1. Cocaine and Other Sympathomimetics

2. Objectives: 1- Acquire the skills of taking focused history and physical examination for cocaine and other sympathomimetics intoxicated patients in the ED 2- Acquire the basic treatment approach to this group of patient. 3- Understand the pahto physiological and pharmacological effects of sympathomimetics. 4- Understand the role of healthcare professionals in poison control and prevention

3.  Cocaine, amphetamines, and derivatives of amphetamines are called sympathomimetics.  These agents cause central nervous system (CNS) stimulation and a cascade of physiologic effects. PERSPECTIVE

4. CLINICAL EFFECTSOF SYMPATHOMIMETICS

5.  Acute cocaine use causes release of dopamine, epinephrine, norepinephrine, and serotonin.  These neurotransmitters most important effects are adrenergic stimulation by norepinephrine and epinephrine.  Norepinephrine causes vasoconstriction by stimulating alpha-adrenergic receptors on vascular smooth muscle. PRINCIPLES OF DISEASE Pathophysiology of Cocaine

6. PRINCIPLES OF DISEASE Pathophysiology of Cocaine  Epinephrine increases myocardial contractility and heart rate through stimulation of beta 1 - adrenergic receptors.  In addition to causing catecholamine release, the reuptake of these stimulatory neurotransmitters from synaptic clefts is inhibited, altering the normal balance between excitatory and inhibitory tone in the CNS.  Subsequent stimulation propagates peripheral catecholamine release

7. Zohair Al Aseri MD,FRCPC EM & CCM How cocaine increases sympathetic tone by increasing neurotransmitters in the synapse.

8.  Cocaine metabolism occurs in the liver and the plasma.  In the liver, primarily to the active metabolite norcocaine, which potentiates the parent drug.  In the plasma, to ecgonine methyl ester via pseudocholinesterase (plasma cholinesterase).  This difference may account for the differences in duration of action with different routes of administration. Zohair Al Aseri MD,FRCPC EM & CCM PRINCIPLES OF DISEASE Pathophysiology of Cocaine

9.  The water-soluble salts of cocaine (cocaine hydrochloride and cocaine sulfate) are available as a white crystalline powder that is taken intranasally or dissolved and injected intravenously.  Oral administration is rare except for patients who are smuggling or concealing drugs. Zohair Al Aseri MD,FRCPC EM & CCM Cocaine Formulations

10.  excitation of the sympathetic nervous system.  Patients with moderate toxicity are alert and awake but may have diaphoresis, tachycardia, mydriasis, and hypertension without organ damage.  A more severely intoxicated patient may present agitated, combative, and hyperthermic.  Signs and symptoms of end-organ damage may be present, including acute hypertensive emergencies. Zohair Al Aseri MD,FRCPC EM & CCM CLINICAL FEATURES

11. Initial assessment and treatment should focus on rapidly fatal complications  Hyperthermia  hypertensive emergencies  cardiac dysrhythmias. Zohair Al Aseri MD,FRCPC EM & CCM

12.  sequelae include  aortic dissection  pulmonary edema  myocardial ischemia and infarction  intracranial hemorrhage, strokes  infarction of the anterior spinal artery. Zohair Al Aseri MD,FRCPC EM & CCM Hypertensive Emergencies

13. Vasospasm can compromise perfusion to various organs. Intestinal infarctions and mesenteric ischemia can occur, particularly in body packers with large oral ingestions. Other local ischemic events include retinal vasospasm, renal infarctions, and placental insufficiency and infarction in the gravid uterus. Zohair Al Aseri MD,FRCPC EM & CCM Hypertensive Emergencies

14.  may not be noted until cardiac output abruptly diminishes, and the patient suddenly loses consciousness.  sinus tachycardia is most common  atrial fibrillation and other supraventricular tachycardias and ventricular dysrythmias Cardiac Dysrhythmias

15.  oropharyngeal burns from the high temperature required to volatilize the drug.  Pneumothorax, pneumopericardium, and pneumomediastinum occur from inhalational barotrauma.  Intranasal cocaine use is associated with sinusitis and naso palatine necrosis or perforation.  Intravenous users have a high risk of infection with blood-borne viruses, local abscesses, and systemic bacterial infections, including botulism, and endocarditis. Zohair Al Aseri MD,FRCPC EM & CCM Other Complications

16.  Transdermal injection of cocaine, or “skin popping,” has similar types of complications. Zohair Al Aseri MD,FRCPC EM & CCM Other Complications

