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Module 1 - Cardiovascular Drugs

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	Date and Author:	Sep 19, 2008 3:59 am by murshida
	Comment:	none
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[[toc]]
= =
=MODULE 1 =

=__**Cardiovascular Drugs**__=

===Objectives===
At the end of this module, students should be able to:
 the mechanisms underlying the toxicity
· Undertake a risk assessment of poisoning
· Develop an approach for the treatment of mixed cardiovascular drug overdose
----
=== ===
 

= Beta Blockers and Calcium Channel Blockers=

===Objectives===
* Understand the mechanism of toxicity of CCBs and beta-blockers.
* Understand how this explains differences within each class in the toxicity in overdose.
* List the most common clinical manifestations of poisoning with CCBs and beta-blockers.
* Recognise situations where the use of antidotes may be indicated.
* Recognise situations where a sudden deterioration is likely to occur and steps that may be taken to anticipate and/or prevent such deteriorations.

== ==
===**Reading**===

 **//[[3.4.3.4.2 Beta-blockers|Beta Blockers]]
 //**
[[http://www.ncbi.nlm.nih.gov/pubmed/12748150?dopt=AbstractPlus|Boyd R, Ghosh A.]]//Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Glucagon for the treatment of symptomatic beta blocker overdose.//[[javascript:AL_get(this, 'jour', 'Emerg Med J.');|Emerg Med J.]] 2003 May;20(3):266-7. 
[[http://www.ncbi.nlm.nih.gov/pubmed/18288073?dopt=AbstractPlus|Mansell PI]].//Glucagon in the management of deliberate self-poisoning with propranolol.// [[javascript:AL_get(this, 'jour', 'Arch Emerg Med.');|Arch Emerg Med.]] 1990 Sep;7(3):238-40. 
 [[http://www.ncbi.nlm.nih.gov/pubmed/10729673?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Love JN]].Acebutolol overdose resulting in fatalities.[[javascript:AL_get(this, 'jour', 'J Emerg Med.');|J Emerg Med.]] 2000 Apr;18(3):341-4.
** [[http://www.ncbi.nlm.nih.gov/pubmed/18288073?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Pfaender M, Casetti PG, Azzolini M, Baldi ML, Valli A]] .**//Successful treatment of a massive atenolol and nifedipine overdose with CVVHDF.// [[javascript:AL_get(this, 'jour', 'Minerva Anestesiol.');|Minerva Anestesiol.]] 2008 Mar;74(3):97-100.

**//[[2.1.6.1.1 Calcium channel blockers|Calcium Channel Blockers(CCB)]]

//**[[http://www.ncbi.nlm.nih.gov/pubmed/11296202?ordinalpos=25&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Lam YM, Tse HF, Lau CP]].Continuous calcium chloride infusion for massive nifedipine overdose. [[javascript:AL_get(this, 'jour', 'Chest.');|Chest.]] 2001 Apr;119(4):1280-2.
[[http://ccforum.com/content/10/3/212|Philippe ER Lheureux , Soheil Zahir, Mireille Gris, Anne-Sophie Derrey and Andrea Penaloza]]
Bench-to-bedside review: Hyperinsulinaemia/euglycaemia therapy in the management of overdose of calcium-channel blockers
//Critical Care// 2006, **10****:**212
[[http://www.ncbi.nlm.nih.gov/pubmed/9559422?dopt=AbstractPlus|Oe H, Taniura T, Ohgitani N.]]A case of severe verapamil overdose.
[[http://www.ncbi.nlm.nih.gov/pubmed/12101159?dopt=AbstractPlus|Isbister GK]].Delayed asystolic cardiac arrest after diltiazem overdose; resuscitation with high dose intravenous calcium.[[javascript:AL_get(this, 'jour', 'Emerg Med J.');|Emerg Med J.]] 2002 Jul;19(4):355-7.
[[http://www.ncbi.nlm.nih.gov/pubmed/8025446?dopt=AbstractPlus|Buckley NA, Whyte IM, Dawson AH]] Overdose with calcium channel blockers. BMJ. 1994 Jun 18;308(6944):1639.


