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Toxicology Recall > Medications > Flashcards

Medications Flashcards

1
Q

What is acetaminophen?

A

N-acetyl-p-aminophenol (APAP), an analgesic and antipyretic agent

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2
Q

Where is acetaminophen found?

A

Acetaminophen is found in a large number of products, both OTC and prescription. It is combined with opioids to make analgesics such as Percocet, Vicodin and Darvocet, with antihistamines to make sleep aids such as Tylenol PM and with antihistamines and decongestants to form products such as NyQuil and Tylenol Cold preparations.

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3
Q

What is the potentially hepatotoxic single dose of APAP?

A

When there are no coexisting health problems, a single acute overdose of over 150 mg/kg in an adult or 200 mg/kg in children under 12 is potentially hepatotoxic.

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4
Q

How is acetaminophen metabolized?

A

The majority is usually metabolized in the liver through sulfation and glucuronidation with 5% to 10% metabolized by the cytochrome P450 system.

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5
Q

What is the elimination half-life of APAP?

A

4 hours

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6
Q

How does APAP overdose result in toxicity?

A

Acetaminophen overdose overwhelms the sulfation and glucuronidation pathways, shunting metabolism to the cytrochrome P450 system and producing the toxic metabolite.

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7
Q

What is the hepatotoxic metabolite of acetaminophen?

A

N-acetyl-p-benzoquinoneimine (NAPQI)

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8
Q

How is NAPQI normally metaboized by the liver?

A

In sub-toxic doses, NAPQI is quickly conjugated with glutathione in hepatocytes, then renally eliminated. In overdose, the quality of NAPQI overwhelms glutathione stores which results in accumulation of the toxin.

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9
Q

What is the mechanism of toxicity of NAPQI?

A
  1. Chronic alcoholics who overdose (increased risk of liver damage).
  2. Pregnant patients who overdose (increased risk of fetal death)
  3. patient taking inducers of CYP2E1 (e.g. isoniazid).
  4. Patients suffering from malnutrition (lower glutathion stores).
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10
Q

What are the classic clinical stages of acetaminophen poisoning?

A

Stage 1: (time of ingestion to 24 hours) - anorexia, nausea, vomiting.

Stage 2: 24-72 hours post ingestion) - elevation of transaminases, bilirubin and PT; nausea and vomiting may resolve.

Stage 3: 72-96 hours post ingestion) - worsening hepatic necrosis with corresponding elevation in AST and ALT; may progress to coagulopathy, jaundice, hepatic and renal failure, encephalopathy, and death or may progress to stage 4.

Stage 4: (>96 hours post ingestion) - Healing of liver damage with eventual resolution of enzymatic and metabolic abnormalities.

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11
Q

What laboratory tests should be performed for APAP toxicity?

A

Plasma acetaminophen level 4 hours post ingestion for nonextended release preparations. BUN, creatinine, AST, ALT, PT/INR, and glucose are also warranted.

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12
Q

What is the Rumack-Matthew Nomogram?

A

A graph depicting the treatment line for probable hepatic toxicity.

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13
Q

What is the 4-hour treatment level for APAP?

A

150 mcg/mL

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14
Q

Is this the same APAP treatment level as in Europe?

A

No. The original treatment line was APAP of 200 mcg/mL at 4 hours. The level was lowered to 150 mcg/mL in the U.S. to provide an extra margin of safety.

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15
Q

What is the recommended treatment for APAP overdose?

A
  1. Activated charcoal - if presenting within 1 hour of ingestion.
  2. N-acetylcysteine (NAC) - most efficacious if given within 8 hours of ingestion
  3. Antiemetics - ondansetron is preferred; avoid antiemetics with sedative properties or that are metabolized by the liver.
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16
Q

How does NAC work?

A

Acts primarily by repleting glutathione. It also may enhance the sulfation pathway, increase blood flow to the liver, bind NAPQI, and help reduce NAPQI back to acetaminophen.

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17
Q

How is NAC supplied?

A

Both IV and PO formulations. IV form appears to be as efficacious as PO form and can be given over 20 hours as opposed to the 72-hr PO dose.

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18
Q

What is the traditional NAC PO dosing schedule as approved by the U.S. FDA?

A

140 mg/kg x 1 dose, then 70 mg/kg q4 hrs for 17 more doses.

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19
Q

How do you treat a patient who is an unreliable historian with a suspected acetaminophen overdose?

A

In patient with an unknown time of ingestion and a detectable acetaminophen level, treat with NAC until acetaminophen level is undetectable and transaminases are normal or declining.

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20
Q

Does acetaminophen cause acidosis?

A

While not part of the traditional MUDILIES, acetaminophen in very large does appears to act as a metabolic poison and can cause an anion gap metabolic acidosis.

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21
Q

What is Carbamazepine?

A

Examples: Tegretol XR, Equetro, Carbatrol, Epitol, and Tegretol

An anticonvulsant used for the treatment of epilepsy, trigeminal neuralgia, psychiatric illnesses, restless leg syndrome,and alcohol withdrawal.

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22
Q

To which class of drugs is carbamazepine structurally similar?

A

Tricyclic antidepressants; therefore, urine drugs screens may be positive for cyclic antidepressants in patients taking carbamazepine

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23
Q

What is the mechanism of action for carbamazepine?

A

In therapeutic doses, carbamazepine blocks neuonal sodium channels an dis an adenosine receptor agonist. In overdose, it becomes an adenozine recetor antagonist.

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24
Q

What is the rate of absorption for carbamazepine?

A

Absorption is typically slow and erratic. Peak levels can be delayed 6-24 hours following overdose.

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25
Q

Where is carbamazepine metabolized?

A

Liver, by P450 oxidation.

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26
Q

What is considered a therapeutic level of carbamazepine?

A

4-12 mg/L

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27
Q

What neurotransmitter receptors are blocked in carbamazepine toxicity?

A

Adenosine receptors.

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28
Q

What are the clinical effects of carbamazepine toxicity?

A

CNS symptoms predominate with altered consciousness, dizziness, ataxia, HA, and nystagmus. GI symptoms may be present. Severe toxicity can result in cardiac dysrhythmias and seizures.

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29
Q

What cardiac effects have been reported with carbamazepine toxicity?

A

QRS and QTc prolongation leading to ventricular dysrhythmias.

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30
Q

Name the standard treatments for QRS and QTc prolongation.

A

IV sodium bicarbonate and IV magnesium sulfate, respectively.

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31
Q

What endocrine abnormality can result from carbamazepine toxicity?

A

Syndrome of inappropriate anti-diuretic hormone (SIADH).

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32
Q

Are there any specific antidotes for carbamazepine toxicity?

