"dying-back" degeneration of large distal axons

Q: The "dying-back" degeneration of large distal axons is characteristic of which chemical toxicity? 

Answer: Organophosphate (OP) 

Although most critical care medicine curricula emphasize acute management of OP poisoning, one vital and delayed aspect of OP often goes unnoticed. =

OPIDN (OP-induced delayed neuropathy) is characterized by a painful "stocking-glove" paresthesias followed by a symmetrical motor polyneuropathy with flaccid weakness of the lower extremities that ascends to involve the upper extremities, primarily affecting distal muscles; in severe neurotoxicity, proximal muscle groups may also be affected. Sensory disturbances are usually mild. 

It occurs one to three weeks after OP exposure (delayed). Usually transient, but in severe cases, an upper motor neuron syndrome with spasticity of the lower extremities usually causes permanent disability. Electromyograms and nerve conduction studies reveal decreased firing of motor conduction units, and histopathologic sections of peripheral nerves show Wallerian degeneration, commonly known as "dying-back" degeneration, of large distal axons. The underlying mechanism involves inhibition of neuropathy target esterase (NTE), which is found in the brain, peripheral nerves, and lymphocytes, and is basically responsible for the metabolism of various esters in the cytoplasm. 

Other reported long-term effects of OP toxicity are either transient or permanent decreased memory, abstraction, attention, and Parkinsonism. Severity may differ with different brands of OP pesticides. 

#toxicity 

#neurology 

 References: 

 1. Aygun D, Onar MK, Altintop BL. The clinical and electrophysiological features of a delayed polyneuropathy developing subsequently after acute organophosphate poisoning and it's correlation with the serum acetylcholinesterase. Electromyogr Clin Neurophysiol 2003; 43:421. 

 2. Johnson MK. Organophosphorus esters causing delayed neurotoxic effects: mechanism of action and structure activity studies. Arch Toxicol 1975; 34:259. 

 3. Arima H, Sobue K, So M, et al. Transient and reversible parkinsonism after acute organophosphate poisoning. J Toxicol Clin Toxicol 2003; 41:67.

CCB overdose

Q: Hemodialysis should be instituted as early as possible in a Calcium Channel Blocker (CCB) overdose.

A) True

B) False

Answer: B

CCBs are highly protein-bound, so extracorporeal removal via hemodialysis or Continuous Renal Replacement Therapy (CRRT) is usually not effective. Said that it may help in case acute kidney injury or severe acidosis ensues, it can be added as an adjuvant therapy. Extracorporeal membrane oxygenation (ECMO) should be considered early if standard-of-care therapies show no evidence of effectiveness. 

Major components of CCB overdose are:

• Atropine for symptomatic bradycardia
• Intravenous calcium
• Calcium infusion with close monitoring of ionized calcium.
• Glucagon 
• Vasopressors (norepinephrine is preferred)
• Insulin and glucose with monitoring of possible hypokalemia
• Methylene blue 
• High-dose cyanocobalamin

# toxicity

References:

1. Wong A, Hoffman RS, Walsh SJ, et al. Extracorporeal treatment for calcium channel blocker poisoning: systematic review and recommendations from the EXTRIP workgroup. Clin Toxicol (Phila) 2021; 59:361.

2. Slamowitz A, Sweberg T, Labgold K, Nickerson T. Extracorporeal Membrane Oxygenation for Calcium Channel Blocker Intoxication: A Multicenter Retrospective Registry Review. ASAIO J. 2025 Oct 31. doi: 10.1097/MAT.0000000000002593. Epub ahead of print. PMID: 41168146.

3. Saha BK, Bonnier A, Chong W. Rapid reversal of vasoplegia with methylene blue in calcium channel blocker poisoning. Afr J Emerg Med 2020; 10:284.

The time-relationship of 'osmolal gap' and 'Anion gap' in toxic alcohols

Q: In Methanol and Ethylene Glycol toxicity, the time-relationship of 'osmolal gap' and 'Anion gap' is inversely proportional.

A) True

B) False

Answer: A

After ingestion of Methanol and Ethylene Glycol, the osmolal gap continues to drop as the alcohols are metabolized, while the anion gap rises. The following graph best describes the relationship.