17.  Urine drug screening is unlikely to change treatment because it measures a cocaine metabolite (benzoyl ecgonine) that is typically present for 3 days after last use. Urine drug screening may be beneficial in  (1) to document possible abuse or neglect in a child with suggested exposure  (2) to confirm cocaine as the unknown substance in body packers  (3) to differentiate paranoia from drug-induced or psychiatric causes. Zohair Al Aseri MD,FRCPC EM & CCM DIAGNOSTIC STRATEGIES

18.  ECG DIAGNOSTIC STRATEGIES

19.  Severe, persistent headache despite normalization of blood pressure may occur with a SAH and warrants head CT and, if the scan is negative, lumbar puncture.  Urinalysis should be checked for myoglobin, which indicates rhabdomyolysis. Zohair Al Aseri MD,FRCPC EM & CCM DIAGNOSTIC STRATEGIES

20.  Recognize and treat the rapidly life-threatening agitated delirium. Zohair Al Aseri MD,FRCPC EM & CCM MANAGEMENT

21. Zohair Al Aseri MD,FRCPC EM & CCM INITIAL EVALUATION OF PATIENTS WITH SYMPATHETIC STIMULATION

22.  After initial airway assessment physical restraints to obtain complete vital signs and to secure IV access.  IV benzodiazepines may be necessary Zohair Al Aseri MD,FRCPC EM & CCM MANAGEMENT

23.  Vigorous IV crystalloid replacement. Zohair Al Aseri MD,FRCPC EM & CCM Pharmacologic Sedation

24.  rapid cooling.  Patients should have continuous monitoring of core temperature with a rectal probe. Zohair Al Aseri MD,FRCPC EM & CCM Hyperthermia

25.  Benzodiazepines restore the CNS inhibitory tone on the peripheral nervous system.  With evidence of end-organ damage, IV nitroglycerin or nitroprusside can be used. Zohair Al Aseri MD,FRCPC EM & CCM Hypertensive Emergencies

26.  Phentolamine, a direct alpha-adrenergic antagonist, is the antihypertensive of choice.  It can be titrated slowly using repeat IV doses of 1 to 5 mg with blood pressure monitoring. Zohair Al Aseri MD,FRCPC EM & CCM Hypertensive Emergencies

27.  The combined use of phentolamine and beta- adrenergic antagonists may result in profound hypotension and is inadequately investigated.  Likewise, data on the use of labetalol are disappointing.  The 2008 American Heart Association Guidelines consider beta-adrenergic antagonists potentially harmful Zohair Al Aseri MD,FRCPC EM & CCM Hypertensive Emergencies

28. chest radiograph to identify  aspirated foreign bodies  pneumothorax or pneumomediastinum from inhalational barotrauma.  Fever and shortness of breath should prompt consideration of pneumonia, pulmonary infarction, or endocarditis with septic pulmonary emboli in IV drug abuse. Zohair Al Aseri MD,FRCPC EM & CCM Cocaine-Related Chest Pain

29.  beta-adrenergic antagonists, including labetalol, are contraindicated during acute cocaine toxicity Zohair Al Aseri MD,FRCPC EM & CCM Cocaine-Related Chest Pain

30.  can be discharged after the acute intoxication resolves. These patients may be extremely sleepy from catecholamine depletion, and it is best to discharge them with a responsible adult.  Patients who develop complications should bead mitted to the intensive care unit for further treatment. Zohair Al Aseri MD,FRCPC EM & CCM DISPOSITION

31.  Patients with chest pain who are acutely intoxicated and who show dynamic changes on the ECG, dysrhythmias, or congestive heart failure or patients requiring vasodilators or reperfusion should be admitted.  These patients require further evaluation of the extent of preexisting reversible ischemia and intervention to encourage cessation of drug use. Zohair Al Aseri MD,FRCPC EM & CCM DISPOSITION

32. Zohair Al Aseri MD,FRCPC EM & CCM ADMISSION CRITERIA FOR COCAINE- RELATED CHEST PAIN

33.  Aftera 12-hour monitored observation period, patients with a benign clinical course and negative serum enzyme markers can be discharged. Zohair Al Aseri MD,FRCPC EM & CCM DISPOSITION

34.  Enhance release of catecholamines from presynaptic nerve terminals  Usually taken as pills, but occasionally are crushed and injected.  CNS stimulation results in nearly identical sympathomimetic effects to those from cocaine, but not with the same frequency or intensity. Zohair Al Aseri MD,FRCPC EM & CCM OTHER STIMULANTS Amphetamines