A

No

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33
Q

What is the indication for isoniazid (INH) therapy?

A

Tuberculosis

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34
Q

What is the mechanism of action of INH?

A

Isoniazid is a prodrug an dmust be activated by bacterial catalase; it inhibits the synthesis of mycolic acid in the mycobacterial cell wall.

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35
Q

How is INH metabolized?

A

Hepatic

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36
Q

What is the half-life of INH?

A

0.5-1.6 hours in fast acetylators, 2-5 hours in slow acetylators.

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37
Q

What is the mechanism of toxicity in INH?

A

INH metabolites inhibit pyridoxine kinase and bind pyridoxal-5-phosphate, a cofactor for glutamine acid decarboxylase, thereby decreasing levels of the inhibitory neurotransmitter GABA.

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38
Q

What are the signs of acute INH overdose?

A

Nausea, vomiting, slurred speech ataxia, CNS depression and seizures.

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39
Q

What are the metabolic effects of acute INH overdose?

A

A marked lactic acidosis may develop in patients who present with seizures, INH inhibits lactate dehydrogenase that converts lactate to pyruvate, thereby prolonging the metabolic acidosis.

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40
Q

How is the diagnosis of INH overdose made?

A

Generally by history; however, INH toxicity should be in the differential diagnosis for all refractory seizures, especially in high risk patients, (history of HIV, tuberculosis, homelessness, or incarceration).

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41
Q

What are the adverse effects of chronic INH overdose?

A

Peripheral neuritis, optic neuritis, hepatitis, pancreatitis, drug-induced systemic lupus erythematosus, and pyridoxine deficiency.

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42
Q

What drugs are used to treat INH overdose?

A

Pyridoxine (vitamin B6) - 1 g IV for each g of INH ingested or 5 g IV for an unknown amount ingested. Standard seizure treatments also apply (i.e. benzodiazepines).

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43
Q

In what class of drugs is digoxin found?

A

Cardiac glycosides

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44
Q

Where may cardiac glycosides be found in nature?

A

Digitalis purpurea (foxglove), Nerium oleander (oleander), Thevetia peruviana (yellow oleander), Convallaria majalis (lily of the valley), Urginea maritima (red squill), secretions of Buo alvaritus (Colorado River Toad).

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45
Q

What is the mechanism of action of digoxin?

A

Digoxin binds to the extracellular surface of the Na-K-ATPase, blocking its activity and increasing residual sodium inside the cell. This decreased gradient drives the sodium calcium antiporter to extrude sodium from the cell, driving calcium into the cell. The increased calcium inside the cell during systole increases the force of contraction. Digoxin-induced increased in vagal tone decreases SA and AV nodal dromatropy.

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46
Q

What are the adverse effects of sodium-potassium pump blockade?

A

Increasing calcium inside the cell elevates the membrane potential, allowing for easier

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47
Q

What ECG abnormalities are associated with therapeutic dosing of digoxin?

A

Scooped ST segments and T wave inversions in the lateral leads.

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48
Q

Describe the distribution of digoxin.

A

It follows the two-compartment model.

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49
Q

How is digoxin eliminated?

A

Primarily by the kidneys.

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50
Q

What is the therapeutic level of digoxin?

A

0.5-2.0 ng/mL.

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51
Q

What are the signs and symptoms of acute digoxin overdose?

A

GI distress (e.g., nausea, vomiting and abdominal pain), lethargy, confusion, arterial and ventricular ectopy (including progression to VT or VF), sinus bradycardia, sinus arrest, high-degree AV block.

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52
Q

What laboratory abnormality is classically associated with acute digoxin toxicity?

A

Hyperkalemia

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53
Q

What is the most common dysrhythmia associated with digoxin toxicity?

A

PVCs

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54
Q

What dysrhythmia is pathognomic of digoxin toxicity?

A

Biventricular tachycardia

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55
Q

What are the signs and symptoms of chronic digoxin toxicity?

A

GI distress, (e.g. nausea, vomiting, abdominal pain), anorexia with weight loss, delirium, HA, seizures, visual disturbances, weakness, sinus bradycardia, ventricular dysrhythmias (more common than in acute toxicity).

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56
Q

What laboratory testing should be done for digoxin toxicity?

A

Digoxin levels, but these may not accurately indicated severity of ingestion for the initial 6 hours due to distribution kinetics. Serum potassium levels reflect the amount of sodium-potassium pump poisoning in acute overdose.

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57
Q

What is the role of calcium in digoxin toxicity?

A

While normally an integral part of treatment in hyperkalemia, there have been case reports of cardiac standstill when giving calcium for hyperkalemia in digoxin toxicity.

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58
Q

What is the treatment of digoxin overdose?

A
  1. In acute overdose, digoxin-specific antibody (Fab) fragments are indicated for patients with potassium levels > 5.0 mEq/L for high degree heart blocks, and for dysrhythmias.
  2. Standard therapy is indicated for hyperkalemia.
  3. Use caution in cardioversion of atrial dysrhythmias (use lowest energy possible), as the irritable myocardium is prone to ventricular dysrhythmias.
  4. Atropine can be used for bradycardia. Use caution with temporary cardiac pacemakers.
  5. Phenytoin may be used for ventricular irritability if Fab fragments are not available.
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59
Q

Does hemodialysis have a role in cardiac glycoside poisoning?

A

No, as digoxin has a large volume of distribution.

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60
Q

For a known steady state digoxin blood level, what is the dose calculation for Fab fragments?

A

[drug level (ng/mL) X patient weight in kg]/100 = number of vials (round up)

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61
Q

What are the indications for lithium administration?

A

As a mood stabilizer, most often in patients with bipolar disorder.

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62
Q

How is lithium metabolized?

A

Excreted unchanged by the kidney.

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63
Q

What is the etiology of lithium toxicity?

A

Acute toxicity occurs when a patient takes a single large dose. Chronic toxicity usually occurs in those taking their regularly prescribed dose. The levels become toxic through any mechanism which alters renal function, including dehydration, diabetes insipidus, and the use of diuretics, ACE inhibitors, or NSAIDs.

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64
Q

What renal side effect is associated with lithium therapy?

A

Nephrogenic diabetes isipidus.

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65
Q

What are the signs and symptoms of acute lithium toxicity?

A

Nausea and vomiting predominate. With a large enough ingestion, lithium can cause delayed neurological effects after redistribution to the tissues.

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66
Q

What signs and symptoms are seen with chronic lithium toxicity or in patients in later stages of acute toxicity?

A

Tremor, confusion, ataxia, slurred speech, myoclonus, and hyperreflexia are common. Severe poisoning can cause agitated delirium, coma, hyperthermia and convulsions.

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67
Q

What does the ECG show in lithium toxicity?

