Specific Considerations II (Murray 2.8- 2.22) Flashcards
What is serotonin syndrome?
Clinical manifestation of excessive stimulation of serotonin receptors in the CNS. Occurs when excess serotonin accumulates in the CNS due to pharmacological mechanisms.
What is the serotonin syndrome triad?
Mental status changes, autonomic stimulation and neuromuscular excitation
Discuss the features of serotonin syndrome.
Neuromuscular excitation: clonus, hyperreflexia, increased tone, myoclonus, rigidity, tremor. ANS stimulation: diarrhoea, flushing, hypertension, hyperthermia, mydiasis, sweating, tachycardia. Mental state: apprehension, anxiety, agitation, confusion
If undetected what are the life-threatening complications of serotonin syndrome?
Rhabdomyolysis, renal failure, DIC and death
Describe the diagnostic algorythm for serotonin syndrome.
Ingestion or overdose –> spontaneous clonus (if yes then = toxicity, if no then…) —> inducible clonus/ocular clonus (if yes + agitation or diaphoresis or hypertonia and hyperpyrexia = toxicity, if no then…) —> tremor (if yes + hyperreflexia then = toxicity, if no then…) —> not clinically significant toxicity. You can also have clonus + hyperreflexia as a combination = toxicity.
Describe some scenarios in which serotonin syndrome may develop.
(1) No washout between changing drugs, (2) Introduction of new drug, (3) Drug interaction/stacking, (4) Interaction with illicit or herbal drugs, (5) Deliberate self-poisoning
What is the most common and most severe life-threatening combination of drugs that cause serotonin syndrome?
MAOI and SSRI combination
List the drugs/agents implicated in the development of serotonin syndrome.
Analgesia/antitussives (tramadol, pethidine, fentanl, dextromethorphan), Antidepressants (TCAs), Ilicit drugs (amphetamines, MDMA), Herbals (spirulina, St John’s wort), Lithium, MAOIs, SSRIs, SNRI, tryptophan
List the important differentials for serotonin syndrome.
NMS, anticholinergic syndrome and malignant hyperthermia
Differentiate serotonin syndrome, NMS, anticholinergic syndrome and malignant hyperthermia
Obs discussed in a separate question. Onset over days for NMS but minutes-24 hours for MH. <12 hours SS and ACS. Mydriasis in all but MH (= normal). Sweaty and pale in all but ACS (hot, red, dry). Increased tone/rigidity in all but ACS. NMS results in mutism/bradykinesia but the others all in agitated delirium. Pts are hyporeflexic in MH, normal reflexes in ACS, bradyreflexic in NMS and hyperreflexic + clonic in SS.
What drug causes malignant hyperthermia?
Inhaled anaesthetics
What drugs cause neuroleptic malignant syndrome?
Dopamine antagonists
Compare and contrast the obs for serotonin syndrome, NMS, anticholinergic syndrome and MH.
HR, BP, RR and temp are increased in all 4
What is a possible antidote for serotonin syndrome? What dose?
Cyprohepatadine, give orally/NGT - 8 mg every 8 hours for 24 hours. Others: olanzapine, chlorpromazine
What is cyprohepatadine?
An antihistamine with anti-serotonergic effects
How long should patients with mild serotonin syndrome be observed for?
At least 8 hours (12 hours if slow-release). If any ALOC/delirium then admit for up to 24 hours and then discharge.
What is anticholinergic syndrome best described as?
Agitated delirium with variable signs of peripheral muscarinic blockade
What are the clinical features of anticholinergic syndrome?
Central Features: agitated delirium, fidgeting, picking at the air, restless, mumbling/slurred speech, disruptive behaviour, tremor, myoclonus, coma, seizures. Peripheral Features: mydriasis, tachycardia, dry mouth, dry skin, flushing, hyperthermia, sparse/absent bowel sounds, urinary retention
List 10 classes of drugs with anticholinergic effects.
