NOACs, novel oral anticoagulants

 

NOAC	Trade name	Peak level	Action site (4)	Lower ICH rate than Warfarin (5)	antidote	Reversal by Hemodialysis	other
Dabigatran (2010)	Pradaxa 150 mg/cap BID, 75mg BID when CCr< 30 [1]	0.5—2 hrs.	Thrombin (IIa)	yes	Idarucizumab 2.5gm stat and BID. (6)  four factor prothrombin complex concentrate (4F-PCC)	Helpful (10)	Easily GI bleeding
Rivaroxaban	Xarelto 20mg/tab QD. 15mg QD when CCr<50 [1]	2—4 hrs	Xa	yes	andexanet alfa and four factor prothrombin complex concentrate (4F-PCC)(7*, 8)	will not be dialyzable [11]	Easily GI bleeding
Apixaban	Eliquis 5 mg/tab BID, 2.5 mg BID when > 2 risk factors. [Age ≥ 80; Weight ≤ 60; Serum Creatinine ≥ 1.5 mg/dL] [1]	2—4 hrs. (2)	Xa	yes	andexanet alfa and four factor prothrombin complex concentrate (4F-PCC)(7*, 8)	unclear whether dialysis would be useful [11].	Less significant bleeding, Hazard ratio=0.5 (12)
Edoxaban	Lixiana 60 mg/tab QD, 30mg QD when CCr<30 [1]	1—2hrs (3)	Xa	yes	four-factor prothrombin complex concentrate (4F-PCC) at 50 IU/kg (8, 9)	unclear whether edoxaban can be dialyzed [11].	Less significant bleeding, Hazard ratio=0.83 (12)

 

 * N=56, in setting of ICH, hemostatic efficacy occurred in 64.7% of patients receiving andexanet alfa and 54.8% of receiving 4F-PCC. Thirty-day all-cause mortality was 45.2% for 4F-PCC and 30% for andexanet alfa(7).

 GI = gastro-intestinal.

References

 

1.      Hu A, Niu J, Winkelmayer WC. Oral Anticoagulation in Patients With End-Stage Kidney Disease on Dialysis and Atrial Fibrillation. Semin Nephrol. 2018 Nov;38(6):618-628.

2.      https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/65848

3.      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608015/

4.      Polzin A, Dannenberg L, Thienel M, Orban M, Wolff G, Hohlfeld T, Zeus T, Kelm M, Petzold T. Noncanonical Effects of Oral Thrombin and Factor Xa Inhibitors in Platelet Activation and Arterial Thrombosis. Thromb Haemost. 2021 Feb;121(2):122-130.

5.      Katsanos AH, Schellinger PD, Köhrmann M, Filippatou A, Gurol ME, Caso V, Paciaroni M, Perren F, Alexandrov AV, Tsivgoulis G. Fatal oral anticoagulant-related intracranial hemorrhage: a systematic review and meta-analysis. Eur J Neurol. 2018 Oct;25(10):1299-1302.

6.      Lindeman E. Målstyrd antidotterapi vid reversering av dabigatran [Goal-directed administration of antidote for reversal of dabigatran anticoagulation]. Lakartidningen. 2017 Dec 5;114:ESF3. Swedish.

7.      Vestal ML, Hodulik K, Mando-Vandrick J, James ML, Ortel TL, Fuller M, Notini M, Friedland M, Welsby IJ. Andexanet alfa and four-factor prothrombin complex concentrate for reversal of apixaban and rivaroxaban in patients diagnosed with intracranial hemorrhage. J Thromb Thrombolysis. 2021 Jun 8. doi: 10.1007/s11239-021-02495-3.

8.      Carpenter E, Singh D, Dietrich E, Gums J. Andexanet alfa for reversal of factor Xa inhibitor-associated anticoagulation. Ther Adv Drug Saf. 2019 Nov 26;10:2042098619888133.

9.      Galbiati G. Successful Cerebral Hemorrhage Control with Prothrombin Complex Concentrate in a Patient on Edoxaban Therapy: A Case Report. J Blood Med. 2020 Jan 30;11:35-38.

 

10.  Awad NI, Brunetti L, Juurlink DN. Enhanced elimination of dabigatran through extracorporeal methods. J Med Toxicol. 2015 Mar;11(1):85-95.

11.  Crowther M, Crowther MA. Antidotes for novel oral anticoagulants: current status and future potential. Arterioscler Thromb Vasc Biol. 2015 Aug;35(8):1736-45.

