Illicit Drug Use in Medicine

1. Illicit Drug Use in Medicine Nithya Swamy Resident’s Conference October 7, 2008

2. Introduction • 4.7% of the world’s population participate in illicit drugs • In the US, of those 12 years or older • 8-9% of individuals in the US abuse illicit drugs • 46.1% have tried it in their lifetime • Drug use or drug withdrawal can be the cause of a presenting illness or it can mask an underlying illness • It is important to recognize the symptoms of drug intoxication and how to treat it

3. Goals of Presentation • Drug Use Stats in the US • How Drugs Work • Cases/Common Recreational Drugs • Street Lingo • Drug Effects • Management and Treatment

4. Drug Use in the US Drug use at least once in the last 30 days among those 12 and older • 22.5 million > 12y were classified with drug abuse or drug dependence. This includes tobacco, alcohol and illicit drugs. • 26% American Indian or Alaska Native • 12.2% for mixed races • 11.1% Caucasian • 10.2% Hispanic • 9.3% African-American • 6.0% Asian • Random Scary Fact: By eighth grade, 52 percent of teenagers have consumed alcohol, 41 percent have smoked cigarettes, and 20 percent have used marijuana.

5. Drug Use in the US • 25-40% of hospitalizations in the US involve substance abuse • 10-16% of outpatients have substance use problems • 16,000 deaths/year are due to illicit drug use whether directly or indirectly (HIV/AIDS, hepatitis, tuberculosis, homicides, and other violent crimes and incidental injuries) • Cost: $531 billion dollars annually ($181 billion in illicit drugs, $168 billion for tobacco and $185 billion for alcohol) • 527000 ER visits each year

6. Drug Use in the US • 6-7% of senior citizens admitted exhibit symptoms of alcoholism. Prevalence of problem drinking in the nursing homes is high as 49% • In this subpopulation, the majority are women. • They are more prone to dependence on prescription medications 2/2 overmedication by their own physicians • Opiods for pain and sedative/hypnotics for anxiety or insomnia • Random Scary Fact #2: Health care workers are at increased risk of addiction due to high stress jobs and access to drugs. • Anesthesiologists, surgeons, and emergency room physicians are at highest risk for drug dependence.

7. How Drugs Work • Acute Drug Use: • Release and Prolonged action of dopamine and serotonin within the reward circuit. • Reward Circuit (mesolimbic system) • Addictive drugs lead to the release of dopamine. Dopamine binds to D1 receptor triggering a signaling cascade that leads to a pleasurable response. • There is also a 2nd cascade activated involving a cAMP dependent PK which activated a CREB tf which when activated inhibits dopamine release. • In drug users this pathway is chronically active resulting in the need for larger doses to achieve the same pleasurable response.

8. DSM IV SUBSTANCE DEPENDENCIES 303.90 Alcohol 304.40 Amphetamines 304.30 Cannabis 304.20 Cocaine 304.50 Hallucinogens 304.60 Inhalants 305.10 Nicotine 304.00 Opiods 304.70 PCP 304.10 Sedative, Hypnotic or anxiolytic 304.80 Polysubstance dependence 304.90 Other (or unknown) substance

9. The Drugs

10. Alcohol

11. Short Term Effects • Euphoria: BAC = 0.03 to 0.12% • Lethargy: BAC = 0.09 to 0.25% • Confusion: BAC = 0.18 to 0.30% • Ataxia • Stupor: BAC = 0.25 to 0.40% • Anterograde amnesia • Coma: BAC = 0.35 to 0.50% • Death: BAC more than 0.50% • Alcohol->Acetylaldehyde->Acetic Acid->fats, CO2, Water • Death in the acute phase: • Alcohol poisoning and respiration depression, loss of gag reflex and asphyxiation • Wernicke encephalopathy: ataxia, ophthaloplegia, confusion and impairment of short-term memory. Lesions in the CNS & PNS. Heavy alcohol use interferes with thiamine breakdown. • Tx: Thiamine IV/IM

