - orthostatic hypotension, falls
○ Possible EKG changes, arrhythmias (prolonged QT and PR, AV block) * In OVERDOSE=widened QRS
○ Require diet modification to avoid HTN crisis (avoid tyramine containing foods)
○ Cannot be combined with other antidepressants (risk of serotonin syndrome) or sympathomimetic drugs; avoid with cough syrup or Demerol
○ SERIOUS RISK OF OD- even one week’s supply can be lethal!
What is Serotonin Syndrome?
Generally the cause of too many serotonergic agents (polypharmacy)
● Signs: agitation, diaphoresis, tachycardia, autonomic instability (htn common), clonus (more in LEs), tremor (more in LEs), hyperreflexia (unique – can distinguish from other syndromes; more in LEs), increased bowel sounds
● Management:
o Discontinue agent/drug
o Supportive care (IV fluids, intubation, induce paralysis)
o Control agitation (benzodiazepines)
o 5-HT2A antagonists: cyproheptadine, olanzapine
o Control autonomic instability and control of hyperthermia
o Propranolol, bromocriptine, and Dantrolene are NOT recommended
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. Indications for Lithium and its side effects. What other drugs can be used as mood stabilizers?
● Indications: mood stabilizer (common for bi-polar)
● Side Effects: Tremors, Lethargy, Confusion, Seizures, Coma, Gastrointestinal effects (Nausea, Vomiting, Crampy abdominal pain, Diarrhea)
○ Signs of serious toxicity: Altered mental status; Muscle fasciculations; Stupor; Seizures, Coma, Hyperreflexia,Cardiovascular collapse.
○ Needs to be monitored every 6mo (can be toxic to kidneys/thyroid)
● Other Mood Stabilizers: anti-convulsants, 2nd generation anti-psychotics
What is the neurobiology of Schizophrenia?
● Dopamine Hypothesis: dopamine hyperactivity in the mesolimbic pathway causes the positive symptoms of psychosis.
● Glutamate Hypothesis: Faulty NMDA synapses on GABA interneurons in PFC cause overstimulation of glutamatergic cortico-brainstem neurons and downstream over activation of mesolimbic dopaminergic neurons.
○ Corticobrainstem glutamatergic neurons indirectly innervate the mesocortical dopaminergic pathway, so the same faulty NMDA synapses on GABA interneurons in PFC cause hypo-activation in the mesolimbic circuit, and therefore the negative symptoms of schizophrenia
. What are the side effects of D2 receptor blockers? What are the differences between first and second generation antipsychotics. What are the side effects of antipsychotics: weight gain, decreased sweating,
● Side effects of D2 receptor blockers (1st generation): more likely to cause mvmt problems and hyperprolactinemia
● 1st Generation Antipsychotics (typical receptors): D2 blockade drugs; target mesolimbic (affects pos. symptoms like hallucination) and mesocortical (affects neg. symptoms like impaired speech/motor function/depression) but also affects 2 other tracts which may lead to rigidity, dyskinesia
● 2nd Generation Antipsychotics (atypical receptors): work at D2 receptors and serotonergic receptors (less likely to cause mvmt problems and hyperprolactinemia than 1st generation drugs)
● There was no significant differences in effectiveness between 1st and 2nd generation antipsychotics
● Side Effects of Antipsychotics:
○ First generation: more likely to cause mvmt problems and hyperprolactinemia
○ Second generation: more likely to cause: HTN, metabolic syndrome, diabetes, wt gain
What is Neuroleptic Malignant syndrome?
● Rare, but life threatening reaction to neuroleptic medications ● Cardinal Features: ○ Severe muscular rigidity ○ Hyperthermia (temp > 38 deg C) ○ Autonomic instability ○ Changes in level of consciousness
What is Tardive Dyskinesia
● Unwanted/involuntary movements of the mouth, jaw, and face
● May be caused by use of antipsychotics (FGAs)
What is the mechanism of action of Baclofen and Botox and what would be the criteria for their use? How long does it take for Botox to start working?
● Botox MOA: Prevent Ach release at alpha motor nerve ending
● Botox Indications: spasticity, migraines, dystonia, eye mvmt abnormalities, comedic
● How long does Botox start working: 48- 72 HOURS
● Baclofen MOA: binds to GABAs receptor, blocks influx of Ca+ into presynaptic terminal → reduced neurotransmitter release and membrane hyperpolarization
● Baclofen Indications: spasticity: spinal cord injury and MS in adults (No clear improvement of gait or ADL’s)
What is the pathophysiology of Alzheimers?
● AD pathophysiology: Excessive amount of tau/inadequate Tau clearance; Excessive beta amyloid production
○ Brain shrinkage, loss of cholinergic neurons in frontal cortex, amyloid plaques, and intraneuronal neurofibrillary triangles made up of Tau protein
What categories of drugs are used in treatment of Alzheimers?
Treatment: Blocking acetylcholinesterase enzyme to make more Ach present
○ Acetylcholinesterase inhibitors (AChEI’s): prevents breakdown of ACh
○ Glutamate modulators: modulates glutamine by antagonizing NMDA receptor
○ Behavioral treatments:
■ Environment: quiet, familiar, with labels on doors, and good lighting
■ Depression: Use SSRI’s
■ Agitation: use neuroleptics
What are the major categories of drugs used to treat Parkinson’s Disease(Dopamine agonists, L-dopa/carbidopa, anticholinergics)? Know their mechanism of action. What is the difference between L-dopa and dopamine? Why is carbidopa added to L-Dopa?
Dopamine agonist MOA:
- Activates dopamine receptors?
· L-Dopa/Carbidopa MOA: replaces dopamine in CNS, with dopa decarboxylase inhibitor, which doesn’t cross the BBB and inhibits the conversion of levodopa to dopamine outside the brain
· Anticholinergics MOA: decreases CNS acetylcholine and restores the balance between dopamine and acetylcholine
· Diff b/w L-dopa and dopamine: Pure dopamine cannot cross the blood brain barrier, but L-dopa can.
· Carbidopa added to L dopa: carbidopa inhibits enzymes that break down L-dopa
What are the common side effects of AEDs? Besides seizures, what other indication is there for AEDs.
● Side effects of AEDs: SEDATION, Drowsiness, “Brain fog”, Depression, Dizziness
● Other Uses of AEDs: Bipolar disorder, neuropathic pain, migraines, bipolar disorder
What is a positive screening test for intrathecal baclofen?
● Drop in spasticity scale or hypotonia without respiratory difficulty
