Psychiatry - Pharmacology

Benzodiazepines

• SSRIs
• SNRIs
• buspirone

• Methylphenidate
• amphetamines

• "Mood stabilizers"
• -Lithium
• -valproid acid
• -carbamazepine

Atypical antipsychotics

SSRIs

• SSRIs
• SNRIs
• TCAs
• buspirone
• mirtazapine (especially with insomnia)

• SSRIs
• clomipramine

• SSRIs
• venlafaxine
• benzodiazepines

SSRIs

Antipsychotics

SSRIs

Antipsychotics (e.g., haloperidol, risperidone)

Methylphenidate, dextroamphetamine, methamphetamine

• Mechanism:
• -↑ catecholamines at the synaptic cleft, especially NE and dopamine

• Clinical use:
• -ADHD
• -Narcolepsy
• -Appetite control

Haloperidol, trifluoperazine, fluphenazine, thioridazine, chlorpromazine (haloperidol + "-azines")

• Mechanism:
• -All typical antipsychotics block dopamine D2 receptors (↑ [cAMP])

• Clinical use:
• -Schizophrenia (primarily positive symptoms)
• -psychosis
• -acute mania
• -Tourette's syndrome

• Toxicity:
• -lipid soluble, stored in body fat → slowly removed from body
• -Extrapyramidal system (EPS) side effects: dyskinesias
• -Endocrine side effects: dopamine receeptor antagonism → hyperprolactinemia → galactorrhea
• -Blocking muscarinic receptors: dry mouth, constipation
• -Blocking α₁ receptors: hypotension
• -Blocking histamine: sedation
• -Neuroleptic malignant syndrome
• -Tardive dyskinesia

• 4 hr acute dystonia (muscle spasm, stiffness, oculogyric crisis)
• 4 day akathisia (restlessness)
• 4 week bradykinesia (parkinsonism)
• 4 mo tardive dyskinesia

• Rigidity, myoglobinuria, autonomic instability, hyperpyrexia
• Tx: dantrolene, D₂ agonist (e.g., bromocriptine)

• *Think FEVER:
• -Fever
• -Encephalopathy
• -Vitals unstable
• -Elevated enzymes
• -Rigidity of muscles

• Stereotypic oral-facial movements as a result of long-term antipsychotic use
• Often irreversible

• High potency: Trifluoperazine, Fluphenazine, Haloperidol (Try to Fly High)
•      - neurologic side effects (extrapyramidal symptoms)
• Low potency: Chlorpromazine, Thioridazine (Cheating Thieves are low)
•      - non-neurologic side effects (anticholinergic, antihistamine, and α₁-blockade effects)

• Olanzapine, clozapine, quetiapine, resperidone, aripiprazole, ziprasidone
• *It's atypical for old closets to quietly risper from A to Z

• Mechanism: not completely understood
• -Varied effects on 5-HT₂, dopamine, and α- and H₁-receptors

• Clinical use:
• -Schizophrenia (both positive and negative symptoms)
• -Bipolar disorder
• -OCD
• -Anxiety disorder
• -Depression
• -Mania
• -Tourette's syndrome

• Toxicity:
• -Fewer extrapyramidal and anticholinergic side effects than traditional antipsychotics
• -Olanzapine/clozapine: weight gain
• -Clozapine: agranulocytosis (monitor WBC count weekly), seizures
• -Ziprasidone: prolong QT interval

• Second generation antipsychotic drugs:
• -fewer "extrapyramidal" AEs
• -more effective for negative symptoms
• -less elevation of prolactin
• -Metabolic syndrome

• First generation antipsychotic drugs:
• -Extrapyramidal side effects (parkinsonism)
• -dystonia, akathisia, parkinsonian syndrome

Mechanism: not known

• Clinical use: mood stabilizer
• -bipolar disorder (blocks relapse and acute manic events
• -SIADH

• Toxicity:
• LMNOP
• -Lithium side effects:
• -Movement (tremor)
• -Nephrogenic diabetes insipidus
• -HypOthyroidism
• -Pregnancy problems
• -sedation
• -edema
• -heart block
• -polyuria (ADH antagonist → nephrogenic DI)
• -Fetal cardiac defects: Ebstein anomaly, malformation of great vessels

