Week 10: Psychotherapeutics Flashcards
Schizophrenia: General pathophysiology (2)
- Excessive DA receptor activation
- Insufficient glutamate receptor activation
Compare and contrast first-generation (conventional) antipsychotics to second-generation (atypical) antipsychotics (4)
Both are equally effective
- 1st gen are cheaper than 2nd gen
- 1st gen causes extrapyramidal symptoms (ex. tremors)
- 2nd gen causes metabolic effects and carries risk for CV events + premature death
Extrapyramidal side effects (EPS): 4 types and treatments
4 types: Pseudoparkinsonism, acute dystonia, akathisia, and tardive dystonia
Only the first three can be treated with drugs
Neuroleptic malignant syndrome: Symptoms (8) and treatments (2)
Symptoms:
- Rigidity
- Sudden high fever
- Sweating
- ANS instability
- BP changes
- Dysrhythmias
- Seizures
- Loss of consciousness
- Coma
Treatment: Supportive measures and withdrawal of antipsychotic med
Main differences between neuroleptic malignant syndrome and serotonin syndrome
Cause:
- NMS: Antipsychotic medications
- SS: Drugs that inc. 5-HT
Symptoms:
- NMS: Rigidity, dec. bowel activity, normal pupils
- SS: Tremor/hyperreflexia, hyperactive bowel activity, dilated pupils
Onset and duration:
- NMS: Gradual onset, long duration
- SS: Rapid onset, short duration
Haloperidol: Class, indications, MOA, AE (10)
Class: High potency first-generation antipsychotic
Indications: Schizophrenia
MOA: Block dopamine receptors in mesolimbic area of the brain
- May also block ACh, histamine, NE
AE:
- EPS
- Neuroleptic malignant syndrome
- Anticholinergic effects
- Orthostatic hypoTN
- Neuroendocrine effects
- Seizures
- Sexual dysfunction
- Agranulocytosis
- Severe dysrhythmias
- Dermatologic effects
Haloperidol: What’s unique? (3)
- Generally preferred for initial therapy
- EPS symptoms present earlier
- Lower frequency of all other AEs
Chlorpromazine: Class, indications, MOA, AE (10)
Class: Low potency first-generation antipsychotic
Indications: Schizophrenia
MOA: Block dopamine receptors in mesolimbic area of the brain
- May also block ACh, histamine, NE
AE:
- EPS
- Neuroleptic malignant syndrome
- Anticholinergic effects
- Orthostatic hypoTN
- Neuroendocrine effects
- Seizures
- Sexual dysfunction
- Agranulocytosis
- Severe dysrhythmias
- Dermatologic effects
Second Generation Antipsychotics: Indications, MOA, AE (8)
Indications: Schizophrenia
MOA: Blockade of DA, 5-HT receptors
- Also can block a1, histamine, and muscarinic receptors
AE:
- EPS
- Metabolic effects (DM, weight gain, hyperlipidemia)
- Agranulocytosis
- Seizures
- Myocarditis
- Orthostatic hypoTN
- Higher risk mortality w/ dementia
- Avoid drugs that suppress bone marrow
Second-generation antipsychotics: What’s unique? (2)
- Lower EPS but higher metabolic effects
- Very expensive
Depression: General pathophysiology
Deficiency of NE, 5-HT, or both
Fluoxetine: Class, indications, MOA, AE (8), drug interactions (9)
Class: SSRI
Indications: Depression and/or anxiety
MOA: Blocks reuptake of 5-HT = inc. serotonin available
AE:
- Nausea
- Agitation/insomnia
- Sexual dysfunction
- Weight gain
- Dec. platelet aggregation
- Serotonin syndrome risk
- Withdrawal syndrome with abrupt discontinuation
- In late pregnancy: Withdrawal and pulmonary HTN in newborn
Drug interactions:
- Inc. risk of serotonin syndrome: MAOIs, SNRIs, TCAs, analgesics, triptan antimigraine drugs
- Tramadol
- Linezolid (antibiotic that inhibits MAO)
- Inc. bleeding risk: Antiplatelets and Anticoagulants
