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.
What are the medical complications of chronic alcohol abuse?
Cardiac (AF, cardiomyopathy), Electrolytes (hypo-everything), Endocrine (hypoglycaemia, hypogonadism, OP, steatosis), Haem (anaemia, coagulopathy, macrocytosis, thrombocytopenia, leukopenia), GI (hepatitis, cirrhosis, gastritis, malabsorption syndromes, varices, GI haemorrhage, pancreatitis), Malignancy (breast, CRC, hepatic, larynx, oesophagus, oropharynx), Malnutrition (folate, pallegra, scury, stomatitis), Neurological (dementia, Korsakoff, Wernicke’s, peripheral neuropathy, cerebellar degeneration), Psychiatric (hallucinations, depression, suicide, delusions)
Name two screening tools that can be used to identify patients with ETOH use disorder.
CAGE and AUDIT questions
Discuss the CAGE questionairre.
Cut down: ever tried to cut down your drinking. Annoyed: ever been annoyed when someone critises your drinking. Guilty: ever feel guilty about drinking. Eye-opener: do you need an eye opener in the morning.
Discuss a brief intervention model that can be used to decrease ETOH consumption in non-dependent patients.
FRAMES: feedback, responsibility, advice, menu, empathy, self-efficacy
In what timeframe does withdrawal in ETOH-dependent patients usually develop?
Witihn 6-24 hours since cessation/reduction in alcohol consumption.
Describe alcohol withdrawal.
Autonomic excitation (24-48 hour peak): tremor, anxiety, sweaty, tachy, hypertension, nausea/vomiting, hyperthermia. Neuro-excitation (12-48 hour peak): hyperreflexia, nightmares, hallucinations, seizures. DTs.
Discuss delirium tremens.
Mortality approaching 8% affecting up to 20% of patients admitted. Confusion/ALOC, autonomic hyperactivity, respi/CV collapse, death
What are conditions associated with regular ETOH intake?
Wernicke’s, dehydration, hypoglycaemia, electrolyte abnormalities, coagulation disorders, anaemia, ETOH gastritis/UGIB, pancreatitis, liver disease + encephalopathy, SDH, alcoholic ketoacidosis.
List the signs associated with Wernicke’s encephalopathy.
Acute confusional state, reduced LOC, coma, memory disturbance, ataxia, ophthalmoplegia, nystagmus, unexplained hypotension, hypothermia
What are the constituents on an AWS?
Orientation, agitation/anxiety, hallucinations, perspiration, tremor, temperature
What is the initial thiamine dose in AWS?
200 mg IV TDS for the first 24 hours then review
List the long-term effects of amphetamine abuse.
Medical: cardiomyopathy, poor dentition, weight loss. Psychiatric: confusion, emotional lability, insomnia, memory loss, paranoia, paranoid psychosis. Social: relationship damage, neglect of responsibilities
When it comes to tachyphylaxis from amphetamine use, what is this due to?
Depleted neurotransmitter concentrations.
Discuss amphetamine withdrawal.
Usually peak symptoms at 2-4 days post-cessation but can continue for up to 2 weeks. Rarely symptoms are severe enough to warrant a referral. Usually psychiatric symptoms: depression, fatigue, insomnia, increased apetite and cognitive impairment.
How do opioids work?
Agonistic activity at the CNS mu-receptors. They mediate their effects by decreasing intracellular cAMP via membrane-bound G-proteins. Downregulation occurs with prolonged exposure.
Discuss opioid withdrawal.
Intense craving, dysphoria, autonomic hyperactivity and GI distress mainly. Others: anxiety, yawning, lacrimation, salivation, rhinorrhoea, anorexia, cramping, nausea/vomiting, diarrhoea, mydriasis, piloerection, diaphoresis, flushing, hypertension/tachycardia.
What are four features of other withdrawal syndromes that do not occur with opioid withdrawal?
