Toxicology Flashcards

Question

Mechanism of action and clinical effect of Digoxin

Answer 1

MOA: inhibits cardiac membrane Na-K-ATPase → ↑ INTRAcellular Na, ↑ EXTRAcellular K ↑ intracellular Na → dysfunction of Na-Ca exchange → ↑ intracellular Ca → ↑ Ca-induced Ca release in sarcoplasmic reticulum → more powerful muscle contraction and ↑ CO. Clinical effects: - ↑ force of myocardial contraction → ↑ CO in pts with heart failure - ↓ AV conduction to slow ventricular rate in Afib

Answer 2

1. Hyperkalemia 2. Directly blocks generation of impulses in SA node 3. Depresses conduction through AV node 4. ↑ sensitivity of SA/AV nodes to catecholamines

Answer 3

Most common: ↑↑ PVCs Specific dysrhythmias (not pathognomonic) - Afib with slow/regular ventricular rate (AV dissociation) - Non-paroxysmal junctional tachycardia (70-130bpm) - Atrial tachycardia with block (atrial rate usually 150-200bpm) - Bidirectional ventricular tachycardia *** Digoxin can produce virtually any dysrhythmia or conduction block, and bradycardias are as common as tachycardias

Answer 4

1. Oleander - Nerium oleander 2. Lily-of-the-valley - Convallaria majalis 3. Aconitine, a Na-channel opening xenobiotic found in common Monkshood (aconitum napellus)

Answer 5

1. Based on ingested dose: Amount ingested x 0.8 (bioavailability of dig tablets) e.g. 40yoF ingested fifty 0.25mg tablets Amount ingested = 0.25mg x 50 x 0.8 = 10mg 1 vial = 0.5mg digoxin, therefore administer 20 vials 2. Based on steady-state digoxin concentration (measured 6-8h after ingestion) ( Serum dig concentration x weight in kg ) / 100 + # vials e.g. 20kg child with dig level 16ng/mL 8h after ingestion unknown # of digoxin tablets ( 16 x 20 ) / 100 = 3 vials *** divide by 100 in children, 1000 in adults

Answer 6

1. Hyperkalemia (acute poisoning, chronic may present with hypokalemia) - Caution with K repletion; K may increase with administration of DigiFab 2. Hypocalcemia - Ca held intracellularly - Caution with Ca repletion or CaGluconate administration for HypoK; theoretical "stone heart syndrome" 3. Hypomagnesemia - required for K repletion, suppression of tachydysrhythmias

Answer 7

1. DigiFab 2. Phenytoin - if DigiFab unavailable or while being prepared - may enhance AV conduction - 100mg bolus q5min until dysrhythmia improves OR max 18mg/kg reached 3. Lidocaine - only if contraindication to Phenytoin or max dose of phenytoin has been reached - 1.5mg/kg IVP → 1-4mg/min infusion (30-50 µg/kg/min). ** most other cardiac drugs (isoproterenol, procainamide, amiodarone, βblockers, CCBs) may worsen dysrhythmias or depress AV conduction in dig poisoned patients and should not be used.

Answer 8

1. Bradycardia 2. Hypotension 3. Unconsciousness 4. Respiratory arrest/insufficiency 5. Hypoglycemia (uncommon in adults) 6. Seizures (esp with propanolol) 7. Symptomatic bronchospasm (uncommon) 8. VT or VF 9. Mild hyperK (uncommon) 10. Hepatotoxicity, mesenteric ischemia, renal failure (very rare)

Answer 9

1. Fluids 2. Atropine 3. Calcium - final common pathway for stimulation of β-adrenergic receptors, therefore ↑ in intracellular Ca and deleterious effects on Ca transport may contribute to β-blocker toxicity - give CaCl 1-2g or CaGluconate 3-6g over 10min 4. Glucagon - has inotropic and chronotropic effects, stimulates production of intracellular CAMP, indepent of β-adrenergic receptor. Also counteracts hypoglycemia. - Give 5-10mg IV bolus 5. High-dose insulin - profound inotrope with vasodilating properties - MOA involves optimization of use of carbohydrates for fuel and modulation of intracellular Ca - 1U/kg bolus, followed by 1U/kg/h titrate up to 10U. + DEXTROSE and K repletion 6. Sodium Bicarbonate - Na-channel blockade from β-blockers with membrane-stabilizing activity (propanolol) that cause QRS widening - 1-2 mEq/kg IV q3-5min until QRS <120ms 7. Vasopressors - when MAP <60mmHg after fluid resuscitation, Ca, atropine, Glucagon, and insulin 8. Salvage therapies - IV fat emulsion (IFE), IABP, LVAD