12. Long Term Effects • Brain • Impairs brain development and neurogenesis • Myopathy in the proximal muscles: 50% • Polyneuropathy • Wernicke-Korsakoff: • Korsakoff’s psychosis: progression from Wernicke’s; anterograde and retrograde amnesia, anisocoria, confabulation, ataxia, tremors & lack of insight. • Long-term tx with thiamine but at this point, may never return to their baseline. • Heart: • Dilated cardiomyopathy and CHF • Tx: ACE I, BB, Diuretics, or heart transplant • GI: mucosal damage • Inflammation of GI tract • Impairs esophageal motility, esophagitis, Barrett’s, esophageal Ca, Mallory Weiss • Steatohepatitis • Alcoholic hepatitis: Inflammatory response to fatty accumulation: jaundice, ascites, AST>ALT, encephalopathy, increased PT • Tx: cortiocosteroids, sometimes pentoxyfilline • Cirrhosis: fibrosis and altered architecture • Portal HTN: gastric & esophageal varices • Coagulopathy • Ascites, encephalopathy and hepatorenal syndrome • Tx: symptomatic: lactulose, vitamin K or FFP, nadalol

13. Alcohol Withdrawal • High mortality rate if not effectively treated. • Alcohol’s primary effect is the stimulation of GABA and promotes CNS depression • When abruptly stopped, the CNS undergoes uncontrolled synapse firing. • Leads to anxiety, shakiness, diaphoresis, insomnia, tachycardia, tremor and in more severe cases seizures & delirium tremens • DT: autonomic instability, hallucinations • Treatment: symptomatic and supportive: • Benzodiazepines followed by taper, vitamin and fluid replacement

14. Case • A 35 year old male presents to the ER and is hyperactive and tremulous. His girlfriend brought him in for AMS. He keeps saying he is “the authority of the human mind” and that because of that, people are trying to kill him. His girlfriend reports he has not slept much in days. • Physical Exam: • H: 5’9; 95lb. T: 103.6, HR: 115, BP: 178/110, • Pupils are equal but dilated, dry membranes with very poor dentition • CV: Irregular rhythm and tachycardic • What drug has he been taking?

15. Amphetamines

16. Common Amphetamines: (aka Pep Pills, Uppers, Rippers, Sparklers) • Amphetamine Sulphate: • Speed, benzedrine, bennies, sulph, whiz, billy • Dextroamphetamine: • Dexedrine, Dexy’s Midnight Runners, Dexies • Methamphetamine: • Methedrine, Crank, Crystal Meth, Ice, Meth, Redneck cocaine, Tina, Geek

17. Amphetamines are stimulants that increase levels of the neurotransmitters: norepinephrine, serotonin and dopamine. • It stimulates NT release and at high doses inhibits NT uptake • Routes: smoking, injection, snorting and rectally • Intoxication: • Short term: mydriasis, hyperactivity, increased physical activity, decreased appetite, tachypnea, tachycardia, irregular heartbeat, hypertension & hyperthermia. • symptomatic tx with benzos and antipsychotics • Long term: extreme weight loss, hypoglycemia, severe dental problems, anxiety, confusion, insomnia, intracerebral hemorrhage, mood disturbances, and violent behavior. Also, psychotic features, including paranoia, visual and auditory hallucinations, and delusions.

18. Overdose: • Sympathetic overload: diaphoresis, tachycardia, vasoconstriction, hypertension, hyperthermia • Hyperthermia and vasoconstriction can lead to rhabdomyolysis, renal failure, CV collapse & death. • Withdrawal: • 7 -10 days • Hypersomnia • Depression • Hyperphagia • Treatment: • No medications, primarily behavioral rehab

19. Chronic use: Noninvasive human brain imaging studies have shown alterations in the activity of the dopamine system that are associated with reduced motor performance and impaired verbal learning.Recent studies revealed severe structural and functional changes in areas of the brain associated with emotion and memory

20. Case • A 37 yo female presents drowsy and disinhibited. She keeps trying to get out of bed and when she does, she is staggering. She is difficult to understand as her speech is slurred and she is obviously confused. She becomes more somnolent and soon becomes difficult to arouse. He breathing decreases and she requires intubation. Her husband says “she takes some pills everyday. She has to take them because if she stops, she has a fit” • PE: • T: 95, P: 85, R 18, BP: 76/50 • Eye: lateral nystagmus • What kind of drug is she on?

