AcknowledgmentsDepartment of Forensic & Toxicology

Prof.Dr.Khadija MostafaDr.Nancy Zaghloul

Dr.Sara KhaterDr.Yasmen El-Kashef

For their continuous help and valuable efforts..

Misr University for Science & Technology

- Group -Mohamed AshrafHatem El-Sheemy

Reem AdelAsmaa EzzatEman RoshdyMarco Ezzat

Mahmoud MamdouhGad Ahmad

.ContentMechanism

of ActionSource

Epidemiology

Investigations Treatment

Route of admin.

Clinical Manifesations

.Discovery & Source

Discovery

For over a thousand years South American indigenous peoples have chewed the leaves of Erythroxylon coca, which grew primarily in

Peru and Bolivia. a plant that contains vital nutrients as well as numerous alkaloids, including cocaine.

Cocaine is a powerfully addictive stimulant that directly affects the brain

It may be administered by a doctor for limited medical uses, such as local anesthesia for:1. eye2. ear3. Some throat surgeries.4. decreasing bleeding during

nasal surgery

Source

Salt• Cocaine is a weakly alkaline compound

(alkaloid), and can therefore combine with acidic compounds to form various salts. The hydrochloride (HCl) salt of cocaine is by far the most commonly encountered.Base• Cocaine is practically insoluble in water

whereas hydrochloride salt is water-soluble

Form

.Route of Adminstration

Snifing

Smoking as free base (crack)

IV route usually with heroin

.Route of Adminstration

.Mechanism of Action

Mechanism of Action

Inhibits reuptake of dopamine

& interferes with

catecholamine

Inhibits serotonin

Inhibits Na channels

Cocaine

Mechanism of Actionventral tegmental area

the nucleus accumbens caudate nucleus

‘reward pathway

inhibits removal of dopamine from the synaptic cleft

dopamine re-uptake transporters Cocaine

Persists of dopamine

Nerve impulses Euphoria

.Uses

.Uses

USES

Anesthesia

Anti-arrhythmic

anorexigenic Sport doping

.Clinical Manifestations

Side Effects

Clinical Manifestations

Clinical Manifestations

Convulsions, Seizures and sudden death from high doses (even one time)

Paranoid, Angry, hostile and anxious

don’t eat or sleep properlygreatly increased heart rate, muscle spasms and convulsions.

Contracted blood vesselsIncreased rate of breathing Dilated pupils

Short- term Intense euphoria Then: intense depression

Appearance

Dilated pupils

Nosebleeds (snorting)

Track marks (injecting)

Runny nose (snorting)

Burned lips or fingers

(smoking)

Heart

Fast heart rate

Enlarged Heart Heart attacks

Constricted blood vessels

Cardiac arrest

Clinical Manifestations: Signs

Mental State

Euphoria

Poor judgment Delusions

Paranoia

Hallucinations

Long use..Depressio

n

Agitation Exhaustion

Intense cravings

Long periods of sleep

ApathyApathyOver

confidence

Clinical Manifestations: Signs

more of the drug is required to create an effect similar to earlier use.

Tolerance for the drug increases

seriously distressed about life without good reasonstrong cravings for the drug

suffer physical and mental deteriorationdepression agitation nervousness Tiredness

Long- term Intense euphoria Then: intense depression

Some scientific studies have documented that babies born to mothers who abuse cocaine during pregnancy “crack babies” mostly are:• Prematurely delivered.• Low birth weights.• Smaller head circumferences. • Shorter in length.• Reduced intelligence • Brain damage

Clinical Manifestations: Maternal Transmission

.Epidemiology

History?

Epidemiology: GlobalCocaine Trade Traffic routes

• After cannabis, cocaine is the most frequently used illegal drug globally.• Between 14 and 21 million people use the drug each year. • Use is highest in North America followed by Europe and South America. • Between one and three percent of people in the developed world use cocaine at some point.

Epidemiology: USA

= Size of illegal Drug Trade Market in Egypt

18.4 Billion EGP

15.7 Billion Plant Source

2.4 Billion Natural

2 million Synthetic

Epidemiology: Drugs in Egypt

2.5% of Gross national income

Source: Central Agency for Public Mobilization and Statistics - EGYPT

2015

اإلحصاء و العامة للتعبئة المركزي الجهاز

Epidemiology: Addiction in Egypt32,457 File

35,580 Accused 20

14Ministry of Interior - Egypt

2014

National Institute of Addiction Research

Marital Status

Socio-economic status

DHS 2005

53%

11%

36%

SingleMarriedDivorced or widowed

Abdelmohsen et al 2011

13%

27%60%

High MiddleLow

Abbasiya Hosp. 16,521 20

15

No. of Addicts went seeking treatment

Epidemiology: Cocine and other drugs

Among 330 Egyptian substance abusers

@ outpatient addiction clinic of Heliopolis Psychiatric Hospital - Cairo

2015

...Why?

1gm

بكام؟

So expensive .. And hard to afford

.Investigations

• Cocaine toxic effect starts to appear if the concentration is higher than 1 mg/L.