12.  https://jtp.taiwan-pharma.org.tw/139/013.html

 

 

edited by Yu-Jang Su  Aug, 17, 2021.

COVID-19 impacts on Poisoning

l  Decrease in the number of toxic effects by contacting with venomous animals and plants (ICD10: T63) in 2020, especially 2020 Q1-Q2 (-44.8%, -20.1%). The major cause is the staying home policy. 

l  Number of suicide overdose (ICD: T39, T42, T43, T50, T54, T58, and T60), increased during 2020 Q1 and Q2 (+15.5% and +11.4%). Indeed, the COVID-19 leads to a mental impact on everyone. 

l  Significant decrease in the number of uses of illicit drugs especially in 2020 Q1 and Q2 (-37.5% and -66.7%).

Ref:  https://pubmed.ncbi.nlm.nih.gov/34312037/

edited by Yu-Jang Su  July 29, 2021.

Special Odor in Poisoning

 

Bitter Almond odor: cyanide

https://pubmed.ncbi.nlm.nih.gov/33643738/

-          only 40-45% of people can detect the bitter almond odor. (ref:https://www.mdpoison.com/media/SOP/mdpoisoncom/ToxTidbits/2018/June%202018%20ToxTidbits.pdf)

 

 Garlic-like odor: Selenium, Arsenic

https://pubmed.ncbi.nlm.nih.gov/31775070/

 

 faint odor of Pears: Chloral hydrate

Ref: https://first10em.com/chloral-hydrate-toxicity/

 

 Rotten eggs odor: hydrogen sulfide  

https://pubmed.ncbi.nlm.nih.gov/24328850/

 

 sweet, Pungent odor: Toluene

https://www.epa.gov/sites/production/files/2016-09/documents/toluene.pdf

 

 Others: https://fpnotebook.com/er/Toxin/TxnIndcdOdrs.htm

edited by Yu-Jang Su   June 26, 2021

 

Acetaminophen Overdose

 

Substance

-          Acetaminophen

 

Common name or Trade name

-          普拿疼

-          Paracetamol.

Involving system

-          Hepatic toxicity. [1]

 

Presentation  [1]

-          GI upset in initial 24 hours, nausea, anorexia, malaise、looking pale、sweating.

-          2 to 3^rd day: elevated GOT and GPT; RUQ abdominal pain, decrement of urine amount.

-          3^rd to 4^th day: hepatocellular damage, abdominal pain, jaundice, coagulopathy, hepatic encephalopathy or coma. Lethal possibility.

-          4^th day to 3^rd week resolution of hepatic function.  

-          Rumack-Matthew Nomogram to estimate the toxicity severity [2].

Antidote and Treatment [1]

-          GI decontamination

-          Activated charcoal and laxative agent

-          N-acetylcysteine (NAC) oral 140 mg/ kg, every 4 hours 70 mg / kg * 17 doses.

-          If nausea, vomiting，change into IV form，and treated for 48 hours.  

-         Mechanism: reduce NAPQI damage to hepatic cell. Needs to administrate within 8 hours, if not, hepatoxicity was 5.5-fold higher for cases [3]

-         IV formula: intravenous loading regimen: 150 mg/kg over 15 min, followed by 50 mg/kg over 4 h, and then 100 mg/kg over 16 h [4].

-           

Disposition [1]

-          Poor outcome when ABG PH< 7.3, PT > 100 seconds, creatinine > 3.3mg/dL, Gr. III to IV hepatic encephalopathy.

-          Admit to ICU when hemodynamic unstable, shortness of breath, coma, acute kidney failure, massive GI bleeding. Severe acidosis.  

-          If hepatic failure, needs hepatic transplantation.  

 

References

[1] 乙醯氨酚服用過量 台灣醫界 49(9).

 

[2]. Seifert SA, Kirschner RI, Martin TG, Schrader RM, Karowski K, Anaradian PC. Acetaminophen concentrations prior to 4 hours of ingestion: impact on diagnostic decision-making and treatment. Clin Toxicol (Phila). 2015;53(7):618-23. doi: 10.3109/15563650.2015.1059942. Epub 2015 Jun 24. PMID: 26107627.