===Problems ===
====//[[Problems for Discussion- 2- Beta Blockers and Calcium Channel Blockers(CCB)#problem 1|1 , 2]]//====

=**Clonidine ** =

===Objectives===
* Understand the mechanism of toxicity of clonidine.
* Understand the particular risks of clonidine toxicity in children.
* Explain the management of cardiovascular toxicity from clonidine overdose.
* Detail the role and limitations of any potential antidotes for clonidine toxicity.
* Outline the type of preparations that contain imidazoline compounds that can cause an identical poisoning to clonidine.

===Reading===

**__//[[Clonidine]]
//__**
[[http://file:///C:/Documents%20and%20Settings/Administrator/Application%20Data/Mozilla/Firefox/Profiles/wm5a387v.default/zotero/storage/4798/entrez.html|Romano MJ, Dinh A.]]A 1000-fold overdose of clonidine caused by a compounding error in a 5-year-old child with attention-deficit/hyperactivity disorder.[[javascript:AL_get(this, 'jour', 'Pediatrics.');|Pediatrics.]] 2001 Aug;108(2):471-2. 
[[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1174908|S N Hunyor, K Bradstock, P J Somerville, and N Lucas.]]Clonidine overdose.Br Med J. 1975 October 4; 4(5987): 23.
[[http://www.ncbi.nlm.nih.gov/pubmed/923317?dopt=AbstractPlus|Williams PL, Krafcik JM, Potter BB, Hooper JH, Hearne MJ.]]Cardiac toxicity of clonidine.[[javascript:AL_get(this, 'jour', 'Chest.');|Chest.]] 1977 Dec;72(6):784-5.
 
=== ===
===Problems===
====//[[Problems for Discussion- 2- Clonidine|1 , 2 ]]//====

= Ergots=

===Objectives===
* Understand the mechanism of action of these agents.
* Detail the groups of patients at risk of ergot poisoning.
* Outline and differentiate acute and chronic ergot poisoning.
* Detail the management options, including risks and benefits, of the different agents used to treat ergot poisoning.

===Reading===

**//[[2.1.11.4.5.1 Ergot Alkaloids|Ergots]]

//** [[http://www.ncbi.nlm.nih.gov/pubmed/10082701?ordinalpos=33&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum|Liaudet L, Buclin T, Jaccard C, Eckert P]].Severe ergotism associated with interaction between ritonavir and ergotamine.[[javascript:AL_get(this, 'jour', 'BMJ.');|BMJ.]] 1999 Mar 20;318(7186):771
 [[http://www.ncbi.nlm.nih.gov/sites/entrez|Verloes A, Emonts P, Dubois M, Rigo J, Senterre J]].Paraplegia and arthrogryposis multiplex of the lower extremities after intrauterine exposure to ergotamine. [[javascript:AL_get(this, 'jour', 'J Med Genet.');|J Med Genet.]] 1990 Mar;27(3):213-4.
 
===Problems===
====//[[Problems for Discussion- 2- Ergots|1 , 2]]// ====

=== ===
=**Vasodilators** =

===Objectives===
* Understand the mechanism of action of these agents and how these may manifest in overdose.
* Outline what additional toxicity may occur with these agents
* Detail who are more susceptible to nitrate and nitroprusside toxicity.
* Detail the use of specific antidotes for treating some of these agents in overdose.
* Understand the supportive management that should be adopted for these agents in overdose, detail which are likely to require treatment with vasopressors and how they should be administered.

===Reading===

**//[[2.1.6.2.5 Vasodilators|Vasodilators]]//**

[[http://www.ncbi.nlm.nih.gov/sites/entrez|Robin ED, McCauley R.]]Nitroprusside-related cyanide poisoning. Time (long past due) for urgent, effective interventions. [[javascript:AL_get(this, 'jour', 'Chest.');|Chest.]] 1992 Dec;102(6):1842-5.
[[http://www.ncbi.nlm.nih.gov/pubmed/1928887?ordinalpos=48&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Varon J, Duncan SR.]]Naloxone reversal of hypotension due to captopril overdose.[[javascript:AL_get(this, 'jour', 'Ann Emerg Med.');|Ann Emerg Med.]] 1991 Oct;20(10):1125-7.
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1497172&dopt=Abstract|Mortensen ME, Bolon CF, Kelley MT, Walson PD, Cassidy S.]] Encainide overdose in an infant. Ann Emerg Med 1992; 21(8): 998-1001.
[[http://www.ncbi.nlm.nih.gov/pubmed/7905816?dopt=AbstractPlus|Kollef MH]].Labetalol overdose successfully treated with amrinone and alpha-adrenergic receptor agonists.[[javascript:AL_get(this, 'jour', 'Chest.');|Chest.]] 1994 Feb;105(2):626-7.

