Neuroleptic Malignant Syndrome (NMS)
- NMS is a rare but life-threatening reaction to antipsychotic medications characterized by a combination of hyperthermia, muscle rigidity, autonomic dysfunction, and altered mental status.
- Medications:
- Typical antipsychotics (e.g., Haloperidol, Chlorpromazine)
- Atypical antipsychotics (e.g., Olanzapine, Risperidone)
- Anti-emetics (e.g., Metoclopramide)
- Withdrawal from Parkinson’s disease medications (e.g., Levodopa)
- Risk Factors: High doses, rapid dose escalation, dehydration, agitation, and prior episodes of NMS.
- Signs and Symptoms:
- Hyperthermia: Body temperature >38°C, often >40°C.
- Muscle Rigidity: “Lead-pipe” rigidity, generalized muscle stiffness.
- Autonomic Instability:
- Tachycardia, labile blood pressure, diaphoresis
- Dysrhythmias, elevated CK
- Altered Mental Status:
- Agitation, delirium, coma
- Diagnosis:
- Primarily clinical, supported by:
- Elevated creatine kinase (CK) (often >1000 IU/L)
- Leukocytosis
- Myoglobinuria (risk of rhabdomyolysis)
- Elevated liver enzymes
- Treatment:
- Discontinuation: Stop the offending antipsychotic medication.
- Supportive Care:
- IV fluids, cooling measures for hyperthermia
- Monitoring and management of cardiovascular and respiratory status
- Pharmacologic Treatment:
- Benzodiazepines for agitation and muscle relaxation
- Dopamine agonists (e.g., Bromocriptine) or dantrolene (muscle relaxant) in severe cases
- ICU care: For intensive monitoring and treatment.
- Prevention:
- Gradual titration of antipsychotics.
- Monitoring for early signs of NMS in high-risk patients.
- Avoiding re-challenge with antipsychotics if the patient has a history of NMS.
2. Serotonin Syndrome
- Serotonin Syndrome is a potentially life-threatening condition caused by an excess of serotonin in the central nervous system.
- Causes:
- Medications:
- SSRIs (e.g., Fluoxetine, Sertraline)
- SNRIs (e.g., Venlafaxine, Duloxetine)
- MAOIs (e.g., Phenelzine, Selegiline)
- Tricyclic Antidepressants (e.g., Amitriptyline, Clomipramine)
- Other serotonergic drugs (e.g., Tramadol, Linezolid, MDMA)
- Over-the-counter supplements like St. John’s Wort
- Signs and Symptoms:
- Cognitive:
- Agitation, confusion, hypomania
- Hallucinations, coma (in severe cases)
- Autonomic:
- Hyperthermia, diaphoresis
- Tachycardia, hypertension
- Shivering, mydriasis
- Neuromuscular:
- Tremor, hyperreflexia, clonus (inducible and spontaneous)
- Myoclonus, muscle rigidity, ataxia
- Diagnosis:
- Primarily clinical based on history and physical examination.
- Hunter Criteria: A patient must have taken a serotonergic agent and meet one of the following:
- Spontaneous clonus
- Inducible clonus and agitation or diaphoresis
- Ocular clonus and agitation or diaphoresis
- Tremor and hyperreflexia
- Hypertonia, temperature >38°C, and ocular or inducible clonus
- Treatment:
- Discontinuation: Stop all serotonergic agents.
- Supportive care: IV fluids, oxygen, sedation with benzodiazepines.
- Antidote: Cyproheptadine (a serotonin antagonist) can be used in moderate to severe cases.
- Cooling measures: For hyperthermia.
- ICU care: For severe cases requiring more intensive monitoring and support.
- Prevention:
- Avoiding combinations of serotonergic drugs.
- Educating patients about the risks of over-the-counter supplements and drug interactions.
3. Lithium Toxicity
- Lithium is commonly used for mood stabilization in bipolar disorder but has a narrow therapeutic index, making toxicity a significant concern.