A

T-wave flattening or inversions. Prolongation of the QT interval has also been reported.

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68
Q

What important considerations must be observed when ordering lithium levels?

A
  1. Peak levels may be delayed, so serial levels should be obtained.
  2. Avoid lithium heparin tubes as they can cause false positive results.
  3. A patient with chronic toxicity can have significant clinical findings even with a mildly elevated serum level.
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69
Q

What is a therapeutic drug level range for lithium?

A

0.6-1.2 mEq/L

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70
Q

What must be considered if hemodialysis is employed for lithium toxicity?

A

Lithium commonly redistributes from the tissues into the serum, and serum lithium levels will rebound.

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71
Q

What drug interaction can be seen with lithium?

A

Combining lithium with serotonergic drugs (e.g. SSRIs) can precipitate serotonin syndrome.

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72
Q

For which indications is valproic acid prescribed?

A
  1. Seizures disorders (prophylaxis or to abort status epilepticus)
  2. Affective disorders
  3. Chronic pain (not an approved use)
  4. Migraine headache prophylaxis
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73
Q

Where is valproic acid metabolized?

A

Liver

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74
Q

What is the toxic dose?

A

Although highly variable, 200-400 mg/kg may cause coma. >400 mg/kg has an increased risk for an adverse outcome.

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75
Q

What organ system is most affected by an acute VPA overdose?

A

CNS - causes depression

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76
Q

With chronic VPA therapy, what organ may be adversely affected?

A

The liver - hepatic failure can occur

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77
Q

What metabolic complications can be seen with VPA ingestion?

A

Primarily hyperammonemia (without coexisting hepatic failure) may be seen with therapeutic use or following overdose. Anion gap metabolic acidosis may be seen in acute overdose with very large ingestions.

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78
Q

What is considered a toxic VPA level?

A

Levels > 150 mg/L (therapeutic usually 50-120 mg/L)

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79
Q

How should a VPA overdose be treated?

A

Multi-dose activated charcoal has bee used to increase elimination. Valproate-induced hyperammonemic encephalopathy may be treated with carnitine and lactulose. Hemodialysis may be used for patients with marked acidosis or very high serum concentrations.

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80
Q

What hematologic abnormality may be seen in overdose

A

Bone marrow suppression can occur after massive overdose. This presents within 3 to 5 days and resolves spontaneously a few days later.

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81
Q

What is the basic mechanism of action of the type I antidysrhythmics?

A

They reduce excitability of cardiac tissue by preventing fast acting sodium channels from converting from an inactivated state to a resting or “ready” state, thereby decreasing the number of active sodium channels available to generate an action potential.

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82
Q

What is the physiology behind the mechanism of type I antidysrhythmics?

A

By inhibiting the fast acting sodium channels that are normally active during the upstroke (phase 0) of the action potential in cardiac tissue, the slow the rate of depolarization and propagation of conduction through the myocardium.

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83
Q

How are type I antidysrhythmics further subdivided?

A

Based on their effects on the duration of the action potential (AP)

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84
Q

What are the effects of type Ia, Ib and Ic agents on the action potential?

A

Ia - prolong
Ib - shorten
Ic - no effect on the AP

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85
Q

Which class of type I antidysrhythmics binds primarily to inactivated sodium channels?

A

Ib

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86
Q

Which class of type I antidysrhythmics also acts at myocardial potassium channels responsible for repolarization?

A

Ia and Ic

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87
Q

How dose this potassium efflux blockade (type Ia and Ic) affect the EKG?

A

Prolongs the QTc

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88
Q

What rhythm can result from QTc prolongation?

A

Torsade de points

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89
Q

What are type Ia antidysrhythmics agents

A

Procainamide (prototypical type Ia agent)
Quinidine
Disopyramide

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90
Q

What are the physiologic effects of type I antidysrhythmics agents at high concentrations?

A
  1. Prolonged AV conduction
  2. Depressed ventricular conduction velocity, resulting in prolonged QRS duration
  3. Delayed repolarization, resulting in prolonged QT interval and progression to torsade de points
  4. Decreased cardiac contractility and excitability
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91
Q

What organ systems are affected by type Ia toxicity?

A

Mostly CNS and cardiovascular effects

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92
Q

What are the clinical signs and symptoms of type Ia agent toxicity?

A
  1. CNS - anticholinergic toxidrome with AMS (quinidine and disopyramide), seizures, respiratory depression, coma.
  2. CV - wide QRS -complex tachycardia (sodium channel blockade), anticholinergic-induced tachycardia, depressed contractility, and subsequent hypotension when confounded by alpha-adrenergic blockade or ganglionic blockade.
  3. GI - nausea, vomiting, diarrhea, hypoglycemia
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93
Q

Which type I antidysrhythmic agent is associated with a drug-induced lupus syndrome when used chronically?

A

Procainamide

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94
Q

What is cinchonism?

A

Syndrome of headache, tinnitus, vertigo, deafness, and visual disturbances.

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95
Q

What agent is associated with cinchonism after chronic use?

A

Quinidine

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96
Q

What is the management of type Ia cardiac toxicity?

A

Sodium bicarbonate for ventricular tachydysrhythmias and undifferentiated wide-complex tachycardias. Other agents, such as lidocaine, phenytoin, or pacing can be used.

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97
Q

What is the prototypical type Ib agent?

A

Lidocaine

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98
Q

Name some other type Ib agents.

A

Tocainamide, mexiletine, phenytoin

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99
Q

Do type Ib agents cause QRS widening?

A

No, these agents have binding properties that are fast-on, fast-off and the preferentially bind to the sodium channel in the inactive state. in contrast, both type Ia and Ic agents may cause QRS widening.

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100
Q

What are the CNS effects with type Ib overdose?

A

CNS stimulation, confusion, seizures, respiratory arrest

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101
Q

What are the effects of toxic exposure to type Ib agents?

A

Asystole, sinus arrest, AV block, cardiac arrest

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102
Q

Can type Ib agents be associated with torsade de pointes?

A

No. They have no effect on potassium channels, and do not prolong the QTc.

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103
Q

Which of these agents is associated with agranulocytosis?

A

Tocainide

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104
Q

What are some examples of type Ic agents?

A

Flecainide, encainide, propafenone, moricizine

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105
Q

What are the effects of toxic exposure to type Ic agents?

A

Ventricular dysrhythmias, bradycardia, SA and AV block, asystole

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106
Q

What electrolyte disturbance increases the cardiac toxicity of all type I agents?

A

Hyperkalemia

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107
Q

According to the Cardiac Arrhythmia Suppression Trial (CAST), which of these agents have been shown to increase overall mortality?

