Delirium tremens
Life-threatening alcohol withdrawal syndrom that peaks 2-4 days after last drink - autonomic hyperactivity (eg tachycardia, temors, anxiety, seizures) - Treatment: benzodiazepines
Atypical antipsychotics
Aripiprazole, asenapine, clozapine, olanzapine, quetiapine, iloperidone, paliperidone, risperidone, lurasidone, ziprasidone Mechanism: Most are D2 antagonists; aripiprazole is D2 partial agonist.Varied effects on 5-HT2, dopamine, and α- and H1-receptors. Clinical use: Schizophrenia – both positive and negative symptoms. Also used for bipolar disorder, OCD, anxiety disorder, depression, mania, Tourette syndrome.- Use clozapine for treatment-resistant schizophrenia or schizoaffective disorder and for suicidality in schizophrenia. Adverse effects:- All – prolonged QT interval, fewer EPS and anticholinergic side effects than typical antipsychotics- "-pines" – metabolic syndrome (weight gain, diabetes, hyperlipidemia)- Clozapine: agranulocytosis (monitor WBC weekly) and seizures (dose related)- Risperidone: hyperprolactinemia (amenorrhea, galactorrhea, gynecomastia)- Ziprasidone: prolonged QT interval
Lithium
Mechanism: not established; possibly related to inhibition of phosphoinositol cascade. Indications:- Acute mania- Bipolar maintenance Baseline studies:- Blood urea nitrogen, creatinine, calcium, urinalysis- Thyroid function tests- ECG in patients with coronary risk factors Contraindications:- Chronic kidney disease- Heart disease- Hyponatremia or diuretic use Adverse effects:Acute:- Tremor, ataxia, weakness- Vomiting, diarrhea- Polyuria, polydipsia- Cognitive impairmentChronic:- Nephrogenic diabetes insipidus- Chronic kidney disease- Thyroid dysfunction- Hyperparathyroidism- Teratogenesis (Ebstein anomaly)
Buspirone
Stimulates 5-HT1A receptors. Clinical use: Generalized anxiety disorder - Does not cause sedation, addiction, or tolerance.- Takes 1-2 weeks to take effect.- Does not interact with alcohol (vs. barbiturates, benzodiazepines).
Selective serotonin reuptake inhibitors (SSRIs)
Fluoxetine, fluvoxamine, paroxetine, sertraline, escitalopram, citalopram. Mechanism: 5-HT-specific reuptake inhibitors Clinical use: Depression, generalized anxiety disorder, panic disorder, OCD, bulimia, social anxiety disorder, PTSD, premature ejactulation, premenstrual dysphoric disorder. Adverse effects: - Headaches- Nausea, GI distress- Insomnia/sedation- SIADH, sexual dysfunction (anorgasmia, ↓ libido).- Paroxetine: Anticholinergic effects, cytochrom P-450 inhibitor, weight gain- Citalopram: QT prolongation (avoid in patients with recent MI) It normally takes 4-8 weeks for antidepressents to have an effect.
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Venlaflaxine, desvenlafaxine, duloxetine, levomilnacipran, milnacipran. Mechanism: Inhibit 5-HT and norepinephrine reuptake Clinical use: Depression, general anxiety disorder, diabetic neuropathy. Venlafaxine is also indicated for social anxiety disorder, panic disorder, PTSD, OCD. - Duloxtetine is also indicated for fibromyalgia. Adverse effects: ↑ BP, stimulant effects, sedation, nausea
Serotonin syndrome
Can occur with any drug that ↑ 5-HT (eg, MAO inhibitors, SNRIs, TCAs) - 3A's: neuromuscular Activity (clonus, hyperreflexia, hypertonus, tremor, seizure)Autonomic stimulation (hyperthermia, diaphoresis, diarrhea)Agitation Treatment: cyproheptadine (5-HT2 receptor antagonist)
Tricyclic antidepressants (TCA)
Amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, doxepin, amoxapine. Mechanism: Inhibit 5-HT and norepinephrine reuptake. Clinical use: Major depression, OCD (clomipramine), peripheral neuropathy, chronic pain, migraine prophylaxis. Nocturnal enuresis (imipramine, although adverse effects may limit use). Adverse effects: - Sedation- α1-blocking effects including postural hypotension, and atropine-like (anticholinergic) side effects (tachycardia, urinary retention, dry mouth).- 3˚ TCAs (amitriptyline) have more anticholinergic effects than 2˚ TCAs (nortriptyline). - Prolong QT-interval- Tri-C's: Convulsions, Coma, Cardiotoxicity (arrhythmia due to Na+ channel inhibition); also respiratory depression, hyperpyrexia. Confusion and hallucination in the elderly due to anticholinergic side effects (nortriptyline better tolerated in the elderly). Treatment: NaHCO3 to prevent arrhythmia.
