PHCT Midterm Reviewer.pdf

PHCT MIDTERMS Week 6: Respiratory Drugs Respiratory Drugs: Dextromethorphan PPA and related decongestants Theophylline Anti-inflammatory Agents Dextromethorphan Found in many over-the-counter cough and cold preparations. Opioid without analges...

PHCT MIDTERMS Week 6: Respiratory Drugs Respiratory Drugs: Dextromethorphan PPA and related decongestants Theophylline Anti-inflammatory Agents Dextromethorphan Found in many over-the-counter cough and cold preparations. Opioid without analgesic effect, no addictive properties Often found in combination products containing antihistamines, Examples: Nyquil, Robitussin DM, Triaminic DM, and Vick Pediatric decongestants, or acetaminophen. Formula 44. Antitussive, cough suppressant Characteristics: Toxic Dose: Dextromethorphan is the d-isomer of 3-methoxy-N- Symptoms usually occur when ingested exceeds 10mg/kg. methylmorphinan, a synthetic analogue of codeine. (The l-isomer is Usual recommended adult daily dose: 60-120 mg/d; in children aged the opioid analgesic levorphanol) 2-5 years, up to 30 mg/d. Has no apparent analgesic or addictive properties and produces Clinical Presentation: relatively mild opioid effects in overdose. Mild intoxication: Clumsiness, Ataxia (lack of muscle coordination), Also has anticholinergic properties. Nystagmus (involuntary movement of eyes), Restlessness, Visual Well-absorbed orally, and effects are apparent within 15-30 minutes. and auditory hallucinations. Duration of effect is normally 3-6 hours. Severe poisoning: Stupor (reduced responsiveness), Coma, Respiratory depression (co-ingestion with alcohol), Pupils may be Mechanism of Toxicity: dilated or constricted, Seizures after ingestions of 20-30 mg/kg. Both dextromethorphan and its o-demethylated metabolite appear With therapeutic doses taking MAOI (increased level of NE, to antagonize N-methyl-D-aspartate (NMDA) glutamate receptors. Epinephrine, Dopamine, Serotonin): Severe hyperthermia, Muscle (excitatory neurotransmitter) (inhibit - dissociative & psychoactive rigidity, Hypertension (excessive vasoconstriction) related to effects → altered mental status, hallucination, and neuro psychotic serotonin syndrome. affects) Treatment: Inhibits reuptake (increased level neurotransmitter) of serotonin, may lead to serotonin syndrome (increased level of serotonin Emergency and supportive measures. confusion, agitation, tachycardia, hypertension, mydriasis) in Specific drugs and antidotes: Although naloxone (opioid overdose patients taking monoamine oxidase inhibitors. antidote) has been reported effective in doses of 0.06-0.4 mg, other Serotoninergic effects, as well as NMDA glutamate receptor cases have failed to respond to as much as 2.4 mg. If the patient inhibition, may explain the acute and chronic abuse potential of exhibits signs of opioid intoxication (CPR → coma, pinpoint pupil, dextromethorphan. respiratory depression), administer 0.4-2 mg naloxone IV, with repeat doses as needed. Decontamination: Activated Charcoal. C/I: emesis PPA & Related Decongestants Phenylpropanolamine (PPA) - also used as an appetite suppressant. Toxic Dose: causes hemorrhagic stroke PPA, phenylephrine, and ephedrine have low toxic ratios. Phenylephrine, Ephedrine, Pseudoephedrine - available in Toxicity after ingestion of 2-3 times the therapeutic dose; nonprescription nasal decongestants and cold preparations. pseudoephedrine: symptoms after 4-5 times the therapeutic dose. Usually also contain antihistamines and cough suppressants Patients with autonomic insufficiency or on MAOI may develop Sympathomimetic Drugs (Sympathetic Agonist enhances severe hypertension after subtherapeutic doses. sympathetic effects - alpha and beta and dopamine receptor) Clinical Presentation: Mechanism of Toxicity: Hypertension (alpha1 - BV - constriction major toxic effect), PPA and phenylephrine: Direct alpha-adrenergic agonists. PPA Headache, Confusion, Seizures, Intracranial hemorrhage, produces mild β1-adrenergic stimulation and acts in part indirectly Bradycardia or AV block (atrioventricular block delay or interruption by enhancing norepinephrine release in electrical conduction in the atria), Myocardial infarction. Ephedrine and pseudoephedrine: Both direct and indirect alpha- and beta-adrenergic activity. They clinically produce more beta- adrenergic stimulation than PPA or phenylephrine 1 PHCT MIDTERMS Treatment: Emergency and supportive measures. Specific drugs and antidotes: o Hypertension: Treat hypertension if the diastolic pressure is higher than 100-105 mm HG. Use phentolamine or nitroprusside (vasodilators) o Caution: do not use beta blockers alone w/o first giving a vasodilator place the patient in an upright position o Arrhythmias (irregular heartbeat): Give propranolol or esmolol (betablockers) o Caution: do not treat AV block or sinus bradycardia associated with hypertension (If the patient has bradycardia, do not administer beta blockers.) Ipecac-induced emesis, activated charcoal, and cathartic for decontamination. Enhanced elimination: Urinary acidification for PPA, ephedrine, and pseudoephedrine. But may also aggravate myoglobin deposition in the kidney if the patient has rhabdomyolysis (damaged skeletal muscle breaks down rapidly) Theophylline Methylxanthine (oral) used for asthma treatment. Clinical Presentation: IV infusions of aminophylline for bronchospasm, congestive heart Acute single overdose (1 take, excessive amounts): Tremor, Anxiety, failure, and neonatal apnea. Tachycardia, Hypokalemia, Hypophosphatemia, Hyperglycemia, Metabolic acidosis, ventricular arrhythmias, Status Epilepticus Orally used in sustained-release preparations (Theo-Dur, Slo- (continuous prolonged seizure without regaining consciousness), phyllin, Theobid). seizures (serum levels > 100 mg/L). Mechanism of Toxicity: Chronic intoxication: Vomiting, Tachycardia, Hypokalemia, Inhibit phosphodiesterase at high levels, increasing cAMP. (Cyclic Hyperglycemia, Hypotension (rare), Seizures (serum levels, 40-60 adenosine monophosphate) mg/L). Stimulate beta-adrenergic receptors. (Beta 2 – lungs) Treatment: Release endogenous catecholamines. Emergency and supportive measures. Antagonist of adenosine receptors. Specific drugs and antidotes: Toxic Dose: o Use low dose propranolol, 0.01-0.03 mg/kg IV (non-selective Acute single dose of 8-10 mg/kg produces therapeutic level of 15-20 beta blocker) mg/L. o Esmolol, 25-50 µg/kg/min (non-selective beta blocker) Acute oral overdose of more than 50 mg/kg can result in levels above o Use