21. Barbiturates

22. COMMON BARBITURATES: • Amobarbital: • Downers, blue heavens, blue velvet, blue devils • Pentobarbital: • Nembies, yellow jackets, abbots, Mexican yellows • Phenobarbital: • Purple hearts, goof balls • Secobarbital: • Reds, red birds, red devils, lilly, F-40s, pinks, pink ladies, seggy • Tuinal: • Rainbows, reds and blues, double trouble, gorilla pills, F-66s

23. Barbiturates are CNS depressants: mild sedation and anesthesia. • Anxiolytics, hypnotics and anticonvulsants • Potentiates inhibitory GABA receptor and a glutamate receptor • Upregulates CYP 450 in the liver • Routes: Oral and IV/IM • Sx: Respiratory depression, hypotension. Fatigue, hypothermia, irritability, dizziness, sedation, lateral & vertical nystagmus, confusion and ataxia. • Drug users often abuse barbiturates to counteract the symptoms of stimulants like cocaine or meth • Commonly abused barbiturates are short acting

24. Overdose can lead to respiratory failure and death • Tx: symptomatic and charcoal • Withdrawal: 12-20h after the last dose. Symptoms include anxiety, irritability, elevated heart and respiration rate, muscle pain, nausea, tremors, nightmares, insomnia, vivid dreams, hallucinations, confusion, and seizures • Tx: stabilization with an intermediate acting barbiturate like pentobarbital. Newer techniques involve loading doses of phenobarbital titrated to the clinical or toxic effects. Eventually they require a gentle taper and rehab

25. Case • A 45 year old physician presents complaining of anxiety, palpitations and profuse sweating. He did not sleep the night before. He has his sunglasses on and he’s asking you to whisper b/c anything louder hurts his years • PE: He seems anxious and agitated. • T:98.6, P: 110, R: 33 BP: 150/95 • What drug is he withdrawing from?

26. Benzodiazepines

27. COMMON BENZODIAZEPINES: • Alprazolam (Xanax) • Lorazepam (Ativan) • Clonazepam (Klonopin) • Diazepam (Valium): Valley Girl • Triazolam (Halcion) • Street Names: BZDs, Benzos, Downers, Goofballs, Heavenly Blues, Robital, Stupefy, Tranx

28. Psychoactive drugs with hypnotic, sedative, anxilytic, anticonvulsant, muscle relaxant and amnesic properties mediated by slowing of the CNS. • Tolerance develops quickly and higher doses are required to achieve the same effect. • Often, by 4-6 months, benzos have little efficacy • Benzodiazepines can give rise to physiologic and psychologic dependence based on the drug's dosage, duration of therapy and potency. • Benzos are rarely the sole drug of abuse. An estimated 80 percent of benzodiazepine abuse is part of polydrug abuse, most commonly with opioids.

29. Overdose: respiratory depression, hallucinations, coma. Mortality rates are not as high as barbiturates • Tx: supportive; flumazenil is used only for severe cases, as it can cause acute withdrawal and subsequent seizures. • Flumazenil should only be used if Benzodiazepines is the only drug of abuse. • Withdrawal: Anxiety, tachycardia, hypertension, diaphoresis, insomnia and sensory hypersensitivity. • Tx: Taper with a longer acting benzo like chlordiazepoxide

30. Case • A 26 year old male presents to the ED complaining of progressively worsening productive cough and shortness of breath for 3 days. He does have chest pain but attributes it to his persistent cough. His sputum is productive of white foamy sputum. • When you are assessing him, his breathing becomes more labored and eventually he has to be intubated. He progressively becomes hypotensive and requires pressors. An TTE is done at the bedside and reveals severe dilated cardiomyopathy with an EF of 15%. • What is the offending drug?

