WHAT IS COCAINE?• Cocai ne (benzoyl -m hyl -ecgoni ne) (C 21N 4) i s et 17H O a cr yst al l i ne al kal oi d pr epar ed f r omt he l eaves of t he Er yt hr oxyl on coca pl ant .• Cocai ne i s a bi t t er , w t e, odor l ess, cr yst al l i ne hi dr ug.• A ccor di ng t o t he N i onal I nst i t ut e of D ug A at r buse (N D ), cocai ne i s:“A pow f ul l y addi ct i ve dr ug I A er t hat can be sni f f ed, i nj ect ed, chew or sm ed oked.”
CO NE HAS BEEN CLASSI FI ED AS A SCHEDU I I DRUG BY THE CAI LEUNI TED STATES.
FORMS OF COCAINE 1. C ocai ne hydr ochl or i de (pow ) : pr epar ed by der di ssol vi ng t he al kal oi d i n hydr ochl or i c aci d, f or m ng a w er sol ubl e sal t . i at 2. C ack cocai ne : pr oduced w r hen cocai ne hydr ochl or i de i s m xed w t h sodi umbi car bonat e i i and w er , and t hen heat ed. at
ROUTE OF ADMINISTRATION• C ocai ne can be adm ni st er ed as a dr ug of abuse i n t he i f ol l ow ng w i ays :• 1. Cocai ne hydr ochl or i de :• Sni f f ed (i nt r anasal ),• sm ng, oki• i nt r avenous i nj uct i on (i ncl udi ng bei ng m xed w t h her oi n i i or i ngest i on)
• 2. C ack cocai ne : i nhal at i on of vapour f r omheat ed r f oi l or pi pe.
O SET & D R TI O O A TI O N UA N F C NFO C C I N D R O A E EPEN S O TH R U O D N E O TE FA M N STR TI O . DI I A N Route onset Duration inhalation 7S 20 min IV 15 S 22-30 min Nasal 3 min 45-90 min oral 10 min 60 min
COCAINE MECHANISM OF ACTION• Cocaine binds to dopamine re-uptake transporters on the pre- synaptic membranes of dopaminergic neurones.• This binding inhibits the removal of dopamine from the synaptic cleft and its subsequent degradation by monoamine oxidase in the nerve terminal.
COCAINE MECHANISM OF ACTION• Dopamine remains in the synaptic cleft and is free to bind to its receptors on the post synaptic membrane, producing further nerve impulses.• This increased activation of the dopaminergic reward pathway leads to the feelings of euphoria and the ‘high’ associated with cocaine use.
WHEN GIVEN LOCALLY• Cocaine produces anesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves.• This is achieved by reversibly binding to and inactivating sodium channels.• Sodium influx through these channels is necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve.• When a nerve loses its ability to propagate an impulse, the individual loses sensation in the area supplied by the nerve.
THERAPEUTIC USES OF COCAINE• Cocaine is used by health care professionals to temporarily numb the lining of the mouth, nose, and throat (mucous membranes) before certain medical procedures (e.g., biopsy, stitches, wound cleaning).• It is an anesthetic that works quickly to numb the area about 1-2 minutes after application.• Cocaine also causes blood vessels to narrow, an effect that can decrease bleeding and swelling from the procedure.• It is also sometimes used in palliative care of terminally ill patient.
METABOLISM OF COCAINE Serum half life of 45-90 minutes Only 1% of the drug is recovered in urine after ingestion Cocaine can be detected in blood or urine only for several hours after its use Cocaine metabolites are detectable for 2-5 days Hair analysis provides a very sensitive marker for cocaine use within the preceding weeks to months
EFFECTS OF COCAINE1. Initial Low Doses :A. Physical Effects :1. Tachycardia, tachypnoea,2. hypertension,3. Dilated pupils (& flattened lenses),4. sweating5. reduced appetite, reduced need for sleep, reduced lung function,6. dry mouth,7. impaired motor control & performance of delicate skills and driving.
B- Psychological Effects :1. Euphoria, sense of well being,2. impaired reaction time and attention span,3. impaired learning of new skills.
