Transcript Drug induced coma & Party drugs by Dr ML Tse

Drug Induced Coma
&
Abusive Drugs
Dr. ML Tse
Basic Concept
• Brain activity = Interplay of neuron
depolarization
• Ion channel activities
• Voltage-gated IC & Ligand-linked IC
• Opening / Closing Production /
Destruction control by receptor activites
Molecular Basics
• Receptors
– Ligand linked ionophore
– G-protein coupled  Cyclase activation  ion
channels
– Steroid hormone receptors  DNA
– Tyrosine kinase receptor (Insulin, growth
factors)
Cellular Basics of
Neurotransmission
• Neurotransmission
+/--  Ionophores
Na,Ca,
K, Cl
Depolarization
Repolarization
Rest
-70mV
Cellular Basics of
Neurotransmission
• Neuromodulation
– Receptor mediated
– Non-receptor mediated NO,
CO
Basic Neuropharmacology
• Amino Acid Transmitters
major CNS transmitters
– Excitatory
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• Purinoreceptors
• Inhibitory
Glutamate (Glu)
Aspartate
Cystate
Homocystate
– Inhibitory
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-aminobutyric acid (GABA)
Glycine
Taurine
-alanine
• Adenosine
Glutamate Receptors
• AMPA (-amino-3hydroxy-5-methyl-4isoxazole propionate)
• NMDA (N-methyl-Daspartate)
• Kainate
• mGlu: Metabotrophic
receptor
N-methyl-D-aspartate Receptor
GABAA Receptor
Convulsant
Glutamate
Glutamic
Acid
Glutamic acid decarboxylase
Pyridoxal Phosphate
Hydrazines
Isoniazid
GABA
Adenosine Receptor
• Diffuse CNS Inhibition
“Blake” effect
• Sleep induction
• Endogenous anticonvulsant
• xanthines
antagonist
Serotonergic Pathways
• 5 HT
Raphe pons
– Midline of pons
– locus ceruleus,
interpeduncular nucleus
– Pacemaker like 1—5
spikes / sec
– Inhibitory modulation
– 2 systems: fine axons and
beaded large axons
– Fine 5HT axons damage
by MDMA
– Pineal gland
NE pathways
Locus Ceruleus
• Locus Ceruleus in caudal
pons
• 5 major tracts
• ,12, 1
•  Morphine, endorphins,
• 2 agonist (clonidine)Firing
• Amphetamines, TCA,
Opioid withdrawal Firing
• Global orientation to
external stimuli
Dopaminergic Pathways
Putamen
caudate
Prefrontal cortex
ventral tagamental
limbic
Substantia nigra
• Complex : utra short ;
intermediate length; long
systems-midbrain to
neostriatum and limbic
system
• D1 – 5 R
• Learning behaviour,
memory, motor
• ?Final common pathway
for addiction
• Amphetamine, cocaine 
antipsychotics 
Cholinergic Pathways
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Poorly understood
Acetycholine
Diffuse innervation
Cognition,
consciouness
• Anti-cholinergics,
organophosphates
• Alzheimer’s ?choliner
gic dysfunction
Consciousness
Background Arousal
Prefrontal cortex
Limbic system
Sensory Afferent
Hyppocampus
Basal Ganglions
Efferent
Drug Induced Coma
• Direct effect on neurons
– Receptor mediated
– Non-receptor mediated
• Secondary Insult due metabolic
disturbance
– Seizure, coma, death as the final common
pathway of intoxication
Management
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Decontamination: ?cyanide
ABC, prevent secondary insult
H’stix
History
Toxidrome:
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Focal signsCT brain
Opioid, DUMBBELL, Serotonergic, Anti-cholinrgic,etc, convulsants….
Trial of naloxone
Stable unconscious Vs Unstable Unconscious
ECG: rate, QRS, QTc
Therapeutic use of other antidote
• ABG: ?MUDPILE; Osmolar gap,
– Lactic acidosis with normal PaCO2 ?cellular asphysants
• Panadol level-co-ingestion?1 in 500
• CXR, AXR
• ??Urine screening
• Supportive
Abusive Substances
Sedative-Hypnotics
• Benzodiazepines (since 1955)
– GABAA R agonist Cl channel sedative,anxiolytic,
muscle relaxing, amnesic
– Peripheral benzodiazepine receptors (whole body):
mitochondrial outer membrane – adrenal, pituitary,
reproductive, heart ; RBC
• GHB -hydroxybutyrate (since 1960s)
– Bodybuilding, Mood-enhancer, Date-rape
– Receptor in basal ganglion
–  GH, enkephalin dopamine
Benzos OD
• Sleep like toxidrome
• Children: ataxia
• Paradoxical CNS effects: delirium, psychosis,
nightmares with age
• Death due to combined overdose
• Dx co-ingestion & supportive Mx
• Routines screening not helpful:
– False –ve:
• active metabolites,
• triazolam & aprazolam: low active serum concentration
• Flunitrazepine, clonazepine –ve immunoessay
– +ve result:
• Co-ingestion common
• Co-morbidity
BenzosOD
• Routine flumazenil not recommended
• Contraindications:
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Seizure Hx
Co-ingestion
Long term user
ECG evidence of TCA
Abnormal vitals
• Withdrawal
– Anxiety, panic attacks, headache, tremors,
paresthesia, seizure
GHB
• Toxidrome: cyclical coma:deep
coma/agitated episodes, resp depression,
rigidity, myoclonus face limbs, bradycardia
• Typically pull out the ET tube and fully
awake in 6 hrs
• Flumazenil not consistent
• Withdrawal?
