Pharmacology of MDMA, Ketamine and · PDF fileContents Pharmacology of MDMA, ketamine and...
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Pharmacology of MDMA, Ketamineand Methamphetamine
By
Kenneth KC Lee BS(Pharm), MPhil, PhD
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Contents
Pharmacology of MDMA, ketamine andmethamphetamine :
1. Mechanism of action and pharmacokinetics
2. Toxicities and adverse effects
3. Abuse
4. Summary
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MDMA
• Full name : 3,4-methylenedioxymethamphetamine• Street names : Adam, E, Ecstasy, M&M, XTC,
“Fing Tao” etc• A “rave-party” drug• Pharmacological classification : a phenyl-
ethylamine compound structurally related toamphetamine with CNS st imulat ion andhallucinogenic effects
• Legal classification in HK : Dangerous Drug
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Pharmacology
• Major mechanism of action : by centralstimulation and a rapid and brief liberation ofnoradrenaline from peripheral adrenergicterminals → sympathomimetic effects
• recent findings : mechanism of action could berelated to a serotonin-depletion effect* →“serotonin syndrome”
* Fleckenstein, Gibb, Hanson, Eur J Pharmacol, 2000
Wallace, Gudelsky, Vorhees, Psychopharmacol, 2001
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Pharmacology (cont’d)
• Pharmacokinetics :
- absorption : oral
- onset of action : 20 min
- duration of effect : up to 8 hours or more
- excretion : renal
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Toxicity and Adverse Effects
• Class effects of the amphetamine group
- acute and chronic
• MDMA-specific effects
- acute and chronic
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Toxicity and Adverse Effects
• General amphetamine effects :
I. Acute :
- CNS : restlessness, dizziness, tremor, hyperactive reflexes, talkativeness, tenseness, irritability, weakness, insomnia, fever, euphoria (sometimes), fatigue and depression after stimulation
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- psychotric effects : paranoid hallucinations, panic states, suicidal or homicidal tendencies, aggressiveness, changes in libido, anxiety, delirium
- cardiovascular effects : pallor, flushing, palpitation, arrhythmias, anginal pain, hypertension,circulatory collapse
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- GI : dry mouth, metallic taste,anorexia, nausea & vomiting,diarrhoea, abdominal cramps
- fatal poisoning → convulsions,coma, cerebral haemorrahges,cardiovascular collapse
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II. Chronic effects :• Weight loss, psychotic reaction with vivid
hallucinations and paranoid delusions,incipient schizophrenia
• recovery usually rapid after discontinuationof drug
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MDMA-specific Adverse Effects
1. “Serotonin Syndrome” :
- Diagnostic criteria : mental status changes(confusion, hypomania), agitation, myoclonus,hypereflexia, diaphoresis, shivering, tremor,diarrhoea, incoordination, fever
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“Serotonin Syndrome” (cont’d)
- Manifestations :1. Cognitive and behavioral changes – disorientation, hallucinations, dizziness etc2. Autonomic dysfunction – tachycardia, hypertension, flushing, salivation, hyperthermia etc3. Neuromuscular effects : muscle rigidity, bruxism, trismus4. Disseminated intravascular coagulopathy (DIC), rhabdomyolysis, renal failure, acute respiratory d i s t r e s ssyndrome (ARDS) etc
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MDMA-specific Adverse Effects (cont’d)
2. Acute symptomatic hyponatraemia with thesyndrome of inappropriate antidiuretic-hormone secretion (SIADH)
- cause : MDMA-induced increasedsecretion of vasopressin → ↓↓↓↓ Na
- if fluid intake increased → ↓↓↓↓↓↓↓↓ Na →hyponatraemic coma
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MDMA-specific Adverse Effects (cont’d)
3. Others :- “flashbacks”- parkinsonism- chronic paranoid psychosis- jaundice- subarachnoid haemorrhage- cerebral infarction
4. Drug-drug interactions : with monoamine oxidaseinhibitors, other anti-psychotic agents
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Abuse of MDMA
• Forms : mostly as round tablets of variouscolours with different logos, less oftenpowders and capsules
• Hallucinogenic dose : 50-150mg• Adul terants : “ Ice” , methaqualone ,
ketamine, phenobarbitone, caffeine,benzodiazepines, paracetamol
• Serious risk for uninformed users
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Ketamine
• Full name : Ketamine hydrochloride
• Street name : Special K, “K”
• Pharmacological classification : anaestheticagent for minor human and veterinarysurgical procedures
• Legal classification : Dangerous Drug
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Pharmacology
• Mechanism of act ion : by blockingactivation of non-competitive N-methyl-D-aspartate (NMDA) receptors → a state of“dissociative anaesthesia” → sensory loss,analgesia, amnesia but without actual lossof consciousness
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Pharmacology (cont’d)
• Pharmacokinetics :
- onset of action : IV – seconds
IM – 4 min
- duration : 15-30 min
- excretion : renally excreted after liver metabolism
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Toxicity and Adverse Effects
• Emergence reactions : common during recovery,i n c l u d e u n p l e a s a n t d r e a m s , c o n f u s i o n ,hallucinations and irrational behaviour (childrenless susceptible), reduced by prior administrationof a benzodiazepine
• “out-of-body” state/experience : a psychologicaldissociation, “near death experience”
• “flashbacks”
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Toxicity and Adverse Effects (cont’d)
• Hyper- and hypotension, arrhythmias,brady- or tachycardia
• Respiratory suppression, apnoea• Long term effects : impaired memory,
learning and attentional mechanisms;compulsive repeated use
• Drug-drug interactions : with other anti-psychotic agents
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Abuse of Ketamine
• Forms : powder for snorting, injection forliquid
• Adulterants : often mixed with MDMA,“Ice”, benzodiazepines etc
• Hallucinogenic dose : 30mg po
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Methamphetamine
• Full name : methamphetamine/methylamphetamine hydrochloride
• Street names : crank, “Ice” for the high-purity crystalline smokeable form
• Pharmacological classification :amphetamine-type CNS stimulant withhallucinogenic effects
• Legal classification : Dangerous Drug
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Pharmacology
• Mechanism of action : similar to MDMA• Medical uses : appetite-suppressant, hyperactivity,
narcolepsy• Pharmacokinetics :
- well absorbed orally and through mucous membrane of respiratory tract (inhalation)- instantaneous “high” after IV (a “rush”) or inhalation- duration of action : 8-24 hrs- excretion : renal excretion after hepatic metabolism
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Toxicity and Adverse Effects
• Instant “rush” after inhalation or injection
• “crashing” after drug effect wears off :profound sleep
• Depression and fatigue, sometimes suicidal
• Tendency to progress to compulsive use
• Tolerance after prolonged use
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Toxicity and adverse effects (cont’d)
• Hyperthermia, hypertension, tachycardia,dysrhythmias
• CNS effects : insomnia, auditory hallucinations,confusion, delusions, paranoia, aggressivebehaviour, suicidal
• High doses : extreme suspiciousness, overtparanoid psychosis → unpredictable violentbehaviour
• Drug-drug interactions : with MAOIs, other anti-psychotic agents
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Abuse of Methamphetamine
• Forms : by inhalation of the vapourizedcrystals , by IV injection
• Adulterants : often with MDMA, ketamine,or benzodiazepines
• Hallucinogenic dose : 20-25mg
• Tolerance develops after prolonged use
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Summary
• MDMA, ketamine and methamphetaminehave high potential for abuse
• Tolerance and dependence are common
• Combined use poses high risk of fatalpoisoning