Chasing the Dragon -How to Manage Your Patients When They Are Acutely Intoxicated

1. Chasing the Dragon-How to Manage Your Patients When They Are Acutely Intoxicated Surgical Grand Round October 3, 2012 University of Tennessee Health Science Center

2. Objectives • Identify the signs and symptoms associated with acute intoxication from illicit substances • Review the appropriate management of acute intoxication by the substances covered in this presentation • Identify professionalism issues associated with the management of acutely intoxicated patients

3. Most common drug encountered will be ethanol • CH3CH2OH • Focus of this talk will be on other illicit drugs

4. Marijuana

5. Marijuana • Psychoactive properties due to delta-9-tetrahydrocannabinol (THC) • THC content has increased from 1-5% in the 1960’s to 10-15% today. • Typically causes euphoria with decrease in anxiety, alertness, depression and tension. • Can cause anxiety, dysphoria and panic • Perceptual changes such as colors being brighter and music more vid • Distorted time and spatial perception • Can cause hallucinations • Mystical thinking, increased self consciousness, depersonalization, transient grandiosity, paranoia and other signs of psychosis can occur

6. Marijuana • Decreases reaction time, impairs attention, concentration, short term memory and risk assessment. • Impaired motor coordination and interferes with complex tasks that require divided attention. • Impairment of cognition, coordination and judgment lasts much longer. • Psychomotor impairment last for 12-24 hours

7. Marijuana • Physiologic signs • Tachycardia • Hypertension • Tachypnea • Conjunctival injection • Dry mouth • Increased appetite

8. Cocaine

9. Cocaine • Benzoylmethylecognine • methyl (1R,2R,3S,5S)-3-(benxoyloxy)-8-methyl-8-azabicyclo [3.2.1] octane-2-carboxylate • “Coca” from the coca plant and the alkaloid suffix“-aine” • Crystalline tropane alkaloid • Stimulant, appetite suppressant and local anesthetic

10. Cocaine • Found in leaves of Erytholoxum coca plant • People have been chewing the leaves of the coca plant for 2000 years with little risk of abuse • 1860-Cocaine isolated by Albert Niemann • Coca-Cola contained 0.75 mg of cocaine/ounce until 1903. • Cocaine still available as a 4% or 10% solution for use as a local anesthetic

11. Cocaine • 14 millions users worldwide, 6.4 million in North America • Usage in UK and Spain has reached the same level as that of the US • Very little cocaine usage in Africa, Asia, Eastern Europe and Oceania • Most common illicit drug associated with emergency room visits (31% or 450,000 visits)

12. Cocaine • Serotonin-norepinephrine-dopamine reuptake inhibitor or triple reuptake inhibitor (TRI) • Has hydrophilic and lipophilic portions of the molecule. This allows it to cross the blood-brain barrier easily • Highly addictive due to effects on mesolimbic reward pathway • Also blocks membrane voltage-gated sodium channels

13. Cocaine • Two forms-base and salt • Cocaine base-crack or free base. Low melting point (98°C) so it is easy to smoke. Water insoluble so can’t be used for injection • Cocaine salt-High melting point (195°) so cannot be smoked. Water soluble so easy to inject and insufflate (snort). • Rapidly taken up by most organs including liver, heart, kidney and adrenal gland. • Found in blood, urine, hair, sweat, saliva, breast milk and meconium after usage

14. Cocaine • Onset-inhaled or iv-seconds. Intranasal-20-30 min and GI-90 min. • 95% is metabolized by hydrolysis of ester bonds. Carboxyesterases in liver hydrolyze it to benzoylecgonine. Butyrylcholinesterase throughout the body hydrolyzes cocaine to ecgonine methylester • 5% n-demethylated to norcaine by P450 system • Eliminated in the urine, largely as benzoylecgonine. This is what is tested for in UDS

15. Cocaine • Typical doses-12-15 gm orally (coca leaves), 20-100 mg intranasally, 10-50 mg iv or 50-200 mg inhaled • Intended effects-increased energy, alertness and sociability; elation or euphoria; and decreased fatigue, need for sleep and appetite • Adverse effects-dysphoric mood (anxiety or irritability), panic attacks, paranoia, grandiosity, impaired judgment, psychotic symptoms such as hallucinations and delusions

16. Cocaine • 40% of cocaine users suffer from sleep disturbance, weight loss, paranoia or hallucinations. • Restlessness, agitation, tremor, dyskinesia, repetitive or stereotyped behaviors such as picking at the skin can also occur. • Sensitization and tolerance can occur with chronic use of cocaine. • Chronic cocaine abuse associated with cognitive impairment including visuo-motor performance, attention, verbal memory and risk-reward decision-making. It is also associated with suicide ideation and attempts

17. Cocaine • When combined with ethanol, cocaine forms benzoylmethylecgonineor ethyl cocaine via transesterification. • Ethyl cocaine half-life is 13 hours and is vasoconstrictive, cardiotoxic, dysrhythmogenic and neurotoxic. • Inhibits dopamine reuptake as potently as cocaine • 24% of cocaine is converted to ethyl cocaine when taken iv, 18% when insufflated.

