Pharmacology of Mood Disorders & Psychosis Flashcards by Sarah Axelrath

Absorbption, distribution, and metabolism of anti-psychotics

Oral absorption is incomplete with significant first-pass effect

Highly lipid solubility leads to concentration in the CNS, which extends clinical half-life beyond plasma half-life; crosses placenta

Metabolized to polar substance for excretion by hepatic CYP450; can be excreted in breast milk

How well did you know this?

Not at all

Perfectly

Dosage formulations for antipsychotics

Oral - immediate release for chronic dosing, 1-2x/day

IM - for rapid treatment of acute psychosis or for patients who can’t take oral meds

IM depot - improves adherence to maintenance therapy; administered every 2-4 weeks

How well did you know this?

Not at all

Perfectly

Typical antipsychotics - Mechanism

High D2/5HT2A blocking ratio

Good D2 block is associated with high efficacy against positive symptoms AND high incidence of extrapyramidal side effects

How well did you know this?

Not at all

Perfectly

Typical antipsychotics - agents

Haloperidol - High clinical potency due to greater D2 blocking activity; effective in lower doses but higher risk of EPS

Chlorpromazine - Lower clinical potency due to lesser D2 blocking activity; less risk of EPS but higher doses produce other side effects including antimuscarinic (dry mouth, tachycardia, urinary retention, constipation), alpha-1 blockade (hypotension) and antihistamine (sedation)

How well did you know this?

Not at all

Perfectly

Atypical antipsychotics - Mechanism

Low D2/5HT2A blocking ratio - associated with better efficacy against negative symptoms and increased efficacy in treatment-resistant individuals

How well did you know this?

Not at all

Perfectly

Atypical antipsychotics - Agents

Clozapine
Risperidone
Olanzapine
Aripiprazole

How well did you know this?

Not at all

Perfectly

Clozapine

Atypical antipsychotic effective in patients who are refractory to other drugs

Reserved for this indication due to 1-2% incidence of agranulocytosis

How well did you know this?

Not at all

Perfectly

Extrapyramidal symptoms

Caused by dopaminergic blockade; high with Haloperidol

Acute dystonia - treated with antimuscarinic agents

Akathisia - motor restlessness, inability to sit still

Pseudoparkinsonism (tremor, bradykinesia, rigidity) - treated with anticholinergic agents or Amantadine

Tardive dyskinesias

How well did you know this?

Not at all

Perfectly

Tardive dyskinesias

Extrapyramidal symptom with onset 3-6 months; characterized by involuntary, repetitive movement of lips and tongue with chorea of arms and legs

May worsen with withdrawal of the antipsychotic drug and is usually irreversible; overall incidence 20-40% with chronic treatment

How well did you know this?

Not at all

Perfectly

Other side effects of antipsychotic agents

Metabolic effects via block of hypothalamic DA receptors - Type 2 DM, weight gain, hypertension, hyperglycemia, hypercholesterolemia; more common with atypical agents

Altered thermoregulation via block of hypothalamic DA

Lowered seizure threshold

How well did you know this?

Not at all

Perfectly

Tricyclic antidepressants - Agents

Amitriptyline
Imipramine
Desipramine

How well did you know this?

Not at all

Perfectly

SSRIs - Agents

Fluoxetine
Paroxetine
Sertraline
Citalopram

How well did you know this?

Not at all

Perfectly

Buproprion - Mechanism & Side effects

NE and DA reuptake inhibitor (NDRI)

Side effects: anxiety, insomnia, higher seizure risk; contraindicated in patients with eating disorders or history of seizures

No sexual side effects, weight neutral

How well did you know this?

Not at all

Perfectly

Venlafaxine - Mechanism & Side effects

5HT and NE reuptake inhibitor (SNRI)

Side effects: 
Diastolic hypertension
Sweating
Sexual side effects
Withdrawal syndrome with "electric shock" sensation

How well did you know this?

Not at all

Perfectly

Trazodone - Mechanism

Serotonin antagonist / reuptake inhibitor (SARI)

Weak antidepressant, mainly used for insomnia

Side effects: drowsiness, dizziness

How well did you know this?

Not at all

Perfectly

TCADs - Mechanism

Blocks reuptake of NE, 5HT and DA (at high doses)

Also blocks H1 histaminic, muscarnic cholinergic, and alpha-1 receptors

How well did you know this?

Not at all

Perfectly

SSRIs - Side effects

Study These Flashcards

Acute (diminish over time): Nausea, diarrhea, insomnia, dry mouth

Chronic: Weight gain, sexual dysfunction, cognitive blunting

Flu-like withdrawal syndrome

DDIs with MAOIs & inhibitors of CYP450

TCADs - Side effects

Study These Flashcards

Anticholinergic effects (blurred vision, constipation, dry mouth, urinary retention, glaucoma)
Orthostasis
Weight gain
Sexual side effects

Fatal in overdose due to seizure and cardiac arrhythmia

MAOIs - Mechanism

Study These Flashcards

Blocks degradation pathway for NE and 5HT, allowing greater release into the synapse; inhibition is irreversible and persists after drug is no longer detectable in the plasma

Effective in non-responsive patients, especially atypical depression

MAOIs - Adverse Effects

Study These Flashcards

Anti-cholinergic (dry mouth, constipation, urinary retention)
Sexual side effects
Weight gain
Overdose causing seizures, shock, hyperthermia

