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wikitox:2.1.11.4.5.1_ergot_alkaloids [2018/09/01 09:00] (current)
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 +Link to [[:​wikitox:​problems_for_discussion_2_ergots|Problems for Discussion]]
 +
 +----
 +
 +====== Ergot Alkaloids ======
 +
 +===== OVERVIEW =====
 +
 +While death has been reported from ergotamine toxicity in clinical practice the major problem is ischaemia. This can occur in any vascular bed, but is most commonly reported in the limbs. Ischaemia can occur idiosyncratically within the normal therapeutic dose range as well as in overdose. The incidence of adverse effects increases with increasing dose.
 +
 +===== SUBSTANCES INCLUDED IN THIS CATEGORY =====
 +
 +Cafergot tablets, Circanol tablets, Dihydroergocornine,​ Dihydroergocristine,​ Dihydroergosine,​ Dihydroergotamine,​ Dihydroergotaxime,​ Ergobasine, Ergocornine,​ Ergocristine,​ Ergocryptine,​ Ergometrine,​ Ergonovine, Ergosine, Ergotamine, Ergotamine Tartrate, Ergotaxime, Gynergen, Lergotrile, Lingraine Sublingual Tabs, Lisuride, Lysergol, Medihaler Ergotamine Aerosol, Metergoline,​ Methergin, Methylergometrine ester, Methylergonovine,​ Methysergide,​ Orgraine
 +
 +
 +===== MECHANISM OF TOXIC EFFECTS =====
 +
 +Ergotamine causes vasoconstriction by peripheral alpha agonism. There is a synergistic effect with other vasoconstrictive neuropeptides (angiotensin,​ [[:​wikitox:​3.2.1.3_toxidromes|catecholamines]],​ nicotine). Histology of the small vessels shows endothelial damage with associated thrombosis. This may be a primary effect of ergotamine rather than an effect secondary to prolonged vasoconstriction.
 +
 +
 +===== KINETICS IN OVERDOSE =====
 +
 +==== Absorption ====
 +
 +Oral bioavailability is low (< 10%), due to poor absorption and a signifiant first-pass effect. Rectal or IM administration will result in enhanced bioavailability.
 +
 +==== Distribution ====
 +
 +Peak ergotamine concentrations occur within 2 hours, and it is rapidly cleared from the plasma. In therapeutic use the effect on peripheral vessels can last for 24 hours, but in acute or chronic toxicity effects can persist for considerably longer. This is presumed to reflect slow dissociation from peripheral receptors, and/or the presence of active metabolites.
 +
 +====   ====
 +
 +====   ====
 +
 +==== Metabolism - Elimination ====
 +
 +Virtually all ergot alkaloids are metabolised hepatically,​ with subsequent biliary excretion of metabolites.
 +
 +===== CLINICAL EFFECTS =====
 +
 +Symptoms due to ischaemia can result from vasoconstriction in any vascular bed.\\
 +Ergotism includes two types of clinical manifestations which may occur together or separately.
 +
 +  * Peripheral vasoconstriction:​
 +      * dysaethesia and/or gangrene of the extremities ('St. Anthony'​s fire')
 +      * formication
 +      * cardiac ischaemia / infarction
 +      * mesenteric or renal ischaemia / infarction
 +      * vomiting
 +  * CNS effects:
 +      * vomiting (dopaminergic stimulation of emetic centre)
 +      * headache
 +      * delirium
 +      * seizures
 +      * cerebrovascular ischaemia / infarction
 +
 +
 +==== Acute effects ====
 +
 +Increased tone of smooth muscles, vomiting, burning pain in the abdomen, diarrhoea, thirst, uterine bleeding, tachycardia,​ hypotension,​ anxiety, vertigo, disturbances of consciousness,​ psychotic disturbance and coma.
 +
 +==== Chronic effects ====
 +
 +From ingestion, injection or application to mucous membranes. \\  \\ NOTE: Additional acute manifestations may include paroxysmal hypertension,​ and severe dysuria. In cases of peripheral vascular disorders, vasodilating agents may be of value, but management requires hospitalisation.
 +
 +===== INVESTIGATIONS =====
 +
 +Full Blood Count, electrolytes,​ creatinine & urea. Cardiac enzymes ECG.
 +
 +
 +===== DIFFERENTIAL DIAGNOSIS =====
 +
 +Ischaemia from any medical cause.\\
 +Vasospasm secondary to other pharmaceutical agents (amphetamines,​ [[:​wikitox:​2.1.11.4.8.1_cocaine|cocaine]]).