18. Cocaine • Monoamine reuptake inhibitor • Na-channel blockade • Excitatory amino acid stimulation

19. Cocaine Indirect sympathomimetic agent Stimulates α-1, α-2, β-1, and β-2 adrenergic receptors largely mediated by increases in norepinephrine and to a lesser extent epinephrine Preferential α effects on the cardiac and peripheral vasculature. Additional cardiac effects via β agonism Blocks the dopamine transporter protein, which pumps dopamine out of the synaptic cleft and into the presynaptic neuron Results in enhanced and prolonged dopaminergic effects on the postsynaptic neuron

20. Cocaine • Euphoria associated with serotonin reuptake inhibition in CNS • Slows or block nerve conduction by blocking membrane voltage-gate Na channels in nerves. • In high doses, affects Na channels in the heart with prolonged QRS and negative inotropy. • Increases concentrations of the excitatory amino acids glutamate and aspartate in CNS, particularly in Nucleus accumbens. Glutamate is main excitatory amino acid in the CNS.

21. Cocaine • Acute Intoxication • Agitation • Dilated Pupils • Euphoria • Tachycardia and Hypertension • Fever

22. Cocaine • Causes arterial vasoconstriction and enhanced thrombus formation • Causes tachycardia, hypertension, increased myocardial oxygen demand and increase vascular shearing forces • Causes coronary vasoconstriction and 5% of patients who seek care in ED have myocardial ischemia • High doses can lead to decrease LV function and heart failure. • Can cause supraventricular and ventricular dysrhythmias • Aortic dissection and rupture occur rarely

23. Cocaine • Cause psychomotor agitation, seizures, coma, headache, intracranial hemorrhage and focal neurologic symptoms • Psychomotor agitation can cause hyperthermia when peripheral vasoconstriction prevents the body from dissipating head. Mortality can be as high as 33% when hyperthermia develops. • Seizures occur in 3-4% of cocaine-related ED visits • Can get angioedema and pharyngeal burns during inhalation • Cocaine uses have a high incidence of perforated ulcers • Can cause ischemic colitis, intestinal infarction and metabolic acidosis. • Intestinal obstruction-consider body-packing

24. Cocaine • Differential Diagnosis includes • Amphetamine Abuse • Phencyclidine Abuse • Hypoglycemia • Hypoxia • Alcohol and sedative-hypnotic withdrawal • Neuroleptic malignant syndrome • Serotonin syndrome • Heat-related illness • Thyroid storm • Subarachnoid Hemorrhage • CNS Infections • Seizures • Psychiatric diseases

25. Cocaine • Treatment • ABC’s-Avoid succinylcholine for RSI • Cooling if hyperthermia present • Benzodiazepine • Phentolamine (only if hypertension refractory to benzodiazepine) • IV fluids • No β-Blockers

26. Heroin

27. Heroin Opium is crude substance isolated from opium poppy Opium has been used by humans since 4000 BC 1804-Friederick Sertürner isolated morphine 1874-Heroin (diacetylmorhine or morphine diacetate) synthesized by C.R. Alder White. Added two methyl groups to morphine isolated from opium

28. Heroin • Opioids activate specific transmembrane neurotransmitter receptors (μ,κ,δ) that couple G proteins. • Activation of endogenous μ opioid receptors results in effects of reward, withdrawal and analgesia. • 2.4 million people in US have used Heroin. • Heroin has a half-life of 30 min. • Duration of action 4-5 hours,due to active metabolites including morphine • Heroin is metabolized to 6-monoacetylmorphine (6-MAM) which is detectable on urine testing

29. Heroin • Symptoms • Depressed mental status • Decreased respiratory rate • Decreased tidal volume • Decreased bowel sounds • Miotic (constricted) pupils

30. Heroin • Treatment • ABC’s-Particular attention to airway and breathing • Naloxone-0.2-1 mg depending on symptoms. 2 mg if cardiopulmonary arrest. • Supportive care

31. PCP

32. PCP • Phencyclidine or1-(1-phenylcyclohexyl)piperidine. • 1926-first synthesized • 1952-patented by Parke-Davis and marketed as Sernyl. • It is a dissociative anaesthetic • Peak abuse was in the late 1970’s. 710 reported cases of PCP intoxication in the US in 2010. • Early 1970’s-ketamine was isolated as a derivative of PCP. It is 5-10% as potent as PCP