Altered mental status, delirium, hyperthermia, seizures
What co-morbidities should you consider/are often associated with opioid misuse?
Alcohol/sedative-hypnotic withdrawal, dehydration, electrolyte imbalance, infective complications of IVDU, psychiatric morbidities
What are the three management options for opioid withdrawal?
(1) Opioid replacement therapy (methadone, buprenorphine), (2) Antagonis detoxification (naltrexone), (3) Symptomatic treatment
List the drugs considered sedative-hypnotic agents.
Benzos, barbiturates, non-benzo agents (zolpidem, zopiclone), baclofen, GHB, chloral hydrtae and paraldehyde
When do the symptoms of sedative-hypnotic withdrawal typically present?
Day 2-10 typically. However, intrathecal administration/GHB can occur within hours
What two withdrawal symptoms are not particularly lethal compared to the others?
Opioid and cannabis withdrawal syndromes as compared to ETOH/sedative-hypnotic withdrawal
What are the usual differences between alcohol and sedative-hypnotic withdrawal?
Psychomotor and ANS signs (ie insomnia, anorexia, irritability, perceptual disturbances, hallucintaions) are more prominent with sedative-hypnotic withdrawal as compared to ETOH withdrawal.
Increased spasticity in association with a withdrawal syndrome is typical of what drug?
Baclofen
Define solvent.
A liquid that has the ability to dissolve, suspend or extract another material without chemical change to either the material or solvent. This includes aliphatic, cyclic, aromatic and halogenated hydrocarbons, ethers, esters, glycols, ketones, aldehydes and amines.
What is the solvent with the highest abuse potential?
Toluene, found in glues, spray paints and lacquers
Discuss the mechanism of organic solvent toxicity.
Lipophilic and potent CNS depressants. Micro-aspirations, pneumonitis with some cadiac sensitisation to catecholamines resulting in cardiac dysrhythmias and sudden cardiac death. Some neuropsychiatric consequences.
Discuss acute solvent inhalational exposure.
Primarily affects the CNS: ALOC similar to ETOH intoxication. Psychomotor function impairment, patients are euphoric, disinhibited, lethargic and ataxic. Slurred speech, inappropriate. Can cause seizures and coma. Chemical pneumonitis is common as is contact irritation to mucous membranes.
What two solvents are associated with sudden death and how does this occur?
Associated with all solvents but in particular butane and propane. Mechanisms may include asphyxiation or cardiac dysrhythmias.
Discuss chronic inhalational abuse.
Long-term toluene exposure leads to persistent neurotoxicity with neuropsychological impairment, structural/functional brain abnormalities. Impaired cognition, poor working memory and worsens pre-existing problems. Issues with metabolic/electrolyte abnormalities
Outline the electrolyte and metabolic derrangements you expect to find in patients with chronic inhalational solvent abuse.
Normal anion gap metabolic acidosis due to renal tubular acidosis. Acidaemia, hyperchloraemia and hypokalaemia may be profound (25% of chronic abusers have a serum K+ <2 mmol/L).
What are the effects of toluene/solvents on the fetus?
Fetal solvent syndrome is similar to FAS as solvents are highly lipid soluble.
Are body stuffers or body packers more likely to fall sick with toxidromes?
Body stuffers; rapid concealment of multiple drugs, more likely to leak, poorer quality containers (aluminum foil, plain plastic bag). Often in the stomach, vagina or rectum.
What patients are suitable for discharge from the ED after suspected body packing?
Those who do not have CT evidence of body packing and are aysmptomatic
Describe how long to keep patients that have body packed for in hospital.
Until expected number of packets are out, three packet-free stools + repeat CT NAD. Usually this is 5 days.
In what patients can a CT scan reliably help with knowing the number of packets a body packer has concealed?
If they have <15 packets
In what type of body packer is whole bowel irrigation not indicated?
In those who have ingested heroin because there is an antidote
Discuss osmolarity and osmlolality.
