Pharm Week 7 Objectives: Psychotherapeutic Drugs PDF

**Pharm Week 7 Objectives: Psychotherapeutic Drugs** **[DEPRESSION]** - **Explain the clinical manifestation and etiology of clinical depression:** - **Manifestations:** - **Emotional:** Persistent sadness, hopelessness, anhedonia (loss of interest in activities...

**Pharm Week 7 Objectives: Psychotherapeutic Drugs** **[DEPRESSION]** - **Explain the clinical manifestation and etiology of clinical depression:** - **Manifestations:** - **Emotional:** Persistent sadness, hopelessness, anhedonia (loss of interest in activities), feelings of worthlessness or guilt, sense of dejection - **Cognitive:** Difficulty concentrating, indecisiveness, recurrent thoughts of death or suicide. - **Physical:** Changes in sleep (insomnia/hypersomnia), anorexia and weight loss (or sometimes hyperphagia and weight gain), fatigue, psychomotor agitation or retardation - **Etiology:** - **Biological Factors:** Neurotransmitter imbalances (serotonin, norepinephrine, dopamine), genetic predisposition, neuroendocrine abnormalities. - **Psychosocial Factors:** Chronic stress, trauma, or significant life changes. - **Environmental Factors:** Social isolation, poor support systems, adverse socioeconomic conditions. - **Categorize drugs used for mood and emotional disorders based on their classification and drug action:** - **Antidepressants:** - **Classification:** 1. Selective Serotonin Reuptake Inhibitors (SSRIs) 2. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) 3. Tricyclic Antidepressants (TCAs) 4. Monoamine Oxidase Inhibitors (MAOIs) 5. Atypical Antidepressants - **Drug Action:** - primarily aimed at correcting neurotransmitter imbalances (serotonin, norepinephrine, and dopamine) through various mechanisms such as reuptake inhibition or enzyme inhibition to improve mood and alleviate depression - **Mood Stabilizers:** - **Classification:** 6. Lithium 7. Antiepileptics/Anticonvulsants - **Drug Action:** - Stabilize mood swings, particularly in bipolar disorder, by modulating neurotransmitter activity and reducing abnormal brain activity - lithium modulating second messenger systems - antiepileptics acting on ion channels and neurotransmitter activity - **Antipsychotics:** - **Classification:** 8. Typical Antipsychotics (e.g., Haloperidol), 9. Atypical Antipsychotics (e.g., Aripiprazole, Risperidone) - **Drug Action:** - Target dopamine and serotonin receptors to manage psychotic features: symptoms of psychosis, mania, and mood disturbances - Typical agents being more potent in D2 blockade (but with a higher risk of EPS) - Atypical agents offering a broader receptor profile with a different side-effect spectrum - **Anxiolytics:** - **Classification:** 10. Benzodiazepines (e.g., Diazepam, Lorazepam) 11. SSRI's - **Drug Action:** - ↓ anxiety by enhancing the effect of GABA (a neurotransmitter that promotes relaxation) or by ↑ serotonin levels - **Stimulants:** - **Classification:** 12. Methylphenidate 13. Amphetamines 14. Methylxanthines 15. Miscellaneous CNS Stimulants - **Drug Action:** - ↑ levels of dopamine and norepinephrine to improve attention, focus, and energy in conditions like ADHD - **Sedative-Hypnotic:** - **Classification:** 16. Benzodiazepines (e.g., Diazepam, Lorazepam) 17. SSRI's - **Drug Action:** - Cause generalized CNS depression which manifests as sedation, hypnosis (sleep induction), and anxiolysis. - May produce tolerance with chronic use and have potential for psychological or physical dependence. These agents have NO analgesic properties. - **Identify the mechanism of action, precautions, contraindications and adverse effects and drug interactions:** **[ANTIDEPRESSANTS]** 1. **Selective Serotonin Reuptake Inhibitors (SSRIs): Citalopram, Fluoxetine, Escitalopram, Sertraline** - **MOA:** selectively block neuronal reuptake of serotonin (5-hydroxytryptamine \[5-HT\]), a monoamine neurotransmitter - As a result of reuptake blockade, the concentration of 5-HT in the synapse ↑ causing ↑ activation of postsynaptic 5-HT receptors. - **Precautions:** Contraindicated for pt's on MAOIs (combo can be fatal: serotonin syndrome need to wait 5 weeks after D/C MAOI before starting SSRIs) - Caution in use with anticoags (both categories of drug are protein bound) - Pregnancy: autism? Persistent pulmonary hypertension of the newborn? - Caution in use with bipolar disorder (risk of switching to manis) - Closely monitor for ↑ suicidal ideation - **Adverse Effects:** nausea, headache, sexual dysfunction (especially anorgasmia), insomnia or drowsiness, nervousness and anxiety, mania, sweating, seizures, ↓ appetitive and weight loss, agitation, serotonin syndrome - **Drug Interactions:** Avoid combination with MAOIs; caution with other serotonergic drugs (SNRIs, TCAs, MAOIs, atypical antidepressants, triptan antimigraine drugs, Flexeril, St, John's Wort) due to the risk of serotonin syndrome - drugs that inhibit CYP2D6 (and thereby ↑ fluoxetine levels): tramadol (an analgesic), and linezolid (an antibiotic that inhibits MAO) - Fluoxetine and ↑ levels of TCAs and lithium 2. **Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Desvenlafaxine, Duloxetine, Levomilnacipran, Venlafaxine** - **MOA:** lock neuronal reuptake of serotonin and NE, with minimal effects on other transmitters or receptors - Pharmacologic effects are similar to those of the SSRIs - SSRIs may be better tolerated. - **Precautions:** Monitor blood pressure (especially with Venlafaxine) and use caution in patients with hypertension - Use late in pregnancy can result in a neonatal withdrawal syndrome characterized by irritability, abnormal crying, tremor, respiratory distress, and possibly seizures - Abrupt discontinuation can cause an intense withdrawal syndrome. Symptoms include anxiety, agitation, tremors, headache, vertigo, nausea, tachycardia, and tinnitus (taper dose over 2-4 weeks) - **Adverse Effects:** Nausea (37% to 58%), headache, anorexia, nervousness, sweating, somnolence, and insomnia. Dose-dependent weight loss may occur secondary to anorexia, dry mouth, dizziness, sustained diastolic HTN, sexual dysfunction (impotence, anorgasmia) - **Drug Interactions:** Similar risk for serotonin syndrome when combined with other serotonergic medications 3. **Tricyclic Antidepressants (TCAs): Amitriptyline, Imipramine, Doxepin, Clominpramine** - - TCAs ↑ the concentration of these transmitters at CNS synapses and thereby intensify their effects - Inhibit reuptake of both norepinephrine and serotonin, ↑ their synaptic concentrations - - Can cause toxicity: OD can be life-threatening (don't prescribe for more than 1 week at a time for an acutely depressed patient) - - - - - - Avoid with MAOIs, sympathomimetic drugs, anticholinergic agents (including antihistamines) 4. **Monoamine Oxidase Inhibitors (MAOIs):** - **MOA:** Inhibit the monoamine oxidase enzyme responsible for breaking down serotonin, norepinephrine, and dopamine. - **Precautions:** - **Food Interactions:** Avoid tyramine-rich foods (aged cheeses, cured meats, fermented foods, avocados, meats that are fermented, smoked or aged, liver, bologna, pepperoni, salami, dried or cured fish, yeast extract, some imported beers, chianti wine, protein dietary supplements, soy sauce shrimp paste) to prevent hypertensive crisis - **Adverse Effects:** Orthostatic hypotension, weight gain, sexual dysfunction, CNS stimulation (xxcessive stimulation can produce anxiety, insomnia, agitation, hypomania, and even mania. - **Drug