• *Narrow therapeutic window; monitor serum levels closely
• Excretion: kidney (most is reabsorbed at proximal convoluted tubules following Na⁺ reabsorption)

Mechanism: Stimulates 5-HT_1A receptors

• Clinical use:
• -Generalized anxiety disorder
• -Does not cause sedation, addiction, or tolerance
• -Takes 1-2 weeks to take effect
• -No interaction with alcohol (vs. barbiturates, benzodiazepines)

*I'm always anxious if the bus will be on time, so I take buspirone

• Antidepressants mechanism of action
• NE reuptake: SNRIs, Desipramine, maprotiline
• 5-HT reuptake: Fluoxetine, trazodone
• α₂-receptor: Mirtazapine
• MAO inhibitors

• Fluoxetine, paroxetine, sertraline, citalopram
• *Flashbacks paralyze senior citizens

Mechanism: Serotonin-specific reuptake inhibitor

• Clinical use: normally takes 4-8 weeks for antidepressants to have an effect
• -Depression
• -Generalized anxiety disorder
• -Panic disorder
• -OCD
• -Bulimia
• -Social phobias
• -PTSD

• Toxicity:
• -Fewer than TCAs
• -GI distress, sexual dysfunction (anorgasmia, ↓ libido)
• -Serotonin syndrome: any drug that ↑ serotonin (MAO inhibitors, SNRIs, TCAs)
•      - hyperthermia, confusion, myoclonus, cardiovascular collapse, flushing, diarrhea, seizures
•      - Tx: cyproheptadine (5-HT₂ receptor antagonist)

Venlafaxine, duloxetine

Mechanism: Inhibit serotonin and NE reuptake

• Clinical use:
• -Depression
• -Venlafaxine: also used in generalized anxiety and panic disorders
• -Duloxetine: diabetic peripheral neuropathy
• -Duloxetine has greater effect on NE

• Toxicity:
• - ↑ BP most common
• - stimulant effects
• - sedation
• - nausea

Amitriptyline, nortriptyline, imapramine, desipramine, clomipramine, doxepin, amoxapine ("-iptyline" or "-ipramine")

• Mechanism:
• -Block reuptake of NE and serotonin

• Clinical use:
• -Major depression
• -bedwetting (imipramine)
• -OCP (clomipramine)
• -Fibromyalgia

• Toxicity:
• -anti-histamine side effects: sedation
• -α₁-blocking effects: postural hypotension
• -anticholinergic side effects (tachycardia, urinary retention, dry mouth) (amitriptyline > nortriptyline)
• -Tri-C's: Convulsions, Coma, Cardiotoxicyity (arrhythmias)
• -respiratory depression
• -hyperpyrexia
• -Confusion and hallucinations in elderly (use nortriptyline)

Tx: NaHCO₃ for cardiovascular toxicity

• Tranylcypromine, Phenelzine, Isocarboxazid, Selegiline (selective MAO-B inhibitors)
• **MAO Takes Pride In Shanghai

• Mechanism:
• -Nonselective MAO inhibition ↑ levels of amine neurotransmitters (NE, serotonin, dopamine)

• Clinical use: 
• -Atypical depression
• -Anxiety
• -Hypochondriasis

• Toxicity:
• -Hypertensive crisis ( with ingestion of tyramine - wine and cheese)
• -CNS stimulation
• -Contraindicated with SSRIs, TCAs, St. John's Wort, meperidine, dextromethorphan (prevent serotonin syndrome)

• Bupropion
• Mirtazapine
• Maprotiline
• Trazodone

• Mechanism: unknown → ↑ NE and dopamine
• Toxicity: stimulant effect (tachycardia, insomnia), headache, seizures in bulimic patients
• *No sexual side effects
• Other uses: smoking cessation

• Mechanism: 
• -α₂-antagonist (↑ release of NE and serotonin)
• -potent 5-HT₂ and 5-HT₃ receptor antagonist

Toxicity: sedation (desirable in depressed pts with insomnia), ↑ appetite, weight gain, dry mouth

• Mechanism: Blocks NE reuptake
• Toxicity: sedation, orthostatic hypotension

• Mechanism: Primarily inhibits serotonin reuptake
• Clinical use: insomnia
• -High doses needed for antidepressant effects
• Toxicity: sedation, nausea, priapism, postural hypotension
• *Trazobone due to male-specific side effects