#toxicity

References:

1. Kraut JA, Mullins ME. Toxic Alcohols. N Engl J Med. 2018 Jan 18;378(3):270-280. doi: 10.1056/NEJMra1615295. Erratum in: N Engl J Med. 2019 Jan 10;380(2):202. doi: 10.1056/NEJMx180046. PMID: 29342392.

2. Gallagher N, Edwards FJ. The Diagnosis and Management of Toxic Alcohol Poisoning in the Emergency Department: A Review Article. Adv J Emerg Med. 2019 May 22;3(3):e28. doi: 10.22114/ajem.v0i0.153. PMID: 31410405; PMCID: PMC6683589.

Clinical exam in acute opioid toxicity

Q: Which of the following is a more reliable sign of acute opioid toxicity? - select one

A) Depressed mental status

B) Decreased respiratory rate

C) Miotic pupils

Answer: B

In acute opioid toxicity, pupils are expected to be constricted, but they can be normal or even larger. It also depends on the type of opioid, like meperidine, overdose tends to present with normal pupils. The co-ingestion of sympathomimetics or antimuscarinics can cause pupils to be larger on exam. In comparison, a decreased respiratory rate of less than 12 by manual counting on the best side is a better toxicity of acute opioid toxicity.

Bradycardia or hypotension from histamine release may occur, but it can't predict opioid toxicity unless the history is very clear. Similarly, normal capnography or hypothermia should not be relied on too much.

Mental status can range from coma to euphoria. The occurrence of a seizure should raise the possibility of tapentadol, tramadol, or meperidine overdose.

Hypoxia and traumatic brain injury (TBI) can be the cause, result, or simultaneously occurring features and require prompt address.

#toxicity

References:

1. Fahmy NR, Sunder N, Soter NA. Role of histamine in the hemodynamic and plasma catecholamine responses to morphine. Clin Pharmacol Ther 1983; 33:615.

3. Viglino D, Bourez D, Collomb-Muret R, et al. Noninvasive End Tidal CO2 Is Unhelpful in the Prediction of Complications in Deliberate Drug Poisoning. Ann Emerg Med 2016; 68:62.

4. Palkovic B, Marchenko V, Zuperku EJ, Stuth EAE, Stucke AG. Multi-Level Regulation of Opioid-Induced Respiratory Depression. Physiology (Bethesda). 2020 Nov 1;35(6):391-404. doi: 10.1152/physiol.00015.2020. PMID: 33052772; PMCID: PMC7864237.

An anti-hypertensive in scorpion envenomination

Q: Which of the following anti-hypertensives is found to be of benefit in scorpion envenomation?

A) Amlodipine

B) Losartan

C) Metoprolol

D) Hydrochlorothiazide

E) Prazosin

Answer: E

Antivenom for scorpion bites is not readily available, and when available, it is usually species-specific. It is almost an art to know the right venom for the right scorpion species. Interestingly, a simple antihypertensive, prazosin, has been found to be of value in Grade II* or higher scorpion envenomation, particularly with Hottentotta (Mesobuthus) species. It may reduce the risk of death from scorpion envenomation from 25 percent to almost nil. Also, it may expedite the recovery by preventing cardiogenic pulmonary edema. 

Due to its relatively few side effects, it is recommended as an adjuvant treatment in almost all venomations, including those involving Androctonus, Buthus, Leiurus, or Tityus species. Prazosin works by mitigating excessive catecholamine release and progression to cardiotoxicity! The recommended prazosin dose is 0.5 mg every three hours until systemic toxicity resolves.

#toxicity

* There are four grades, as per escalation of toxicity severity

References:

1. Bawaskar HS, Bawaskar PH. Scorpion sting: update. J Assoc Physicians India 2012; 60:46.

2. Gupta V. Prazosin: a pharmacological antidote for scorpion envenomation. J Trop Pediatr 2006; 52:150.

3. Al-Asmari AK, Al-Seif AA, Hassen MA, Abdulmaksood NA. Role of prazosin on cardiovascular manifestations and pulmonary edema following severe scorpion stings in Saudi Arabia. Saudi Med J 2008; 29:299.