Interactions:** Concomitant use with SSRIs, TCAs, sympathomimetics, antihypertensive drugs, meperidine 5. **Atypical Antidepressants** - **MOA:** Inhibits norepinephrine and dopamine reuptake. - **Precautions/Contraindications:** Contraindicated in patients with seizure disorders (@ doses \>450mg/day, avoid rapid dose titration) - avoid use with seizure risk factors: head trauma, preexisting seizure disorder, CNS tumor, other meds that ↓ seizure threshold - small risk of causing psychotic symptoms (hallucinations and delusions) - ↑ suicide risk in children, adolescents, young adults - avoid in patients with eating disorders - **Adverse Effects:** Insomnia, agitation, and lowered seizure threshold - **Drug Interactions:** drugs that inhibit CYP2B6 (which ↑ bupropion levels: sertraline, fluoxetine, paroxetine), MAOIs (↑ risk of bupropion toxicity; D/C 2 weeks before starting bupropion), other seizure-lowering agents, alcohol B. **Mirtazapine** - **MOA:** Antagonizes presynaptic α2 receptors (enhancing norepinephrine and serotonin release) and blocks certain serotonin receptors blocks histamine receptors and thus promotes sedation and weight gain - **Precautions:** metabolic effects, hepatic/CV considerations, contraindicated with hypersensitivity to mirtazapine - **Adverse Effects:** Sedation/somnolence (also exacerbated by alcohol, benzos, and other CNS depressants), weight gain, ↑ cholesterol, sexual dysfunction (minimal) - **Drug Interactions:** CNS Depressants, other serotonergic drugs, MAOIs C. **Trazodone** - **MOA:** Serotonin receptor antagonist and weak reuptake inhibitor - **Precautions:** contraindicated with concurrent MAOI therapy; not to be used with known sensitivity to trazodone - **Adverse Effects:** Sedation, orthostatic hypotension, rare risk of priapism - **Drug Interactions:** CNS Depressants, serotonergic agents, cardiac conduction (caution with drugs that prolong QT interval) - **Identify treatment algorithm for treatment of clinical depression:** - **\ ** - **Identify the adverse effect of Serotonin Syndrome and drug interactions that can increase the risk of Serotonin Syndrome:** - **Key Features of Serotonin Syndrome** 1. **Mental Status Changes** - Agitation, confusion, restlessness, anxiety, or excitement 2. **Autonomic Hyperactivity** - Tachycardia (rapid heart rate), hypertension (high blood pressure) - Hyperthermia (elevated body temperature), diaphoresis (excessive sweating) - Pupillary dilation 3. **Neuromuscular Abnormalities** - Tremor, clonus (involuntary muscle contractions), hyperreflexia (exaggerated reflexes) - Muscle rigidity (especially in severe cases) - Incoordination 4. **Gastrointestinal Symptoms** - Nausea, vomiting, diarrhea - Severe cases can lead to seizures, arrhythmias, rhabdomyolysis (muscle breakdown), and even coma or death if untreated. - **Drugs and Interactions Increasing Serotonin Syndrome Risk** 1. **Antidepressants** - SSRIs (e.g., Fluoxetine, Sertraline) combined with MAOIs (e.g., Phenelzine, Tranylcypromine) - SSRIs combined with SNRIs (e.g., Venlafaxine) or TCAs (e.g., Amitriptyline) - MAOIs combined with other serotonergic agents (e.g., meperidine, tramadol) - Atypical antidepressants (e.g., Trazodone, Mirtazapine, Bupropion) when added to other serotonergic drugs 2. **Analgesics** - Tramadol, Meperidine, Fentanyl, Methadone, Tapentadol can have serotonergic activity - Combining these with SSRIs, SNRIs, or MAOIs increases risk 3. **Triptans (for Migraine)** - Sumatriptan, Rizatriptan, etc. used with SSRIs or SNRIs can precipitate serotonin syndrome 4. **Linezolid (Antibiotic)** - Has MAO-inhibiting properties; concurrent use with SSRIs/SNRIs can raise serotonin levels 5. **St. John's Wort (Herbal Supplement)** - Can