beta blockers cautiously in patients with a prior history of 100 mg/L and significant toxicity. asthma or wheezing Ipecac-induced emesis, activated charcoal, and cathartic for decontamination. Bronchodilators - Β2 agonists Mechanism of action: Stimulate ß2-receptors → activating adenylyl cyclase → increases intracellular production of CAMP → bronchodilation, improved mucociliary clearance, and reduced inflammatory cell mediator release suffix –”terol” Uses Bronchodilators–non-selective Short acting rapid onset first line in the Tx of acute o reserved for special situations (cardiac stimulation) Salbutamol (Albuterol) exacerbation of BA primary reliever medication Drugs Dose Long-acting slow onset prophylactic agent (acute attacks) Epinephrine SC (0.4 mLof 1:1000 Onset: 15 minutes for controlling nocturnal attacks solution) inhaled - Duration: 60–90 controller medication 320 g per puff mins Long acting with rapid onset controller usually given through Ephedrine Lower potency inhalation Isoproterenol Inhaled: 80–120 g Onset: 5 minutes Duration: 60–90 mins Selective B2 agonists Drugs Route Remarks Albuterol Oral, MDI metered dose inhaler Terbutaline SC inj. (0.25 mg) For severe asthma Metaproterenol Oral, MDI Salmeterol& Formoterol long-acting DOA: 12 (Long-acting beta hours agonist) 2 PHCT MIDTERMS Anticholinergic/Antimuscarinic Bronchodilators Anticholinergic: tachycardia, constipation, flushing, urinary retention, dry mouth Drugs Characteristics Duration of Action o Ipratropium, Tiotropium. ipratropium bromide quaternary ammonium 3-5 hrs o Datura stramonium/ D. metel derivative of atropine → prototype of o Mechanism: Block muscarinic receptors, preventing anticholinergic drug acetylcholine binding, blocking airway smooth muscle contraction. tiotropium longer-acting selective 24 hrs antimuscarinic agent o Clinical characteristics: Useful in COPD, better safety profile compared to β2 agonists. Anti-inflammatory Agents Mast cell stabilizers Class Examples Uses Mast cell stabilizers Cromolyn sodium (disodium cromoglycate) Also used in allergic rhinoconjunctivitis storage of histamine activation → degranulation Prophylaxis of exercise induced asthma → bronchoconstriction Nedocromil o Side effects: bronchospasm (acute administration) o Management: pre administration of β2 agonist o Mechanism: Stabilizes mast cell membrane by increasing chloride ion conduction thus inhibiting cellular activation Class Example/s Mechanism of action Adverse effect/s Lipoxygenase inhibitor Zileuton inhibits 5 lipoxygenases thereby Hepatotoxic preventing leukotriene synthesis Check ALT (liver enzyme) (inflammatory mediator) initiation monthly (3months) 2-3 months for 1 year annually HA, abdominal pain, asthenia, nausea, dyspepsia and myalgia. Leukotriene receptor blockers Montelukast Zafirlukast prevents the binding of LTD4 to Churg-Strauss syndrome (hepatotoxic) cysteinyl leukotriene 1 (CysLT1) (Inflammation of small to medium- Used in NSAID induced asthma receptor thus inhibiting its effects on sized blood vessels) airways. (Prevent leukotriene receptors from binding.) Corticosteroids o Mechanism of Action: Corticosteroids bind to glucocorticoid receptors on the cytoplasm of cells. The activated receptor regulates transcription of target genes. o For prevention of nocturnal asthma: oral or inhaled corticosteroids are most effective when given in the late afternoon. o Aerosol treatment: is the most effective way to decrease the systemic adverse effects of corticosteroid therapy o Side effects: inhaled topical corticosteroids can cause oropharyngeal candidiasis. o Management: gargle water and spit after each inhaled treatment. ▪ Budesonide ▪ Oral: Prednisone ▪ Fluticasone ▪ Beclomethasone 3 PHCT MIDTERMS Week 7: Analgesic Drugs ACETAMINOPHEN Acetaminophen (Biogesic, Tempra, Tylenol) is a widely used drug After 24-48 hours: prothrombin time (measures the time it takes for found in many over the counter and prescription analgesics and cold the plasma of blood to clot) and transaminase levels rise, hepatic remedies. necrosis is evident. (Increased transaminase levels: ALT (alanine transaminase) and AST (aspartate transaminase) → liver damage → Active metabolite of phenacetin and is responsible for its analgesic hepatic necrosis effect. If acute hepatic failure occurs, hepatic encephalopathy (liver It is a weak (cyclooxygenase) COX-1 and COX-2 inhibitor. dysfunction → accumulation of neurotoxic substance → Adults: sulfation, glucuronidation bloodstream → CNS - CNS manifestations: confusion, slurred Children: sulfation speech, decreased cognitive function) and death may ensue, acute renal failure. Mechanism of toxicity: Diagnosis: Overdose of acetaminophen metabolite exceeds glutathione capacity, and the metabolite reacts with hepatic macromolecules, Specific levels: Obtain a 4-hour post-ingestion acetaminophen level causing liver injury. and use the nomogram to predict the range of severity. Active metabolite is N-acetyl-p-benzoquinone imine. Falsely elevated acetaminophen levels may occur in the presence of high levels of salicylate and other interference by certain methods. Same mechanism occurs in renal damage owing to renal metabolism. Other useful laboratory studies: Electrolytes, Glucose, BUN, Creatinine, Liver transaminases, Prothrombin time. Overdose during pregnancy has been associated with fetal death and spontaneous abortion (Pregnancy Category B) → Animal Treatment: reproduction studies have failed to demonstrate a risk to the fetus Emergency and supportive measures: and there are no adequate and well-controlled studies in pregnant o Spontaneous vomiting may delay the administration of women. antidote and charcoal and should be treated with Toxic dose: metoclopramide. Acute ingestion of more than 140 mg/kg in children or 6 g in adults is o Liver transplant may be necessary for massive hepatic failure. potentially hepatotoxic. Specific drugs and antidotes: Children < 10-12 years old are less susceptible due to the smaller o If the serum level falls above the lower line on the nomogram contribution of cytochrome P-450 to acetaminophen metabolism. or if stat serum levels are not immediately available, start Chronic alcoholics and patients with induced cytochrome P-450 antidotal therapy with acetylcysteine, 140 mg/kg orally. have lower margin of safety (prone to poisoning) because of the o Antidote for acetaminophen poisoning: N-acetylcysteine possible production of more toxic metabolites. (causes depletion of (mucolytic, precursor of glutathione (cysteine) → increases glutathione) production of glutathione to metabolize/decrease NAPQI Chronic toxicity has been reported after daily consumption of high Decontamination: therapeutic doses by alcoholics. o Prehospital: Administer activated charcoal, if available. Toxicity: increased NAPQI → decreased glutathione (react to hepatic Ipecac-induced emesis may be useful for initial treatment of cells causing injury) glutathione detoxifies the toxic metabolite of children at home if it can be given within 30 minutes of paracetamol, NAPQI exposure. Fatal dose: o Hospital: Administer activated charcoal and a cathartic. Ingestion of 15 g of acetaminophen may be fatal, death being caused Gastric emptying is not necessary if charcoal can be given by severe hepatotoxicity with centrilobular necrosis (cell death → promptly. death of hepatocytes which are liver cells), sometimes associated o "It is not allowed to administer ipecac and activated charcoal with acute renal tubular necrosis. at the same time." Clinical presentation: Enhanced elimination: Hemoperfusion (undergoes an adsorbent Early after acute acetaminophen overdose: Anorexia, material such as activated charcoal and synthetic resins) removes Nausea/Vomiting. acetaminophen from blood effectively (but is not generally indicated because of activated charcoal’s efficacy SALICYLATES Salicylates are widely used for their analgesic and anti-inflammatory 1981 – aspirin recognized for preventing second heart attacks properties. 1998 – aspirin 81mg launched 2001 – aspirin used within 4 hours of heart attack can reduce risk of They are found in a variety of prescription and over-the-counter fatality by up to 25% analgesics, cold preparations, and topical keratolytic products 2002 – aspirin recognized by Health Canada as preventing first non- (methyl salicylate), and even Pepto-Bismol (bismuth subsalicylate). fatal heart attacks 4 indications of aspirin: anti-inflammatory, analgesic, antipyretic, Before the introduction of child-resistant containers, salicylate antiplatelet (inhibits platelet aggregation) overdose was one of the leading causes of accidental death in History – Salicylates children. 1897 – ASA developed 1915 – aspirin distributed to doctors, becomes #1 drug worldwide 4 PHCT MIDTERMS Mechanism of toxicity: o Chronic intoxication: Chronic therapeutic concentrations in arthritis patients range from 100 to 300 mg/L (10-30 mg/dL). A Salicylates have a variety of toxic effects: level greater than 600 mg/L (60 mg/dL) accompanied by o Hyperventilation leading to respiratory alkalosis (increased acidosis and altered mental status is considered very blood pH (alkaline/basic) due to loss of carbon dioxide from dangerous. lungs → decrease in carbonic acid) , metabolic acidosis Other useful laboratory studies: Electrolytes (anion gap calculation), (decreased blood pH because of buildups of acid such as glucose, BUN, creatinine, prothrombin time (PT), arterial blood lactate and ketones) contributing to dehydration (due to gases, chest x-ray. central stimulation of the respiratory center). Treatment: o Uncoupling of oxidative phosphorylation and interruption of glucose and fatty acid metabolism. Emergency and supportive measures: o Cerebral and pulmonary edema that may be related to o Maintain the airway and assist ventilation if necessary. alteration in capillary integrity. Administer supplemental oxygen. Obtain serial blood gases and chest x-rays to observe for pulmonary edema. o Platelet function is altered, and prothrombin time is prolonged. o Treat coma, seizures, pulmonary edema, and hyperthermia. Dose: o Treat metabolic acidosis with intravenous sodium bicarbonate. Do not allow the serum pH to fall below 7.4. Average therapeutic single dose: 10 mg/kg. o Replace fluid and electrolyte deficits caused by vomiting and Usual daily therapeutic dose: 40-60 mg/kg/d. hyperventilation with intravenous crystalloid solutions. Aspirin tablet: 325-650 mg acetylsalicylic acid. o Monitor asymptomatic patients for a minimum of 6 hours. Toxic dose: Admit symptomatic patients to an intensive care unit. Acute ingestion of 150-200 mg/kg will produce mild intoxication; Specific drugs and antidotes: acute ingestion of 300-500 mg/kg is likely to produce severe o There is no specific antidote for salicylate intoxication. intoxication. o Sodium bicarbonate is frequently given both to prevent Chronic intoxication may occur with ingestion of more than 100 acidemia and to promote salicylate elimination by the mg/kg/d for 2 or more days. kidneys. Clinical presentation: o Antidote for aspirin (acidic) poisoning: sodium bicarbonate Acute ingestion: (basic) o Vomiting after ingestion. Decontamination: o Hyperpnea, tinnitus (ringing of ears), and lethargy. o Prehospital: Administer activated charcoal. Ipecac-induced o Mixed respiratory alkalemia and metabolic acidosis. emesis for initial treatment of children. o Coma, seizures, hypoglycemia, hyperthermia, and pulmonary o Hospital: Administer activated charcoal and cathartic orally edema (severe intoxication). or by gastric tube. o Death caused by CNS failure and cardiovascular collapse. Enhanced elimination: o Salicylism (vomiting, tinnitus, decreased hearing, and o Urinary alkalinization: Effective in enhancing urinary excretion vertigo)—reversible by reducing the dosage. of salicylate. o Contraindicated to children with viral infection → Reye’s o Acidic drug – basic environment → ionized → easily excreted Syndrome (a rare condition that affects your brain, blood and in the urine. liver. It occurs among children who take aspirin to treat a viral o Acidic drug – acidic environment/ basic drug – basic infection.) → Fatal encephalopathy of the kidney and brain. environment → non-ionized → absorbed into the Chronic intoxication: bloodstream o Young children and confused elderly are the usual victims. o Hemodialysis: Very effective in rapidly removing salicylate and correcting acid-base and fluid abnormalities. Indications o Cerebral and pulmonary edema are more common with acute for hemodialysis include: intoxication. ▪ Patients with acute ingestion and serum levels > 1200 o Nonspecific confusion, dehydration, and metabolic acidosis mg/L (120 mg/dL), or with severe acidosis and other are attributed to sepsis, pneumonia, or gastroenteritis. manifestations of intoxication. Diagnosis: ▪ Patients with chronic intoxication with serum levels > Not difficult if there is a history of acute ingestion, accompanied by 600 mg/L (60 mg/dL) accompanied by acidosis, typical signs and symptoms. confusion, or lethargy, especially if the patient is elderly or debilitated. In the absence of a history of overdose, diagnosis is suggested by the characteristic arterial blood gases, which reveal a mixed respiratory o Hemoperfusion: Very effective but does not correct acid-base alkalemia and metabolic acidosis. or fluid disturbances. Specific levels: Obtain stat and serial serum salicylate o Repeat-dose activated charcoal therapy: Effectively reduces concentrations. Systemic acidemia increases brain salicylate serum salicylate half-life, but not as rapidly effective as concentration, worsening toxicity. dialysis, and frequent stooling may contribute to dehydration and electrolyte disturbances. o Acute ingestion (within 4 hrs): Salicylate levels are plotted on the nomogram to estimate toxicity. 