 

[3] Downs JW, Cumpston KL, Kershner EK, Troendle MM, Rose SR, Wills BK. Clinical outcome of massive acetaminophen overdose treated with standard-dose N-acetylcysteine. Clin Toxicol (Phila). 2021 Feb 23:1-8. doi: 10.1080/15563650.2021.1887493. Epub ahead of print. PMID: 33620007.

 

[4]. Waring WS. Novel acetylcysteine regimens for treatment of paracetamol overdose. Ther Adv Drug Saf. 2012 Dec;3(6):305-15. doi: 10.1177/2042098612464265. PMID: 25083244; PMCID: PMC4110842.

edited by Yu-Jang Su   May 16, 2021

 

Ricin intoxication

 

Substance

蓖麻

 

Common name or Trade name

- contains Ricin 蓖麻毒素

-          Ricinus communis；

-          castor oil plant

-          本草綱目:李時珍曰︰仁甘辛有毒热，氣味颇近巴豆，亦能利人，故下水汽。其性善走，能開通諸竅經絡，故能治偏風、失音口噤、口目斜、頭風七竅諸病，不止于出有形之物而已。蓖麻油能拔病氣出外，故諸膏多用之。 此药外用屢奏奇勋，但内服不可輕率爾。或言捣膏以箸点于鹅馬六畜舌根下，即不能食，或点肛内，即下血死，其毒可知矣[1]。

-          Toxic substance: Ricin [2].

-          ricin-intoxicated patients worldwide described were found in Asia (38% cases), America (30%) and Europe (24%). Intoxication was mostly accidental (74%) [3].  

 

Involving system

-          Route: intravenous home-made castor bean extract, died 6 days after intoxication [4].

-          Route: oral ingestion of the beans. Injection of ricin is believed to be more lethal［5］．

-          Hepatotoxicity [6].

 

Presentation  

 

-          Ricin injection (738 µg of ricin A-chain (∼10.5 µg/kg) 3 ml Injection (IM). resulted in a near-fatal poisoning that evolved with septic shock-like syndrome, multiple organ dysfunction and necrotizing fasciitis [7].

-          Severe abdominal cramps and nausea after injection of a castor bean extract［5］.

-          A fulminant diarrhea developed, resulting in hypovolemic shock and cardiorespiratory collapse.

-          acute gastroenteritis-like disease as primary manifestations leading to severe fluid and electrolyte imbalance.

-          The mechanism of death was peripheral vascular collapse and progressing multiple organ failure (MOF) occurring 10h-72h after intoxication. [3].

 

 

Antidote and Treatment

 

-          No antidote.

-          Symptomatic treatment consisting mostly to rehydration with intravenous fluids and digestive decontamination performed with activated charcoal and/or gastric lavage [3]

This decontamination treatment administered early has been very effective [3] Prompt treatment with supportive care was necessary to limit morbidity and mortality.

-           

Disposition

-          if rapid deterioration of his hemodynamic function: transferred to ICU [5].　

-          Watch out if an outbreak of serious respiratory or gastrointestinal illness [3].

 

References

 

[1]. 中醫寶典. http://zhongyibaodian.com/bcgm/bima.html

 

[2].認識中藥蓖麻籽.香港中藥藥劑師協會https://www.cmpa.org.hk/%E8%AA%8D%E8%AD%98%E4%B8%AD%E8%97%A5%E8%93%96%E9%BA%BB%E5%AD%90/

 

[3]. Abbes M, Montana M, Curti C, Vanelle P. Ricin poisoning: A review on contamination source, diagnosis, treatment, prevention and reporting of ricin poisoning. Toxicon. 2021 May;195:86-92. doi: 10.1016/j.toxicon.2021.03.004. Epub 2021 Mar 9. PMID: 33711365.

 

[4]. Staňková M, Handlos P, Švidrnoch M, Maier V. Fatal intoxication by intravenous injection of castor bean (Ricinus communis L.) extract-a case study. Int J Legal Med. 2020 Nov;134(6):2133-2141. doi: 10.1007/s00414-020-02340-x. Epub 2020 Jun 17. PMID: 32548760.

 

[5]. Verougstraete N, Helsloot D, Deprez C, Heylen O, Casier I, Croes K. Lethal Injection of a Castor Bean Extract: Ricinine Quantification as a Marker for Ricin Exposure Using a Validated LC-MS/MS Method. J Anal Toxicol. 2019 Apr 1;43(3):e1-e5. doi: 10.1093/jat/bky100. PMID: 30590581.