enhance serotonin and raise risk when combined with SSRIs, SNRIs, or other serotonergic drugs 6. **Dextromethorphan (Cough Suppressant)** - At high doses or in combination with other serotonergic agents can contribute to serotonin syndrome 7. **Illicit Drugs** - MDMA ("ecstasy"), LSD, and other psychoactive substances can significantly raise serotonin - **Recognize the suicide risk associated with antidepressant therapy:** - Antidepressants can be highly effective for treating major depressive disorder and other mood conditions. However, they carry a recognized risk of ↑ SI thoughts and behaviors in certain populations - **Black Box Warning:** - FDA has issued a Black Box Warning for all antidepressants regarding an increased risk of SI and behavior in young individuals, particularly during the early weeks of treatment or when doses are changed (↑ or ↓) - - Early in treatment, improvements in energy and motivation can occur before mood fully improves, potentially enabling a person to act on pre-existing suicidal thoughts - Biological changes in neurotransmitter levels can also transiently affect mood and behavior. - **Who is at Highest Risk:** - Age: Children, adolescents, and adults under 25 - Past Suicidal Ideation/Attempts: Individuals with a history of suicidal behavior are more vulnerable - Bipolar Disorder: Antidepressants can precipitate mania, which may include high-risk behaviors - **Follow Up/Monitoring:** - Patients/caregiver should meet with the prescriber at least weekly during the first 4 weeks of treatment - then biweekly for the next 4 weeks, - then once 1 month later, and periodically thereafter - **Symptoms of decline:** anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, hypomania, emergence of suicidality - **Considerations:** - Prescriptions should be written for the smallest number of doses consistent with good patient management - Dosing of inpatients should be directly observed to ensure that each dose is swallowed and not "cheeked" to prevent the patient from accumulating multiple doses that might be taken with suicidal intent - **Identify the specific food-drug interactions & drug-drug interactions regarding with the MAOIs:** - **Food-Drug Interactions:** Tyramine-Rich Foods MAOIs inhibit the breakdown of tyramine in the gut and liver - Elevated tyramine can trigger a hypertensive crisis (sudden, severe increase in blood pressure). Patients on MAOIs should avoid or significantly limit: - **Aged cheeses**:, cheddar, Swiss, blue cheese, Parmesan - **Cured, smoked, or processed meats:** salami, pepperoni, bologna - **Fermented foods:** sauerkraut, kimchi, pickles - **Soy products:** soy sauce, miso, tofu, tempeh - **Yeast extracts:** Marmite, Vegemite - **Certain alcoholic beverages:** tap or home-brewed beers, some imported beers, red wine, Chianti - **Other tyramine-rich items:** Overripe fruits, dried fish, fava beans - **Other Dietary Considerations:** - **Caffeine:** high doses of caffeine can increase the risk of elevated blood pressure and palpitations. - **Chocolate:** Contains small amounts of tyramine and phenylethylamine; generally safe in moderation, but high intake may pose a risk. - **Drug-Drug Interactions:** - **Serotonergic Drugs** - Combining MAOIs with drugs that increase serotonin can lead to serotonin syndrome, a potentially life-threatening condition characterized by mental status changes, autonomic instability, and neuromuscular abnormalities. - **SSRIs** (Fluoxetine, Sertraline, Paroxetine) - **SNRIs** (Venlafaxine, Duloxetine) - **TCAs** (Amitriptyline, Imipramine) - **Tramadol, Meperidine** (opioid analgesics with serotonergic properties) - **Triptans** (migraine medications) - **Linezolid** (antibiotic with MAO-inhibiting