A

Flecainide, encainide, moricizine

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108
Q

Which type I agents (Ia, Ib, or Ic) are most associated with pro-arrhythmic effects?

A

Type Ic: thus, these agents are typically used only for dysrhythmias that are refractory to other drugs

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109
Q

What is the mechanism of action of type II agents?

A

Beta-adrenergic receptor blockade leading to decreased cAMP leading to inhibition of sodium and calcium currents

110
Q

What cardiac tissues are most sensitive to the antidysrhythmic actions of type II antidysrhythmic agents?

A

AV node

111
Q

What are the effects of excessive beta-adrenergic blockade in patients requiring antidysrhythmics?

A

Same as those for patients taking beta blocker for other medical problems, including bronchospasm, bradycardia, hypotension, and first-degree hearth block, but these patients are more prone to the depressive effects on cardiac output.

112
Q

Which type II agent is associated with coma, respiratory depression and convulsions?

A

Propranolol. Because it is lipophilic, it has more severe CNS toxicity. It also has myocardial sodium channel blocking activity and can therefore lead to prolongation of the QRS complex.

113
Q

What metabolic disturbances can occur with type II agent toxicity?

A

Hyperkalemia and hypoglycemia

114
Q

Hypotension induced by overdose of beta-blockers can be reversed with which drug?

A

Glucagon

115
Q

What other therapy has been utilized to treat persistent hypotension and bradycardia induced by beta-blockers?

A

Hyperinsulinemia/euglycemia therapy

116
Q

What is the basic mechanism of action of type III antidysrhythmics?

A

Delays repolarization, prolonging the action potential an increasing the effective refractory period by blocking the potassium current

117
Q

At therapeutic levels of type III agents, what EKG changes can be seen

A

PR and QTc prolongation

118
Q

Upon which cardiac tissues do type III agents act?

A

Atrial and ventricular

119
Q

What dysrhythmia may be induced by these type III agents?

A

Torsade de pointes

120
Q

Can these type III agents cause toxic effects at therapeutic doses?

A

Yes. Because they have a narrow therapeutic index, these agents can be highly toxic with even small ingestions?

121
Q

What other actions does sotalol (type III agent) have?

A

Type II effects (beta-adrenergic blockade) at low doses and mixed type II and type III effects at high does

122
Q

What other cardiovascular disturbances can sotalol precipitate?

A

Bradydysrhyhthmias and hypotension

123
Q

Which agent initially releases and later inhibits catecholamine release?

A

Bretylium

124
Q

What can Bretylium (type III agent) cause?

A

Transient hypertension followed by hypotension that may last for hours after administration.

125
Q

Although amiodarone primarily acts as a type III agent, what other properties does it possess?

A

Types I, II and IV (all of them)

126
Q

Because amiodarone has type II (beta-adrenergic blocking) and type IV (calcium channel blocking) effects, what can amiodarone do to the heart rate?

A

Slows heart rate - bradycardia

127
Q

How does this affect the arrhythmogenicity of this type II agent (i.e. amiodarone)?

A

Reduces the propensity to cause new dysrhythmias

128
Q

What extra-cardiac side effects are associated with chronic amiodarone use

A

Pulmonary fibrosis, hypo- and hyperthyroidism, corneal deposits leading to vision loss and grayish discoloration of skin

129
Q

What is the mechanism of action of type IV antidysrhythmic agents?

A

Calcium channel blockade that slows calcium entry into the myocardial cells leading to decreased cardiac contractility and decreased AV nodal conduction

130
Q

What changes are typically seen on EKG at therapeutic levels?

A

PR interval prolongation

131
Q

Which calcium channel blockers (CCB) are antidysrhythmic agents?

A

Verapamil and diltiazem

132
Q

What are the toxic effects of calcium channel blockade?

A

AV block, bradycardia, hypotension, CNS depression

133
Q

What drug interactions might exacerbate these effects of calcium channel blockade?

A

Concomitant use with beta blockers, especially when given parenterally

134
Q

CCBs in overdose are associated with what adverse insulin effects?

A
  1. Prevention of insulin release from pancreateic beta cells

2. Peripheral insulin blockade

135
Q

In severe CCB overdose, what is more commonly seen, hyperglycemia or hypoglycemia?

A

Hyperglycemia

136
Q

What specific drugs can be use din type IV agent toxicity?

A
  1. Calcium chloride or calcium gluconate can initially be use to augment calcium flow.
  2. Glucagon, adrenergic agents (e.g. epinephrine), and amrinone may increase intracellular cAMP to overcome calcium channel blockade.
  3. Hyperinsulinemia-euglycemia therapy has been shown to improve contractility.
137
Q

Are CCBs dialyzable?

A

No. CCBs are highly protein bound and therefore, not dialyzable.

138
Q

Angiotensin-converting enzyme inhibitors (ACE inhibitors). What commercially available medications are found in this class?

A

Captopril, enalopril, ramipril, quinapril, perindopril, lisinopril, benazepril, fosinopril

139
Q

What is the mechanism of action of ACE inhibitors?

A

ACE converts inactive angiotensin I to angiotensin II in the pulmonary vasculature. Angiotensin II stimulates both vasoconstriction and release of aldosterone and vasopressin, resulting in increased BP. ACE inhibitors decrease production of angiotensin II, leading to decreased BP.

140
Q

What clinical uses exist for ACE inhibitors?

A
  1. Treatment of hypertension
  2. Prevention of diabetic renal failure in patients suffering from diabetic nephropathy
  3. Prevention of CHF and other cardiac events, even in the absence of hypertension.
141
Q

What are the adverse effects of ACE inhibitors?

A

Dry persistent cough, angioedema, hypotension, hyperkalemia, headache, dizziness, fatigue, nausea, renal impairment

142
Q

How does ACE inhibitor-related angioedema present?

A

Well-demarcated, nonpitting edema, most commonly of the tongue and mucous membranes of the upper airway, lips and eyes; usually painless and nonpruritic.

143
Q

When dose ACE inhibitor-related angioedema occur?

A

At anytime during treatment, with reports of days to many years after initiation.

144
Q

What is the incidence of ACE inhibitor-related angioedema?

A

Commonly reported as 0.1%-0.2%. Some report incidence approaching 0.7%

145
Q

What peptide is thought to cause both ACE inhibitor-related angioedema and cough?

A

Bradykinin, normally degraded by ACE

146
Q

What is the treatment of angioedema?

A

Airway management should be primary concern. IV diphenhydramine, corticosteroids, and SQ epinephrine should be considered inappropriate cases, but these agents may not significantly alter clinical progression.

147
Q

What are the predominate signs and symptoms of ACE inhibitor overdose?

