WHAT IS COCAINE?

• Cocaine (benzoyl-methyl-ecgonine) (C17H21NO4) is a crystalline alkaloid prepared from the leaves of the Erythroxylon coca plant .

• Cocaine is a bitter, white, odorless, crystalline drug.

• According to the National Institute of Drug Abuse (NIDA), cocaine is:“A powerfully addictive drug that can be sniffed, injected, chewed or smoked.”

COCAINE HAS BEEN CLASSIFIED AS A SCHEDULE II DRUG BY THE UNITED STATES.

FORMS OF COCAINE

1. Cocaine hydrochloride (powder) : prepared by dissolving the alkaloid in hydrochloric acid, forming a water soluble salt.

2. Crack cocaine : produced when cocaine hydrochloride is mixed with sodium bicarbonate and water, and then heated.

ROUTE OF ADMINISTRATION

• Cocaine can be administered as a drug of abuse in the following ways :

• 1. Cocaine hydrochloride :

• Sniffed (intranasal),

• smoking,

• intravenous injuction (including being mixed with heroin or ingestion)

• 2. Crack cocaine : inhalation of vapour from heated foil or pipe.

• 3. Coca leaves : chewed/ ingested.

ONSET & DURATION OF ACTION   FOR COCAINE DEPENDS ON THE ROUTE OF ADMINISTRATION.

Duration onset Route

20 min 7 S inhalation

22-30 min 15 S IV

45-90 min 3 min Nasal

60 min 10 min oral

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 COCAINE 1. Initial Low Doses :

A. Physical Effects :

1. Tachycardia, tachypnoea,

2. hypertension,

3. Dilated pupils (& flattened lenses),

4. sweating

5. 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.

2- Increased doses :

A- Physical Effects :

1. Seizures,

2. cardiac arrhythmias,

3. myocardial infarction,

4. stroke,

5. respiratory arrest.

B- Psychological Effects :

1. Anxiety,

2. irritability,

3. insomnia,

4. depression, paranoia,

5. aggressiveness,

6. impulsivity,

7. delusions,

8. agitated/ excited delirium,

9. reduced psychomotor function.

3- Chronic Use :

A- Physical Effects :• Erosions,

• necrosis and perforation of nasal septum,

• anosmia, rhinorrhoea and nasal eczema (snorting),

• chestpains, muscle spasms,

• sexual impotence,

• weight loss, malnutrition, vascular disease.

B- Psychological Effects :• Dependence,

• disturbed eating and sleeping patterns

SYSTEMIC EFFECT OF COCAINE

SYSTEMATIC FINDINGSCARDIOVASCULAR SYSTEM:

Acute Cardiovascular Pathology Cocaine is directly toxic to cardiac myocytes, and this cardiotoxic

effect does not depend on theroute of administration, and may not necessarily have to occur at large doses. Neither does itappear 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-adrenergicstimulation (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 cardiacischaemia due to prolonged coronary artery vasoconstriction.

• A cocaine-induced rise inintracellular 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 DRUG ADDICTION

1. 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 high temperature. May feel cold on the outside. Shows bruising easily - temp 106 degrees (anal)7. Pulmonary insult - heat fumes and chemicals in lungs cause lungs to collapse.8. Paranoid miscalculation - accidental death due to delusions and hallucinations.9. Suicide - during post-cocaine depression10. Needle borne - infections from needle use.11. Allergic Reaction - anticholinesterase (enzyme) deficiency 10-20 mg. of cocaine will kill them - the drug never gets destroyed and recycles continuously throughout 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.

EUPHORIAPositive Reinforcement

CRAVINGNegative Reinforcement

Brain Reward Neuroadaptations

Cycle of Cocaine Addiction

CocaineUse

This addiction has biological, behavioral & psychological aspects

CocaineSeeking

Behavior

Treatment interventions are designed to reduce euphoria & craving

TOXICITY

Toxic effects of cocaine result from:

• Vasospasm (MI, CVA)

• Electrophysiological effects

• Seizures

• Cardiac arrhythmias

• Hypertension (bleeds)

TOXICITY

Cardiac complications of cocaine use:

• Angina

• Myocardial infarction

• Cardiomyopathy

• Myocarditis

TOXICITY

Other medical problems:

• Hyperpyrexia

• Intestinal ischemia

• Renal failure

• Perforated nasal septum

• Low birth weight, spontaneous abortion

• Psychosis/Depression/Anxiety

PROGRESSIVE COMPLICATIONS OF COCAINE DEPENDENCE

• Death (MI, hyperthermia, hemorrhage, violence)

• Medical (cardiac, seizures, stroke, renal)

• Psychiatric (psychosis, depression, panic, suicide)

• Legal (incarceration: possession, dealing, prostitution, theft)

• Family (child neglect, violence, divorce)

• Occupational (job loss: absenteeism, poor performance)

• Financial (drug procurement, loss of income)

Denial shields patients from their predicament

• Those who use cocaine heavily or regularly find it extremely difficult to stop and often suffer through serious withdrawal symptoms such as:

TREATMENT OF STIMULANT DEPENDENCE

• Provider requires specialized knowledge

• Patient requires motivation• Patient may not want to stop using drugs

• Attitude/Compliance is important

• Recovery requires sacrifice

• Clinical course involves relapse/progression

ASSESSMENT & TREATMENT

• Comprehensive Assessment

• Medical

• Psychiatric

• Psychiatric

• Psychosocial

• Abstinence Initiation

• Readiness for change

• Relapse Prevention

• Different levels of care

• Inpatient, IOP, outpatient

TREATMENT MODALITIES

• Intervention

• Abstinence-based AA/NA model

• Individual, group, & family therapy

• Pharmacotherapy

TREATMENT OF COCAINE DEPENDENCE - PSYCHOSOCIAL

0%

5%10%

15%20%

25%30%

35%40%

12 Weeks

Individual Drug counseling

Group Drug Counseling

Cognitive Behavioral Therapy

Supportive/expressive Therapy

Individual drug counseling is effective

TREATMENT OF STIMULANT DEPENDENCE - MEDICATIONS

There are no medications with proven efficacy for stimulant dependence

TREATMENT OF COCAINE DEPENDENCE - MEDICATIONS

• Possible medications include:

• Modafinil - blocks euphoria

• Propranolol - reduces stress

• Baclofen - reduces cue-craving

• Topiramate - relapse prevention

• Disulfiram - reduces alcohol use, increases DA

• Cocaine vaccine - blocks euphoria

Treatment of Cocaine Dependence - Medications

0

1

2

3

4

5

6

7

8

Weeks of cocaine Abstinence

*Cocaine / alcoholdependent

**Cocaine / opiatedependent

DisulfiramControl

Disulfiram is Effective in Cocaine Dependent Patients With and Without Alcohol Dependence

*(Carroll, 1998, ** George, 1999)

0%

10%

20%

30%

40%

50%

60%

% of patients continuously abstinent, weeks 8-13

TopiramatePlacebo

Cocaine withdrawal predicts medication outcome

Topiramate Prevents Relapse

*

*P =.048

PREPARED BY

الشرعبي/ د مجاهدالشميري/ د عبداللهالجشاعه/ د مجيبالعبسي/ د فراس

Thank you