=== ===
===Problems===
====//[[Problems for Discussion- 2- Vasodilators|1 , 2 , 3]]//====

= =
= =
=Antiarrhythmics=

===Objectives===
* Understand how the presentation of Class 1A agents parallels that of other drugs.
* Relate the common clinical presentation and time course of type 1B agents in overdose.
* Detail how the acute and chronic presentations of antiarrhythmics poisoning may differ.

===Reading===

**//[[3.4.3.4 Antiarrhythmics|Antiarrhythmics]]//**

[[http://www.ncbi.nlm.nih.gov/pubmed/9140253?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Yasui RK, Culclasure TF, Kaufman D, Freed CR]].Flecainide overdose: is cardiopulmonary support the treatment?[[javascript:AL_get(this, 'jour', 'Ann Emerg Med.');|Ann Emerg Med.]] 1997 May;29(5):680-2.
[[http://www.ncbi.nlm.nih.gov/pubmed/9528738?ordinalpos=31&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Katz AM]].Selectivity and toxicity of antiarrhythmic drugs: molecular interactions with ion channels.[[javascript:AL_get(this, 'jour', 'Am J Med.');|Am J Med.]]1998 Feb;104(2):179-95.
[[http://www.ncbi.nlm.nih.gov/pubmed/11726437?dopt=AbstractPlus|Gilbert TB]].Cardiac arrest from inadvertent overdose of lidocaine hydrochloride through an arterial pressure line flush apparatus.[[javascript:AL_get(this, 'jour', 'Anesth Analg.');|Anesth Analg.]] 2001 Dec;93(6):1534-6, table of contents.
[[http://www.ncbi.nlm.nih.gov/pubmed/9825278?dopt=AbstractPlus|Brazil E, Bodiwala GG, Bouch DC.]]Fatal flecainide intoxication.[[javascript:AL_get(this, 'jour', 'J Accid Emerg Med.');|J Accid Emerg Med.]] 1998 Nov;15(6):423-5.

=== ===
===Problems===
====//[[Problems for discussion- 2- Antiarrhythmics|1 , 2 , 3]]// ====
==== ====

= =
=Cardiac glycosides=

===Objectives===
* To be able to recognise the major sources of poisoning by naturally occurring cardiac glycosides.
* To be able to perform a risk assessment following digoxin acute deliberate self-poisoning or accidental paediatric ingestion.
* To be able to discuss the risk factors for chronic digoxin intoxication.
* To be able to discuss the pharmacokinetics and pharmacodynamics of digoxin.
* To be able to recognise the clinical, biochemical and electrocardiographic manifestations of acute and chronic cardiac glycoside intoxication.
* To be able to discuss the mechanism of action of digoxin-specific antibodies.
* To be able to calculate an appropriate dose of digoxin-specific antibody in a variety of clinical situations.