Lality: per kg of solvent, larity: per litre of solvent
What is the formula for osmolarity?
It is: 2x [Na] + [urea] + [glucose] + [ethanol]
What is the formula for osmolar gap?
Osmolar gap = measured osmolality - calculated osmolarity
What is a normal osmolar gap?
<10
What are exogenous agents associated with an elevated osmolar gap?
Acetone, ethanol, ethylene glycol, glycerol, glycine, isopropyl alcohol, mannitol, methanol and proylene glycol (dilutent in medications)
What are non-toxicological causes for an elevated osmolar gap?
DKA, alcoholic ketoacidosis, chronic renal failure, ^ chol, ^ protein, massive hypermagnasaemia, severe lactic acidosis, shock, trauma, burns
If a patient has an osmolar gap >50, what should be at the forefront of your mind?
Significant toxic alcohol ingestion
What are two reasons why a normal osmolar gap does not exclude toxic alcohol ingestion?
(1) Small concentrations are not detected by the osmolar gap but can still cause significant symptoms, (2) Late in clinical course, the parent alcohol compound is metabolised to non-osmotically active compounds
What are some conversion factors for the toxic alcohols?
Multiply the osmolar gap by the following: ETOH 4.6, ethylene glycol/isopropyl alcohol by 6, methanol by 3 and propylene glycol by 7.2
What is a normal anion gap?
8-16 mmol/L
How do you correct for hypoalbuminaemia?
For every 10 g/L below normal, add 2.5 to the anion gap
What is the formula for anion gap?
Anion Gap = Na - [HCO3 + Cl]
What are two things about acid-base disturbances that can be said for anion gaps >20 and >30?
> 20: 2/3rds have a metabolic acidosis, >30: metabolic acidosis is invariably present
List the causes of an anion-gap acidosis.
Carbon monoxide/cyanide, Alcohol/toxic alcohols, Toluene, Meformin/methanol, Uraemia, DKA, Paracetamol/propylene glycol/paraldehyde, Iron/ioniazid, Lactic acidosis, Ethylene glycol, Salicylates/starvation ketoacidosis.
List the causes of low anion-gap.
Increased unmeasured cations: ^ Ca, ^ Mg, lithium, multiple myeloma. Decreased unmeasured anions: dilution, hypoalbuminaemia. Artefactual hyperchloraemia: bromism, iodism, ^ triglycerides
What are the two ways in which you can classify non-anion gap metabolic acidosis?
(1) Drugs, GI bicarb loss, rapid rehydration with normal saline, renal bicarb loss. (2) USED CARP
What is the mnemonic for non-anion gap metabolic acidosis?
USED CRAP: ureterostomy, small bowel fistula, extra chloride, diarrhoea, carbonic anhydrase inhibitors, adrenal insufficiency, renal tubular acidosis, pancreatic fistula
List the causes for metabolic alkalosis.
Administration of bases (antacids, dialysis, milk-alkali syndrome), GI acid loss (protracted vomiting/NGT suction), Renal bicarb retention (chronic hypercapnoea, hypochloraemia, hypokalaemia), Urinary acid loss (adrenogenital, Bartter’s, Cushings syndromes, licorice, diuretics, primary hyperaldosteronism), Volume contraction
List the acute and chronic causes for respiratory acidosis.
Acute: airway obstruction, aspiration, bronchospasm, drug-induced CNS depression, hypoventilation of CNS/muscular origin, pulmonary disease. Chronic: kyphoscoliosis, lung diseases, NMD, obesity
List the causes of respiratory alkalosis.
CNS-hyperventilation: increased ICP, CVA, psychogenic. Hypoxia-hyperventilation: altitude, anaemia, V/Q mismatch. Pulmonary: CCF, mechanical hyperventilation, pneumonia, PE. Sepsis. Toxins: nicotine, salicylate, xanthines
What are the causes of a high lactate?
