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wikitox:clonidine [2024/04/22 20:37] – kharriswikitox:clonidine [2025/02/17 00:28] (current) – kharris
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-Link to [[:wikitox:problems_for_discussion_2_clonidine|Problems for Discussion]]\\ +====== Centrally-acting Anti-hypertensives (α-adrenoceptor agonists) ======
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- <font 36px/inherit;;#c12b04;;inherit>Centrally acting antihypertensives (α-adrenoceptor agonists)</font> +
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 ===== Overview ===== ===== Overview =====
  
 +\\
 Common agents: Clonidine, guanfacine and moxonidine. Common agents: Clonidine, guanfacine and moxonidine.
  
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 ===== Mechanism of Toxic Effects ===== ===== Mechanism of Toxic Effects =====
  
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 Action is via central α2- receptor stimulation in the vasomotor centre of the medulla, leading to enhanced activity of inhibitory neurons and subsequent decrease in sympathetic outflow. Action is via central α2- receptor stimulation in the vasomotor centre of the medulla, leading to enhanced activity of inhibitory neurons and subsequent decrease in sympathetic outflow.
  
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 ===== Risk Assessment ===== ===== Risk Assessment =====
  
 +\\
 Ingestions of greater than 10mcg/kg of clonidine can cause significant effects in children. Ingestions of greater than 10mcg/kg of clonidine can cause significant effects in children.
  
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 ===== Kinectics in Overdose ===== ===== Kinectics in Overdose =====
  
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 **Absorption** **Absorption**
  
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 ==== Distribution ==== ==== Distribution ====
  
 +\\
 Volume of distribution is 3-6L/kg with rapid distribution to the CNS. Protein binding is 20-40%. Volume of distribution is 3-6L/kg with rapid distribution to the CNS. Protein binding is 20-40%.
  
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 ===== Clinical Effects ===== ===== Clinical Effects =====
  
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 Due to rapid absorption clinical effects usually appear early with onset typically 30-60mins post ingestion. Due to rapid absorption clinical effects usually appear early with onset typically 30-60mins post ingestion.
  
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 **CVS:** **CVS:**
 +
   * Early transient hypertension, secondary to peripheral α1-agnoist effect, is seen in up to a third of patients and can be severe in those with renal disease.   * Early transient hypertension, secondary to peripheral α1-agnoist effect, is seen in up to a third of patients and can be severe in those with renal disease.
   * Bradycardia is common (higher degrees of heart block can be seen but are rare) and sometimes associated with hypotension.   * Bradycardia is common (higher degrees of heart block can be seen but are rare) and sometimes associated with hypotension.
  
 **Other effects:** **Other effects:**
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   * Hypothermia   * Hypothermia
  
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 ===== Investigations ===== ===== Investigations =====
  
-Besides the standard investigations, there are no specific laboratory tests that are useful in clonidine overdose. Normal urine toxicology screens are not useful for detecting clonidine.+ \\ Besides the standard investigations, there are no specific laboratory tests that are useful in clonidine overdose. Normal urine toxicology screens are not useful for detecting clonidine.
  
   * ECG – sinus bradycardia or heart block   * ECG – sinus bradycardia or heart block
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 ===== Differential Diagnosis ===== ===== Differential Diagnosis =====
  
-Opioid toxicity: CNS depression, miosis, respiratory depression.+ \\ **Opioid toxicity**: CNS depression, miosis, respiratory depression.
  
-Beta-blocker toxicity: Bradycardia, hypotension.+**Beta-blocker toxicity**: Bradycardia, hypotension.
  
-Organophosphates: CNS depression, miosis, bradycardia, hypothermia.+**Organophosphates**: CNS depression, miosis, bradycardia, hypothermia.
  
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-===== References =====+===== Further Reading =====
  
- \\ [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8329790|Raber JH, Shinar C, Finkelstein S.]] Clonidine patch ingestion in an adult. //Ann Pharmacother//  1993 Jun;27(6):719-722 \\ [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2209040|Fiser DH, Moss MM, Walker W.]] Critical care for clonidine poisoning in toddlers. //Crit Care Med//  1990 Oct;18(10):1124-1128 \\ +  - Fiser DH, Moss MM, Walker W. Critical care for clonidine poisoning in toddlers. Crit Care Med 1990;18(10):1124–8. {{:wikitox:fisher-critical_care_for_clonidine_poisoning_in_toddlers.pdf|PDF}} 
-Anderson RJ, Hart GR, Crumpler CP, Lerman MJ. Clonidine overdose: report of six cases and review of the literature. //Ann Emerg Med//  1981 Feb;10(2):107-112 \\ [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9633978|Erickson SJ, Duncan A.]] Clonidine poisoning–an emerging problem: epidemiology, clinical features, management and preventative strategies. //J Paediatr Child Health//  1998 Jun;34(3):280-282 \\ [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9095013|Nichols MH, King WD, James LP.]] Clonidine poisoning in Jefferson County, Alabama. //Ann Emerg Med//  1997 Apr;29(4):511-517 \\ [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6604383|Ciaccheri M, Dolara A, Manetti A, Botti P, Zorn M, Peruzzi S.]] A-V block by an overdose of Clonidine. //Acta Cardiol//  1983;38(3):233-236 \\ [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2353431|Bamshad MJ, Wasserman GS.]] Pediatric clonidine intoxications. //Vet Hum Toxicol//  1990 Jun;32(3):220-223 \\ [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1969468|Wiley JF 2d, Wiley CC, Torrey SB, Henretig FM.]] Clonidine poisoning in young children. //J Pediatr//  1990 Apr;116(4):654-658 \\ [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=382842|Conner CS, Watanabe AS]]. Clonidine overdose: a review. //Am J Hosp Pharm//  1979 Jul;36(7):906-911 \\ [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6889062|Yagupsky P, Gorodischer R.]] Massive clonidine ingestion with hypertension in a 9-month-old infant. //Pediatrics//  1983 Oct;72(4):500-502 \\ +  - Isbister GK, Heppell SP, Page CB, Ryan NM. Adult clonidine overdose: prolonged bradycardia and central nervous system depression, but not severe toxicity. Clin Toxicol (Phila) 2017;55(3):187–92. {{:wikitox:adult_clonidine_overdose_prolonged_bradycardia_and_central_nervous_system_depression_but_not_severe_toxicity.pdf|PDF}} 
-Moxonidine [[http://www.australianprescriber.com/magazine/29/1/25/7/new-drugs-796/moxonidine|Aust Prescr 2006;29:25-7]] \\  \\ +  - Toce MS, FreimanE, O’Donnell KA, Burns MM. Clinical effects of pediatric clonidine exposure: a retrospective cohort study at a single tertiary center. J Emerg Med 2021; 60(1): 58-66. {{:wikitox:toce-paediatric_clonidine.pdf|PDF}} 
-6- Dec-2014+  - Seger DL, Loden JK. Naloxone reversal of clonidine toxicity: dose, dose, dose. Clin Toxicol 2018; 56(10): 872-879. {{:wikitox:seger-clonidinenaloxone.pdf|PDF}}