properties) - **St. John's Wort** - **Other Atypical Antidepressants** (Trazodone, Mirtazapine, etc.) - **Important:** A washout period (usually 2 weeks, or 5 weeks after stopping Fluoxetine) is recommended when switching from these agents to an MAOI or vice versa - **Sympathomimetic Drugs** - MAOIs can intensify the effects of sympathomimetics, leading to dangerous elevations in blood pressure - **Decongestants** (pseudoephedrine, phenylephrine) - **Stimulants** (amphetamines, methylphenidate) - **Illicit drugs** (cocaine, MDMA) - **Other Interactions** - **Antihypertensives:** Effects may be unpredictable; some may have potentiated hypotensive effects, while others can interact dangerously with MAOIs - **Anesthetics:** Caution with certain anesthetic agents that can affect catecholamines or serotonin. - **Buspirone:** Risk of elevated blood pressure and serotonin syndrome **[BIPOLAR DISORDER]** - **Categorize drugs used for bipolar disease based on their classification and drug action:** - **Lithium:** Regulates neurotransmitter activity and stabilizes mood. - **Anticonvulsants:** Such as valproic acid (Depakene), lamotrigine (Lamictal), and carbamazepine (Tegretol). They stabilize mood by reducing abnormal electrical activity in the brain **2. Antipsychotics:** These are used to manage symptoms of mania and sometimes depression. - **Atypical Antipsychotics:** Such as aripiprazole (Abilify), quetiapine (Seroquel), and olanzapine (Zyprexa). They work by altering the effects of neurotransmitters in the brain, particularly dopamine and serotonin **3. Antidepressants:** These are used to treat depressive episodes but are often combined with mood stabilizers to prevent triggering mania. - **Selective Serotonin Reuptake Inhibitors (SSRIs):** Such as fluoxetine (Prozac) and sertraline (Zoloft). They increase serotonin levels in the brain. - **Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs):** Such as venlafaxine (Effexor) and duloxetine (Cymbalta). They increase both serotonin and norepinephrine levels **4. Benzodiazepines:** These are used short-term to manage anxiety and agitation. - **Examples:** Clonazepam (Klonopin) and lorazepam (Ativan). They enhance the effect of the neurotransmitter GABA, producing a calming effect - **Identify the mechanism of action, precautions, contraindications and adverse effects and drug interactions: Lithium, Antiepileptics (valproic acid, carbamazapine), Antipsychotics:** A screenshot of a black screen Description automatically generated **Antiepileptics:**  A screenshot of a black and white medical list Description automatically generated  - **Discuss sodium requirement and concerns about hyponatremia for clients on lithium:** - **Kidney Handling of Lithium:** - Lithium is reabsorbed in the kidneys similarly to sodium - When sodium levels are ↓, the kidneys ↑ sodium (and lithium) reabsorption - **Impact of Low Sodium (Hyponatremia):** - **↑ Lithium Reabsorption:** A ↓ in dietary sodium or hyponatremia causes the kidneys to conserve sodium. This inadvertently ↑ lithium reabsorption, ↑ blood lithium levels - **Risk of Toxicity:** ↑ lithium levels can lead to toxicity, presenting as tremors, confusion, gastrointestinal distress, and, in severe cases, neurological impairment or seizures - **Clinical Recommendations:** - **Consistent Sodium Intake:** Clients should aim to maintain a stable, balanced sodium intake rather than adopting extreme low-sodium diets. - **Adequate Hydration:** Dehydration (from illness, excessive sweating, etc.) can ↓ sodium levels and should be avoided - **Monitor Diuretic Use:** Thiazide diuretics can ↓ sodium levels and should be used cautiously with lithium - **Regular Laboratory Monitoring:** Routine checks of serum lithium