SS in MDMA

Q: A 22-year-old female is admitted to the ICU with a clinical diagnosis of serotonin syndrome (SS) after being found having trismus and 'acting weird' at a dance club on Saturday night. Friends informed about ingesting 'ecstasy' prior to the party. Which concomitant drug is suspected to increase the risk of SS with ecstasy (MDMA)?

Answer: SSRI

Unfortunately, 3,4-methylenedioxymethamphetamine (MDMA), popularly known as ecstasy or Molly, is widely available in society. With the rise of use of Selective Serotonin Reuptake Inhibitors (SSRIs) in society, particularly among college-going students, the concurrent use of MDMA and SSRIs greatly increases the risk of SS. 

MDMA causes SS via stimulation of massive serotonin release. 

#toxicity

#pharmacology

References:

1. Mueller PD, Korey WS. Death by "ecstasy": the serotonin syndrome? Ann Emerg Med 1998; 32:377.

2. Singh AN, Catalan J. Rave drug (ecstasy) and selective serotonin reuptake inhibitor anti-depressants. Indian J Psychiatry. 2000 Apr;42(2):195-7. PMID: 21407935; PMCID: PMC2957712.

3. Dobry Y, Rice T, Sher L. Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors. Int J Adolesc Med Health. 2013;25(3):193-9. doi: 10.1515/ijamh-2013-0052. PMID: 24006318.

MALA and metformin level

Q: A serum metformin level usually correlates with the severity of the poisoning, known as MALA (Metformin Associated Lactic Acidosis).

A) True

B) False

Answer: B

Serum metformin level is usually not ordered during suspected MALA for two reasons. First, it takes several days to report the level. Second, serum metformin concentrations typically do not correlate with the severity of toxicity or patient outcomes; however, a caveat of 'treatment bias' may be present, as by the time the level is reported, patients may be treated differently across institutions based solely on clinical signs and suspicion. Additionally, associated factors, such as renal insufficiency, may have played a role.

That said, some experts still advocate obtaining a serum metformin level, as it has a good negative predictive value. An undetectable metformin concentration basically rules out MALA.

#toxicity

#pharmacology

#acid-base

References:

1. Vecchio S, Giampreti A, Petrolini VM, et al. Metformin accumulation: lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy. Clin Toxicol (Phila) 2014; 52:129.

2. Dell'Aglio DM, Perino LJ, Kazzi Z, et al. Acute metformin overdose: examining serum pH, lactate level, and metformin concentrations in survivors versus nonsurvivors: a systematic review of the literature. Ann Emerg Med 2009; 54:818.

3. Kajbaf F, De Broe ME, Lalau JD. Therapeutic Concentrations of Metformin: A Systematic Review. Clin Pharmacokinet 2016; 55:439.

Burton line

Q: 62 years male who has worked at a shooting range his entire life is admitted to the ICU with accelerated hypertension. Patient on history taking also complains of colicky abdominal pain getting worse over the years, arthralgia, myalgia, fatigue, insomnia, decreased libido, loss of short-term memory, irritability, tremor, and depression. On exam, a Burton line was noted on the gums. CBC is reported with basophilic stippling. Which poisoning is expected?

Answer: Lead

Burton line is a bluish gingival pigmentation at the gum-tooth line. This occurs due to the reaction of lead with bacteria in dental plaque that causes the formation of lead sulfide. If present with other symptoms, it is probably lead toxicity, which can be proven otherwise. 

At shooting ranges, dust generated from the use of leaded bullets and leaching from bullets is a known cause of higher blood lead levels.

#toxicity

References:

1. Helmich F, Lock G. Burton's Line from Chronic Lead Intoxication. N Engl J Med. 2018 Nov 8;379(19):e35. doi: 10.1056/NEJMicm1801693. PMID: 30403939.

2. Karami M, Mohammed LM, Dehghan SF, Hashemi SS, Baiee H. Burton's Line on the Gum Seen in Lead Poisoning Among Petroleum Refinery Workers in Kirkuk City, Iraq: A Case Series. Cureus. 2024 May 10;16(5):e60050. doi: 10.7759/cureus.60050. PMID: 38854344; PMCID: PMC11162749.

3. Morita T, Nishizawa T, Morikawa T. Burton line and basophilic stippling in lead poisoning. CMAJ. 2024 Apr 14;196(14):E487. doi: 10.1503/cmaj.231405. PMID: 38621780; PMCID: PMC11019604.

