Pharm - Tx of OD (part 1)

Question 1

contraindications to the use of activated charcoal

Answer 1

a. Depressed mental status w/o airway protection (risk of aspiration) – never intubate just to give AC
b. Late presentation of a poisoning (not likely to still be in stomach)
c. Increased risk and severity of aspiration associated w/ AC use (ex: hydrocarbon)
d. Need for endoscopy (will impair visibility)
e. Toxins poorly absorbed by AC (lithium, alkali, mineral acids, alcohols)
f. Presence of intestinal obstruction or concern for decreased peristalsis

Question 2

AC should be withheld in the following situations:

Answer 2

i. Nontoxic ingestions
ii. Pts who present when poison absorption is considered complete
iii. Poisons not bound by AC
iv. Pts whose risk of complications (aspiration) is unacceptably high

Question 3

mechanism of action of activated charcoal

Answer 3

Highly adsorbent powder w/ extensive surface area made of a carbon based network that includes functional groups that adsorb chemical w/I minutes of contact, preventing GI adsorption and subsequent toxicity.

Question 4

the appropriate dose of activated charcoal for children (single dose)

Answer 4

i. AC:toxin ratio of 10:1
ii. Kids <1 y/o: 10-25g or 0.5-1 g/kg
iii. Kids 1-12 y/o: 25-50g or 0.5-1 g/lg (max dose 50g)

Question 5

the appropriate dose of activated charcoal for adults (single dose)

Answer 5

Adolescents/adults: 25-100g (with 50g representing usual adult dose)

Question 6

appropriate dose of AC for multiple doses

Answer 6

i. Optimal dosing not established
ii. After initial dose, administer at rate of at least 12.5 g/hr or equivalent given in divided doses 50g Q4 hours or 25g Q2 hours

Question 7

mechanism of action for multi-dose activated charcoal

Answer 7

i. Interrupting enterohepatic recirculation
ii. Facilitating diffusion of poison or drug from the body into the gut (gut dialysis)
iii. Reducing absorption of extended or delayed released drug formulations

Question 8

stage I of an acetaminophen intoxication

Answer 8

(0. 5 - 24 hrs)
i. N/v, diaphoresis, pallor, lethargy, and malaise. Some remain asx.
ii. Labs typically nl
iii. Serum aminotransferases are often nl but may rise as early as 8-12 hrs after ingestion in severely poisoned pts

Question 9

stage II of an acetaminophen intoxication

Answer 9

(24-72 hrs)

i. Hepatotoxicity and occasionally nephrotoxicity occur
ii. Initially, stage I sx resolve and pts appear to improve clinically while worsening subclinical elevation of hepatic aminotransferases develop
iii. Of those that develop hepatic injury, over ½ will demonstrate AST/ALT elevation w/I 24 hrs and all have elevations by 36 hrs
iv. As stage II progresses, pts develop RUQ pain w/ liver enlargement and tenderness
v. Elevations of PT and total bilirubin, oliguria, and renal function abnormalities may become evident

Question 10

stage III of an acetaminophen intoxication

Answer 10

(72-96 hrs)

i. Liver function abnormalities peak
ii. Systemic sx of stage I reappear in conjuction w/ jaundice, confusion, marked elevation in hepatic enzymes, hyperammonemia, and bleeding diathesis
iii. Sign of severe hepatotoxicity include plasma ALT/AST levels that often exceed 10k, prolongation of PT/INR, hypoglycemia, lactic acidosis, total bili concentration > 4.0 mg/dL
iv. Acute renal failure occurs in 10-25% of pts w/ significant hepatotoxicity and in more than 50% of those w/ frank hepatic failure
v. Death most commonly occurs in this stage, usu from multiorgan system failure

Question 11

Stage IV of an acetaminophen intoxication

Answer 11

(4 day - 2 weeks)

i. Pts who survive stage III enter a recovery phase
ii. Can be slower in severely ill patients; sx and labs may not normalize for weeks
iii. Histologic changes in the liver vary from cytolysis to centrilobular necrosis b/c it is the area of greatest concentration of CYP2E1 and the site of max production of NAPQI
iv. Histologic recovery lags behind clinical recovery taking up to 3 mos. When recovery occurs, it is complete w/o chronic hepatic dysfunction.

Question 12

antidote of choice in an acetaminophen toxic ingestion

Answer 12

N-acetylcysteine

Question 13

mechanism of action of n-acetylcysteine in treatment of an acetaminophen overdose

Answer 13

a. NAPQI is a byproduct of acetaminophen metabolism that is extremely toxic to the liver
b. Ordinarily, NAPQI is detoxified by glutathione, which is synthesized from cysteine, glutamate, and glycine – cysteine being the rate limiting factor
c. When glutathione is depleted from acetaminophen OD, acetylcysteine can be readily absorbed and rapidly enter cells, hydrolyzed to cysteine, providing the limiting substrate for glutathione synthesis

Question 14

two FDA protocols for the use of n-acetylcysteine in the treatment of an acetaminophen overdose.