levels, electrolytes (including sodium), and kidney function are essential, especially if dietary habits or medications change - **Identify the clinical manifestations of lithium toxicity and normal therapeutic levels for lithium:** A screenshot of a medical information Description automatically generated **[ANTIPSYCHOTICS]** - **Discuss the rationale for selecting a specific antipsychotic drug for the treatment of schizophrenia:**  A close-up of a list of words Description automatically generated  **Key Considerations When Choosing an Antipsychotic** - Most FGAs and SGAs are equally effective, except for clozapine, which is more effective than the rest - Although FGAs pose a greater risk for EPS, SGAs pose a significant risk for metabolic effects, which may be more detrimental than EPS - FGAs cost much less than SGAs 1. **Symptom Type:** - Positive symptoms → FGAs or high-potency SGAs (Risperidone, Olanzapine) - Negative symptoms → SGAs (Clozapine, Quetiapine, Olanzapine) 2. **Side Effect Profile:** - If EPS risk is a concern → Avoid FGAs, use **Aripiprazole or Quetiapine** - If weight gain is a concern → Avoid Olanzapine, Clozapine - If prolactin elevation is a concern → Avoid Risperidone - If a patient has diabetes or dyslipidemia an FGA might be a good choice, as might aripiprazole or ziprasidone, two SGAs with a ↓ risk for metabolic effects 3. **Patient-Specific Factors:** - **History of poor adherence** → Consider **long-acting injectable (LAI) formulations** - **Treatment resistance** (failed 2 or more antipsychotics) → **Clozapine is recommended** **Conclusion** - **Categorize drugs used for psychoses based on their classification and drug action** A table with words and a list of drugs Description automatically generated - **Identify the mechanism of action, precautions, contraindications and adverse effects and drug interactions of the Typical (1st generation) and Atypical (2nd generation)** +-----------------------+-----------------------+-----------------------+ | Category | Typical | Atypical | | | Antipsychotics | Antipsychotics | | | | | | | 1^st^ Generation, | 2^nd^ Generation, | | | FGAs | SGAs | +=======================+=======================+=======================+ | Generic Names | Haloperidol, | Risperidone, | | | Fluphenazine, | Olanzapine, | | | Chlorpromazine, | Quetiapine, | | | Perphenazine, | Aripiprazole, | | | Thioridazine, | Clozapine, | | | Loxapine, | Paliperidone, | | | Trifluoperazine | Ziprasidone, | | | | Lurasidone | +-----------------------+-----------------------+-----------------------+ | Mechanisms of Action | **Strong dopamine D2 | **D2 receptor | | | receptor blockade** | blockade + 5-HT2A | | | in the mesolimbic | (serotonin) | | | pathway → reduces | antagonism** → | | | **positive symptoms** | balances dopamine in | | | (hallucinations, | different pathways, | | | delusions) | treating both | | | | **positive & negative | | | | symptoms** | +-----------------------+-----------------------+-----------------------+ | Precautions | - **High risk of | - **Metabolic | | | EPS** | risks** (weight | | | | gain, diabetes, | | | - Avoid in | hyperlipidemia) | | | **elderly | | | | dementia-related | - Avoid in | | | psychosis** (↑ | **elderly | | | risk of death) | dementia | | | | patients** | | | - **QT prolongation | | | | risk** (esp. | - **Risperidone can | | | Haloperidol, | ↑ prolactin | | | Thioridazine) | levels** | | | | | | | | - Clozapine | | | | requires | | | | **regular WBC | | | | monitoring** | | | | (risk of | | | | agranulocytosis) | +-----------------------+-----------------------+-----------------------+ | Contraindications | -- | - **Clozapine | | | -- | contraindicated | | | | in | | | +------------------+ | agranulocytosis** | | | | - Parkinson's | | | | | | disease | | - Avoid in **severe | | | | (**worsens | | metabolic | | | | motor | | disorders** | | | | symptoms**) | | | | | | | | - Avoid in patients | | | | - Severe liver | | with **history of | | | | or heart | | neuroleptic | | | | disease | | malignant | | | | | | syndrome (NMS)** | | | | - **CNS | | | | | | depression | | | | | | (alcohol, | | | | | | benzodiazepi | | | | | | nes, | | | | | | opioids)** | | | | | | | | | | | | - Seizure | | | | | | disorders | | | | | | (lowers | | | | | | threshold) | | | | | +------------------+ | | +-----------------------+-----------------------+-----------------------+ | Adverse Effects | - **EPS**: | - **↓ EPS risk** | | | dystonia, | (except | | | akathisia, | Risperidone) | | | tardive | | | | dyskinesia, | - **Weight gain, | | | parkinsonism | metabolic | | | | syndrome** | | | - **Neuroleptic | (Olanzapine, | | | malignant | Clozapine) | | | syndrome (NMS)**: | | | | rigidity, fever, | - **Hyperprolactine | | | autonomic | mia** | | | instability - | (Risperidone, | | | Sedation, weight | Paliperidone) | | | gain | | | | | - **QT | | | - **QT | prolongation** | | | prolongation, | (Ziprasidone) | | | arrhythmias** | | | | | - **Agranulocytosis | | | - **Anticholinergic | (Clozapine)** | | | effects** (dry | | | | mouth, | | | | constipation, | | | | blurred vision, | | | | urinary | | | | retention) | | +-----------------------+-----------------------+-----------------------+ | Drug Interactions | -- | - **↑ risk of | | | -- | serotonin | | | | syndrome** with | | | +------------------+ | antidepressants | | | | - **Avoid with | | | | | | CNS | | - **Avoid other | | | | depressants* | | dopamine | | | | * | | blockers** (e.g., | | | | (↑ sedation, | | Metoclopramide → | | | | respiratory | | ↑ EPS) | | | | depression) | | | | | | | | - **Clozapine + | | | | - **Avoid with | | smoking = ↓ drug | | | | drugs that | | levels** | | | | prolong QT | | | | | | interval** | | | | | | (antiarrhyth | | | | | | mics, | | | | | | macrolides, | | | | | | fluoroquinol | | | | | | ones) | | | | | | | | | | | | - **Levodopa & | | | | | | dopamine | | | | | | agonists ↓ | | | | | | efficacy** | | | | | +------------------+ | | +-----------------------+-----------------------+-----------------------+ - **Differentiate classification of first-generation antipsychotics based on potency (low-high potency)**  **Key Differences by Potency:** - **Low-potency FGAs** → More **sedation, anticholinergic effects, and hypotension** but **less EPS**. - **High-potency FGAs** → More **EPS and prolactin elevation**, but **less sedation & anticholinergic effects**. - **Medium-potency FGAs** → Balanced effects between **sedation and EPS risks** - **Differentiate between Neuroleptic Malignant Syndrome and Serotonin Syndrome** +-----------------------+-----------------------+-----------------------+ | Feature | Neuroleptic Malignant | Serotonin Syndrome | | | Syndrome (NMS) | (SS) | +=======================+=======================+=======================+ | Cause | Dopamine **D2 | Excess **serotonin** | | | receptor blockade** | (caused by SSRIs, | | | (caused by | SNRIs, MAOIs, TCAs, | | | antipsychotics, | triptans, MDMA, St. | | | especially | John\'s Wort) | | | **1st-generation | | | | FGAs**) | | +-----------------------+-----------------------+-----------------------+ | Onset | -- | Rapid (Hours to 2-72 | | | -- | Hours) | | | | | | | ------------------- | | | | ------ | | | | Gradual (Days to We | | | | eks) | | | | ------------------- | | | | ------ | | +-----------------------+-----------------------+-----------------------+ | Key Symptoms | - **\"Lead pipe\" | - **Neuromuscular | | | muscle