DLA5- Toxicology (common drugs)

Question 1

describe the typical presentation of salicylate (ASA) overdose (hint- 2 main features, include brief mechanism)

Answer 1

Mixed respiratory alkalosis and metabolic acidosis:

-Hyperventilation via stimulation of respiratory center

• ASA is weak acid:
• -> too much causes impaired renal function => sulfuric / phosphoric acid accumulation
• uncouples oxidative phosphorylation + inhibits Krebs cycle => inc anaerobic metabolism –> inc ketones and lactic acid

Question 2

ASA overdose:

• (1) typical progression if untreated
• (2) Tx

Answer 2

1:

• eventual depressant effects of ASA on respiratory center => death via respiratory depression / paralysis (respiratory acidosis)
• circulatory collapse via vasomotor depression

2- IV fluids, IV NaHCO3 (for acidosis and promote ASA excretion) —– severe cases require hemodialysis

Question 3

Acetaminophen toxicity:

• (1) is the main effect
• (2) is the main mediator, describe formation and mechanism

Answer 3

Hepatic Necrosis:

• 5% acetaminophen metabolized into NAPQI (N-acetyl-p-benzoquinoneimine)
• in small amounts detoxified via glutathione detoxification
• if glutathione stores become depleted (high doses) => NAPQI damages cellular proteins –> heptocyte death

Question 4

describe the progression of acute acetaminophen toxicity

Answer 4

1) initially asymptomatic or mild GI upset
2) (24-36hrs) liver injury: elevated aminotransferases, hypoprothrobinemia

3) (severe cases) fulminant liver failure –> hepatic encephalopathy –> death
[possible renal failure also]

Question 5

describe acetaminophen toxicity Tx

Answer 5

1) supportive therapy + gastric lavage
2) N-acetylcysteine (acetadote) –> AEs: rash, n/v/d, anaphylaxis
3) possible liver tranplant (if fulminant liver failure)

Question 6

list the many possible effects of Amphetamine / stimulant overdose

Answer 6

• restlessness, agitation
• acute psychosis
• HTN, tachycardia
• prolonged muscular hyperactivity –> dehydration, hypotension
• seizures + muscular hyperactivity –> hyperthermia, rhabodomylosis –> brain damage, hypotension, coagulopathy, renal failure

Question 7

describe Tx of stimulant (amephetamine) overdose

Answer 7

(no specific antidote)
supportive therapy:
-ammonium chloride to acidify urine to enhance elimination

• phentolamine / nitroprusside for HTN
• propanolol / esmolol for tachycardia
• IV benzodiazepines for seizures

-cool down measures for hyperthermia OR neuromuscular paralysis if very severe

Question 8

describe the effects of Anticholinergic overdose (note- can be due to drugs with anticholinergic activity as additional action)

Answer 8

• skin flushed (red as a beet)
• hyperthermia (hot as a hare)
• dry mucous membranes (dry as a bone)
• blurry vision (blind as a bat)
• confusion, delirium (mad as a hatter)

Question 9

describe Tx for anticholinergic overdose

Answer 9

Physostigme (AChE inhibitor):
-peripheral and central
-small IV doses, slow infusion (or causes bradycardia, seizures)
[not in TCA overdose]

benzodiazepine, antipsychotic for seizures if necessary

Question 10

describe presentation of β-blocker overdose (include most toxic agent)

Answer 10

(propanolol is most toxic, non-selective)
-QRS widening via Na+ channel blockade in heart => ventricular arrhythmia

• seizures, coma (propanolol is lipophilic –> crosses BBB)
• bradycardia, hypotension

Question 11

______ is the Tx for β-blocker overdose, describe brief mechanism

Answer 11

IV glucagon- inc intracellular [cAMP] that β-blockers dec

Question 12

describe presentation of Ca channel blocker overdose

Answer 12

• depresses sinus node automaticity + slows AV conduction

- dec CO and BP => serious hypotension

Question 13

______ is the main Tx for Ca channel blocker overdose

______ may be useful is treating some Sxs

Answer 13

IV Ca++ –> inc cardiac contractility (not as usefule for nodal block, circulatory collapse)

-glucagon, epinephrine to inc BP and HR

Question 14

describe the main effects of TCA overdose, include of actions that TCAs may have

Answer 14

blockade of Na+ fast channels –> slows conduction –> wide QRS, depressed contractility => arrhythmia, hypotension, AV block

-anticholinergic, antiadrenergic, antihistamine

Question 15

• (1) is drug of choice for TCA overdose in general
• (2) is specific for TCA cardiac effects

-(3) has been deemed ineffective, and (4) is avoided as seen in anticholinergic overdose Tx

Answer 15

1- norepinephrine
2- sodium carbonate (bolus)

3- dopamine
4- physostigme

Question 16

list the two main serious adverse effects seen with MAOI use and describe Tx

Answer 16

Tyramine Reaction:

• α-adrenergic blockade, phentolamine
• combined α-/β-adrenergic blockade (labetalol)

Serotonin Syndrome:

• cyproheptadine (5-HT2 antagonist)
• benzodiazepines for seizures, rigidity, agitation

Question 17

______ is used for opioid overdose

Answer 17

Naloxone or nalmefene (opioid antagonists)

to prevent respiratory depression

Question 18

Overdose with sulfonylureas, meglitinides causes (1). It can be treated with (2), and if that fails then (3)- (4) is an alternative to (3).

Answer 18

1- hypoglycemia
2- glucose bolus infusion
3- octreotide (somatostatin analog)
4- diazoxide (inhibits insulin release)

Question 19

Neuroleptic Malignant syndrome is a common severe side-effect of using (1); (2) describes the management of this syndrome

Answer 19

Antipsychotics

• discontinue antipsychotic
• dantrolene or bromocriptine are drugs of choice