33. PCP • Three primary sites of action in CNS • N-methyl-D-aspartate (NMDA) receptor complex. • Dopamine, norepinephrine and serotonin reuptake complex • Sigma receptor complex

34. PCP • PCP binds to NMDA receptor complexes in the hippocampus, neocortex, basal ganglia and limbic system. • NMDA antagonism at these sites produces acute psychosis which mimics schizophrenia. • It also leads to excess excitatory neurotransmitter release (glutamate, aspartate and glycine) which can cause agitation and seizures. • Inhibits reuptake of dopamine, norepinephrine and serotonin in neurons. • These actions contribute to adrenergic and dopaminergic effects of acute intoxication • Sigma receptor effects may explain psychotic, anticholinergic and movement abnormalities seen with acute intoxication

35. PCP • PCP can be injected, insufflated, smoked and ingested • PCP displays first order pharmacokinetics. Half-life of 7-26 hours. • Primarily eliminated by liver • Presenting symptoms are very variable. Adrenergic stimulation is typical but patients may have CNS stimulation or depression. • Patients can progress to coma unexpectedly. • Tachycardia and hypertension are common.

36. PCP • Patients can be hyperthermic or hypothermic. • Psychomotor agitation is common as is violence. • Associated with • Rhabdomyolysis • Seizures • Hypoglycemia • Prolonged comatose state

37. PCP • Treatment • ABC’s • Benzodiazepines • Droperidol or Haloperidol for refractory psychosis • Barbiturate or Propofol for severe refractory psychomotor agitation or status epilepticus • Supportive care for associated symptoms i.e. rhabdomyolysis

38. LSD

39. LSD • Lysergic acid diethylamine • 1938-synthesized by Albert Hofmann • Originally marketed as anesthetic agent and adjunct for psychoanalysis • Causes altered thinking processes, closed and open eye visuals, synesthesia, an altered sense of time and spiritual experiences.

40. LSD • Usually ingested, although can be injected • Dose is usually 20-30 mcg • No documented deaths from intoxication • May temporarily impair judgment and understanding of common dangers, making the user more susceptible to accidents • Can cause dissociative fugue state with certain medications including lithium and tricyclic antidepressants

41. LSD • Treatment • Place patient in calm, safe environment • May use benzodiazepines • Avoid neuroleptics because they may worsen hallucinations and delusions • Rarely, other supportive care

42. Methamphetamine

43. Methamphetamine • Sympathomimetic amine and is a phenethylamine • 1893-First synthesized • 1923-Pharmaceutical formulations used to treat nasal congestion and asthma • Used in World War II to increase alertness and decrease fatigue • After cannabis, most widely abused drug in the world

44. Methamphetamine • Dextromethamphetamine is a stimulant. It is FDA-approved for treatment of ADHD and obesity. Trade name is Desoxyn. • Levomethamphetamine is CNS-inactive and used as non-prescription over-the-counter nasal decongestant • Methamphetamine has an additional methyl group compared to amphetamine which increases the lipophilicity and CNS activity of methamphetamine

45. Methamphetamine • It is an indirect neurotransmitter and lacks direct adrenergic effects • Incorporated into cytoplasmic vesicles where it displaces epinephrine, norepinephrine, dopamine and serotonin into the cytosol. • These neurotransmitters diffuse out of the neuron and into the synapse where they activate postsynaptic receptors • It also inactivates neurotransmitter reuptake transporter systems

46. Methamphetamine • These processes result in adrenergic stimulation. • The lone modulator of these effects is degradation by catechol o-methyl transferase (COMT) • Methamphetamine can be smoked, injected, insufflated, or ingested • Methamphetamine is eliminated by cytochrome CYP2D6 in the liver, other hepatic pathways and by the kidney

47. Methamphetamine • Signs • Diaphoresis • Hypertension • Tachycardia • Severe agitation • Psychosis

48. Methamphetamine • Patients may appear malnourished, agitated and disheveled • Violence is associated with intoxication • Can see hypervigilance and akathisia • Severe intoxication can lead to sudden cardiovascular collapse, seizures, altered mental status requiring intubation, rhabdomyolysis, cardiac ischemia, MI, cardiomyopathy and death

49. Methamphetamine • Treatment • ABC’s • Benzodiazepines • Antipsychotics (ziprasidone, droperidol, haloperidol) • Neuromuscular blockade with nondepolarizing agents for severe hyperthermia. No succinylcholine. • Other supportive care i.e. sodium bicarbonate, IV fluids, ACLS for cardiopulmonary arrest

50. MDMA