Substance abuse. Eran Kozer MD Pediatric Emergency Medicine Assaf Harofeh Medical Center

Transcription

1 Substance abuse Eran Kozer MD Pediatric Emergency Medicine Assaf Harofeh Medical Center

2 Outline Case presentation Ethanol Marijuana Opioids Cocaine Amphetamines Designer drugs LSD & other hallucinogens PCP and ketamine

3 Outline Pharmacology (brief) Clinical aspects No discussion of treatments

4 Case Presentation At 4 am a 17 year old boy was found by his parents in his bed with generalized tonic clonic seizures. Taken to the ED (still seizing) P 114 bpm, temp C RR 20/min, BP 103/70 mm Hg, O 2 sat 97%.

5 History of complex partial seizures starting at 10 years of age Treated with carbamazepine Seizure free for 5 years Off medications for the last 2 years

6 No recent febrile illness or trauma No petechiea or needle pricks Parents were not aware of substance abuse Lab normal glucose and electrolytes Bicarbonate 13 mmol/l, Anion gap 32 mmol/l, osmolal gap - 26mmol/kg

7 DO you think the boy s symptoms were caused by substance abuse? A Yes B No C Can't tell

8 Which tests will you order? Urine tox screen Ethanol serum level Non of the above

9 Ethanol Rapid absorption from GI tract (<60 min) One standard drink (15g ethanol bottle of beer, glass of wine, 30 ml liquor) raises ethanol serum level by 36mg/dl Enhancement of GABA activity in GABA receptors Blockade of NMDA (N-methyl-D-aspartate) receptors

10 Ethanol level was 50 mg/dl

11 Clinical manifestations low dose Selective CNS depressant at low doses Depress areas of highly integrated functions Loss of restrains & disinhibition Paradoxical stimulation Emotional liability Basic personality features are enhanced

12 Clinical manifestations high dose General CNS Depressant at high dose Irritability Abusive behavior and aggression Confusion, dysarthria, disorientation, lethargy Loss of protective reflexes Coma (blood ethanol >300 mg/dl) Death

13 So, is it a mixed overdose? Which of the following drugs may cause seizures? Marijuana? Yes No

14 Marijuana Active ingredient THC Immediate effect when smoked Peak effect min Duration 1-4h Binding to specific cannabinoid receptors in the cortex

15 Marijuana Clinical effects Alteration of sensation, perception, cognition, psychomotor functions Euphoria, relaxation, sensory alterations Loss of motor skills and judgment Acute psychosis (not common) Seizures - rare

16 Marijuana Physiological effects Increased heart rate Hypotension/ hypertension Tremor, muscle weakness Bronchodilation Conjunctival injection Increased appetite Urinary retention

17 Marijuana Chronic heavy users Effects on the lungs Tolerance Dependence (psychological and physiologic) Withdrawal symptoms (sleep disturbances, irritability, nausea, decreased appetite)

18 Back to the case Treated with benzodiazepines and phenytoine. Seizures stopped after 1 hour CT Scan ordered

19 27-year-old man found at home with decreased level of consciousness, aphasia, and spastic quadraparesis Axial CT scan obtained through brain at level of third ventricle shows symmetric white matter hypoattenuation in optic radiations and posterior limbs of internal capsule, simulating dragon's claws. Keogh, C. F. et al. Am. J. Roentgenol. 2003;180: Copyright 2007 by the American Roentgen Ray Society

20 which substance did he use? Cocaine Marijuana LSD Heroin

21 Chasing the Dragon Inhalation of heated heroin Pharmacokinetic similar to IV Spongiform leukoencephalopathy Initial symptoms may occur after 2 weeks Bradykinesia, ataxia, speech abnormalities Spasticity or hypotonia Death in 25% of the cases

22 Opioids Extract of poppy plant Available in various formulations administration by all possible routes (parenteral, oral, transdermal, transmucosal, intranasal, rectal, inhalation)

23 Brief History Written evidence of opium use from 1500 BC 1804 morphine isolated 1830 s Opium Wars between China and England 1874 Heroin synthesized (marked by Bayer as antitussive agent)