A

Acute ACE inhibitor overdose does not often result in significant toxicity. Hypotension and, occasionally, bradycardia may occur. Hyperkalemia may be seen, even in therapeutic doses.

148
Q

What treatments are recommended for overdose of ACE inhibitors?

A
  1. Activated charcoal, if given within 1 hr of overdose.
  2. Supportive care (e.g. IV fluids for hypotension)
  3. Rarely, vasopressors may be indicated in refractory hypotension
  4. If hyperkalemia develops, treat with standard therapies
149
Q

Angiotensin Receptor Blockers: What commercially available medications are found in the class?

A

Valsartan, telmisartan, losartan, irbesartan, olmesartan, candesartan, eprosartan.

150
Q

What is the mechanism of action of angiotensin receptor blockers?

A

Angiotensin receptor blockers prevent activation of angiotensin II (AT1) receptors, reducing BP. Angiotensin II normally stimulates vasoconstriction, aldosteron, and vasopressin release leads to increased BP.

151
Q

What clinical uses exist for angiotensin receptor blockers?

A
  1. Treatment of hypertension in patients intolerant of ACE inhibitors
  2. Some efficacy in treatment of CHF and prevention of diabetic renal failure in patients with diabetic nephropathy
152
Q

What are the adverse effects of angiotensin receptor blockers?

A

Dizziness, headache, hyperkalemia, first-dose orthostatic hypotension, and rare cases of angioedema

153
Q

What are the signs and symptoms of angiotensin receptor blocker overdose?

A

Acute angiotensin receptor blocker overdose data is limited. Hypotension and bradycardia may occur in rare cases. Hyperkalemia may be seen, even in therapeutic doses.

154
Q

What treatments are recommended for angiotensin receptor blocker overdose?

A
  1. Activated charcoal, if given within 1 hr of overdose
  2. Supportive care (e.g. IV fluids for hypotension)
  3. Rarely, vasopressors may be indicated in refractory hypotension.
  4. If hyperkalemia develops, treat with standard therapies.
155
Q

What are tricyclic antidepressants (TCA)?

A

Ring-structured antidepressants used to treat disorders such as depression, chronic pain, migraines, and attention deficit hyperactivity disorder (ADHD).

156
Q

What are some examples of commonly prescribed TCAs?

A

Amitriptyline, amoxapine, clomipramine, dothiepin, doxepin, imiprimine, maprotiline, nortriptyline, protriptyline, trimipramine

157
Q

What should the clinician anticipate in the TCA overdose patient?

A

Be prepared for RAPID deterioration, which includes CNS depression, seizures, dysrhythmias, and/or cardiovascular instability. Even an asymptomatic patient can decompensate in <1 hr following overdose.

158
Q

What are the reported ECG manifestations of TCA toxicity?

A
  1. Sinus tachycardia
  2. QRS complex widening >100 msec
  3. QTc prolongation that can result in torsades
  4. Often negative S wave in lead 1 and a tall, positive R wave in aVR (“terminal R wave”)
  5. Right bundle branch block and VT in sever ingestions.
159
Q

Which EKG findings predict serious toxicity?

A

A QRS interval > 100 msec and/or a terminal R wave in lead aVR measuring over 3 mm in height. One study showed that half of the patients with a QRS interval >160 msec experienced dysrhythmias.

160
Q

What are the 7 mechanisms of TCA toxicity and the subsequent effects of each?

A
  1. Fast cardiac Na+ channel blockade - slows phase 0 depolarization, widening the QRS; decreased cardiac contractility and dromotropy lead to hypotension.
  2. Cardiac K+ efflux channel blockade slows phase 3 repolarization of the action potential, resulting in elongation of the QT interval.
  3. Alpha 1-adrenergic receptor blockade - peripheral vasodilation leads to hypotension.
  4. Cholinergic (muscarinic) receptor blockade - anticholinergic toxidrome.
  5. Histaminergic (H1) receptor blockade - sedation and seizures.
  6. GABA receptor blockade - seizures
  7. Presynaptic monamine reuptake inhibition (serotonin, norepinephrine, dopamine) - tachycardia and hypertension seen during initial stages of toxicity, followed by hypotension due to depletion of norepinephrine.
161
Q

What are the hallmark signs of TCA toxicity?

A
  1. Cardiotoxicity - dysrhythmias and/or QRS duration >/= 100 msec
  2. CNS toxicity - seizures and/ore AMS
162
Q

Which TCAs have been reported to cause isolated status epilepticus with no QRS widening or anticholinergic signs?

A

Amoxapine and maprotiline

163
Q

What considerations should be made regarding the TCA toxic patient experiencing seizures?

A
  1. Treat seizures with IV benzos
  2. Avoid phenytoin as it may exacerbate cardiac Na+ channel blockade
  3. Monitor for acidosis and hyperthermia
  4. Avoid paralytic agents, as they can mask seizure activity
164
Q

How should the TCA overdose be treated?

A
  1. QRS prolongation - sodium bicarbonate
  2. Hypotension unresponsive to IV fluids and sodium bicarbonate - direct vasopressors (e.g. epinephrine; avoid dopamine).
  3. Seizures - benzodiazepines
  4. QT prolongation - magnesium sulfate
165
Q

Does sodium bicarbonate treat seizures?

A

No, seizures are caused by other mechanisms. However, sodium bicarbonate can attenuate the acidosis caused by prolonged seizure activity that may predispose the patient to dysrhythmias.

166
Q

Are there any other contraindicated treatments?

A
  1. Physostigmine has been reported to induce seizure activity and asystole.
  2. Flumazenil may induce seizure activity.
  3. Type Ia and Ic antidysrhythmics may increase QRS interval and the likelihood of dysrhythmias.
167
Q

Monoamine oxidase inhibitors (MAOIs)?

A

An enzyme that degrades biogenic amines. It, along with catechol-O-methyl transferase (COMT), prevents the build-up of biogenic amines in the neuronal synapse.

168
Q

What are the indications of MAOIs

A
  1. Sever depression (especially atypical depression).
  2. Phobias and anxiety disorders
  3. Parkinson’s disease (selegiline only)
169
Q

What are the broad classes of MAOIs?

A
  1. 1st generation - isocarboxazid, phenelzine, tranylcypromine.
  2. 2nd generation - selegiline, moclobemide
170
Q

What are the sub-types of MAO, and where are they found?

A
  1. MAO-A – found in neurons, the liver and intestinal walls.
  2. MAO-B – found in neurons
171
Q

Which neurotransmitters are preferentially degraded by MAO-A

A

Biogenic amines - serotonin, tyramine, norepinephrine

172
Q

Which neurotransmitters are preferentially degraded by MAO-B?

A

Dopamine

173
Q

What are some common foods that interact with MAOIs?