SYSTEMATIC FINDINGSCARDIOVASCULAR SYSTEM :Acute Cardiovascular Pathology Cocaine is directly toxic to cardiac myocytes, and this cardiotoxic effect does not depend on the route of administration, and may not necessarily have to occur at large doses. Neither does it appear that pre-existing cardiovascular pathology is a pre- requisite for cocaine toxicity
Acute Myocardial Infarction• The mechanism of cocaine related myocardial infarction is likely to be multifactorial in nature, and could be related to focal vasoconstriction of coronary arteries, or spasm of these arteries.• Cocaine acts both directly and indirectly on vascular smooth muscle, via-adrenergic stimulation (noradrenaline) and an independent, dose-related effect.• Cocaine also increases coronary vascular resistance at a time when it is increasing heart rate and myocardial oxygen demand
• Cardiac Arrhythmias• Cocaine is a Class II antiarrhythmic agent, and exerts its actions by blocking sodium channels.• In large doses it is arrhythmogenic, possibly due to it’s effects on catecholamines rather than any direct effect, or due to secondary arrhythmias following cardiac ischaemia due to prolonged coronary artery vasoconstriction.• A cocaine-induced rise in intracellular calcium may also be responsible.
RESPIRATORY SYSTEM Non-specific findings at autopsy include pulmonary edema and congestion, possible due to excess catecholamine release. Specifically, cocaine use has been associated with : granulomas in the lungs, and this may represent either impurities in the drug, or more likely poly drug abuse Spontaneous pneumothorax or pneumopericardium Haemoptysis Pulmonary hypertension
GASTROINTESTINAL TRACT The pathological findings in the gastrointestinal tract of a cocaine abuser are similar to those found in experimental animals treated with high levels of catecholamines, i.e.: Ulceration and perforation Ischaemic colitis Severe bowel ischaemia and gangrene (vasoconstriction of mesenteric vasculature) Peptic ulcer perforation (due to a disruption of the internal elastic lamina of the small vessels supplying the ulcerated area
URINARY SYSTEM Cocaine use is known to have caused:• Renal infarction• Renal thrombosis• Haemolytic uraemic syndrome• Rhabdomyolysis with myoglobinuric renal failure
CENTRAL NERVOUS SYSTEM• Due to cocaine’s ability to produce hyperpyrexia, combined with it’s effects on neurotransmitters, the drug may contribute to seizure formation as well as hyperthermia. Seizures may be ‘primary’, due to cocaine lowering the seizure threshold, or ‘secondary’ to cardiac effects such as ventriculartachycardia and fibrillation.
11 WAYS TO DIE FROM COCAINE DRUGADDICTION1. Acute hypertensive crises - quickly elevating blood pressure - blows out a weak blood vessel in brain causing cerebral hemorrhage.2. Hypertension chronic users may weaken blood vessels in their brain. Die from strokes or complications after.3. Acute hypotension - no blood with oxygen to the brain causing an anaphylaxis - allergic reaction.4. Status epilepticus - repeated convulsions - increased EEG activity.5. C.N.S. Rebound - physical and emotional depression - depressed medullary/respiratory centers of the brain knock you OUT - this is the most common cause of cocaine death.
6. Hyperpyrexia - Cocaine can raise the body to an extremely hightemperature. May feel cold on the outside. Shows bruising easily - temp 106degrees (anal)7. Pulmonary insult - heat fumes and chemicals in lungs cause lungs tocollapse.8. Paranoid miscalculation - accidental death due to delusions andhallucinations.9. Suicide - during post-cocaine depression10. Needle borne - infections from needle use.11. Allergic Reaction - anticholinesterase (enzyme) deficiency 10-20 mg. ofcocaine will kill them - the drug never gets destroyed and recycles continuouslythroughout the body.
COCAINE RISK FOR ABUSE OR DEPENDENCE Community-based interview surveys suggest that up to one in six persons who use cocaine will become dependent.. Users Heavier users and users who take the drug Intravenously or by smoking are more likely to become dependent than lighter users or intranasal and oral users..addicts The greater abuse potential of intravenous or smoked cocaine is attributed to the faster rate of drug delivery to the brain (within 10 seconds), & faster onset of psychological effects . Route This faster onset is associated with a more intense pleasurable response (the so-called "rate hypothesis" of psychoactive drug action
COCAINE ADDICTION• Why is cocaine so highly addictive?• Next to methamphetamine,* cocaine creates the greatest psychological dependence of any drug. It stimulates key pleasure centres within the brain and causes extremely heightened euphoria.• The addictive properties of cocaine are thought to be due to brain dopamine D2-receptor stimulation.
Cycle of Cocaine AddictionThis addiction has biological, behavioral & psychological aspects Cocaine Use EUPHORIA Positive Reinforcement Brain Reward Neuroadaptations Cocaine Seeking Behavior CRAVING Negative ReinforcementTreatment interventions are designed to reduce euphoria & craving
TOXICITYToxic effects of cocaine result from:• Vasospasm (MI, CVA)• Electrophysiological effects • Seizures • Cardiac arrhythmias• Hypertension (bleeds)