Answer 10

1. Cardiovascular: hypotension, sinus bradycardia/arrest, AV block/dissociation, junctional rhythm, asystole. 2. Pulm: respiratory depression, apnea, pulmonary edema, ARDS 3. GI: N/V, bowel infarction (rare) 4. Neuro: lethargy, confusion, slurred speech, coma, seizure (uncommon), CVA (rare) 5. Metabolic: lactic acidosis, hyperglycemia, hyperkalemia 6. Dermatologic: flushing, diaphoresis, pallor, peripheral cyanosis

Answer 11

Phase 1: Resuscitation - IV fluid bolus, Calcium, Atropine Phase 2: Stabilization - Ca infusion, High-dose insulin+glucose infusion, catecholamine infusion, transcutaneous/transvenous cardiac pacing, invasive monitoring Phase 3: Salvage therapies - Methylene blue (increases systemic vascular resistance), IV fat emulsion (IFE), IBP, consider LVAD

Answer 12

Binds to pre-synaptic α2-adrenergic receptors in brain → inhibiting NE release in neurons in nucleus tractus solitaries

Answer 13

``` Bradycardia Hypotension ↓ mental status Miosis Hypothermia ```

Answer 14

1. Fluid resuscitation for hypotension 2. Catecholamines if not responsive to fluids - NE to maintain MAP of 60 3. Consider naloxone, up to 10mg if pt obtunded or with unprotected airway

Answer 15

Low doses - venous dilation Higher doses - arterial dilation Nitrates are converted to nitrites in GI tract (esp in infants <4mo) Nitrites >> nitrates - oxidize Fe2+ to Fe3+ in hemoglobin → methemoglobinemia → ↓ O2 carrying capacity

Answer 16

1. Hypotension, typically accompanied by reflex tachycardia 2. Headache 2/2 rapid dilation of meningeal arterioles 3. S&S of methemoglobinemia - fatigue, dyspnea, weakness, dizziness, drowsiness, coma, seizure, death

Answer 17

Common products: windshield wiping fluid, antifreeze, embalming fluid, cleaning solution, enamels/paint/stains, paint remover

Answer 18

Methanol is primarily metabolized in liver by alcohol dehydrogenase into formaldehyde. Formaldehyde is metabolized by aldehyde dehydrogenase into formic acid.

Answer 19

Formic acid

Answer 20

*** VISUAL DISTURBANCES - targets optic disk of retina and retrolaminar optic nerve - presents with seeing spots, blurred vision (snowstorm), altered visual fields, blindness. ↓ pupillary response to light, hyperemia of optic disc → peripapillary retinal edema, loss of optic disk cupping → ↓ visual fields and central scotomata GI symptoms - n/v from mucosal irritation → hemorrhagic gastritis. Acute pancreatitis. CNS effects similar to etoh - slurred speech, ataxia, confusion, CNS depression

Answer 21

- Anion gap metabolic acidosis + elevated osmolar gap | - Methanol concentration: <20mg/dL not associated with toxicity, > 50mg/dL indicates serious exposure.

Answer 22

- IV sodium bicarb for pH <7.3 - Fomepizole - inhibits alcohol dehydrogenase, prevents metabolism of methanol to formaldehyde - loading dose 15mg/kg → 10-mg/kg doses BID up to 48h → 15mg/kg - Hemodialysis indications: pH < 7.3, renal failure, vision abnormalities with known methanol exposure, electrolyte imbalances unresponsive to tx (e.g. hyperK), hemodynamic instability, serum methanol concentration >50mg/dL

Answer 23

Antifreeze | Brake fluids, industrial solvents, paints, cosmetics

Answer 24

Ethylene glycol → glycoaldehyde by alcohol dehydrogenase Glycoaldehyde → glycolate by aldehyde dehydrogenase Glycolate → Glyoxylic and oxalic acid

Answer 25

Glyoxylic acid → profound metabolic acidosis Oxalic acid + Ca → calcium oxalate crystals → precipitate in proximal renal tubules → ATN and renal failure → deposit in brain/intestinal mucosa/lungs/heart/spleen → systemic hypocalcemia

Answer 26

1. Acute neurologic stage (<12h) - inebriation and euphoria similar to etoh. Severe poisoning - CNS depression → coma, hypotonia, seizures. Additional findings: nystagmus, ataxia, myoclonic jerks. Cerebral edema from CaOxalate deposition 2. Cardiopulmonary stage (12-24h) - tachycardia, severe metabolic acidosis, compensatory tachypnea. Hypoxia, pulmonary edema, ARDS. Multiorgan failure with circulatory collapse. *** Most deaths during this stage. 3. Renal stage (24-72h) - Acute renal failure from CaOxalate crystal deposition. + CVA tenderness, hematuria, proteinuria. 4. Delayed neuro sequelae - bulbar palsy 5-20d post-ingestion, with CN VII most commonly implicated, also opthalmoplegia, diplopia, nystagmus, facial drop, facial sensory loss, hearing loss, dysphagia, vertigo. * ** Facial auditory nerve oxalosis; predelicition for CN VII and VIII