- Causes:
- Overdose: Intentional or accidental.
- Drug interactions: NSAIDs, ACE inhibitors, diuretics (especially thiazides) increase lithium levels.
- Dehydration: Increased lithium reabsorption in the kidneys.
- Renal impairment: Reduced clearance of lithium.
- Signs and Symptoms:
- Early (mild to moderate toxicity):
- Nausea, vomiting, diarrhea
- Tremor, mild ataxia
- Lethargy, weakness
- Late (severe toxicity):
- Severe ataxia, muscle rigidity
- Confusion, stupor, seizures, coma
- Renal failure
- Diagnosis:
- Serum lithium levels: Therapeutic range is 0.6-1.2 mEq/L. Levels >1.5 mEq/L indicate toxicity.
- Electrolytes and renal function: Assess for dehydration and renal impairment.
- ECG: Look for QT prolongation and other cardiac effects.
- Treatment:
- Discontinuation: Stop lithium immediately.
- Hydration: IV fluids to enhance renal excretion.
- Gastrointestinal decontamination: Gastric lavage and activated charcoal if the patient presents shortly after ingestion.
- Hemodialysis: Indicated for severe toxicity (levels >4.0 mEq/L or severe symptoms) or renal failure.
- Prevention:
- Regular monitoring of serum lithium levels.
- Educating patients on maintaining hydration and avoiding drugs that interact with lithium.
- Adjusting doses in cases of renal impairment.
4. QT Prolongation
- Signs and Symptoms:
- Syncope
- Palpitations
- Torsades de pointes (a specific type of polymorphic ventricular tachycardia)
- Sudden cardiac death
- Common Drugs:
- Antipsychotics (e.g., Haloperidol, Ziprasidone)
- Antidepressants (e.g., Citalopram, Escitalopram)
- Antiarrhythmics (e.g., Amiodarone, Sotalol)
- Antibiotics (e.g., Macrolides, Fluoroquinolones)
5. Hepatotoxicity
- Signs and Symptoms:
- Jaundice
- Elevated liver enzymes (AST, ALT, ALP)
- Fatigue, nausea, vomiting
- Abdominal pain
- Common Drugs:
- Acetaminophen (overdose)
- Statins (e.g., Atorvastatin, Simvastatin)
- Antiepileptics (e.g., Valproate, Phenytoin)
- Antibiotics (e.g., Isoniazid, Amoxicillin-clavulanate)
6. Rhabdomyolysis
- Signs and Symptoms:
- Muscle pain and weakness
- Dark, cola-colored urine
- Elevated creatine kinase (CK)
- Myoglobinuria, acute kidney injury (AKI)
- Common Drugs:
- Statins (e.g., Atorvastatin, Simvastatin)
- Antipsychotics (e.g., Olanzapine)
- Illicit drugs (e.g., Cocaine, Heroin)
- Severe exercise or trauma can also contribute
7. Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)
- Signs and Symptoms:
- Flu-like symptoms (fever, malaise)
- Painful red or purplish rash that spreads and blisters
- Mucosal involvement (oral, ocular, genital)
- Skin peeling and necrosis
- Common Drugs:
- Antiepileptics (e.g., Lamotrigine, Carbamazepine)
- Antibiotics (e.g., Sulfonamides, Penicillins)
- NSAIDs (e.g., Ibuprofen)
- Allopurinol
8. Agranulocytosis
- Signs and Symptoms:
- Severe neutropenia (absolute neutrophil count <500 cells/mm³)
- Fever, sore throat, infections
- Weakness, fatigue
- Common Drugs:
- Clozapine (antipsychotic)
- Carbimazole (antithyroid drug)
- Sulfonamides (antibiotic)
- Antiepileptics (e.g., Carbamazepine)
9. Neutropenia
- Signs and Symptoms:
- Low neutrophil count
- Increased susceptibility to infections
- Fever, sore throat, mouth ulcers
- Common Drugs:
- Chemotherapy agents (e.g., Cyclophosphamide)
- Immunosuppressants (e.g., Methotrexate)
- Antithyroid drugs (e.g., Methimazole)
- Clozapine
10. Thrombocytopenia
- Signs and Symptoms:
- Low platelet count
- Easy bruising, petechiae
- Bleeding gums, nosebleeds
- Prolonged bleeding from cuts
- Common Drugs:
- Heparin (Heparin-induced thrombocytopenia)
- Chemotherapy agents
- Quinine
- Valproate
11. Acute Kidney Injury (AKI)
- Signs and Symptoms:
- Reduced urine output (oliguria)
- Elevated serum creatinine and BUN
- Fluid retention (swelling in legs, ankles)
- Fatigue, confusion
- Risk Factors:
- Elderly patients
- Patients with pre-existing kidney disease
- Patients with heart failure or other conditions causing reduced renal perfusion
- Patients on high doses or prolonged courses of these medications
- Prevention:
- Avoiding the concurrent use of these medications if possible
- Regular monitoring of renal function (serum creatinine, blood urea nitrogen (BUN), and electrolytes)
- Educating patients about the risks of combining these medications
- Ensuring adequate hydration, especially in patients requiring these medications for chronic conditions
- Common Drugs:
- Triple Whammy : When these three classes of drugs are used together, they can have a compounded negative effect on kidney function:
- NSAIDs reduce renal blood flow by constricting the afferent arterioles.
- ACE inhibitors/ARBs reduce the pressure within the glomerulus by dilating the efferent arterioles.
- Diuretics decrease blood volume, further reducing renal perfusion.
- Contrast agents (for imaging studies)
- Aminoglycosides (e.g., Gentamicin)
12. Ototoxicity
- Signs and Symptoms:
- Hearing loss
- Tinnitus (ringing in ears)
- Balance disturbances (vertigo)
- Common Drugs:
- Aminoglycosides (e.g., Gentamicin)
- Loop diuretics (e.g., Furosemide)
- Chemotherapy agents (e.g., Cisplatin)
- High-dose Aspirin
13. Hyponatremia
- Signs and Symptoms:
- Nausea, headache
- Confusion, seizures
- Muscle cramps, weakness
- Fatigue
- Common Drugs:
- SSRIs (e.g., Fluoxetine, Sertraline)
- Diuretics (e.g., Thiazides)
- Carbamazepine
- Desmopressin
14. Hyperglycemia
- Signs and Symptoms:
- Increased thirst, frequent urination
- Fatigue, blurred vision
- Headaches
- Unintentional weight loss
- Common Drugs:
- Corticosteroids (e.g., Prednisone)
- Antipsychotics (e.g., Olanzapine, Quetiapine)
- Thiazide diuretics
- Beta blockers
15. Hyperkalemia
- Signs and Symptoms:
- Muscle weakness, paralysis
- Cardiac arrhythmias (e.g., peaked T waves on ECG)
- Fatigue, nausea
- Palpitations
- Common Drugs:
- ACE inhibitors (e.g., Lisinopril)
- ARBs (e.g., Losartan)
- Potassium-sparing diuretics (e.g., Spironolactone)
- NSAIDs
16. Angioedema
- Signs and Symptoms:
- Swelling of the face, lips, tongue, and throat
- Difficulty breathing, swallowing
- Abdominal pain (if intestines involved)
- Common Drugs:
- ACE inhibitors (e.g., Lisinopril)
- ARBs (e.g., Valsartan)
- NSAIDs
- Penicillins
17. Anaphylaxis
- Signs and Symptoms:
- Rapid onset of difficulty breathing, wheezing
- Swelling of the face and throat
- Rash, hives
- Hypotension, shock
- Common Drugs:
- Penicillins
- Cephalosporins
- NSAIDs
- Contrast media
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