5 PHCT MIDTERMS NSAIDs These are chemically diverse group of agents that share similar Other useful laboratory tests: CBC, electrolytes, glucose, BUN, pharmacologic properties and are widely used for control of pain creatinine, liver transaminases, prothrombin time (PT), urinalysis and inflammation. Treatment: Overdose by most of the agents in this group usually produces only mild gastrointestinal upset. Emergency and supportive measures: NSAIDS: COX inhibitors o Treat seizures, coma, and hypotension if they occur. Nonselective NSAIDs (mefenamic acid, ibuprofen, diclofenac): COX 1 (production of prostaglandin (defensive factor of GIT) → o Antacids may be used for mild GIT upset. perforation in GI tract) and COX 2 (production of leukotriene → no o Replace fluid losses with intravenous crystalloid solutions. inflammation/pain) inhibition Specific drugs and antidotes: Ulcer pain reliever: selective COX 2 inhibitors Indoleacetic acid o There is no specific antidote for most NSAID overdoses. o Indomethacin o Vitamin K(phytonadione) (pro-coagulant) may be used for o Sulindac patients with prothrombin time (PT) caused by o Tolmetin hypoprothrombinemia (deficiency of the blood-clotting Pyrazoles substance prothrombin, resulting in a tendency to prolonged o Phenylbutazone bleeding) to enhance clotting o Oxyphenbutazone Salicylates Decontamination: o ASA o Prehospital: Administer activated charcoal if available. o Diflunisal no antipyretic effect Ipecac-induced emesis may be considered for immediate o Methyl salicylate treatment Ketorolac alternative to morphine for nonsurgical procedures Propionic Acid o Hospital: Administer activated charcoal and a cathartic orally o Ibuprofen or by gastric tube. o Naproxen Enhanced elimination: o Ketoprofen Oxicams o Hemodialysis and hemoperfusion are generally not effective o Piroxicam in removing NSAIDs due to their high protein binding (highly Fenamates protein bound) and large volume of distribution. o Mefenamic acid o Charcoal hemoperfusion for phenylbutazone overdose may o Meclofenamic acid be effective. Mechanism of toxicity: Toxicity effects may be attributed to inhibition of cyclooxygenase CNS, hemodynamic, pulmonary, and hepatic dysfunction also occur with some agents Acute or chronic intoxication may affect gastric mucosa and renal blood flow due to a decrease in prostaglandins Toxic dose: Generally, intoxication occurs after ingestion of more than 5-10 times the usual therapeutic dose Clinical presentation: NSAID overdoses are generally asymptomatic or have mild GIT upset (nausea, vomiting, abdominal pain, sometimes hematemesis (vomiting of blood)). Occasionally patients exhibit drowsiness, lethargy, ataxia, nystagmus, tinnitus and disorientation. Oxyphenbutazone, phenylbutazone, mefenamic acid, piroxicam and ibuprofen overdose produce: o Seizures o Coma o Renal failure o Cardiorespiratory arrest o Hepatic dysfunction o Hypoprothrombinemia o Metabolic acidosis Diflunisal overdose produces same toxicity as with salicylate poisoning. Diagnosis: Diagnosis is usually based primarily on a history of ingestion of NSAIDs, because symptoms are mild and nonspecific and quantitative levels are not usually available. 6 PHCT MIDTERMS Week 8: Chemotherapeutic Drugs Chemotherapeutic Drugs: o Dapsone o Amantadine o Quinine o Chloroquine and Aminoquinolines o Isoniazid ANTI-MICROBIALS The antibiotic class of drugs has proliferated immensely since the IV. Diagnosis first clinical use of sulfonamide in 1936 and the mass production of Diagnosis is usually based on the history of exposure. penicillin in 1941. o Specific levels: Serum levels are particularly useful for o Co-trimoxazole is a combination of trimethoprim and predicting toxic effects of aminoglycosides (Kanamycin, sulfamethoxazole and is in a class of medications called Amikacin, Gentamicin) chloramphenicol, and vancomycin. sulfonamides. o Other useful laboratory studies: CBC, electrolytes, glucose, In general, harmful effects have resulted from allergic reactions or BUN and creatinine, liver function tests, urinalysis, inadvertent IV overdose. Serious toxicity from single acute ingestion methemoglobin level. is rare. V. Treatment I. Mechanism of toxicity Emergency and supportive measures. Depends on the agent. Specific drugs and antidotes: In some cases, toxicity is an extension of pharmacologic effects, allergic or idiosyncratic reactions. 1. Trimethoprim poisoning: Administer leucovorin (Wellcovorin, Citrovorum factor, Folinic acid). II. Toxic dose ▪ To treat unintentional folic acid antagonist overdose, Toxic dose is highly variable. leucovorin (derivative/analog of folic acid that helps Life-threatening reactions may occur after subtherapeutic doses in restore normal folate levels) is usually given hypersensitive individuals. intravenously as soon as possible after the overdose III. Clinical presentation ▪ Trimethoprim inhibits the enzyme dihydrofolate reductase After acute overdose, most agents cause only nausea, vomiting, and diarrhea. ▪ Sulfonamides/Dapsone/para-aminosalicylic acid inhibits the enzyme dihydropteroate synthase 2. Dapsone overdose: Administer methylene blue for symptomatic methemoglobinemia. DAPSONE Antibiotic used to treat leprosy (Hansen's disease → infectious II. Toxic dose condition that causes nerve damage and disfiguring sores on your Therapeutic ranges from 50-300 mg/d. skin) and rare dermatologic conditions Prophylaxis against Pneumocystis carinii in patients with AIDS and Chronic daily dosing of 100 mg has resulted in methemoglobin levels other immunodeficiency disorders of 5-8%. Peak plasma levels occur between 4 and 8 hours after ingestion Death has occurred with overdose of 1.4 g and greater. Metabolized by 2 primary