24 1874 Heroin synthesized (marked by Bayer as antitussive agent)

25 Terminology Opiate alkaloid derived directly from poppy opium (morphine codeine) Opioids agents that are capable of producing opium like effect by binding to opioid receptors

26 Clinical effects CVS peripheral vasodilatation Orthostatic hypotension Flushing GI Reduced motility Reduced gastric acid secretion Increased sphincters tone

27 CNS Sedation coma Seizures (pethidine) Antitusive Respiratory Respiratory depression Bronchospasm Pulmonary edema Other Miosis Pruritus

28 Back to the case The CT scan was normal Slowly recovered Occasional myoclonic jerks Denies substance abuse

29 ?

30 Cocaine Leaves of Erythroxylon Coca Documented use from the 6 th century Local anesthetics solutions

31 "...This Intellectual beverage contains the valuable NERVE STIMULANT and TONIC properties of the coca plant...

32 Pharmacology Mucosal absorption respiratory gastrointestinal Genitourinary (vagina, urethra) Onset of action 1-3 min peak min Intravenous / Smoking Onset of action - seconds peak 5 min

33 CNS Effects CNS stimulation cortex first Restlessness, excitement, increased motor activity Mediated at part by inhibition of dopamine reuptake Lower motor centers Seizures

34 CNS Effects TIA Increased risk of stroke Subarachnoid hemorrhage Dystonic reactions Migraine type headaches Leukoencephalopathy Cerebral vasculitis Psychiatric manifestations

35 Other clinical manifestations (partial list) Hyperthermia Myocardial ischemia Dysrhythmias Cardimyopathy (dilated) DVT Pulmonary effects (asthma exacerbation pneumothorax, hemorrhage etc.)

36 Amphetamines Methamphetamine (crack, speed) 3,4 Methylenedioxymethamphetamine (MDMA) - Ecstasy Designer Amphetamines

37 Khat (gat) Cathinone

38 Amphetamines Clinical manifestations Stimulation of adrenergic receptors in the CNS and peripheral nervous system Similar to cocaine but tend to be longer

39 Amphetamines setting Rave parties Speed runs (days up to weeks)

40 Amphetamines CNS effects Agitation Seizures (less common than cocaine) Intracerebral hemorrhage Headache Euphoria Anorexia Bruxism

41 Amphetamines CNS effects Choreoatheotid movements Compulsive behavior Hyperreflexia Hyperthermia (central)

42 Amphetamines CNS effects Paranoid psychosis Dopaminergic activity Tend to reoccur May lead to suicide and homicides

43 Amphetamines Other effects CVS Hypertension, tachycardia, dysrhythmias, MI, aortic dissection, vasospasm Diaphoresis, tachypnea, mydriasis, tremor, nausea.

44 Amphetamines Other effects Rhabdomyolysis, muscle rigidity Acute lung injury Ischemic colitis

45 Amphetamines lab abnormalities Leukocytosis Hyperglycemia Hyponatremia Elevated CK Elevated liver enzymes Myoglobinuria

46 Designer drugs Legal highs Designed by pharmacists to bypass legislation Not included in the Dangerous Drug Ordinance Sold over the internet Street shops

47 Other phenethylamines (2C drugs) Synthetic cannabinoids Synthetic cathinones (bath salts) Piperazines

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49 Phenethylamines (2C drugs) A clinical picture of both stimulatory and hallucinogenic effects Tachycardia, hypertension, euphoria, agitation, psychosis, and hallucinations Other effects seen with serotonergic and sympathomimetic toxicity No data on long term effects

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52 Paramethoxymethamphetamine (PMMA), a hallucinogenic synthetic substituted amphetamine Was marketed in Israel because it was not included in the Israeli Controlled Substances Act (CSA).

53 PMMA and paramethoxyamphetamine (PMA) belong to a group of methoxylated phenethylamine derivatives PMA enhances the release of serotonin, inhibits its reuptake and metabolism Little effect on the dopaminergic system PMA has monoamine oxidase (MAO)-A inhibitory properties.