Answer 14

a. Oral administration (72 hr protocol)

b. IV administration (20 hr protocol)

Question 15

oral dosing regimen for n-acetylcysteine in the treatment of an acetaminophen overdose

Answer 15

a. Loading dose of 140 mg/kg PO, followed by

b. Dose of 70 mg/kg PO q 4 hrs for a total of 17 doses

Question 16

adverse reactions of n-acetylcysteine

Answer 16

a. 10-20% of pts treated w/ IV n-acetylcysteine develop an allergic or anaphylactic rxn that vary in severity
i. Monitor closely and have drugs to tx anaphylaxis
ii. In the case of a severe reaction, stop infusion
b. About 33% of pts develop n/v:
i. Can tx w/ ondansetron
ii. If pt vomits w/I 60 min. of oral dose, repeat

Question 17

duration of treatment of n-acetylcysteine in the treatment of an acetaminophen overdose`

Answer 17

a. Oral: 72 hrs
b. IV: 20 hrs
c. Can tailor to clinical endpoints by monitoring ALT, serum acetaminophen concentration and INR

Question 18

the prognosis of person with an acetaminophen overdose`

Answer 18

a. Nearly always good if the antidote is administered in a timely fashion
b. No deaths have been reported in any of the large studies of acetaminophen OD, provided that NAC was given w/I 10 hrs of ingestion, regardless of the initial serum acetaminophen concentration
c. Hepatic failure and death occur when tx is delayed

Question 19

symptoms of a beta blocker overdose

Answer 19

a. Sx develop in 2-6 hrs
i. EXCEPT: sotalol and XR meds which are delayed up to 24 hrs
b. Cardiovascular effects:
i. Bradycardia and hypotension are the MC
ii. In severe OD: can see profound myocardial depression and cardiogenic shock
iii. Ventricular dysrhythmias are more frequenly in propranolol and acebutolol b/c of their increased membrane-stabilizing activity
c. Other potential effects of severe toxicity:
i. Mental status changes, including delirium, coma, and seizures
1. Propanolol more likely to cause seizure b/c very lipophilic
ii. Respiratory depression
iii. Bronchospasm
iv. Hypoglycemia – early recognition and prompt tx is critical

Question 20

specific toxicities associated with acebutalol

Answer 20

i. Cardioselective agent w/ partial agonist activity and significant membrane stabilizing activity (MSA)
ii. One of the most toxic beta blockers in OD
iii. Toxicity may predispose to ventricular repolarization resulting in arrhythmias

Question 21

specific toxicities associated with propanolol

Answer 21

i. Have MSA which can cause cardiovascular toxicity

Question 22

specific toxicities associated with sotalol

Answer 22

i. Class III antidysrhythmic properties w/ beta adrenergic antagonism
ii. Prolongs the action potential duration and increases the refractory period by blocking delayed K channels
iii. Causes QTc prolongation increasing risk of developing Torsades

Question 23

Use of atropine for beta blocker OD

Answer 23

For symptomatic bradycardia

Question 24

Use of glucagon for beta blocker OD

Answer 24

i. First-line, antidotal tx for beta blocker OD
ii. It increases the intracellular Ca pool for release to augment contractility
iii. Effective initially but becomes ineffective d/t tachyphylaxis
iv. Effect is increase in pulse or BP

Question 25

Use of calcium for beta blocker OD

Answer 25

i. An additional tx that can be given based on the severity of the presentation
ii. Dose differs depending on salt used – MUST monitor serum concentrations b/c can give lethal dose

Question 26

Use of vasopressor for beta blocker OD

Answer 26

Epi is started if atropine plus IV fluids plus glucagon and Ca is not entirely effective

Question 27

Use of insuline/glucose infusions for beta blocker OD

Answer 27

Consider in pts who do not respond to other tx

Question 28

Use of atropine for CCB OD

Answer 28

i. Should be administered to any pt w/ symptomatic bradycardia
ii. However, it is often ineffective after significant CCB exposure

Question 29

Use of glucagon for CCB OD

Answer 29

increases intracellular levels of Ca

Question 30

Use of calcium for CCB OD

Answer 30

Used to overcome the cardiovascular effects of CCBs

Question 31

Use of vasopressor for CCB OD

Answer 31

Need a direct acting agent w/ positive inotrope and chronotrpe and vasoconstrictive effects

Question 32

Use of insulin/glucose infusions for CCB OD

Answer 32

Has positive inotropic effects in pts w/ CCB toxicity