A

Primarily tyramine-containing products, including beer, fava beans, aged cheese, aged meats, pickled foods, red wine, yeast extracts, and pepperoni

174
Q

What is the mechanism by which foods cause MAOI toxicity?

A

MAOIs inhibit intestinal MAO-A, allowing dietary tyramine to be absorbed in the intestine. Tyramine indirectly releases norepinephrine, causing a hyper-adrenergic response.

175
Q

Which MAOIs are less likely to cause food interactions?

A

Selegiline is selective for MAO-B
Moclobemide binds reversibly to MAO.

Both are unlikely to cause food interactions

176
Q

Name some common drugs that may precipitate a hyperadrenergic response in association with MAOIs

A

Amphetamines, cocaine, phentermine, PCP

177
Q

What is the mechanism of hyperadrenergic response in MAOI toxicity?

A

These drugs cause release of norepinephrine from the presynaptic terminal, resulting in a sympathomimetic syndrome.

178
Q

What hyperthermic syndrome can result from MAOI use?

A

Serotonin syndrome

179
Q

Which medications increase this risk if MAOI associated serotonin syndrome?

A

Concurrent use of any medication that increases serotonin levels, including SSRIs, LSD, dextromethorphan, meperidine, and tramadol.

180
Q

What are the clinical signs of serotonin syndrome?

A

AMS, hyperthermia, autonomic instability, hyperreflexia and clonus.

181
Q

What is the primary treatment for serotonin syndrome?

A

Benzodiazepines for sedation, aggressive cooling for hyperthermia and IV fluids.

182
Q

What 5-HT2a antagonist is considered and “antidote” for serotonin syndrome?

A

Cyproheptadine

183
Q

Are there any drawbacks to using cyproheptadine?

A

It can only be administered PO, and it has anticholinergic properties.

*Cyproheptadine (antihistamine) may help with improve mild to moderate side effect symptoms but is generally not recommended for OD or coingestions

184
Q

What are the clinical signs of an acute MAOI overdose?

A

Severe hypertension, hyperthermia, delirium, seizures, cardiovascular collapse, and multi-system organ failure.

185
Q

What is the treatment of MAOI toxicity?

A

Supportive care. Short-acting IV agents should be used to control hypertension, beta-blockers, are contraindicated secondary to risk of worsening hypertension due to unopposed alpha-adrenergic activity. As vital signs may be labile, hypotension should be treated with a direct-acting agent like norepinephrine. First-line treatment for seizures is benzodiazepines; however pyridoxine (Vit. B6) should be considered in refractory seizures, as some of the MAOIs are derived from hydrazine.

186
Q

What other common drugs exhibit MAOI-like activity?

A

Procarbazine and linezolid

187
Q

What is the mechanism of selective serotonin reuptake inhibitors (SSRIs)?

A

SSRIs are used to treat depression. They cause inhibition of serotonin reuptake into the presynaptic neuron, resulting in increased serotonin in the synaptic cleft.

188
Q

Why are SSRIs preferred over TCAs?

A

Safety profile; unlike TCAs, SSRIs are lethal only in very high doses and essentially lack serious cardiovascular effects.

189
Q

What are some common SSRIs?

A
  • Citalopram (Celexa)
  • Escitalopram (Lexapro)
  • Fluoxetine (Prozac)
  • Paroxetine (Paxil, Pexeva)
  • Sertraline (Zoloft)
190
Q

What are some common adverse effects of SSRIs?

A

Nausea, drowsiness, HA, vivid dreams, weight gain, anorgasmia

191
Q

What is the clinical presentation of an SSRI overdose?

A

CNS effects - sedation, ataxia, tremor, lethargy, seizures, coma.

192
Q

Is there a specific treatment for SSRI overdose?

A

No

193
Q

What is serotonin syndrome?

A

A constellation of varied symptoms that occurs secondary to a large dose of a serotonergic drug or combination of two or more serotonergic agents.

*AMS, hyperthermia, autonomic instability, hyperreflexia and clonus.

194
Q

Name some of the agents that induce serotonin syndrome.

A
  1. Medications that inhibit serotonin reuptake (e.g. SSRIs, CAs, venlafaxine [Effexor], meperidine [Demerol], dextromethorphan, tramadol [Ultram]).
  2. Medications that inhibit serotonin breakdown (e.g. MAOIs, linezolid [Zyvox]).
  3. Agents that increase serotonin release (e.g. amphetamines, cocaine, reserpine).
  4. Agents that act as serotonin agonists (e.g. lithium, LSD, sumatriptan [Triptan].
  5. Agents that increase serotonin synthesis (e.g. L-tryptophan).
195
Q

How does serotonin syndrome present?

A

It is classically described as a triad of AMS, autonomic instability, and neuromuscular hyperactivity. It presents as a continuum of symptoms, often starting with milder nonspecific symptoms, such as akathisia, agitation, diaphoresis, tachycardia and hypertension. These progress to delirium, hyperthermia, clonus, and hyperreflexia. If not recognized and treated, it can lead to coma, rigidity, rhabdomyolysis, multi-system organ failure and death.

196
Q

How is serotonin syndrome treated?

A
  1. Discontinue and avoid any serotonergic medications.
  2. Aggressive supportive care is the preferred treatment for this condition. Cyproheptadine is an antihistamine with 5HT2a antagonist properties and has been proposed as a antidote, however, it can only be administered PO and has potential side effects, and has little solid evidence of efficacy.
  3. Benzodiazepines should be given and titrated to control agitation and neuomuscular hyperactivity
  4. Monitor temperature and treat hyperthermia with active cooling.
  5. Monitor for rhabdomyolysis and administer IV fluids.
197
Q

What is the “discontinuation syndrome?”

A

A constellation of withdrawal symptoms seen within 24 hours of stopping or rapidly decreasing the dose of SSRIs.

198
Q

What are the symptoms associated with abrupt discontinuation of SSRIs?

A

Xerostomia (dry mouth), headache, insomnia, tremor, akathisia, “brain zap” or electrical shock sensations.

199
Q

What population is at increased risk for suicide when starting SSRIs?

A

A black box warning exists for patients <18 years of age.

200
Q

What are the clinical uses for oral theophylline?

A

COPD and asthma

201
Q

What is aminophylline, and how does it differ from theophylline?

A

Theophylline ethylenediamine, a salt of theophyline. It is less potent and may be given IV.

202
Q

What are the clinical uses for aminophylline?

A
  1. Refractory asthma
  2. CHF
  3. Nonasthmatic bronchospasm
  4. Neonatal apnea as a respiratory stimulant
203
Q

By what mechanisms does theophylline exert its therapeutic and toxic effects?