31. Cocaine

32. Common Street Names: • Blow, C, California Cornflakes, Nose candy, Coke, Columbian foot soldiers, Flake., Lady C, snowball, tornado, wicky stick, Showbiz Sherbert, White Lady, Shnazzle • Routes: • Freebase: smoking the base form of cocaine. Absorbed directly into the bloodstream from the lungs. Rush is more intense than snorting. • Crack/Cocaine: smokable. Freebase form of cocaine that is made from a reaction between cocaine and sodium hydroxide. • Insufflation (snorting, sniffing, blowing) • Oral: rubbed along gum line: "numbies", "gummers" or "cocoa puffs"

33. Strong CNS Stimulant: increase levels of dopamine through the reward circuit • Acute: • Moderate amounts: vasoconstriction, dilates pupils, hyperthermia, tachycardia, hypertension, euphoria • Large amounts: Intensify the user’s high, but may also lead to bizarre, erratic, and violent behavior. Arrhythmias, tremors, vertigo, muscle twitches, paranoia, or with overdose, cardiac and respiratory arrest • Chronic: • bronchospasm, pruritus, fever, diffuse alveolar infiltrates without effusions, dilated cardiomyopathy, stroke, MI, degradation of septum nasi, shortness of breath, tooth decay, renal failure • Withdrawal • Depressed mood, Fatigue, Generalized malaise, Vivid and unpleasant dreams, Agitation and restless behavior, Slowing of activity and Increased appetite • Low to non-existent mortality; high risk of relapse • Treatment: • Supportive, behavioral treatment and detox

34. Cocaine and ACS • Risk of MI is increased 24-fold in the 1st hour after cocaine use. • 6% of patients with cocaine-associated chest pain are having an AMI. • An additional 15% meet the criteria for ACS. • Ischemia may be delayed for up to 24 hrs after use. • Acute: • Vasoconstriction • Immediate and delayed coronary vasoconstriction • Vasoconstriction may be worsened if cocaine is used with tobacco • Hypercoaguability • Platelet activation & aggregation • Increased oxygen consumption • Chronic: • Early atherosclerosis and coronary ectasia • Cardiomyopathy • EKG: may be normal, non-specific or show ST changes • 56-84% of patients will have an abnormal EKG. • Up to 43% meet EKG criteria for reperfusion therapy.

35. Case • A 17 year old female presents to ED with altered mental status. She has rapid speech and discussing her important role in the universe. She is trying to hug/kiss/grope your male resident. • PE: • T: 105, P: 120 R: 25, BP: 140/90 • Difficult to assess as she can’t stop moving, but you do note she grinding her teeth. • Her lab values are significant for a Na 115 and a Cr 2.0

36. MDMA

37. Common street names: • Ecstasy, Adam, Beans, Ex, hug drug, Jack and Jills, Mandy, Smartees, Sweets, Vitamin E • Routes: oral as capsule or tablet • Semi-synthetic member of amphetamines • Sub-class of phenylethylamines • Considered a stimulant, psychedelic, empathogen (emotional lability) • Affinity for SERTs (serotonin transporter) • MDMA inhibits the reuptake of serotonin and it reverses the action of the transporter so that it begins pumping serotonin into the synapse from inside the cell • Stimulates norepinephrine and dopamine release

38. Acute: • Euphoria, decreased anxiety, intimacy, decreased appetite, urinary retention, pupil dilation, increased energy, tachycardic, hypertensive, also, oral fixation such jaw clenching and teeth grinding. • Danger signs: Hyperthermia, Dehydration, Hyponatremia and Serotonin syndrome • Chronic: Serotonergic change • Overdose: Serious adverse events in MDMA users may be an interaction of the drug with a preexisting medical condition. • Risk of adverse event after MDMA consumption is thought to be increased by preexisting cardiovascular problems, such as cardiomyopathy, hypertension, viral myocarditis, and congenital cardiac conduction abnormalities • Neuro: subarachnoid hemorrhage, intracranial bleeding, cerebral infarction due to MDMA-induced increases in blood pressure may occur in people with preexisting congenital AVMs or cerebral angiomas. • Hyperpyrexia: resulting rhabdomyolysis and renal failure • Hyponatremia: Convulsions • Tx: SSRIs prevent neurotoxicity. Symptomatic with benzos or dantrolene

39. Case • A 42 year old cachectic male presents with a RR of 4 and is unresponsive. His pupils were constricted but reactive. The paramedics gave him a medication in which he woke up and reported he took some “cheeba”. Later, he reported he was freezing and had rigors. He also had diffuse abdominal cramping, vomiting and persistent diarrhea. • Name that drug!