Party Pills
Opioid
• Opium, extract of poppy (Papaver somniferum)
contains ≥10% morphine
• Heroin (diamorphine) since 1874, marketed by
Bayer 1898, preferred : euphoric, rush
Opioid Receptors
• : euphoria, analgesia, respiration
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: miosis, spinal analgesia
: ?analgesia, dopamine nigrostriatal
: not considered as opioid R,
,: ??
G-protein linked
Euphoria, addiction : Dopamine release &
-R stimulation in mesolimbic system
Clinical Presentation
• M & M more due to IV use, cutting agent,
contaminant, poor health
• Overdose:
– Typical toxidrome
• Fentanyl: muscle rigidity, urine screen -ve
• Dextromethorphan: anti-cholinergic
• Methadone: choreoathetosis
– pulmonary edema
• Direct effect
• Neurogenic: acute withdrawal on naloxone, high PaCO2
• Forceful inspiration against closed glottisnegative
intrathoric pressure
• Withdrawal
• Bodypacker
Pitfalls in Mx
• Urine immunoessay
– +ve codeine, poppy seed
– --ve synthetic opioid
• Naloxone
– Bag-valve mask ventilation
– Small incremental dose
0.1mg
– Adequate respiration as
end-point
– Infusion: 2/3 effective bolus
/ hour
Party Drugs
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Amphetamines
LSD
Ketamine
Cocaine
Nematazepam
Clinical Presentation
• Acute
– Bad trips
– Injury
– Specific problems related to the substance
• Chronic
– Poor immune, poor health
– Psychiatric: brain damage?
Party Pills
• Ecstacy
– May or may not
contains MDMA
– ketamine, MA,
barbituate,
benzo, panado
– Different strength
• Unpredictable
effect
Trip
Good Trip
Bad Trip
Amphetamines
• Speed sulph, uppers,
whizz: powder form
• Ice: crystalized form
of metamphetamine
epinephrine
Methamphetamine
amphetamine
Amphetamines
• 179 entries of
designer
amphetamines
Phenylethylamines I Have Known And Loved
Amphetamine
• Presynaptic Dopamine and Catecholamine
release
• Peripheral  and  Sympathomimetic
• Central:
– NE  Alertness
– DA Glu behavioral and psycho
– 5-HT (high dose) thermoregulation,
psychosis
MDMA
( 3,4methylenedioxymethamphetamine)
MDMA
serotonin
MDMA
• Ecstasy, XTC, Adam
• Stimulant(amphetamine) + mild
hallucinogenic (weak LSD)
Clinical Presentation
• Tweaking
Clinical Presentation
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Heat stroke
Intracerebral haemorrhage
Dysrrhythmias
Cerebral infarct
Myocardial ischaemia
Pneumothorax, pneumomediastinum
Hyponatraemia
Rhabdomyolysis
Injury
Fine-5HT neuron damage in braincognitive, psychiatric,
behavioral problem
Rx
• Benzodiazepine: usually at toxicological
dose
• Haloperidol
• Minimize physical restrain
• Cooling
Cocaine
• Leaves of coca plant
in S. America
• Use in religious rituals
since 6th century
• Identified in 1857
• Add in Coca-cola
• >6 Million >12y.o.
Americans had tried
Cocaine powder
Crack cocaine
Cocaine
• Fast Na channel blockage
• Catecholamine reuptake inhibition
• CNS stimulation: cortexbrain stem
– DA reuptake inhibition
–  excitatory amino acids
• Activemetabolites: benzoylecgonine,
norcocaine
• More dangerous with alcohol
Clinical Presentation
• Hyperthermia
• Myocardial ischaemia, dysrhythmia, aortic
dissection
• ICH, Cerebral infarction, seizures
• PneumoT / M, Pulmonary edema
• Rhabdomyolysis
• Gut ischaemia
• Cardiomyopathies
Cocaine
• Benzo for agitation, HT
• IV Nitrate, phentolamine,
morphine,verapamil for ACS
• Diltiazem, Verapamil for atrial arrhythmia
• NaHCO3, lignocaine, amiodarone for
ventricular arrhythmia
• Torsade (K channel blocking): MgSO4
Hallucinogens
• Lysergamids
– LSD: D-lysergic acid diethylamide
• Indolealkylamines
– Ibogaie
– Psilocybin
• Phenylethylamines
– Mescaline, MDMA
• Tetrahydrocannibinoids
– Marijunana
– Hashish
• Anticholinergics
– Jimsonweed(Datura stramonium)
LSD
• 1938 by Albert Hoffmann, popularized in
60s
• 5-HT2 antagonist – diminish filtering of
sensory input  hallucination
• Glutamate ,D1, D2
• Indirect sympathetic stimulation in locus
ceruleus
• Psychological effect varies on dose,
emotionexpectations, environment.
LSD
• In the form of
blotting paper
• “Fing-Ba”
Clinical Presentation
• Bad trip: panic reactions, frightening
illusions, sense of loss of self-control
• Hyperthermia
• Mydriasis, HT, tachycardia, diaphoresis–
usually less severe
• Mx:
– Benzodiazepine +/-- haloperidol
– Minimize physical restrain
– Rx hyperthermia and rarely rhabdomyolysis
Ketamine
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Related to Phencyclidine (Angel dust)
Dissociative anaesthetic
Microwaving Ketelar
Out-of body feel
NMDA blockage
Biogenic amine reuptake blockage:
–  NE
–  DA
• Ketamine inhalation
device
• Ketamine powder
Clinical Presentation
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Psychomotor disturbance
Delirious to comatose
Nystamus
Vomiting
Injury
Sympathetic / muscarinic symptoms
Mx: Benzo +/-- Haloperidol , quiet environment
Brain damage– Olney’s lesion: NMDA antagonist
neurotoxicity.