54 Clinical effects Tachycardia Hypertension Hyperthermia Nystagmus Muscle spasm Bruxism Visual hallucinations Cardiac arrhythmias Respiratory failure Renal failure Seizures Death In fatal cases hyperthermia with a core temperature ranging between 39 and 42.8 C

55 Synthetic cannabinoids

56 Synthetic cathinones (bath salts)

57 Piperazines Initially developed as antihelminthic drugs but later studied as antidepressants Piperazines are some of the most common active substances found in drugs purchased on the Internet. Typical users are young males

58 Piperazines Most symptoms with piperazine use resemble a sympathomimetic toxidrome Insomnia, anxiety, headaches, nausea, tremors, shakiness, diaphoresis, dizziness, palpitations, shortness of breath, confusion, hallucinations, and paranoia.

59 Since all of the above may cause seizures what is the next step? Toxicology screen: blood? Toxicology screen: Urine?

60 Toxicology screen: blood Volatile alcohols Acetaminophen Salycilates Others

61 Urine toxic screen Immunoassays: most common but non specific

62 Cannabis metabolites, Cocaine metabolites, Opiate metabolites, Metahdone Amphetamines, Metamphatamines PCP GHB Benzodiazepines, barbiturates TCA

63 Urine toxic screen HPLC (High Pressure Liquid Chromatography) - more than 700 toxins can be identified GCM

64 Drugs that may be missed by toxicology screen LSD Fentanyl Lorazepam Ketamine GHB...

65 LSD & other Hallucinogens Acts on serotonin receptors in the CNS Lysergic acid & derivates Phenylethylamines

66 Other hallucinogenic agents Anticholinergics belladonna alkaloids MDMA Mushrooms

67 LSD & other Hallucinogens Physiologic effects Mydriasis, tachicardia, hypertension, tachypnea hyperthermia, diaphoresis, (mild) Nausea and vomiting Precede hallucinogenic effects

68 LSD & other Hallucinogens CNS effects Dizziness Hyperactivity Muscle weakness Ataxia Altered mental status Coma Hippus (spasmodic rhythmical pupillary dilation and constriction)

69 Psychological effects Usually fully awake Emotional liability Loss of body image Alteration in visual perception Excessive attention to details

70 Psychological effects Usual thoughts may look novel and profound Intensification of sensory perceptions (colures are brighter, sound magnification) Synthesis (hearing colures )

71 Acute psychiatric effects Acute panic reaction (most common) Psychosis Major depression

72 LSD - Long term effects Prolonged psychosis Severe depression Exacerbation of preexisting psychiatric disease

73 Hallucinogen Persisting Perception Disorder (HPPD) Flashbacks (usually of former hallucinogenic experience) May be triggered by stress or illness Few month to 5 years No established treatment

74 Dissociative agents Initially developed as anesthetic agents PCP (phencyclidine) Ketamine

75 Dissociative agents - pathophysiology NMDA receptors in the cortex and limbic structures Antagonize (not competitive) glutamate action Monoaminic reuptake inhibition σ (sigma) receptors Ach receptors

76 Available forms PCP - powder, liquid, tablets, leaf mixture (for smoking), rock crystals Ketamine powder, tablets, liquid; rarely used IV

77 Clinical Manifestations Sympathomimetic effects Hypertension Cerebral hemorrhage (rare) Vomiting (marijuana) Both cholinergic and anticholinergic effects (miosis or mydriasis, bronchospasm, hypersalivation)

78 Clinical Manifestations - CNS Nystagmus Ataxia & altered gait Diplopia Dystonic reactions Myoclonic movements Tremor Seizures (rare)

79 Clinical Manifestations CNS Diminution of sensory modalities Depersonalization, hostility Alteration of body image Dissociation calm; agitated; stupor; delirium; apathy; coma

80 Few words on treatment Don t forget the ABC s Check bedside glucose if the patient is obtunded Thiamine? for ethanol intoxication not routinely used in teenagers Naloxon Other antidotes rarely used

81 What you see may be just the tip of the iceberg