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
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