Type A: imbalance between oxygen supply/demand (CO poisoining, cyanide, high oxygen demand (ie seizure, sepsis, exercise, fever), severe anaemia, severe hypoxia, pscyhogenic hyperventilation). Type B: metabolic causes (beta-2 agonists, cancer, ethanol, hepatic failure, inborn errors of metabolism, ketoacidosis, metformin, sepsis, vitamin deficiency)
How does alcohol cause a high lactate?
Increased hepatic NADH and decreased conversion of lactate to pyruvate
How do you assess the compensation with a metabolic acidosis?
The expected PaCO2 in mmHg is 1.5 x HCO3 + 8 (range: +/- 2)
How do you assess the compensation with a metabolic alkalosis?
The expected PaCO2 in mmHg is 0.7 x HCO3 + 20 (range: +/- 2)
How do you assess the compensation with a respiratory acidosis?
HCO3 should increase by 1 (acutely) or 4 (chronic) for every 10 mmHg increase in PaCO2
How do you assess the compensation with a respiratory alkalosis?
HCO3 should decrease by 2 (acute) or 5 (chronic) for every 10 mmHg decrease in the PaCO2
What drug toxicity will manifest as a R axis deviation and QRS widening?
Fast sodium channel blockade (TCAs, class 1A/1C antiarrhythmics, LAs, phenothiazines, amantadine, carbamazapine, chloroquine, diltiazem, diphenhydramine, chloroquine, propranolol, quinine, propoxyphene)
What drug toxicity will manifest with a prolonged QT interval?
Bloackade of potassium efflux during cardiac repolarisation. Agents include: antipsychotic agents, class 1A/class 1C/III, TCAs, other antidepressants (bupropio, citalopram, moclobemide), antihistamines, chloroquine, quinine, fluoroquinolones, macrolides, methadone)
What are the patterns of ECG changes that you may see with CCBs/beta-blockers or cardiac glycosides?
Bradycardia, AV node conduction slowing
What three electrolyte abnormalities are associated with QT prolongation?
Hypocalcaemia, hypomagnasaemia, hypokalaemia
What is the upper limit of normal of the QRS in cardiac fast sodium channels toxicity?
> 100 ms
What are the three findings associated with severe TCA toxicity?
(1) QRS >100 ms (2.5 small squares) + seizures, (2) QRS > 160 ms (4 small squares) + ventricular dysrhythmias, (3) R axis deviation of the terminal QRS (terminal R wave > 3mm in aVR, R/S ratio >0.7 in aVR)
What are physiological changes that affect drug pharmacokinetics and dynamics during pregnancy?
(1) Absorption: delayed gastric empyting, slow intestinal transit time mean prolonged decontamination time, (2) Blood volume increased by up to 50% - increased VoD and lower plasma levels, increased free drug levels due to plasma protein dilution, (3) Elimination: hepatic enzyme systems are altered by circulating hormones, renal blood flow/GFR increases
What drugs pose a higher risk for the fetus than for a pregnant mother in overdose?
Carbon monoxide, methaemoglobin-inducing agents, lead and salicylates
List drugs that have serious toxicity syndromes when ingested by a child, even if only 1 or 2 tablets are ingested.
Amphetamines, baclofen/carbamazapine/clozapine/chloroquine = coma, dextropropoxyphene, opioids, propranolol (coma), CCBs, sulfonylureas, theophylline, TCAs, venlafaxine
What drugs are unlikely to cause serious toxicity when ingested in 1-2-3 units in children?
Paracetamol, iron, colchicine, digoxin, anticoagulants
How long should children who have potentially ingested tablets be observed for?
Minimum of 12 hours
List some age-related changes that alter how we approach elderly patients with overdoses?
Delayed GI absorption, decreased protein binding (increased free drug levels), reduced hepatic metabolic fucnction, reduced glomerular filtration –> impaired elimination