Antiparkinsonian drugs (amantadine, benztropine), antihistamines, antitussives, antidepressants (TCAs), antipsychotic agents (butyrophenones, phenothiazines - droperidol, haloperidol, chlorpromazine), atypical antipsychotics (olanzapine, quetiapine), anticonvulsant agents (carbamazapine), motion sickness agents (hyoscine), antimuscarinic agents (atropine, glycopyrrolate), topical eye agents (tropicamide), urinary antispasmodic agents (oxybutynin), muscle relaxants, plants/herbals
List the differential diagnosis of anticholinergic syndrome.
Encephalitis, hypoglycaemia, hyponatraemia, ictal phenomenon, NMS, neurotrauma, sepsis, serotonin syndrome, SAH, Wernicke’s encephalopathy
What is the antidote for anticholinergic syndrome?
Physostigmine
What is cholinergic syndrome?
Result of increased acetylcholine at central and peripheral muscarinic and nicotinic receptors
How does cholinergic syndrome arise?
Either acetylcholinesterase enzyme inhibition or direct agonist action at muscarinic or nicotinic receptors
What are most clinically significant cholinergic syndromes caused by?
Organophosphate or carbamate poisonings
What are drugs that can potentially cause cholinergic syndrome?
Organophosphates, carbamates, chemical warfare agents (sarin), dementia drugs (donepezil, galantamine, rivastigmine), drugs for MG (neostigmine, physostigmine, pyridostigmine), muscarinic agents (ACh, bethanechol, carbachol, pilocarpine), nicotinic agents, mushrooms
What is a cholinergic crisis?
Copious secretions, vomiting, diarrhoea, altered mental status. Fasciculations/muscle weakness. Death is usually due to respiratory failure secondary to excessive respi scretions +/- weakness of ventilatory muscles
List the clinical features of a cholinergic syndrome.
CNS: agitation, respi depression, confusion, coma, lethargy, seizures. Neuromuscular: fasciculations, muscle weakness. PSNS Muscarinic: abdo cramping, bradycardia, bronchoconstriction, diarrhoea, lacrimation, miosis, salivation, incontinence, vomiting. SNS Nicotinic: hypertension, mydriasis, sweating, tachycardia
Discuss heart rate with cholinergic syndrome.
Bradycardia secondary to vagal stimulation is expected, tachycardia is also common (secondary to hypoxia, peripheral vasodilatation and nicotinic stimulation)
What is a known consistent feature suspicious for anticholinergic syndrome due to chemical warfare nerve agent poisoning?
Miosis
Discuss the complications of cholinergic syndrome.
Rapid onset respiratory failure, seizures, dehydration, medium/long-term neurological sequelae of organophosphate intoxication
List a comprehensive differential diagnosis for cholinergic syndrome.
Causes of weakness (GBS, snakebite, MG, botulism), cardiotropic intoxication (digoxin, beta-blockers, CCB), gastroenteritis/abdo emergencies, ictal phenomenon, mushroom ingestion, respi disorders (asthma, CCF), salicylate intoxication, serotonin syndrome, sympathomimetic syndrome, theophylline intoxication
What drug can be given in a cholinergic crisis and under what circumstances. The use of pralidoxime is controversial
Atropine can be given if there are objective signs of muscarinic excess (cough, dyspnoea, respi failure, vomiting, diarrhoea, salivation, lacrimation, bradycardia. These can be given in escalating doses until respi secretions are drying.
What is the usual risk assessment prognosis with cholinergic crisis in Australia?
Deliberate self-poisoning and/or paediatric intoxication - regard as life threatening cholinergic crisis
What is neuroleptic malignant syndrome?
Rare but potentially lethal syndrome complicating the use of neuroleptic medications. Characterised by rigidity, ALOC, autonomic instability. The exact cause is unknown but deficiency of dopaminergic neurotransmission at nigrostriatal, mesolimbic and HP axis +/- altered skeletal muscle mitochondrial function.
What is the cause for neuroleptic malignant syndrome?
The exact cause is unknown but deficiency of dopaminergic neurotransmission at nigrostriatal, mesolimbic and HP axis +/- altered skeletal muscle mitochondrial function.