A
  1. Stimulation of beta 1 and beta 2-adrenergic receptors
  2. Inhibition of phosphodiesterase
  3. Inhibition of adenosine receptors
204
Q

What is the significance of theophylline’s adenosine blockage?

A

Adenosine-1 receptors cause feedback inhibition of neuronal firing. Adenosine-2 receptors cause cerebral vasodilatoin. Theophylline toxicity may, therefore, result in refractory seizures with a relative lack of cerebral blood flow.

205
Q

What is the toxic dose for theophylline?

A

> 20 mcg/kg, although toxicity may be seen with lower doses.

206
Q

What serum level signifies a severe theophylline acute overdose?

A

> 80-100 mg/L

207
Q

How does acute theophylline overdose present?

A
  1. Mild or moderate toxicity - GI upset, tachycardia, anxiety, tremor, mild metabolic acidosis, and electrolyte abnormalities.
  2. Severe toxicity - refractory vomiting, hypotension, metabolic acidosis, dysrhythmias, seizures
208
Q

What electrolyte and glucose abnormalities may be seen with acute theophylline overdose?

A

Hypokalemia, hypophosphatemia, hypomagnesemia, hypercalcemia and hyperglycemia.

209
Q

How does chronic theophylline toxicity differ from acute overdose?

A

In chronic toxicity, GI upset, hypokalemia, and hyperglycemia are less common, but severe symptoms (e.g. seizures, dysrhythmias) are more frequently seen than in acute overdose and may occur at lower serum concentrations (even at 40 mg/L).

210
Q

What criteria may be used to positively diagnose theophylline overdose?

A

Serum theophylline levels. The diagnosis is suggested by a history of refractory vomiting, tachycardia, hypokalemia, tremors, hyperreflexia and hyperglycemia

211
Q

What treatments should be performed in the event of theophylline overdose?

A
  1. Primarily supportive
  2. Nonselective beta blockers have been reported to improve hypotension and tachycardia in case reports but should be used cautiously, as no clinical trials have been conducted to determine efficacy .
  3. hypokalemia is usually transient and resolved without intervention.
  4. Multiple-dose activated charcoal may be beneficial, as theophylline undergoes enteroenteric recirculation.
  5. Hemodialysis should be considered for those with severe toxicity.
212
Q

What are the clinical uses of salicylates?

A

Analgesia, anti-inflammatory, anti-pyretic

213
Q

What are common forms of salicylates?

A
  1. Aspirin (acetylsalicylic acid)
  2. Oil of wintergreen (methyl salicylate
  3. Bismuth salicylate
214
Q

How many grams of aspirin are equal to 5 mL of oil of wintergreen?

A

About 7 grams or 21 regular strength aspirin tablets.

215
Q

What factors can dramatically delay absorption in salicylate overdoses?

A
  1. Large tablet masses (bezoars) in the GI tract.
  2. Enteric-coated products
  3. Pylorospasm
  4. Decreased gastric mobility
216
Q

What are the metabolic effects of a salicylate overdose?

A
  1. Respiratory alkalosis - stimulation of the central respiratory center causes hyperpnea and tachypnea. Also occurs to compensate for metabolic acidosis in more severe cases.
  2. Metabolic acidosis - uncoupling of oxidative phosphorylation and interruption of Krebs cycle dehydrogenases leading to increased CO2 production
  3. metabolic alkalosis - may occur secondary to vomiting.
217
Q

How are salicylates eliminated?

A

Hepatic metabolism predominates at therapeutic doses, but due to saturation of hepatic metabolism, renal excretion is also important in overdose.

218
Q

What is the clinical presentation of chronic salicylate toxicity?

A

Hearing loss/tinnitus, confusion, dehydration, metabolic acidosis, seizures, lethargy, pulmonary and cerebral edema, coma.

219
Q

Which has higher morbidity and mortality, acute or chronic salicylate overdose?

A

Chronic

220
Q

What acid-base abnormality is seen on ABG analysis with salicylate overdose?

A

Mixed respiratory alkalosis and metabolic acidosis

221
Q

What is considered a toxic salicylate level?

A

Above 30 mg/dL (300 mg/L). Note the units, as some laboratories report in mg/dL and other is mg/L. Failure to pay attention to this detail can lead to unnecessary transfers and treatment.

222
Q

How often should salicylate levels be drawn following acute overdose?

A

Initially, consider drawing levels every 2 hours until the salicylate level begins declining, then every 4 hours until they return to the therapeutic range.

223
Q

How should a salicylate overdose be treated?

A

GI decontamination with activated charcoal. Sodium bicarbonate should be given to alkalinize the urine and serum in order to prevent salicylate from crossing the blood-brain barrier and to promote excretion. dialysis should be considered in severe overdoses.

224
Q

Why is charcoal important in treatment for salicylate toxicity?

A

Due to the possibility of delayed absorption, even if administered late, charcoal has the potential to bind a significant amount of the drug.

225
Q

How should sodium bicarbonate be administered for salicylate toxicity?

A

Boluses of 1-2 mEq/kg, followed by an infusion of 5% dextrose in water with 150 mEq of sodium bicarbonate to maintain the urine pH at 7.5 to 8. After assuring urine output, add potassium to each liter of fluid to avoid hypokalemia.

226
Q

If a salicylate toxic patient is intubated, how should they be ventilated?

A

Hyperventilate to compensate for the metabolic acidosis. Placing an acute salicylate overdose on typical ventilator settings may kill patient.

227
Q

What are the indications for urgent hemodialysis?

A
  1. Salicylate level >100 mg/dL after acute overdose.
  2. Salicylate level >60 mg/dL after chronic overdose with AMS or acidosis.
  3. Severe manifestations - coma, seizures, cerebral edema, acute respiratory distress syndrome (ARDS), renal failure, severe/refractory acidosis or electrolyte abnormality.
  4. Inability to tolerate sodium bicarbonate alkalinization (due to renal failure, pulmonary edema, etc.).
228
Q

What are some examples of common skeletal muscle relaxants?

A

Baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, metaxolone, methocarbamol, orphenadrine, tizanidine.

229
Q

Under what class do most of these skeletal muscle relaxants medicines fall?

A

Sedative-hypnotic agents

230
Q

Which three skeletal muscle relaxants are the most abused as recreational drugs?

A

Cyclobenzaprine, carisoprodol (Soma), baclofen

231
Q

Does the clinical presentation of all skeletal muscle relaxants in overdose look the same?

A

No, as this is a broad class of drugs with varying effects on specific receptors.

232
Q

What skeletal muscle relaxant has GABA-B agonist activity?

A

Baclofen. Overdose is consequently associated with coma, respiratory depression, seizures, and bradycardia.