routes–Undergo enterohepatic recirculation Persons with glucose-6-phosphate dehydrogenase (G6PD) Average elimination half-life is 30 hours after a therapeutic dose and deficiency, congenital hemoglobin abnormalities, and underlying as long as 77 hours after an overdose hypoxemia may experience greater toxicity at lower doses. I. Mechanism of toxicity III. Clinical presentation Toxic effects are caused by the p-450 metabolites, including Methemoglobinemia: Causes cyanosis and dyspnea (shortness of methemoglobinemia, sulfhemoglobinemia, Heinz body hemolytic breath), may persist for several days. Patients appear cyanotic even anemia. after receiving antidotal treatment Methemoglobinemia: Dapsone metabolites oxidize the ferrous iron o Methemoglobinemia is a disorder characterized by the hemoglobin complex to the ferric state. presence of a higher than normal level of methemoglobin (metHb) in the blood. Methemoglobin is a form of hemoglobin Sulfhemoglobinemia: Dapsone metabolites sulfate the pyrrole that does not bind oxygen. When its concentration is elevated hemoglobin ring; an irreversible reaction, and there is no antidote in red blood cells, tissue hypoxia can occur. Hemolysis: Due to depletion of intracellular glutathione by oxidative Sulfhemoglobinemia: Decreases oxyhemoglobin saturation, metabolites. No antidote available unresponsive to methylene blue. 7 PHCT MIDTERMS o Sulfhemoglobinemia is a rare condition in which there is o methylene blue acts to reduce the heme group from excess sulfhemoglobin (SulfHb) in the blood. The pigment is a methemoglobin to hemoglobin greenish derivative of hemoglobin which cannot be converted Decontamination: back to normal, functional hemoglobin. It causes cyanosis even at low blood levels. o Prehospital: Administer activated charcoal Ipecac-induced emesis for initial treatment Hemolysis: Heinz bodies may be seen; hemolysis may be delayed in onset 2-3 days after ingestion. o Hospital: Administer activated charcoal and cathartic IV. Treatment Enhanced elimination: o Repeat-dose activated charcoal Emergency and supportive measures. ▪ Interrupts enterohepatic recirculation and is very Specific drugs and antidotes: Methylene blue for effective methemoglobinemia. ▪ Reduces half-life from 77 to 13.5 hours ▪ Continue charcoal for at least 48-72 hours o Methylene blue is indicated in the symptomatic patient with a o Charcoal hemoperfusion methemoglobin level greater than 15% or with lower levels if ▪ Reduces the half-life to 1.5 hours even minimal compromise of oxygen-carrying capacity is ▪ Effective in a sever intoxication unresponsive to potentially harmful conventional treatment o Owing to its reducing agent properties, methylene blue is employed as a medication for the treatment of methemoglobinemia AMANTADINE Effective in the treatment of Parkinson’s disease → a brain disorder that causes unintended or uncontrollable movements characterized by a reduction in dopamine levels Prophylaxis against parkinsonian side effects of neuroleptic agents Used in therapy of cocaine addiction Antiviral agent, amantadine (Symmetrel) I. Mechanism of toxicity II. Toxic dose Enhances the release of dopamine and prevents dopamine reuptake Not determined. Depends on kidney function. in the peripheral and CNS o Elderly patients with renal insufficiency may develop toxic Has anticholinergic properties, especially in overdose. intoxication with the therapeutic doses III. Clinical presentation IV. Diagnosis Agitation, visual hallucinations, nightmares, tremor, disorientation, Based on history of acute ingestion and symptoms. delirium, slurred speech, ataxia, myoclonus, seizures, heart failure, Specific levels not readily available. Anticholinergic manifestations (→ dry mouth, urinary retention, mydriasis), ventricular arrhythmias. Serum levels above 1.5mg/L have been associated with toxicity. Amantadine withdrawal may result in Other useful laboratory studies: Electrolytes, BUN, creatinine, ECG monitoring. o Hyperthermia o Rigidity V. Treatment Emergency and supportive measures. No known antidote. Treat tachyarrhythmias with beta-blockers such as propranolol or esmolol. Neuroleptic malignant syndrome → can occur in response to antipsychotic medications. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate (NMS) require surgent cooling measures and may respond to specific pharmacologic therapy with dantrolene → directly interferes with muscle contraction by inhibiting calcium ion release resulting in muscle relaxation Decontamination: o Prehospital: Administer activated charcoal Ipecac-induced emesis for initial treatment o Hospital: Administer activated charcoal and cathartic Enhanced elimination: Not effective by dialysis. Amantadine is not effectively removed by dialysis, because the volume of distribution is very large (5 L/kg). The serum elimination half-life ranges from 12 hours to 34 days, depending on renal function o drugs with a high degree of protein binding and large volume of distributions are not efficiently eliminated by hemodialysis or hemoperfusion 8 PHCT MIDTERMS QUININE Optical isomer of quinidine, used for treatment of malaria and for IV. Diagnosis chloroquine-resistant cases Based on history of ingestion and presence of cinchonism (a cluster The bark of the cinchona tree is used to make quinine. of dose-related and reversible side effects of quinine, including tinnitus, decreased hearing, headache, nausea, vomiting, dysphoria Treatment of nocturnal muscle cramps and visual disturbances caused by an overdose of quinine or its Also used as an abortifacient natural source, cinchona bark) and visual disturbances. I. Mechanism of toxicity Specific levels: Plasma quinine levels above 10 mg/L associated Toxic effects include retinal toxicity, photoreceptor and ganglion cell with visual impairment, levels above 20 mg/L with blindness, levels toxicity. above 16 mg/L with cardiac toxicity. II. Toxic dose Other useful laboratory studies: CBC, electrolytes, glucose, BUN, creatinine, arterial blood gases, ECG monitoring. Minimum toxic dose is approx. 