40. Heroin

41. Common Street Names: • Black, Brown Sugar, Cheeba, Diesel, Hero, Horse, Junk, Lady H, Poppy, Smack • Routes: • IV • Insufflation • Smoking • Other: Speedball or snowball • Cocaine plus heroin leading to a more intense rush than one alone

42. Synthetic opiod synthesized from morphine • Crosses blood brain barrier, is converted to morphine and binds opiod receptors • Symptoms • Injection leads to rush of euphoria followed by dry mouth, periods of wakefulness and sleep, mental slowing. Other routes have the same symptoms without the intense rush • Risks: • Infections, HIV, Hepatitis, • collapsed veins, endocarditis, pericarditis • renal insufficiency • chronic constipation • pulmonary complications (pneumonia, respiratory depression). • Vascular and organ damage from toxic contaminants in the heroin

43. Overdose: Respiratory depression, constricted pupils, hypotension, coma, delirium, muscle spasticity • Treatment: Naloxone or Naltrexone • Withdrawal • Occurs 6-24h after last dose • Rebound hyperactivity of the sympathetic nervous system • Sweating, malaise, anxiety, depression, cramps, excessive yawning or sneezing, insomnia, chills, rigors, vomiting, diarrhea, restless leg • Tx: • longer-acting opiod such as methadone or buprenorphine. • Benzos can be used for symptomatic treatment of anxiety, insomnia and muscle spasms. Loperamide is used for diarrhea and Clonidine for hypertension.

44. Prescription Opioids • Commonly abused prescription opioids • OxyContin • Hydrocodone • Methadone • Morphine • Hydromorphone • Fentanyl • Buprenorphine • Similar symptoms to heroin but lack heroin’s potency and therefore its severe intoxication and withdrawal.

45. Case • A 35 year old male presents with a knife in his left shoulder. He does not seem to be in pain, but is very agitated and has to be restrained. According to the police, he started a fight by attacking a large group of people. On admission, he continuously yells the aliens are going to abduct him and that they are talking to him through the TV. • PE: T: 98.6, P: 122, R: 28, BP: 185/115 • Diffusely erythematous • Subconjunctival hemorrhage, Dilated pupils, non-reactive • Dry mucous membranes • Does not withdraw to pain

46. PCP

47. Common Street Names • angel dust, illy, water, BrainTree, fry, dumb dust, rocket fuel, cake, nature boy, love boat, elephant tranquilizer cornbread, Hairy Jerry, George Jefferson • Routes: • Powder: insufflated • Liquid: dipped on cigarettes and marijuana and smoked. IV/IM as well.

48. Dissociative drug causing hallucinogenic and neurotoxic effects. • Blocks conscious mind from other parts of the brain. Depersonalization, derealization and anesthesia. • NMDA receptor antagonist similar to ketamine and dextromethorphan. • Anesthetic • Associated with memory deficits, psychotomimetic effects similar to psychosis. Confusion, difficulty concentrating, agitiation, nightmares, catatonia and ataxia • Effects: • Acute: Diaphoresis, HTN, tachycardia. Also, numbness in the extremities and intoxication, characterized by staggering, unsteady gait, slurred speech, bloodshot eyes, and loss of balance. More prone to physical injury as they can’t feel pain. • Psych: resembles schizophrenia: unpredictable and driven by their delusions. Auditory hallucinations • RED DANES: Rage, Erythema, Dilated pupils, Delusions, Amnesia, Nystagmus, Excitation, Skin Dry. • Rarely, cardiac failure can result.

49. Case • A 68 year old female presents to the ED. She reports seeing “beautiful colors swirling around” as well as being able to “smell the lovely music”. She otherwise will not answer any questions. • PE: T: 94.7, P 50, R 18 BP 120/80 • Drooling, staring at something/nothing in the air. • Pupils dilated but sluggishly reactive • Neuro: Reflexes are 4+ bilaterally • And the drug is……

50. LSD