List the potential clinical features of NMS.
CNS: confusion, delirium, stupor, coma. ANS instability: hyperthermia, tachycardia, hypertension, respiratory changes, cardiac dysrhythmias. Neuromuscular: ‘lead-pipe rigitidy’, bradykinesia/akinesia, mutism/staring, dysarthria, dystonia/abnormal posturing, abnormal involuntary movements, incontinence
What is the criteria for neuroleptic malignant syndrome?
(1) Recent exposure to dopamine antagonist or dopamine agonist withdrawal, (2) Hyperthermia, (3) Rigidity, (4) ALOC, (5) CK elevation x4 upper limit normal, (6) SNS lability = 2 of hypertension, BP fluctuations, diaphoresis, incontinence, (7) Tachycardia + tachypnoea, (8) Negative work-up for infectious, toxic, metabolic and neurological causes
What lab tests may be abnormal in neuroleptic malignant syndrome?
High WCC, altered renal/liver function, metabolic acidosis, hypocalcaemia, hypomagnasaemia, reduced serum iron. CSF may have elevated protein count in 1/3 of patients. EEG shows a metabolic encephalopathy pattern.
How common is NMS?
0.02-0.25% of patients taking neuroleptic medication will develop this. This has not increased with the advent of atypical antipychotics
What are risk factors for NMS?
Younger, male, genetics, psychiatric co-morbidities, use of multiple neuroleptic agents, pre-existing medical conditions (like trauma, malnutrition, infection, premenstrual phase), large increases in doses, depot preparations, parenteral administration, pre-existing brain disorders (tumours, AIDS, encephalitis)
List the differential diagnosis for NMS.
Acute lethal (malignant) catatonia, malignant hyperthermia, serotonin syndrome, anticholinergic syndrome, sympathomimetic syndrome, encephalitis, metabolic encephalopathies
What are the primary differences between NMS and acute lethal malignant catatonia?
NMS is usually characterised by bradykinesia and mutism whereas ALMC is by abnormal posturing and waxy flexibility.
What proportion of patients that have had NMS will have it again if re-exposed?
30-50%
List the complications for NMS.
Respiratory failure, dehydration, renal failure, multi-organ failure, DVT/PE, residual catatonia/parkinsonian symptoms
What are several drugs you may expect to use to treat NMS?
Oxygen, fluids, dextrose, IV benzos, electrolyte preparations (calcium, magnesium), GTN/sodium nitroprusside, ? Utility of bromocriptine
Discuss the roles of antidote therapy in NMS.
Bromocriptine, dantrolene and ECT have not yet been given definite roles in the management of NMS. It is not clear if they improve outcomes or survival.
What is bromocriptine? Discuss dosing bromocriptine.
Dopamine agonist. Can be given orally or via NGT. 2.5mg every 8 hours increasing to 5 mg every 4 hours (30 mg max/day). Results to the ANS symptoms and fever within 24 hours but CNS changes may take days. Should be continued for 1-2 weeks before a tapering dose.
What is dantrolene? Discuss dosing dantrolene.
Indicated for severe muscular rigidity and fever, dopamine agonist. IV 2-3 mg/kg/day up to a total of 10 mg/kg/day. Then change to orally 100-400 mg/day in divided doses for 10 days or switch patient to bromocriptine.
When is ECT indicated in NMS.
Severe NMS refractory to supportive care and antidotes. Severe NMS difficult to differentiate from acute lethal catataonia. Treatment of residual symptoms of NMS. When patients with psychiatric disorders like psychotic depression have NMS.
Discuss the definition of alcohol use disorder.
Large amounts over a longer period of time, persistent desire, great deal of time to obtain alcohol, cravings, impairs other obligations/comitments, ongoing alcohol in spite negative interpersonal problems, recurrent use, continued use in spite person knows it is causing problems, tolerance develops. Presence of 2+ of the above symptoms = mild, moderate = 4-5 and severe = 6+ symptoms.