3-4 g in adults. V. Treatment 1 g is fatal to a child. Emergency and supportive measures. III. Clinical presentation Specific drugs and antidotes: hypertonic sodium bicarbonate 1- Mild intoxication: Nausea, vomiting, cinchonism (tinnitus, deafness, 2meq/kg rapid IV bolus for cardiotoxicity. vertigo, headache, visual disturbances). Stellate ganglion block has previously been recommended for Severe intoxication: Ataxia, obtundation (a state similar to lethargy quinine-induced blindness. in which the patient has a lessened interest in the environment, slowed responses to stimulation, and tends to sleep more than o A stellate ganglion block is an injection of local anesthetic in normal with drowsiness in between sleep states.), convulsions, the sympathetic nerve tissue of the neck. These nerves are a coma, respiratory arrest, cardiotoxicity. part of the sympathetic nervous system. The nerves are located on either side of the voice box, in the neck. Retinal toxicity: Occurs 9-10 hours after ingestion, blurred vision, impaired color perception, constriction of visual fields, blindness, Decontamination: Activated charcoal and cathartic (induce macular edema, disk pallor. Pupils are fixed and dilated, retinal defecation). artery spasm Enhanced elimination: Acidification of urine may slightly increase Other toxic effects: Hypokalemia, hypoglycemia, hemolysis, renal excretion but does not significantly alter the overall elimination congenital malformations in pregnancy. rate. CHLOROQUINE AND AMINOQUINOLINES Used for prophylaxis or therapy of malaria and other parasitic Severe overdose: Convulsions, coma (avoid inducing vomiting with diseases, as well as rheumatoid arthritis. Chloroquine and ipecac or administering emetics in patients experiencing coma or hydroxychloroquine seizures), shock, respiratory or cardiac arrest, quinidine-like cardiotoxicity, severe hypokalemia. Drugs: Chloroquine phosphate (Aralen®), amodiaquine HCl (Camoquin®), hydroxychloroquine sulfate (Plaquenil®), mefloquine Severe chloroquine overdose may cause: (Lariam®), primaquine phosphate, quinacrine HCl (Atabrine®). o Quinidine-like cardiotoxicity may be seen including I. Mechanism of toxicity ▪ Sinoatrial arrest Chloroquine blocks DNA and RNA synthesis and has quinidine-like ▪ Depressed myocardial contractility cardiotoxicity. ▪ QRS or QT interval prolongation Primaquine and quinacrine can cause methemoglobinemia or hemolytic anemia (a disorder in which red blood cells are destroyed ▪ Heart block epinephrine faster than they can be made. The destruction of red blood cells is ▪ Ventricular arrhythmias called hemolysis), especially in G6PD-deficient patients. glucose-6- phosphate dehydrogenase (G6PD) enzyme. G6PD helps red blood Severe hypokalemia cells work and protects them from harmful substances and Primaquine and quinacrine intoxication: GIT upset, severe premature destruction. G6PD deficiency → hemolytic anemia methemoglobinemia, hemolysis, ototoxicity, retinopathy. II. Toxic dose Amodiaquine: Fatal neutropenia. Therapeutic dose of chloroquine phosphate is 500 mg once a week Mefloquine: Dizziness, vertigo, hallucinations, psychosis, seizures. for malaria prophylaxis, or 2.5 g over 2 days for malaria treatment. IV. Diagnosis Deaths reported in children after doses as low as 300 mg; lethal dose Specific levels: Chloroquine levels can be measured in blood but are for adults estimated at 30-50 mg/kg. not generally available. III. Clinical presentation Other useful laboratory studies: Electrolytes, glucose, BUN, Mild to moderate overdose: Dizziness, nausea, vomiting, abdominal creatinine, ECG monitoring. For primaquine or quinacrine, also pain, headache, visual disturbances, auditory disturbances, include CBC, free plasma hemoglobin, methemoglobin. agitation, neuromuscular excitability. 9 PHCT MIDTERMS V. Treatment Enhanced elimination: Ineffective. Emergency and supportive measures. Specific drugs and antidotes: e1-2meq/kg IV Sodium bicarbonate for cardiotoxicity, epinephrine infusion for hypotension, high-dose diazepam (2mg/kg IV, given over30mins) for cardiotoxicity. Decontamination: Activated charcoal and ipecac-induced emesis for initial treatment. ISONIAZID (INH) Hydrazide derivative of isonicotinic acid IV. Diagnosis Bactericidal drug choice for tuberculosis Usually made by history and clinical presentation. Known to cause hepatitis on chronic use Drug-induced seizures and metabolic acidosis on acute isoniazid INH should be considered in any patient with acute onset seizures, overdose especially when accompanied by profound metabolic acidosis. I. Mechanism of Toxicity A. Specific Levels A. Acute Overdose A 5 mg/kg dose produces a peak INH concentration of 3 mg/L at 1 hour. Competes with pyridoxal 5-phosphate (active form of Vit. B6) for glutamic acid decarboxylase. Serum levels higher than 30 mg/L are associated with acute toxicity. Lower levels of GABA lead to uninhibited electrical activity B. Other Useful Laboratory Studies manifested as seizures. Electrolytes Also inhibits hepatic conversion of lactate to pyruvate, resulting in Glucose lactic acidosis. BUN B. Chronic Toxicity Creatinine Competes with pyridoxine (vitamin B6), resulting in peripheral neuritis. Liver function tests (for chronic toxicity) II. Toxic Dose Arterial blood gases A. Acute Ingestion V. Treatment Ingestion of as little as 1.5 g can produce toxicity. A. Emergency and Supportive Measures Severe toxicity is common after ingestion of 80-150 mg/kg. B. Specific Drugs and Antidotes B. Chronic Use Pyridoxine (vitamin B6) terminates diazepam-resistant seizures. 10-20% of patients will develop hepatic toxicity when the dose is 10 C. Decontamination mg/kg/day. Prehospital Less than 2% will develop this toxicity if the dose is 3-5 mg/kg/day. Administer activated charcoal. Older persons are more susceptible to chronic toxicity. Do not induce emesis because of the risk of rapid onset of coma and III. Clinical Presentation seizures. A. Acute Overdose Hospital Slurred speech Administer activated charcoal and cathartic. Ataxia Gastric lavage for massive ingestions. Coma D. Enhanced Elimination Seizures Forced diuresis and dialysis. Hemolysis B. Chronic Therapeutic INH Use Peripheral neuritis Hepatitis Hypersensitivity reactions like lupus erythematosus and pyridoxine deficiency 10 PHCT MIDTERMS Week 9: Cardiovascular Drugs Cardiovascular Drugs Electrical impulses → AV node → bundle of his → Purkinje fibers (ventricle beating) o Anti-arrhythmic Drugs Phases of Action Potential: o Beta-adrenergic Blockers 1. Phase 0: Upstroke, Opening of Na channel depolarization o Vasodilators 2. Phase 1: Early fast repolarization, Closure of Na (+) channel, o Clonidine and Related Drugs opening of K channel (dec. AP) Sinoatrial node → natural pacemaker of the heart, initiates 3. Phase 2: Plateau, sustained inward movement of Ca (+) and outward heartbeat movement of K (Can cause homeostasis) Atrium and ventricle → not synchronized in beating but 4. Phase 3: Repolarization