Monoamine oxidase inhibitors
Tranylcypromine, phenelzine, isocarboxazide, selegiline (selective MAO-B inhibitor) Mechanism: nonselective MAO inhibition ↑ levels of amine neurotransmitters (NE, 5-HT, dopamine) Clinical use: Atypical depression, anxiety. Parkinson disease (selegiline). Adverse effects: - Hypertensive crisis (most notably with ingestion of tyramine) – headache, stiff neck, nausea/vomiting, chest pain, dilated pupils, nosebleed, elevated blood pressure.- CNS stimulation- Contraindicated with SSRIs, TCAs, St. John's wort, meperidine, dextromethorphan (to prevent serotonin syndrome).- Wait 2 weeks after stopping MAO inhibitors before starting serotonergic drugs
Atypical antidepressants
Bupropion: ↑ NE and dopamine- Also used for smoking cessation Mirtazapine: α2-antagonist (↑ release of NE and 5-HT), potent 5-HT2 and 5-HT3 receptor antagonist Trazodone: Primarily blocks 5-HT2, α1-adrenergic, and H1 receptors- used primarily for insomnia Varenicline: nicotinic ACh receptor partial agonist. - used for smoking cessation
Extrapyrimidal symptoms
Hours to days: Acute dystonia (muscle spasm, stiffness, oculogyric crisis). - Treatment: benztropine, diphenhydramine Days to months:- Akathisia (restlessness). Treatment: β-blockers, benztropine, benzodiazepines- Parkinsonism (bradykinesia). Treatment: benztropine, amantadine Months to years: Tardive dyskinesia (orofacial chorea). - Treatment: switch to atypical antipsychotic (eg, clozapine), tetrabenazine, reserpine
Bupropion
Inhibits NE and dopamine reuptake (does not affect serotonin). Approved for depression and smoking cessation. Toxicity: stimulant effects (tachycardia, insomnia), headache, seizures in anorexic/bulimic patients.- Favorable sexual side effect profile- Weight loss
Mirtazapine
α2-antagonist (↑ release of NE and 5-HT), potent 5-HT2 and 5-HT3 receptor antagonist and H1 antagonist. Toxicity: - Sedation (which may be desirable in depressed patients with insomnia)- ↑ appetite, weight gain (which may be desirable in elderly or anorexic patients)- Dry mouth
Trazodone
Primarily blocks 5-HT2, α1-adrenergic, and H1 receptors; also weakly inhibits 5-HT reuptake. Used primarily for insomnia, as high doses are needed for antidepressant effects. Toxicity: sedation, nausea, priapism, postural hypotension.
Vareniciline
Nicotinic ACh receptor partial agonist. Used for smoking cessation. Helps nicotine cravings decline. Toxicity: Sleep disturbance, may depress mood.
Vilazodone
Inhibits 5-HT reuptake; 5-HT1A receptor partial agonist. Used for major depressive disorder. Toxicity: headache, diarrhea, nausea, ↑ weight, anticholinergic effects.May cause serotonin syndrome if taken with other serotonergic agents.
Vortioxetine
Inhibits 5-HT reuptake; 5-HT1A receptor agonist and 5-HT3 receptor antagonist. Used for major depressive disorder. Toxicity: nausea, sexual dysfunction, sleep disturbances (abnormal dreams), anticholinergic effects.May cause serotonin syndrome if taken with other serotonergic agents.
Opioid withdrawal and detoxification
Intravenous drug users at ↑ risk for hepatitis, HIV, abscesses, bacteremia, right-heart endocarditis. - Methadone: Long-acting opiate used for heroin detoxification or long-term maintenance therapy. - Buprenorphine + naloxone: Sublingual buprenorphine (partial agonist) is absorbed and used for maintenance therapy. Naloxone (antagonist, not orally bioavailable) is added to lower IV abuse potential. - Naltrexone: Long-acting opioid given IM or as nasal spray to treat acute overdose in unconscious individual. Also used for relapse prevention once detoxified.
Atomoxetin
Norepinephrine uptake inhibitor Used in ADHD
Trifluoperazine
High potency typical antipsychotic
Fluphenazine
High potency typical antipsychotic Side effect:- Impaired thermoregulation leading to intolerance of extremes in environmental temperature (i.e., hypothermia or hyperthermia)