Flumazenil use in non-benzodiazepine overdose

Q: Flumazenil can be an effective antidote for which other drugs besides benzodiazepines?

Answer: Flumazenil is traditionally used as an antidote in patients with benzodiazepine overdose, but it is effective in overdoses of non-benzodiazepine sleep enhancers, namely zolpidem (Ambien) and zaleplon (Sonata) -popularly known as "Z" drugs.

Flumazenil reverses the effects of benzodiazepines by competitive inhibition at the benzodiazepine binding site on the GABA-a receptor.

Additionally, it has been used in the treatment of hepatic encephalopathy.

#toxicity

#pharmacology

References:

1. Patat A, Naef MM, van Gessel E, Forster A, Dubruc C, Rosenzweig P. Flumazenil antagonizes the central effects of zolpidem, an imidazopyridine hypnotic. Clin Pharmacol Ther. 1994 Oct;56(4):430-6. doi: 10.1038/clpt.1994.157. PMID: 7955804.

2. An H, Godwin J. Flumazenil in benzodiazepine overdose. CMAJ. 2016 Dec 6;188(17-18):E537. doi: 10.1503/cmaj.160357. Epub 2016 Nov 14. PMID: 27920113; PMCID: PMC5135539.

ALDEN

Q: ALDEN is an algorithm to determine the causality of which disease?

Answer: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) 

The most likely etiology of SJS/TEN cases is due to few high-risk medications, usually divided into three categories:

1. Strongly associated
2. Associated
3. Suspected association/lower risk

ALDEN stands for 'algorithm of drug causality for epidermal necrolysis'. It is used to determine the offending drug.

The Six-Point Algorithm is available via any search engine. The likelihood of a patient having SJS/TEN is based on the final score:

Score <0 — Very unlikely

Score 0 to 1 — Unlikely

Score 2 to 3 — Possible

Score 4 to 5 — Probable

Score ≥6 — Very probable

#dermatology

#toxicity

         

         

References:

         

1. Clinical Pharmacology and Therapeutics. Sassolas B, Haddad C, Mockenhaupt M, et al. ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson syndrome and toxic epidermal necrolysis: comparison with case-control analysis. Clin Pharmacol Ther 2010; 88:60. www.nature.com/cpt. Copyright © 2010.

         

         

2. Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 1995; 333:1600.

3. The RegiSCAR Project. Available at: http://www.regiscar.org/index.html (Accessed on May 4, 2025).

mannitol nephrotoxicity syndrome

Q: Acute Kidney Injury (AKI) developed due to mannitol therapy can be quickly reversed by hemodialysis (HD).

A) True

B) False

Answer: A (True)

If mannitol is used at a high dose, leading to an osmolal gap greater than 55 mosmol/kg, it may cause AKI by vasoconstriction. This phenomenon is known as mannitol nephrotoxicity syndrome.

AKI can be avoided by keeping the mannitol dose at the recommended lower level, i.e., 0.25 g/kg every four hours or 1.5 g/kg daily. Fortunately, this AKI is reversible either by stopping the mannitol or with a single or two sessions of HD. Without HD, it may take up to a week or so to get rid of excess mannitol. HD expedites the removal of excess mannitol.

#nephrology

#pharmacology

#toxicity

References:

1. Dorman HR, Sondheimer JH, Cadnapaphornchai P. Mannitol-induced acute renal failure. Medicine (Baltimore) 1990; 69:153.

2. Gadallah MF, Lynn M, Work J. Case report: mannitol nephrotoxicity syndrome: role of hemodialysis and postulate of mechanisms. Am J Med Sci 1995; 309:219.

3. Pérez-Pérez AJ, Pazos B, Sobrado J, et al. Acute renal failure following massive mannitol infusion. Am J Nephrol 2002; 22:573.

Cocaine and adrenergic receptors

Q: Cocaine stimulates which adrenergic receptors? - select one

A) alpha-1

B) alpha-2

C) beta-1

D) beta-2 

E) All of the above

Answer: E

Cocaine is considered highly toxic as it stimulates all adrenergic receptors via increasing levels of norepinephrine, and to a lesser extent, epinephrine. Coronary syndromes occur via the alpha-adrenergic agonist's vasoconstrictive effect in both cardiac and peripheral vasculature.