 +
 +
 +===== TREATMENT =====
 +
 +==== Supportive ====
 +
 +Ensure that the patient is [[:​wikitox:​3.4.8_fluid_resuscitation|well hydrated]], patients may be dehydrated as a consequence of coexistent conditions (e.g. migraine) or as a complication of their ergotamine toxicity. Do not let the patient have any more vasoconstrictive drugs this includes further doses of ergotamine , smoking and sympathomimetics (e.g. amphetamine,​ cocaine) Symptomatic treatment should be given for vomiting and nausea.
 +
 +
 +==== Anticoagulation ====
 +
 +Unless there is a strong [[:​wikitox:​relative_contraindications_to_anticoagulation|contraindication to anticoagulation]] even asymptomatic patients should be given [[:​wikitox:​2.2.7.5.1_anticoagulant|heparin]].
 +
 +
 +==== GI Decontamination ====
 +
 +=== Activated Charcoal ===
 +
 +Single dose [[:​wikitox:​3.2.2.2.3_activated_charcoal|activated charcoal]] is the recommended gastrointestinal decontamination procedure provided the patient has presented within 1-2 hours.
 +
 +
 +==== Enhanced elimination ====
 +
 +Not clinically useful.
 +
 +==== Treatment of specific complications ====
 +
 +**Vasospasm**
 +
 +Ensure the patient is [[:​wikitox:​3.4.8_fluid_resuscitation|volume expanded]].
 +
 +Virtually every vasodilator in existence has been reported to be used in the setting of vasospasm.
 +
 +In the absence of evidence, what you use is more likely to depend on experience and availability.
 +
 +Ideally the patient should be closely monitored for evidence of response. Vascular Doppler studies may be useful in clinically equivocal cases.
 +
 +**//Sodium nitroprusside//​ **
 +
 +Its rapid onset and short duration of action facilitate titration of dose. Infusion is begun at 25 or 50 microg/​minute with increments, if required, of 25 microg every 5-15 minutes to a maximum of 150 microg/​minute.
 +
 +**//​Glyceryl trinitrate//​ **
 +
 +IV infusion (50 mg [10 mL of 0.5% GTN solution in alcohol] in 500 mL 5.0% dextrose at 2-3 microg/kg body weight/​min).
 +
 +**//Other reported treatments//​ **
 +
 +   * Prazosin 1 mg tds orally
 +  * Phentolamine IV 10 mg 8 hourly
 +  * Nifedipine
 +  * Captopril orally
 +  * Prostaglandin Infusion
 +  * Dextran 40
 +  * Cyproheptadine
 +
 +**Ischaemia**
 +
 +In addition to the methods used in treating vasospasm the following should be considered:
 +
 +  * Treatment of any secondary compartment syndrome
 +  * Fibrinolytics (streptokinase)
 +  * For focal spasm, arterial dilation with a balloon tipped catheter may have to be considered
 +  * Hyperbaric oxygen
 +
 +
 +===== LATE COMPLICATIONS,​ PROGNOSIS - FOLLOW UP =====
 +
 + \\ Retroperitoneal,​ pericardial and pleuropulmonary fibrosis are all described with methysergide.
 +
 +===== REFERENCES =====
 +
 + \\ [[http://​www.ncbi.nlm.nih.gov/​entrez/​query.fcgi?​cmd=Retrieve&​db=PubMed&​dopt=Citation&​list_uids=859518|Andersen PK, Christensen KN, Hole P, Juhl B, Rosendal T, Stokke DB.]] Sodium nitroprusside and epidural blockade in the treatment of ergotism. N Engl J Med 1977; 296:​1271-127 \\
 +Carlton MC, Kunkel DB & Curry SC: Ergotism treated with cyproheptadine. J Tox - Clin Tox 1995; 33:552. \\
 +[[http://​www.ncbi.nlm.nih.gov/​entrez/​query.fcgi?​cmd=Retrieve&​db=PubMed&​dopt=Citation&​list_uids=1745181|Edwards RJ, Fulde GWO, McGrath MA.]] Successful limb salvage with prostaglandin infusion: a review of ergotamine toxicity. Med J Aust 1991; 155:​825-827. \\
 +Zavaleta EG, Fernandez BB, Grove MK, Kaye MD. St. Anthony'​s Fire (Ergotamine Induced Leg Ischaemia), A Case Report and Review of the Literature. Angiology 2001; 52(5);​349-356
 +
 +\\
 +
  
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