35. Patients are at risk for  Hyperthermia  hypertensive emergencies  Dysrhythmias  myocardial ischemia  hyperkalemia associated with rhabdomyolysis. Zohair Al Aseri MD,FRCPC EM & CCM OTHER STIMULANTS Amphetamines

36.  Although urine drug screens can identify amphetamines, they are of little utility in treating an intoxicated patient.  The management follows the same guidelines as for cocaine, although the duration of toxicity tends to be longer for amphetamines. Zohair Al Aseri MD,FRCPC EM & CCM OTHER STIMULANTS Amphetamines

37.  Methylenedioxymethamphetamine (MDMA— “Ecstasy,” XTC, Adam) is a chemically modified amphetamine originally taken orally at all-night dance parties, or “raves.” Patients describe the euphoria allowing “closeness to others,” so it is sometimes called the “love drug.” Zohair Al Aseri MD,FRCPC EM & CCM Methylenedioxymethamphetamine

38.  life-threatening hyponatremia  may alter release of endogenous stores of vasopressin.  urine samples with a relatively high urine sodium level, similar to SAIDH.  Unless seizures or other neurologic events are present, patients can be treated supportively with fluid restriction.  Urine can be tested for specific gravity, and a sample should be sent to the laboratory for electrolyte analysis and osmolality. Zohair Al Aseri MD,FRCPC EM & CCM Methylenedioxymethamphetamine MDMA

39.  Normal saline or other crystalloids may worsen the hyponatremia because these patients are likely to retain more free water than sodium.  Their fluid intake should be restricted unless severe hypovolemia exists, and they should be treated with hypertonic saline for neurologic impairment.  A newer treatment for hyponatremia includes vasopressin 2 -receptor antagonists but has not been described for these patients. Zohair Al Aseri MD,FRCPC EM & CCM Methylenedioxymethamphetamine

40.  In contrast to other amphetamines, chronic MDMA use causes potentially irreversible neurologic damage to serotoninergic neurons.  Other MDMA variants, such as 3,4- methylenedioxyethamphetamine (Eve), may cause similar complications Zohair Al Aseri MD,FRCPC EM & CCM Methylenedioxymethamphetamine

41.  Methamphetamine, known as “crank” and “crystal meth,” is a fat-soluble, smokable, designer amphetamine.  Complications from methamphetamine use are similar to those from other sympathomimetics.  The duration of action can be significantly longer, however, with some paranoid delusions persisting for 15 hours. Zohair Al Aseri MD,FRCPC EM & CCM Methamphetamine

42.  Ephedrine is another illicitly used amphetamine- like agent associated with complications of excessive sympathomimetic stimulation. Ephedra, a plant-derived product, also known as a Chinese herbal product, ma-huang,has been associated with strokes and deaths in adolescent users. Zohair Al Aseri MD,FRCPC EM & CCM Ephedrine and Ephedra

43.  Khat is a stimulant agent naturally occurring in the leaves of the plant Catha edulis. These leaves are chewed to extract the active compounds, cathinone and methcathinone, which are stimulants with sympathomimetic effects.  Management and disposition follow the same guidelines as that of cocaine.  Smoking khat does not typically result in clinical effects because the agent degrades with pyrolysis. Illicitly manufactured methcathinone is known as “cat.” Zohair Al Aseri MD,FRCPC EM & CCM Khat and Methcathinone

44.  Some methcathinone users experienced an extrapyramidal syndrome associated with elevated manganese levels likely resulting from an inadvertent contaminant during production or inadequate purification.  The role of chelation therapy for elevated manganese levels is uncertain. Zohair Al Aseri MD,FRCPC EM & CCM Khat and Methcathinone

45. Zohair Al Aseri MD,FRCPC EM & CCM

46. True/False Following are the effects of Symathomimetics, 1- Diaphoresis 2- Bradycardia 3- Agitation/excitation 4- Convulsions 5- Dilated pupils (Mydriasis)

47. True/False Cocaine can cause, 1- severe hypertension 2- Myocardial infarction 3- SAH 4- Pulmonary embolism 5- Hypothermia

48. True/False Following are useful in the treatment of Cocaine toxicity, 1- IV fluids 2- IV benzodiazepines 3- Active cooling 4- Beta-blockers to control hypertension 5- Broad spectrum antibiotics