Venlafaxine: Class, indications, MOA, AE (8), drug interactions (9)
Class: SNRI
Indications: Depression and anxiety
MOA: Blocks reuptake of 5-HT and NE = inc. serotonin and NE available
AE:
- Nausea
- Agitation/insomnia
- Sexual dysfunction
- Weight gain
- Dec. platelet aggregation
- Serotonin syndrome risk
- Withdrawal syndrome with abrupt discontinuation
- In late pregnancy: Withdrawal and pulmonary HTN in newborn
Drug interactions:
- Inc. risk of serotonin syndrome: MAOIs, SSRIs, TCAs, analgesics, triptan antimigraine drugs
- Tramadol
- Linezolid (antibiotic that inhibits MAO)
- Inc. bleeding risk: Antiplatelets and Anticoagulants
SNRIs vs SSRIs
- SSRIs are safer
- SNRIs have more AEs, especially dose-related HTN
Amitriptyline: Class, indications, MOA, AE (6), drug interactions (4)
Class: TCA
Indications: Depression, anxiety, and BPD
MOA: Block the reuptake of 5-HT, NE, and acetylcholine = inc. serotonin, NE, and acetylcholine available
- Not very selective, can also impact other receptors
AE:
- Orthostatic hypoTN
- Anticholinergic effects
- Sedation
- Cardiac toxicity
- Seizure risk
- Toxicity = dysrhythmias, heart block
Drug interactions:
- MAOIs = severe HTN risk
- Direct acting sympathomimetics = HTN/tachycardia risk
- Indirect acting sympathomimetics = dec. responsiveness
- CNS depressants = additive effect
MAOIs, nonselective: Indications, MOA, AE (2), drug interactions (6)
Indications: Depression and anxiety
MOA: Inhibition of MAO
- Inc. of available NE, 5-HT, DA
AE:
- CNS stimulation
- Orthostatic hypoTN
Drug interactions:
- Indirect acting sympathomimetics = HTN
crisis
- MAO inhibition = increased epi, NE, DA. Intensified/prolonged effects!
- TCAs = HTN crisis
- Serotonergic drugs = serotonin syndrome risk
- Antihypertensives = hypotension
- Meperidine = hyperpyrexia risk
MAOIs, MAO-B selective: Indications, MOA, AE (2)
Indications: Depression and anxiety
MOA: Inhibition of MAO-B
- Inc. of available DA
AE:
- CNS stimulation
- Orthostatic hypoTN
MAOIs: What’s unique?
All drugs in current use are IRREVERSIBLE, effects persist 2 weeks
Buproprion: Class, indications, MOA, AE (6)
Class: Atypical antidepressants
Indications: Depression and anxiety
MOA: Unclear, may be due to DA/NE reuptake block
AE:
- Agitation
- Tremor
- Insomnia
- Seizures in high doses
- Weight loss
- GI upset, constipation
Bipolar disorder: General pathophysiology
Disruption of neuronal growth
Bipolar disorder: General considerations for treatment (3)
Acute mania = Mood stabilizer +/- SGA. May also require benzo
Acute depression = Mood stabilizer +/- SGA +/- antidepressant (never antidepressant alone)
Long-term preventative treatment = 1+ mood stabilizer
Lithium: Class, indications, MOA, AE (9), drug interactions (4), PK (2)
Class: Mood stabilizer
Indications: BPD
MOA: Unknown, may be alteration of glutamate uptake/release, 5-HT antagonism, and/or glycogen synthase kinase03 beta inhibition
AE:
- N/V
- Diarrhea
- Thirst, polyuria
- Lethargy
- Slurred speech
- Fine hand tremor
- Renal toxicity
- Hypothyroidism + goiter
- Teratogenesis
Drug interactions:
- Diuretics
- NSAIDS inc. lithium plasma levels
- Anticholinergics
- ACE inhibitors
PK:
- Short half-life, must be administered multiple times per day
- Caution in renal disease
Lithium: Therapeutic index
Very low therapeutic index - must monitor drug levels
Toxicity/overdose = No antidote, supportive treatment, may consider hemodialysis
Valproate // Carbamazepine: Class, indications, MOA
Class: Antiepileptic drugs
Indications: BPD
MOA: Neurotrophic and neuroprotective effects