Answer 27

1. Methanol - formic acid - visual disturbances 2. Ethylene glycol - Glycolic acid, oxalic acid - calcium oxalate crystalluria and renal failure, urinary/oral fluorescence under woods lamp 2/2 fluoresence of antifreeze 3. Profound CNS depression, respiratory depression. ↑ osmolar gap WITHOUT ↑ anion gap, euglycemia

Answer 28

1. Sodium bicarb for metabolic acidosis (pH <7.3) 2. ADH blockade (fomepizole) - prevent further formation of toxic metabolites 3. HD if indicated 4. Pyridoxine + Thiamine for pts with vitamin deficiencies (cofactors for glycolic acid metabolism)

Answer 29

Rubbing alcohol, antifreeze, disinfectants, cleaning solutions, hair/skin products, hand sanitizers.

Answer 30

Isopropyl alcohol → acetol (hydroxyacetone) by acetone monooxygenase → → propylene glycol, methylglyoxal, lactate, formate, acetate → glucose

Answer 31

2x as inebriating as etoh Respiratory depression + profound CNS depression Large doses → peripheral vasodilation, ↓ cardiac inotropy → hypotension Topical exposure → corneal de-epithelialization, dermal irritation

Answer 32

1. Viscosity - low viscosity allows spread into airway/lungs. e.g. furniture polish, gasoline, lamp oil. 2. Volatility - high volatility can displace alveolar O2 and cause hypoxia. e.g. Butane and propane. 3. Surface tension - enables a substance to disperse easily. e.g. Turpentine 4. Chemical side chains/substitutions - metals (arsenic), halogens (chloride ions in carbon tetrachloride), and those from aromatic structures (toulene) 5. Lipophilicity - enhances BBB penetration

Answer 33

1. Pulmonary toxicity - low viscosity, high volatility, low surface tension has worse effect. Penetrates lower airways → bronchospasm and direct injury → inflammatory response and pneumonitis. Also impairs surfactant lipid function → alveolar instability and collapse. 2. CNS toxicity - recreational inhalation → systemic absorption without first-pass metabolism → targets NMDA, GABA, dopamine, opioid receptors → mood alteration 3. Cardiac - intentional inhalation → sudden death. Hydrocarbons induce myocardial sensitization to endo/exogenous catecholamines by inhibition of Ca-signaling → precipitates ventricular dysrhythmias and myocardial dysfunction.

Answer 34

Camphor - neurotoxicity and seizures Halogenated - dysrhythmias and hepatotoxicity Aromatics - bone marrow suppression and leukemia Metals (arsenic, mercury, lead) - neurotoxicity Pesticides - cholinergic crises, seizures, respiratory depression

Answer 35

MOA: cholinesterase inhibitor → ↑ ACh accumulation at multiple receptors (ANS, symp/parasymp, skeletal muscle, CNS) ``` DUMBBELS Diarrhea/diaphoresis Urination Miosis (killer) B's: bronchorrhea/bronchospasm/bradycardia Emesis Lacrimation Salivation ```

Answer 36

1. Decontamination 2. Supportive care with emphasis on respiratory stabilization 3. Reversal of ACh excess 4. Reversal of toxin binding at receptor sites on cholinesterase molecule

Answer 37

Organophosphates

Answer 38

Rocuronium - non-depolarizing paralytic that is not metabolized by cholinesterase Succinylcholine requires cholinesterase metabolism; because organophosphates are cholinesterase inhibitors, anticipate prolonged paralysis if succinylcholine is used.

Answer 39

1. Atropine - competitive inhibitor of ACh at muscarinic receptors. 1-3mg IV, double dose q5min until control of muscarinic effects (particularly drying of secretions) → infusion to provide 10-20% of total cumulative dose needed to obtain symptom control per hour. 2. Pralidoxime (2-PAM) - binds to organophosphate-cholinesterase complex → conformational change → cholinesterase resumes normal function. 1-2g bolus followed by infusion (multiple options)

Answer 40

Carbamates are acetylcholinesterase inhibitors vs organophosphates are cholinesterase inhibitors. Carbamate toxicity has shorter duration of effect, no process of aging.

Answer 41

Atropine, same tx as for organophosphate poisoning, monitor respiratory status. Oxime (pralidoxime/2PAM) treatment only for severe poisoning, cannot differentiate between carbamate/organophosphate poisoning.

Answer 42

Dichlorodiphenyltrichloroethane (DDT) - insecticide Hexachlorocyclohexane (Lindane) - available as rx for 2nd line treatment of head-lice and scabies