MAOI DDIs

Study These Flashcards

Interaction with foods high in tyramine (liver/beer/wine/cheese); tyramine displaces NE from storage vesicles causing excessive NE release leading to hypertensive crisis

Interaction with SSRIs/SNRIs, Medperdine (Demerol), and Dextromethorphan (cough suppressant) causing serotonin syndrome

Serotonin syndrome

Study These Flashcards

Increased serotonin in the CNS causes over-stimulation of 5HT2A receptors

Presents as tremor, tachycardia, hypertension, sweating, dilated pupils, hyperreflexia, clonus, and hyperthermia causing metabolic acidosis, rhabdomyolysis, seizures, renal failure, and DIC

Mirtazapine - Mechanism, Uses, and Side effects

Study These Flashcards

Mechanism: Blocks a-2 receptors on serotonergic and adrenergic neurons, enhancing release of 5HT and NE; does NOT affect reuptake systems

Useful due to additional anti-insomnia and anti-anxiety effects; low incidence of sexual side effects

Side effects: Daytime somnolence, weight gain

Benefits of Lithium

Study These Flashcards

Best studied, best proven drug for bipolar disorder

Effective anti-manic, reasonable preventative agent, some antidepressant and anti-suicidal properties

Neuro-regenerative

Cheap

Lithium - Adverse Effects, and DDIs

GI upset, tremor, metallic taste, cognitive dulling Decreased urine concentration / diabetes insipidus, due to decreased ADH secretion (20-30%) Hypothyroidism (5-10%); can cause weight gain Narrow therapeutic window; toxicity/overdose causes confusion, seizures, stupor, coma DDIs: Diuretics decrease renal clearance up to 25% causing increased Li+ plasma levels

MAOIs - Agents

Phenelzine, Selegeline

SSRI Indications

``` Major depressive disorder Generalized anxiety disorder Social anxiety Panic OCD PTSD PMDD ```

Mania - Pharmacologic Treatment Options

Lithium All atypical antipsychotics Divalproex Sodium (Depakote)

Bipolar Depression - Pharmacologic Treatment Options

Olanzapine-Fluoxetine Quetiapine Possibly Lithium, Lamotrigine

Bipolar Maintenance - Pharmacologic Treatment Options

Lamotrigine | Aripiprazole

Bipolar Relapse Prevention - Pharmacologic Treatment Options

Lithium | Olanzapine

What is the overall response and remission rate of antidepressants?

67% overall response rate within 8 weeks; 40% of patients do not respond until week 8, thus 8-14 weeks is considered an adequate trial SSRIs have a 33% rate of remission; all FDA approved antidepressants have comparable rates

Benzodiazepines - Mechanism

Bind to the GABA channel gamma subunit, facilitating channel opening and Cl- influx; does NOT directly initiate Cl- current and requires presence of GABA No effect on excitatory neurotransmitters - graded, dose-dependent CNS depression with ceiling affect below the level of anesthesia

Barbituates - Mechanism

Prolong the effect of GABA on its receptor (presence of GABA is required); at high doses, interact directly with the GABA receptor Also depresses excitatory glutamate transmission - capable of inducing surgical anesthesia

Zolpidem - Mechanism & Uses

Selectively interacts with alpha-1 GABA channels in the cortex ``` Produces hypnosis (sleep) without anxiolysis; less potential for abuse Also used as an anti-convulsant ``` Side effects: Amnesia, additive CNS depression

Flumazenil

Benzodiazepine binding site antagonist; reverses CNS effects of benzodiazepines in overdose or following surgical use

GABA receptor variants - a1 and a2/a5

GABA receptors with a1 subunits are expressed in the cortex; mediate sleep, anticonvulsant, and amnesia effects GABA receptors with a2/a5 subunits are expressed in the limbic system and brain stem; mediate muscle relaxation, motor impairing, anxiolytic, and alcohol-potentiating effects as well as tolerance, dependence, and withdrawal

Benzodiazepines - Metabolism

Metabolized by CYP450 prior to elimination in urine Metabolites of some agents are active, with longer half lives than the parent comopounds leading to accumulation effects such as daytime sedation Lorazepam and Oxazepam are metabolized directly to inactive compounds; better choice in elderly patients or patients with hepatic dysfunction

Benzodiazepines - Adverse Effects

Extension effects: More likely with high doses, longer half life agents, elderly patients, patients with hepatic dysfunction Sedation Performance impairment (drowsiness, incoordination, decreased concentration, cognitive deficits) Anterograde amnesia Physical / Psychologic Dependence Withdrawal syndrome

Barbituates - DDIs

Barbituates are inducers of CYP450 enzymes; major source of clinically significant DDIs leading to declining use

Buspirone

Partial agonist of 5HT1A, located pre-synaptically on nerve terminals Anxiolytic effect only; NO sedation, anticonvulsant, or myorelaxant action Requires 2 weeks for onset of effect and 4-6 weeks for maximal efficacy; must be administered daily (not prn); useful in chronic anxiety

Treatment of GAD

1. Antidepressants - SSRIs, SNRIs 2. Benzodiazepines - Alprazolam/Lorazepam/Oxazepam (shorter acting) vs. Diazepam (longer acting) if both hypnotic and daytime anxiolysis are desired

Pharmacology of Mood Disorders & Psychosis Flashcards

(42 cards)