Contrary to conventional belief, the central and euphoric effects occur via inhibition of neuronal serotonin reuptake, causing psychological addiction. The physiological addiction is primarily due to the dopamine reuptake effect on the dopamine-containing neuronal systems traveling from the limbic region to the frontal cortex. Also, the increased levels of the excitatory amino acids glutamate and aspartate have been described.

#toxicity

References:

1. Nestler EJ. The neurobiology of cocaine addiction. Sci Pract Perspect. 2005 Dec;3(1):4-10. doi: 10.1151/spp05314. PMID: 18552739; PMCID: PMC2851032.

2. Gawin FH. Cocaine addiction: psychology and neurophysiology. Science. 1991 Mar 29;251(5001):1580-6. doi: 10.1126/science.2011738. Erratum in: Science 1991 Aug 2;253(5019):494. PMID: 2011738.

3. Mahoney JJ 3rd, Haile CN, De La Garza R 2nd, Thakkar H, Newton TF. Electrocardiographic characteristics in individuals with cocaine use disorder. Am J Addict. 2017 Apr;26(3):221-227. doi: 10.1111/ajad.12524. Epub 2017 Mar 1. PMID: 28248441.

Sleep disturbance in cannabis withdrawal

Q: Which of the following is preferred for disabling sleep disturbances in Cannabis withdrawal? - select one

A) Zolpidem

B) Eszopiclone

C) Trazodone 

D) Doxylamine

E) L-tryptophan

Answer: A

Severe disabling sleep disturbance can occur in cannabis withdrawal, with a domino effect, with potentially fatal consequences.

Only a handful of medications, including zolpidem, dronabinol, and gabapentin, have been studied and shown to benefit.

The most studied and supportive evidence is available for Zolpidem. 

Nitrazepam, being a benzodiazepine, is usually discouraged due to its potential addiction issues. Nitrazepam is not available in the United States. 

#toxicity

#pharmacology

References:

1. Vandrey R, Smith MT, McCann UD, et al. Sleep disturbance and the effects of extended-release zolpidem during cannabis withdrawal. Drug Alcohol Depend 2011; 117:38.

2. Herrmann ES, Cooper ZD, Bedi G, et al. Effects of zolpidem alone and in combination with nabilone on cannabis withdrawal and a laboratory model of relapse in cannabis users. Psychopharmacology (Berl) 2016; 233:2469.

10:6 rule in Dig toxicity

Q: What is the rule of 10:6 in digoxin toxicity?

Answer:

The 'rule of 10:6 is easy to remember and may be helpful while ordering Digoxin immune Fab (digibind, DigiFab) in patients with digoxin toxicity.

• If an unknown amount is acutely ingested, 10 vials can be administered; an additional 10 vials can be given if necessary.
• In chronic digoxin therapy, where toxicity is suspected, 6 vials are usually sufficient to resolve symptoms.

If required, the digibind dose can be calculated by using the formula:

number of vials = (digoxin concentration) x (patient's weight) / 100

EKG changes are the best way to monitor resolution. Resolution may be visible within 30 minutes, but it takes 2-4 hours to take full effect. 

Each vial of DigiFab contains 40 mg of Fab, which binds 0.5 mg of digoxin. DigiFab is usually given in an IV preparation over 30 minutes, but an IV push can be given in life-threatening situations. It may cause some febrile reactions. It should be avoided in patients with an allergy to sheep protein and papaya extracts.

#toxicity

# pharmacology

Recommended readings:

1. Wei S, Niu MT, Dores GM. Adverse Events Associated with Use of Digoxin Immune Fab Reported to the US Food and Drug Administration Adverse Event Reporting System, 1986-2019. Drugs Real World Outcomes. 2021 Jun;8(2):253-262. doi: 10.1007/s40801-021-00242-x. Epub 2021 Mar 15. PMID: 33721285; PMCID: PMC8128941.

2. Ip D, Syed H, Cohen M. Digoxin specific antibody fragments (Digibind) in digoxin toxicity. BMJ. 2009 Sep 3;339:b2884. doi: 10.1136/bmj.b2884. PMID: 19729422.