• Nearly every organ can be affected by cocaine.• Most of the investigations are Lab

studies:

Investigations

A. Careful History taking if available.B. Lab Studies:

C. ECG: as one of routine investigations for CVS.D. Radiography: chest x-ray: interstitial pneumonitis ,fibrosis.

1. Serum Enzymes (CPK, AST, ALT, SGPT, SGOT..)2. Detection of benzolecogonine (principle metabolite of cocaine) in urine

by thin layer or high preformance or gas chromatography to detect overdose (can be detected up to 2-3 days).

3. Toxicology evaluations: Including for urine, blood, gastric contents, and unknown substances clinging to the patient’s body.

4. Routine investigations: CBC, CK, Urin analysis, ABG analysis, serum electrolytes and kidney function may help

Investigations

.Treatment

Aim: to reduce the CNS and CVS effects of Cocaine by using benzodiazepines initially and then to control clinically significant tachycardia and hypertension and to limit drug interaction while treating the case of toxicity.

Treatment

Cocaine overdose treatment should be based on its effect on the body.

Management • Establish airway, breathing.• Provide Oxygen.• Obtain intravenous access.• Monitor and frequently check vital signs including

temperature; monitor glucose levels for patients with altered mental status.

Treatment

A. Supportive Treatment:

B. GIT Decontamination: Performed only in abscence of seizures

C. Enhanced Elimination:

D. Symptomatic:

1. CNS: Benzodiazepines2. CVS: Anti-hypertensive drugs Anti-Arrahythmatic drugs

Treatment

1. Emesis2. Gastric Lavage

Forced acid duiresis: increase urine execretion of drug but may cause metabolic acidosis

1. Cool quite enviroment2. Lithium for cocaine psychosis3. Propranolol for HTN and tachycardia

Benzodiazepines:• By increasing the action of GABA, a major inhibitory neurotransmitter in the brain,

these drugs may depress all levels of the CNS, including the limbic system and reticular formation.

Lorazepam: • more common to be used with status epilepticus than diazepam , as it work for a

longer time on CNS. it's maximum rate of injection is 2mg/min.. its better to be taken IM in case of difficult vascularf access

Midazolam:• an alternative for termination of persistent (refractory) status epilepticus • it takes about 3 times longer to reach the peak of its effect , but it has twice the

affinity of diazepam for benzodiazepine receptorsDiazepam :• Depresses all levels of CNS (eg, limbic and reticular formation), by increasing GABA

activity.• has a shorter duration of its effect against convulsions so it is considered Third-line

agent in treatment of agitation or seizures and accumulation of active metabolites that may prolong sedation.

Treatment Choices: CNS

Antiarrhythmic agent

Anti-Hypertensive Drugs:

→ Lidocaine: Class IB antiarrhythmic that increases electrical stimulation threshold of ventricle, Its indicated for VF & VT (ventricular tachycardia ) induced by cocaine .

→ Bretylium: Class III antiarrhythmic agent indicated for treatment cases with PVCs (persistent vegetative states ). Should not be used as initial treatment because of its adverse effect , plus what is proven of its catecholamine releasing properties leading to more CNS stimulation and more CVS stimulation.

→ Nitroglycerin (NTG) : VD→ Esmolol :• Beta-blockers with a vasodilator, only to manage life-threatening hypertension, tachycardia,

and aortic dissection unresponsive to other therapeutic interventions as it generally contraindicated in cocaine toxicity.

→ Nitroprusside:• Used to treat acute hypertension. Produces vasodilation and increases cardiac inotropic

activity.if given in high doses ,it can increase myocardial ischemia by increasing heart rate.

so selection of NTG or sodium nitroprusside based on clinician's preference.

Treatment: CVSTreatment Choices: CVS

→ Phentolamine (Regitine)• Alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine

and norepinephrine action, reducing hypertension due to catecholamine effects on alpha-receptors.

→ Sodium bicarbonate (Neut)• Useful for alkalization of urine in patients with rhabdomyolysis. Appropriate for

dysrhythmias from direct toxic effects of cocaine (ie, QRS greater than 100 ms due to sodium channel blockade).

→ Norepinephrine (Levophed)• Stimulates alpha and beta1-adrenergic receptors with alpha-adrenergic

predominance which increases cardiac muscle contractility, heart rate, and vasoconstriction; results are increased systemic BP and coronary blood flow. As a vasopressor, useful in hypotension not responsive to IV fluids alone.

→ Epinephrine:• Most useful drug in cardiac arrest. Increases coronary perfusion pressure.

Treatment: CVSTreatment Choices: CVS

EmesisWhole-bowel irrigation with polyethylene glycol promotes the passage of cocaine packets through the GIT.

Forced acid duiresis: increase urine execretion of drug but may cause metabolic acidosis

Activated charcoal may be empirically used only to minimize systemic absorption of the toxin.

Treatment: Decontamination & enhanced elimination

• Publishing more studies about the prevalence of Cocaine and other drugs used in Egypt.

• Call for more recent studies about relation between socio-economic state and addiction.

Recommendations:

Thank You