233
Q

What two skeletal muscle relaxants induce an anticholinergic syndrome in overdose?

A

Cyclobenzaprine (Flexeril) and orphenadrine (Norflex).

234
Q

Soma equals?

A

Soma = coma

Often abused to potentiate narcotic effect

235
Q

What skeletal muscle relaxant has been associated with SVT and lidocaine-refractory VT in overdose?

A

Orphenadrine (Norflex).

236
Q

Which skeletal muscle relaxant has alpha 2 - adrenergic effects and acts like clonidine following overdose?

A

Tizanidine (Zanaflex) - CNS depression, miosis, bradycardia, and hypotension following overdose)

237
Q

Is there a specific antidote for skeletal muscle relaxant overdoses?

A

No, management is supportive

238
Q

What electrolyte channel is primarily affected by phenytoin?

A

Neuronal sodium channels are blocked

239
Q

Why does rapid IV administration of phenytoin cause myocardial depression and cardiac arrest?

A

While originally thought to come solely from the propylene glycol dilutent, phenytoin also seems to have a direct cardio-depressant effect.

240
Q

How should IV phenytoin be administered?

A

Slowly (maximum 50 mg/min) and with ECG monitoring

241
Q

Is oral phenytoin cardiotoxic?

A

No

242
Q

Why is it important that phenytoin not be administered IM or through an infiltrated IV?

A

It causes tissue necrosis

243
Q

What is fosphenytoin?

A

A disodium phosphate ester of phenytoin that does not contain propylene glycol, is better tolerated IV and can be administered IM.

244
Q

What happens to the half-life of phenytoin as the levels rise?

A

First-order elimination switches to zero-order elimination, and the half-life increases.

245
Q

How is phenytoin metabolized?

A

Cytochrome P450 pathway, resulting in multiple drug interactions.

246
Q

What are the symptoms of mild to moderate phenytoin intoxication?

A

Nystagmus, dysarthria, ataxia, nausea, vomiting and diplopia

247
Q

What are the symptoms of a severe phenytoin intoxication?

A

Stupor, coma, respiratory arrest

248
Q

What are some potential side effects of phenytoin?

A

Fever, rash, blood dyscrasia, hepatitis, Stevens-Jonson syndrome, gingival hyperplasia

249
Q

Can a serum phenytoin level be obtained?

A

Yes, the therapeutic range is 10-20 mg/L

250
Q

What is the correlation between phenytoin levels and symptoms?

A
  1. > 20 mg/L - nystagmus
  2. > 30 mg/L - ataxia, slurred speech, nausea, vomiting
  3. > 40 mg/L - lethargy, confusion, stupor
  4. > 50 mg/L - coma, seizures
251
Q

Is there a specific antidote for phenytoin toxicity?

A

No, treatment is supportive

252
Q

What are the medical preparations of magnesium?

A
  1. Magnesium citrate (i.e oral cathartic)
  2. Magnesium hydroxide (i.e. milk of magnesia as an antacid)
  3. Magnesium sulfate (i.e. epsom salt)
  4. Magnesium IV preparations
253
Q

What is the major source of magnesium in occupational exposures?

A

Inhalation of magnesium oxide dust

254
Q

What is the major source of exposure to magnesium in healthcare setting?

A

Oral and parenteral administration in medicinal preparations

255
Q

What percent of an oral dose of magnesium is absorbed?

A

15%-30% in the small bowel, negligible amount exchanged across the large bowel mucosa

256
Q

How is magnesium filtered and excreted in the body?

A
  1. Filtered at the glomerulus with 95% reabsorbed at the proximal tubule by active transport.
  2. Excess magnesium is excreted in the urine
257
Q

Can hypermagnesemia occur in individuals with normal renal function?

A

Rarely, as the renal elimination rate can exceed the maximum rate of GI absorption.

258
Q

Can a person overdose on oral cathartics/antacids?

A

Most patient with a single acute overdose will have only mild symptoms (nausea, vomiting, diarrhea); however, after a very large ingestion or with multiple repeat overdoses, more severe symptoms may occur.

259
Q

`What are the signs and symptoms of magnesium poisoning?

A

Nausea, vomiting, weakness, flushing, loss of reflexes, sedation, paralysis, dysrhythmias.

260
Q

What neurological signs are seen with acute magnesium toxicity?

A
  1. CNS depression progressing to lethargy and coma
  2. Hyporeflexia and muscular paralysis
  3. Hypotonicity
261
Q

What ECG findings are indicative of hypermagnesemia?

A

Bradycardia, PR interval prolongation, QRS widening

262
Q

For what ECG abnormality is magnesium considered the antidote?

A

QTc prolongation

263
Q

What can increase the renal excretion of magnesium?

A

Hypercalcemic and hypernatremic states, loop diuretics

264
Q

How should I decontaminate a patient from a magnesium exposure and/or hazardous materials scene?

A

Remove the patient from the scene, and gently brush any magnesium off of the patient prior to the use of water for decontamination, as magnesium will readily react with water.

265
Q

What laboratory tests should I get for suspected magnesium exposure/toxicity?

A

Electrolytes with serum magnesium, CBC, BUN, serum creatinine

266
Q

Does the serum magnesium level correspond to the severity of symptoms?

A

Generally yes, but intracellular concentration is more predictive than plasma concentration.

267
Q

What symptoms correspond with a given serum magnesium concentration?

A
  1. 3-9 mEq/L - erythema (cutaneous vasodilation) vomiting, hypotension, hyporeflexia, bradycardia, sedation.
  2. 10-14 mEq/L - muscle paralysis (including respiratory)
  3. > 14 mEq/L - asystolic cardiac arrest
268
Q

Can the inhalation of magnesium dust cause lung injury?

A

Yes, it may incite local injury leading to pulmonary edema. Also, this may lead to systemic toxicity, as magnesium is readily absorbed across alveolar-capillary membranes.

269
Q

What is the treatment of acute magnesium toxicity?

A
  1. Gastric emptying with NG tube may be attempted within 1 hr of ingestion
  2. Calcium for cardiac conduction abnormalities or respiratory symptoms
  3. IV fluids and dopamine for hypotension
  4. Hemodialysis for sever cases
  5. Activated charcoal does not bind magnesium and is ineffective.
270
Q

How does calcium work in magnesium overdose?

A

Direct antagonism of magnesium at neuromuscular and cardiovascular sites

271
Q

What dose of calcium should I give for magnesium overdoses?

A

1 g of IV calcium gluconate slowly (over 3-5 min).

272
Q

Which magnesium-toxic patients should be treated with calcium?

A

Symptomatic patients with serum magnesium > 5 mEq/L

Toxicology Recall (1 decks)

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