===Reading===

**//[[2.1.6.1.2 Cardiac glycosides|Cardiac glycoside]]//**

[[http://www.ncbi.nlm.nih.gov/pubmed/9727817?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Marik PE, Fromm L]].A case series of hospitalized patients with elevated digoxin levels.[[javascript:AL_get(this, 'jour', 'Am J Med.');|Am J Med.]] 1998 Aug;105(2):110-5.
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12801736&dopt=Abstract|de Silva HA, Fonseka MM, Pathmeswaran A, Alahakone DG, Ratnatilake GA, Gunatilake SB, Ranasinha CD, Lalloo DG, Aronson JK, de Silva HJ]]. Multiple-dose activated charcoal for treatment of yellow oleander poisoning: a single-blind, randomised, placebo-controlled trial. Lancet. 2003 Jun 7;361(9373):1935-8.
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10768435|Eddleston M, Rajapakse S, Rajakanthan, Jayalath S, Sjostrom L, Santharaj W et al]]. Anti-digoxin Fab fragments in cardiotoxicity induced by ingestion of yellow oleander: a randomised controlled trial. Lancet 2000; 355(9208):967-972.
[[http://www.ncbi.nlm.nih.gov/pubmed/3094820?dopt=AbstractPlus|Gibb I, Parnham A.]]A star treatment for digoxin overdose?[[javascript:AL_get(this, 'jour', 'Br Med J (Clin Res Ed).');|Br Med J (Clin Res Ed).]] 1986 Nov 1;293(6555):1171-2.
[[http://www.ncbi.nlm.nih.gov/pubmed/6409318?dopt=AbstractPlus|Maheswaran R, Bramble MG, Hardisty CA.]]Massive digoxin overdose: successful treatment with intravenous amiodarone.[[javascript:AL_get(this, 'jour', 'Br Med J (Clin Res Ed).');|Br Med J (Clin Res Ed).]] 1983 Aug 6;287(6389):392-3.
 

=== ===
===Problems===
====//[[Problems for discussion- 2- Cardiac glycoside|1 , 2 , 3]]// ====

= =
= =
=Anticoagulant Poisonings=
=== ===
===Objectives===
* Understand the mechanism of toxicity of coumarin anticoagulants.
* Understand the different scenarios of anticoagulant poisoning.
* Review the literature on the risk of bleeding in patients who are over-anticoagulated.
* Understand the treatment options for anticoagulant poisoning: therapeutic, deliberate and unintentional.

===Reading===

**//[[2.2.7.5.1 Anticoagulant|Anticoagulant Poisonings]]//**

[[http://www.ncbi.nlm.nih.gov/pubmed/7776988?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Cannegieter SC, Rosendaal FR, Wintzen AR, van der Meer FJ, Vandenbroucke JP, Briët E]].Optimal oral anticoagulant therapy in patients with mechanical heart valves.[[javascript:AL_get(this, 'jour', 'N Engl J Med.');|N Engl J Med.]] 1995 Jul 6;333(1):11-7.
[[http://www.ncbi.nlm.nih.gov/pubmed/11075768?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Crowther MA, Julian J, McCarty D, Douketis J, Kovacs M, Biagoni L, Schnurr T, McGinnis J, Gent M, Hirsh J, Ginsberg J.]]Treatment of warfarin-associated coagulopathy with oral vitamin K: a randomised controlled trial.[[javascript:AL_get(this, 'jour', 'Lancet.');|Lancet.]] 2000 Nov 4;356(9241):1551-3.
[[http://www.ncbi.nlm.nih.gov/pubmed/12085076?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Ingels M, Lai C, Tai W, Manning BH, Rangan C, Williams SR, Manoguerra AS, Albertson T, Clark RF]].A prospective study of acute, unintentional, pediatric superwarfarin ingestions managed without decontamination.[[javascript:AL_get(this, 'jour', 'Ann Emerg Med.');|Ann Emerg Med.]] 2002 Jul;40(1):73-8.
[[http://www.ncbi.nlm.nih.gov/sites/entrez|Ramanan AV, Gissen P, Bose-Haider B.]]Intentional overdose of warfarin in an adolescent: need for follow up.[[javascript:AL_get(this, 'jour', 'Emerg Med J.');|Emerg Med J.]] 2002 Jan;19(1):90. 
[[http://www.ncbi.nlm.nih.gov/pubmed/9759690?dopt=AbstractPlus|Chua JD, Friedenberg WR.]]Superwarfarin poisoning.[[javascript:AL_get(this, 'jour', 'Arch Intern Med.');|Arch Intern Med.]] 1998 Sep 28;158(17):1929-32.
[[http://www.ncbi.nlm.nih.gov/pubmed/10654963?dopt=AbstractPlus|Mullins ME, Brands CL, Daya MR.]]Unintentional pediatric superwarfarin exposures: do we really need a prothrombin time?[[javascript:AL_get(this, 'jour', 'Pediatrics.');|Pediatrics.]] 2000 Feb;105(2):402-4. 

=== ===
===Problems===
====//[[Problems for discussion- 2- Anticoagulant poisoning|1 , 2 , 3 , 4]]// ====

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