phase, Closure of Ca channel, K channel simultaneously beating remains open Atrioventricular node → center of atrium and ventricle, receives 5. Phase 4: Diastole or resting state, All channels close electrical impulses from SA node ANTI-ARRHYTHMIC DRUGS Type I: Inhibit fast sodium channels, depress myocardial Clinical Presentation: automaticity, conduction, and contractility. Acts on phase 0 Cardiotoxic effects: sinus bradycardia (condition where the heart Type II: Block beta-adrenergic receptors. On heart (-) ionotropic, rate is slower than normal due to the sinus node (the natural chronotropic, and dromotropic effect → decreased force of pacemaker of the heart) generating electrical impulses at a reduced contraction (bradycardia) betablockers for tachyarrhythmia rate) sinus node arrest, PR, QRS, or QT interval prolongation, polymorphous ventricular tachycardia, hypotension. Type III: Block potassium channels to prolong the duration of the action potential. CNS toxicity (Quinidine and disopyramide): dry mouth, dilated pupils, delirium, seizures, coma. Type IV: Calcium channel blockers. Other effects: nausea, vomiting, diarrhea, cinchonism (tinnitus, Type I Anti-arrhythmic Drugs: vertigo, deafness, visual disturbances with chronic dose). Type Ia: Depressed myocardial contractility with alpha-adrenergic or Examples: Quinidine, Procainamide (Pronestyl®), Disopyramide ganglionic blockade may result in hypotension and occasionally (Norpace®) pulmonary edema. Mechanism: All Type Ia agents can produce seizures, coma, respiratory arrest. Procainamide can cause: GIT upset, lupus-like syndrome condition Depress fast sodium-dependent channels, slowing phase zero of the that mimics systemic lupus erythematosus (SLE) but is triggered by cardiac action potential. certain medications. (butterfly rash) (chronic use). At high concentrations, this results in reduced myocardial Treatment: contractility and excitability, and severe depression of cardiac conduction velocity. Emergency and supportive measures. Reduced myocardial contractility → inhibit Na channels → inhibit Specific drugs and antidotes (e.g., hypertonic sodium bicarbonate). depolarization → inhibit contraction (Helps to counteract the acidosis that can occur during cardiac arrest) Repolarization is also delayed, resulting in a prolonged QT interval that may be associated with polymorphic ventricular tachycardia → A cardiac pacemaker (a medical device implanted in the chest or characterized by a rapid and irregular heartbeat originating from the abdomen to help manage abnormal heart rhythms, known as ventricles, the lower chambers of the heart. arrhythmias. It delivers electrical impulses to the heart to ensure it beats at a normal rate and rhythm) is indicated for patients Additional Properties: unresponsive to sodium bicarbonate therapy. Quinidine and disopyramide also have anticholinergic activity. Decontamination (e.g., activated charcoal). Disopyramide has three important side effects: it is vagolytic, Enhanced elimination (e.g., dialysis for quinidine). Acidification of causing urinary retention, constipation, and dry mouth. urine may enhance elimination but is not recommended. Usage: Dysopyramide, procainamide, and N-acetylprocainamide (NAPA) Quinidine and procainamide are commonly used for suppression of are effectively removed by hemoperfusion or dialysis. acute and chronic supraventricular (rhythm disorders originating Type Ib: above the ventricles, typically in the atria or the atrioventricular (AV) node) and ventricular arrhythmias. (abnormal heart rhythms Examples: Tocainide, Mexiletine, Lidocaine originating from the ventricles, the lower chambers of the heart.) Clinical Presentation: Quinidine has alpha-adrenergic receptor-blocking activity and is one o Sedation of the oldest anti-dysrhythmic drugs. o Confusion Procainamide has ganglionic and neuromuscular blocking activity o Coma (muscle relaxation) o Seizures Toxic Dose: o Respiratory arrest 1 g of quinidine, 5 g of procainamide, or 1 g of disopyramide. 11 PHCT MIDTERMS o Cardiac toxicity o AV block Lidocaine: o Asystole o Lidocaine is an aminoacyl amide synthetic derivative of o Prolonged QRS and QT intervals cocaine. Encainide o It is an antidysrhythmic and local anesthetic agent. Encainide was withdrawn from US and Canadian markets in o Lidocaine is metabolized to two active metabolites, December of 1991 due to increased mortality in the cardiac monoethylglycinexylidide (MEGX) and glycine xylidide (GX); dysrhythmia trial. these metabolites may contribute to toxicity. Encainide, an analog of lysergic acid, is at least 10 times more potent III. Clinical Presentation: than procainamide. Its absorption and hepatic metabolism are A. Tocainide and Mexiletine rapid; these metabolites are as active as the original drug. Side effects may include: Type III Anti-arrhythmic Drugs: o Dizziness o Blocks potassium channels to prolong the duration of the action o Paresthesias → abnormal sensations on the skin, such as potential and the effective refractory period. tingling, prickling, numbness, or "pins and needles," without Bretylium: an obvious physical cause. These sensations can occur in Bretylium is a quaternary benzylammonium compound used for various parts of the body, including the hands, feet, arms, and treating lidocaine-refractory arrhythmias. legs. Causes initial release of catecholamines (NE. epinephrine, o Tremor dopamine → vasoconstriction (if inhibited: vasodilation → o Ataxia hypotension) followed by inhibition, with the major side effect being o GIT disturbance hypotension. Orthostatic hypotension (a condition where a person's blood pressure falls significantly when they stand up from a sitting or Overdose may cause: lying position. This sudden drop in blood pressure can lead to o Sedation dizziness, lightheadedness, and in some cases, fainting) may persist. o Confusion After rapid intravenous injection, transient hypertension, nausea, o Coma and vomiting may occur. o Seizures Amiodarone: o Respiratory arrest Non-competitive beta-adrenergic blocker may cause o Cardiac toxicity (sinus arrest, AV block, asystole, and bradyarrhythmias. hypotension) Side effects include photosensitivity, hyperthyroidism, pulmonary Type Ic: fibrosis, and corneal deposits. Examples: Flecainide, Encainide, Propafenone, Moricizine May release iodine, and chronic use has resulted in altered thyroid function. Thyroid hormones: Thyroxine (T4), Triiodothyronine (T3) Side effects: Has a very long half-life (40-50 days). o Dizziness Acute overdose of