3. Lucyk S. Calculated decisions: DigiFab® (Digibind®) Dosing for Digoxin Poisoning. Emerg Med Pract. 2020 Sep 15;22(Suppl 9):CD1-CD3. PMID: 33476509.

Gabapentin and ETOH disorder

Q: 57 years old male with history of active alcoholism is admitted to the ICU after Motor Vehicle Accident (MVA), requiring orthopedic surgery. The on-call resident wanted to initiate the Enhanced Recovery After Surgery (ERAS) protocol, which includes the use of Gabapentin. It is not a good idea to prescribe Gabapentin to a patient with a history of alcohol abuse.

A) True

B) False

Answer: B

Gabapentin is considered one of the second-line drugs for patients with alcohol abuse. It has been shown to decrease the heavy drinking days. The beneficial effect of Gabapentin gets even more pronounced in withdrawal symptoms, like patient in this question who is at high risk of Delirium Tremens (DT) while recovering in the ICU.

Another such drug described with beneficial effects is Baclofen.

#toxicity

#ETOH-abuse

#pharmacology

References:

1. Mason BJ, Quello S, Goodell V, et al. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med 2014; 174:70.

2. Anton RF, Latham P, Voronin K, et al. Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial. JAMA Intern Med 2020; 180:728.

3. Gratacós-Ginès J, Bruguera P, Pérez-Guasch M, et al. Medications for alcohol use disorder promote abstinence in alcohol-associated cirrhosis: Results from a systematic review and meta-analysis. Hepatology 2024; 79:368.

4. Rose AK, Jones A. Baclofen: its effectiveness in reducing harmful drinking, craving, and negative mood. A meta-analysis. Addiction 2018; 113:1396.

HES

Q: Cannabinoids are? - Select one

A) Hydrophilic

B) Lipophilic

Answer: B

Cannabinoids accumulate in adipose tissues, including central and peripheral adipose tissues, due to their lipophilic nature.

Clinical significance: In patients who are long-term users of cannabinoids, when exposed to fasting, lipolysis occurs in the body, and degradation of cannabinoid into pro-emetic agents precipitates hyperemesis, leading to Cannabinoid Hyperemesis Syndrome (HES). Moreover, if the patient has genetic differences in his cytochrome P450 system, it causes the accumulation of cannabinoid metabolites, making HES worse/intense.

#toxicity

#drug-abuse

#GI

References:

1. Wightman RS, Metrik J, Lin TR, et al. Cannabis Use Patterns and Whole-Blood Cannabinoid Profiles of Emergency Department Patients With Suspected Cannabinoid Hyperemesis Syndrome. Ann Emerg Med 2023; 82:121.

2. Russo EB, Spooner C, May L, et al. Cannabinoid Hyperemesis Syndrome Survey and Genomic Investigation. Cannabis Cannabinoid Res 2022; 7:336.

3. Burillo-Putze G, Richards JR, Rodríguez-Jiménez C, Sanchez-Agüera A. Pharmacological management of cannabinoid hyperemesis syndrome: an update of the clinical literature. Expert Opin Pharmacother. 2022 Apr;23(6):693-702. doi: 10.1080/14656566.2022.2049237. Epub 2022 Mar 20. PMID: 35311429.

Amiodarone and Eye

Q: If corneal microdeposits are noted in patients on Amiodarone therapy, it should be considered serious, and Amiodarone should be stopped immediately to avoid blindness.

A) True

B) False

Answer: B

Corneal microdeposits and/or lenticular opacities are common in patients on amiodarone therapy. This is due to the secretion of amiodarone by the lacrimal gland, which accumulates on the corneal surface. It is popularly known as cat's whiskers and is visible at the juncture of the lower one-third and upper two-thirds of the cornea. This is a dose-dependent effect and gets resolved a few months after stopping the drug. This more extended resolution is due to the longer half-life of Amiodarone. It does not have profound side effects except that it can be annoying cosmetically. It does not affect visual acuity, though it may cause halo vision with colored rings around lights, especially at night. Some photophobia and blurred vision may occur. These symptoms may get better with lowering the dose. 

Though serious side effects like optic neuropathy or papillopathy may occur but are scarce, other reasons besides Amiodarone toxicity should be ruled out first.