rigidity** | hyperactivity** | | | | (tremors, | | | - hyperthermia | hyperreflexia, | | | (fever **\>101.3° | myoclonus, | | | F**), | clonus) | | | | | | | - altered mental | - Fever | | | status (delirium, | | | | agitation) | - autonomic | | | | instability | | | - autonomic | | | | instability | - **altered mental | | | (hypertension, | status** | | | tachycardia, | (agitation, | | | diaphoresis) | hallucinations, | | | | confusion, | | | - dysrhythmias | disorientations, | | | | anxiety, poor | | | - **↑ creatine | concentration) | | | kinase (CK)** | | | | | - **excessive | | | | sweating** | +-----------------------+-----------------------+-----------------------+ | Neuromuscular Signs | - **Severe | - Hyperreflexia | | | rigidity** | | | | | - Clonus | | | - **bradykinesia** | | | | (slow movements) | - Tremors | +-----------------------+-----------------------+-----------------------+ | Fever Severity | -- | Moderate to high | | | -- | fever | | | | | | | ------------------- | | | | -------------------- | | | | **High fever (often | | | | \>40°C / 104°F)** | | | | ------------------- | | | | -------------------- | | +-----------------------+-----------------------+-----------------------+ | Autonomic Instability | -- | Hypertension, | | | -- | tachycardia, | | | | **fluctuating vital | | | ------------------- | signs** | | | --------------------- | | | | ----------- | | | | Hypertension, tachy | | | | cardia, diaphoresis, | | | | labile BP | | | | ------------------- | | | | --------------------- | | | | ----------- | | +-----------------------+-----------------------+-----------------------+ | Lab Findings | -- | - Normal CK | | | -- | | | | | - Possible | | | -- | metabolic | | | -- | acidosis | | | | | | | - **↑ Creatine | | | | Kinase (CK)** | | | | | | | | - **↑ WBC,** | | | | | | | | - **↑ liver | | | | enzymes** | | +-----------------------+-----------------------+-----------------------+ | Treatment | - **D/C | - **D/C | | | antipsychotic** | serotonergic drug | | | | (syndrome | | | - Supportive care | typically | | | (IV fluids, | resolves | | | cooling) | spontaneously)** | | | | | | | - Cooling blankets | - Supportive care | | | | (IV fluids, | | | - Antipyretics | cooling) | | | | | | | - **Dantrolene | - **Benzodiazepines | | | (muscle relaxant | ** | | | ↓ rigidity and | (for agitation & | | | hyperthermia)** | tremors) | | | | | | | - **Bromocriptine | - **Cyproheptadine* | | | (dopamine | * | | | agonistmay | (serotonin | | | relieve CNS | antagonist) | | | toxicity)** | | | | | | | | - Benzos to relieve | | | | anxiety | | | | | | | | - Resumption of | | | | antipsychotics ↑ | | | | risk of NMS | | | | reoccurrence | | | | | | | | wait at least 2 | | | | weeks | | | | | | | | use lowest | | | | effective dose | | | | | | | | avoid high | | | | potency agents | | +-----------------------+-----------------------+-----------------------+ | Mortality Risk | **High (5-25%)** if | **Lower (\~2-12%)** | | | untreated | if untreated | +-----------------------+-----------------------+-----------------------+ - **Explain and be able to differentiate between the symptoms associated with extrapyramidal side effects of antipsychotic drugs (Pseudoparkinson, Tardive dyskinesia, Akathasia, Acute dystonia):** - EPS result from dopamine D2 receptor blockade in the nigrostriatal pathway, commonly seen with FGA (typical) antipsychotics and, to a lesser extent, some SGA (atypical) antipsychotics A table with text on it Description automatically generated - **Mnemonic to Remember EPS Onset & Symptoms: \"ADAPT\"** - **A**cute **D**ystonia (**A**fter hours to days) - **A**kathisia (**A**fter days to weeks) - **P**seudoparkinsonism (**P**ost weeks to months) - **T**ardive Dyskinesia (**T**akes months to years)