amiodarone is not expected to cause toxicity. o Blurred vision Chronic use may cause: o Headache o Ventricular arrhythmias (monomorphic or polymorphic o GIT upset ventricular tachycardia) o Ventricular arrhythmias (monomorphic or polymorphic o Bradyarrhythmias (sinus arrest, AV block) ventricular tachycardia) o May aggravate cardiac failure Clinical Presentation: o Pneumonitis o Hypotension o Bradycardia BETA-ADRENERGIC BLOCKERS Widely used for treating hypertension, angina pectoris, migraine o Atenolol headaches, and glaucoma. o Metoprolol Beta Blockers Membrane Stabilizing Activity: anesthetic like effect, cannot be Types and Characteristics: given as ophthalmic drops (contraindicated in glaucoma) Selective: o Propranolol o Betaxolol o Pindolol o Bisoprolol o Acebutolol o Esmolol o Labetalol o Acebutolol o Metoprolol 12 PHCT MIDTERMS Mixed Alpha and Beta Blocking Effect: Toxic Dose: o Labetalol Ingestion of 2-3 times the therapeutic dose can be life-threatening. o Carvedilol Clinical Presentation: Intrinsic Sympathomimetic Activity: partial agonist effect Cardiac Disturbances: Hypotension, bradycardia, atrioventricular block, intraventricular conduction disturbances, cardiogenic shock, o Acebutolol asystole. o Bisoprolol Central Nervous System Toxicity: Convulsions, coma, respiratory o Carteolol arrest. o Pindolol Other Symptoms: Bronchospasm (especially in asthma patients), o Penbutolol hypoglycemia, hyperkalemia. Non-Selective (β1 (heart) and β2 (lungs) blockers): bronchospasm Diagnosis: o Propranolol Specific Levels: Measurement of beta-blocker serum levels may confirm the diagnosis but is not essential for emergency o Nadolol management. o Timolol Treatment: o Pindolol Emergency and Supportive Measures. o Sotalol Specific Drugs and Antidotes: Glucagon (secreted by the pancreas, Mechanism of Toxicity: increases blood sugar levels (endogenous) 0.1-0.3 mg/kg IV bolus, repeated as needed for bradycardia and hypotension, hypertonic Propranolol: Depresses myocardial contractility and conduction; sodium bicarbonate 1-2 meq/kg for membrane-depressant causes seizures and coma due to lipid solubility. poisoning, isoproterenol, magnesium, or overdrive pacing for Pindolol: May cause hypertension due to beta-agonist activity. torsades de pointes. Sotalol: Prolongs QT interval, may cause torsades de pointes and Decontamination: Activated charcoal, ipecac-induced emesis, ventricular fibrillation. Torsades de pointes → fatal polymorphic cathartics. ventricular tachycardia VASODILATORS Types: Toxic Dose: Alpha-Adrenergic Blocking Agents: Minimum toxic or lethal doses not established. Fatalities reported with indoramin overdose and excessive intravenous phentolamine. o Phenoxybenzamine Clinical Presentation: o Phentolamine Headache, nausea, dizziness, weakness, syncope (fainting), o Tolazaline orthostatic hypotension, warm flushed skin, palpitations, lethargy Selective α1 Inhibitors: and ataxia in children, cerebral and myocardial ischemia, acute o Prazosin 1stselective α1 inhibitor was introduced in the early renal failure. 1970’s Diagnosis: o newer α1 selective agents Diagnosis is based on a history of exposure and the presence of orthostatic o Doxazosin hypotension, which may or may not be accompanied by reflex tachycardia. o Indoramin Specific Levels: Blood levels not routinely available or clinically useful. o Terazosin Laboratory Studies: Electrolytes, glucose, BUN, creatinine, ECG. o Trimazosin Treatment: o Urapidil Emergency and Supportive Measures. Mechanism of Toxicity: Specific Drugs and Antidotes: No specific antidote. Dilate peripheral arterioles, lower blood pressure. Decontamination: Activated charcoal, ipecac-induced emesis, Reflex sympathetic response can cause tachycardia and cathartics, Terazosin and doxazosin are long-acting and eliminated arrhythmias. 60% in feces; thus, repeat-dose activated charcoal for enhanced Prazosin and other newer α1 specific agents are associated with elimination. little or no reflex tachycardia CALCIUM CHANNEL BLOCKERS o Anti-hypertensive Non-Dihydropyridine: o Anti-arrhythmic o Verapamil o Anti-angina o Diltiazem Types: 13 PHCT MIDTERMS Dihydropyridine Family: o Vasopressor support (dopamine, norepinephrine, epinephrine, phenylephrine, vasopressin, metaraminol) o Amlodipine o High-dose insulin infusion with dextrose o Felodipine Rapid transport before the patient deteriorates is crucial. Empiric o Isradipine use of glucagon (adults: 5-15 mg IV) may be warranted for patients o Nicardipine with an unknown overdose presenting with bradycardia or o Nifedipine hypotension. o Nisoldipine Consider using calcium only if a witness confirms a calcium channel blocker overdose; calcium may induce fatal arrhythmias in digoxin Mechanism of Toxicity: overdose, which can present with similar findings. Cardiovascular Effects: Treat hypotension with fluid boluses. If profound hypotension fails to Peripheral vasodilatation respond to fluid resuscitation, administer a dopamine or norepinephrine (increases cardiac force and contraction) drip, if Negative chronotropy permitted by local protocol. Negative inotropy If the patient deteriorates to cardiac arrest from a calcium channel Negative dromotropy blocker overdose, perform prolonged cardiopulmonary resuscitation (CPR) in the field because patients have survived Other Physiologic Responses: neurologically intact after an hour of CPR. Suppression of insulin release Avoid ipecac syrup. Decreased free fatty acid utilization, causing hyperglycemia, lactic Administer activated charcoal (AC) if the patient's airway is acidosis (a condition characterized by an accumulation of lactic protected. acid in the blood, leading to a decrease in blood pH (metabolic acidosis), and depressed cardiac contractility Atropine may be tried if hemodynamically significant bradycardia occurs; however, heart block is usually resistant to atropine in Laboratory Studies: calcium channel blocker toxicity. Lactic acidosis (ABG analysis) Mid-dose dopamine (5-10 mcg/kg/min) may improve heart rate and Serum electrolytes contractility. BUN/creatinine Administer IV calcium gluconate (up to 4 g) or IV calcium chloride (1 g) and/or glucagon (5-10 mg) if hypotension persists. CCB blood levels (generally not available promptly) Serum acetaminophen level Consider dopamine or norepinephrine infusion if a long transport time is likely, as permitted by local prehospital care protocols. Liver function tests Gastric decontamination: Serum digoxin level o Gastric lavage may be useful in early presentations (