 

[6]. Palatnick W, Tenenbein M. Hepatotoxicity from castor bean ingestion in a child. J Toxicol Clin Toxicol. 2000;38(1):67-9. doi: 10.1081/clt-100100920. PMID: 10696929.

 

[7]. Bucaretchi F, Borrasca-Fernandes CF, Prado CC, Lanaro R, Costa JL, Petroni OM, Giraldi T, Blotta MHSL, Justo-Junior AS, Sousa NL, Aragão FJL, De Capitani EM, Hyslop S. Near-fatal poisoning after ricin injection. Clin Toxicol (Phila). 2021 Feb;59(2):158-168. doi: 10.1080/15563650.2020.1771358. Epub 2020 Jun 1. PMID: 32475181.

edited by Yu-Jang Su   April 13, 2021.  

 

Tetrodotoxin

 

Tetrodotoxin (TTX) 

Substance

- Till 2019, around 28 analogs of TTX are known, but only 12 were detected in marine organisms [1]. Potent marine neurotoxin with bacterial origin: ( Pseudoalteromonas tetraodonis), a marine bacterium normally associated with the production of tetrodotoxin in pufferfish[2]).

- in some puffer fish, gastropods(腹足動物), and bivalves(雙殼類)[1].

- heat-stable and acid-stable, nonprotein, alkaloid toxin 

Common name or Trade name

 河豚毒素

Involving system

- blocking voltage-activated sodium channels, terminating nerve conduction and muscle action potentials, leading to progressive paralysis and, in extreme cases, to death from respiratory failure [3].

Presentation [4, 5]

-  Peri-oral paraesthesia (65%--72%)

- weakness of both lower limbs (59—62%%).

- paraesthesia all over the body (49%--64%).

- headache (41%--47%),

- difficulty in respiration (38%)

- nausea and vomiting (22%), blurring of vision (19%)

- vertigo (16%)  

 

Antidote and Treatment

-       Palliative / supportive treatment

-       No antidote. no specific treatment [4]

Disposition 

-       Mortality rate: 12--22%. [4, 5, 6]

REFERENCES

1.     Tamele IJ, Silva M, Vasconcelos V. The Incidence of Tetrodotoxin and Its Analogs in the Indian Ocean and the Red Sea. Mar Drugs. 2019 Jan 5;17(1):28. doi: 10.3390/md17010028. PMID: 30621279; PMCID: PMC6357042.

2.     Lee RD, Jospin G, Lang JM, Eisen JA, Coil DA. Draft Genome Sequence of Pseudoalteromonas tetraodonis Strain UCD-SED8 (Phylum Gammaproteobacteria). Genome Announc. 2015 Nov 5;3(6):e01276-15. doi: 10.1128/genomeA.01276-15. PMID: 26543114; PMCID: PMC4645199.

3.     Cole JB, Heegaard WG, Deeds JR, McGrath SC, Handy SM; Centers for Disease Control and Prevention (CDC). Tetrodotoxin poisoning outbreak from imported dried puffer fish--Minneapolis, Minnesota, 2014. MMWR Morb Mortal Wkly Rep. 2015 Jan 2;63(51):1222-5. PMID: 25551594.

4.     Ahasan HA, Mamun AA, Karim SR, Bakar MA, Gazi EA, Bala CS. Paralytic complications of puffer fish (tetrodotoxin) poisoning. Singapore Med J. 2004 Feb;45(2):73-4. PMID: 14985845.

5.     Chowdhury FR, Nazmul Ahasan HA, Mamunur Rashid AK, Al Mamun A, Khaliduzzaman SM. Tetrodotoxin poisoning: a clinical analysis, role of neostigmine and short-term outcome of 53 cases. Singapore Med J. 2007 Sep;48(9):830-3. PMID: 17728964.

6.     Islam QT, Razzak MA, Islam MA, Bari MI, Basher A, Chowdhury FR, Sayeduzzaman AB, Ahasan HA, Faiz MA, Arakawa O, Yotsu-Yamashita M, Kuch U, Mebs D. Puffer fish poisoning in Bangladesh: clinical and toxicological results from large outbreaks in 2008. Trans R Soc Trop Med Hyg. 2011 Feb;105(2):74-80. doi: 10.1016/j.trstmh.2010.10.002. Epub 2010 Dec 3. PMID: 21129761.

edited by Yu-Jang Su  March 24, 2021.