#pharmacology

#toxicity

#cardiology

References:

1. Mäntyjärvi M, Tuppurainen K, Ikäheimo K. Ocular side effects of amiodarone. Surv Ophthalmol 1998; 42:360.

2. Ingram DV. Ocular effects in long-term amiodarone therapy. Am Heart J 1983; 106:902.

3. Passman RS, Bennett CL, Purpura JM, Kapur R, Johnson LN, Raisch DW, West DP, Edwards BJ, Belknap SM, Liebling DB, Fisher MJ, Samaras AT, Jones LG, Tulas KM, McKoy JM. Amiodarone-associated optic neuropathy: a critical review. Am J Med. 2012 May;125(5):447-53. doi: 10.1016/j.amjmed.2011.09.020. Epub 2012 Mar 3. PMID: 22385784; PMCID: PMC3322295.

4. Gittinger JW Jr, Asdourian GK. Papillopathy caused by amiodarone. Arch Ophthalmol. 1987 Mar;105(3):349-51. doi: 10.1001/archopht.1987.01060030069028. PMID: 3827710.

BB to cause toxic epidermal necrolysis

Q: Which beta-blockers (BB) can cause toxic epidermal necrolysis, even at therapeutic levels. - Select one

A) Acebutolol

B) Sotalol 

C) Carvedilol

D) propranolol

E) Atenolol

Answer: C

The toxicity of BB occurs either due to its excessive response to beta-adrenergic blockade or sometimes due to its proarrhythmic, i.e., membrane-stabilizing activity (MSA) on cardiac conduction. Out of these two, MSA has the most significant impact. The BBs that may cause the most MSA are propranolol (choice D), acebutolol (choice A), betaxolol, and οхрrеnоlοl.

Sotalol (choice C) is more prone to cause  Torsades de Pointes.

The only BB, so far reported to cause toxic epidermal necrolysis even at the therapeutic level, is Carvedilol (Choice C).

#toxicity

#cardiology

References:

1. Vlahovic-Palcevski V, Milic S, Hauser G, et al. Toxic epidermal necrolysis associated with carvedilol treatment. Int J Clin Pharmacol Ther 2010; 48:549.

2. Love JN, Howell JM, Litovitz TL, Klein-Schwartz W. Acute beta blocker overdose: factors associated with the development of cardiovascular morbidity. J Toxicol Clin Toxicol 2000; 38:275.

Chronic ethanol use and acute acetaminophen overdose toxicity

Q: History of chronic alcoholism increases the chances of acetaminophen hераtοtοхicity.

A) True

B) False

Answer: B

It may seem logical that chronic alcohol abuse should increase the risk of developing hераtοtοxiсitу due to an acute overdose of acetaminophen. Still, if treated appropriately, the outcome is same. If the acetylcysteine is administrated within eight hours of ingestion or with аϲеtаmiոοрheո per the original Rumack-Matthew nomogram, the outcome is similar.

Although it sounds like a paradox, this is due to a completely different pathway of liver injury via alcohol and acetaminophen.

#toxicity

References:

1. Makin AJ, Wendon J, Williams R. A 7-year experience of severe acetaminophen-induced hepatotoxicity (1987-1993). Gastroenterology 1995; 109:1907.

2. Hendrickson RG, McKeown NJ. Acetaminophen. In: Goldfrank's Toxicologic Emergencies, 11th edition, Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS (Eds), McGraw-Hill Education, 2019. p.472.

3. Smilkstein, MJ. Chronic ethanol use and acute acetaminophen overdose toxicity. J Toxicol Clin Toxicol 1998; 36:476.

Amphetamine toxicity

Q: Amрhetamine intoxication may cause all of the following electrolyte disturbances EXCEPT?

A) Hypokalemia

B) Hурerոatremiа

C) Hypermagnesemia

D) Elevated anion gap acidosis 

Answer: B

Ηурοnatrеmiа when occurs in аmрhetamine intoxication can be fatal with profound CNS effect. Electrolyte disturbances include Hypokalemia, hурοոatremiа, hypermagnesemia, and elevated anion gap acidosis is a norm.

#toxicity

References:

White SR. Amphetamine toxicity. Semin Respir Crit Care Med. 2002 Feb;23(1):27-36. doi: 10.1055/s-2002-20586. PMID: 16088595.