Answer 43

Highly lipid soluble Affect neuronal voltage-gated Na channels GABA antagonists Manifestations: Hyperexcitability and irritability of both CNS and PNS + ↑ susceptibility to ventricular tachydysrhythmias because of ↑ myocardial sensitivity to circulating catecholamines

Answer 44

Neurologic excitation: muscle fasiculations, ataxia, tremors, delirium, weakness, paralysis, paresthesias, seizures, death Hyperthermia 2/2 muscle fasiculations and seizures. +/- metabolic acidosis, respiratory failure, acute renal failure + Ventricular tachydysrhythmias 2/2 ↑ myocardial sensitivity to circulating catecholamines (often seen at the time of seizures due to catecholamine surge)

Answer 45

Cessation of seizures with benzodiazepines and barbiturates. β-blockers for any life-threatening tachydysrhythmias. External cooling if hyperthermic. IV hydration for metabolic acidosis, rhabdo, AKI Alkalinization for rhabdomyolysis if needed.

Answer 46

Dinitrophenol (DNP), pentachlorophenol, dinitrocresol Used as dyes, wood preservatives, photograph developers, insecticidse. SNP currently used as weight loss supplement.

Answer 47

Substituted phenols uncouple oxidative phosphorylation → ↓ ATP formation and ↑ heat generation Acute toxicity - hyperthermia, tachycardia, diaphoresis, tachypnea. Neuro symptoms: confusion, agitation, seizure, coma. +/- rhabdo, myocardial injury, AKI, hepatic damage Death due to cardiovascular collapse.

Answer 48

Supportive care. Benzos, treatment for hyperthermia, fluid resuscitation, correction of electrolyte derangements. ** consider activated charcoal if pt presents w/in 1h of acute oral ingestion and who is alert/cooperative.

Answer 49

*** Used as herbicides for broad-leaved weeds. MOA unknown, proposed MOA due to cell membrane damage, forms analogues of acetyl-CoA and acts as false cholinergic messengers. At high doses uncouples ox-phos. Ingestion → GI symptoms including vomiting, abd pain, diarrhea, oropharyngeal burning, GI hemorrhage. Primary organ of toxicity: Skeletal muscle. - Muscle fasiculations, weakness, myotonia, ↓ DTRs. May → rhabdo and metabolic acidosis

Answer 50

Paraquat | Diquat

Answer 51

Paraquat >> diquat Causes production of superoxides created during cyclic oxidation-reduction reactions in tissues → oxygen radical damage → cell death ** Paraquat selectively concentrates in the lungs/alveolar cells (high O2 concentrations) → ARDS, progressive pulmonary fibrosis, respiratory failure. Corrosive - n/v, caustic injury to oropharynx, esophagus, GI tract. Dermal exposure can cause corrosive injury to the skin Systemic toxicity → multiorgan failure and death

Answer 52

Corrosive injury to upper airway → intubation Because of O2 radical damage, supplemental O2 with target oxyhemoglobin of 95% Supportive care for multiorgan failure Dialysis indicated to increase elimination if renal failure, metabolic acidosis, or electrolyte imbalance develops as result of poisoning

Answer 53

Pyrethrin - naturally occurring from chrysanthemum plant. Pyrethroids are synthetic derivatives, more stable in environment. Used to treat human infestations of scabies and lice. Block voltage-gated Na channels, voltage-gated Ca channels, and Cl channels on GABA receptors. Sensitivity reactions with skin exposure (erythema) Inhalation → rhinitis, sneezing, oral mucosa irritation, cough, dyspnea, wheezing, chest pain. Ingestion → n/v, abd pain, diarrhea Massive ingestion → neuro symptoms including numbness, tremors, ataxia, paralysis. Tx: supportive care

Answer 54

Glyphosate (Roundup) - one of the most commonly used pesticides in the US. Human toxicity thought to be 2/2 surfactant included in glyphosate preparation. Poor dermal absorption. Concentrated (41%) solutions → mucosal injury. ** Residential concentration is 1%. Unintentional ingestion → mild GI symptoms. Massive ingestions/concentrated ingestion may → sore throat, n/v, abd pain, hyperthermia, respiratory distress, acute lung injury, renal failure, coma. Metabolic acidosis may develop as result of cardiovascular compromise. Poor prognostic features: AMS, hyperK, renal failure Treatment: supportive

Answer 55

Anticholinergic toxin aka Datura stramonium

Answer 56

Anticholinergic toxin aka Atropa belladonna