SUBSTANE OF ABUSE414 PHG

CNS stimulants

• Identify the different classes of CNS stimulants

• Determine pharmacological actions of CNS stimulants.

• Evaluate dependence liability and types of CNS stimulant drugs.

• Build an addiction treatment plan of CNS stimulants.

Learning outcomes

1. Amphetamine–Methamphetamine–Ritaline

2. Cocaine3. Nicotine4. Ephedra5. Khat6. Coca7. Tobaco

CNS stimulants topics

• The main effects are: – increased motor activity – euphoria and excitement – anorexia – with prolonged administration, stereotyped

and psychotic behavior.

Amphetamine

• Effects result mainly from release of catecholamines, especially noradrenaline and dopamine

• Stimulant effect lasts for a few hours and is followed by depression and anxiety

1- Amphetamine

• Tolerance to the stimulant effects develops rapidly, (peripheral sympathomimetic effects may persist).

• Amphetamines may be useful in treating narcolepsy and also (paradoxically) to control hyperkinetic children.

• No longer used as appetite suppressants (risk of pulmonary hypertension) .

Amphetamine

• Amphetamine psychosis, which closely resembles schizophrenia, can develop after prolonged use.

• Their main importance is in drug abuse.

Amphetamine

Methamphetamines

Most abused form of amphetamines

Methamphetamine is generally a white or off-white powder that can be ingested in several ways:

• Orally

• Snorted

• Injected

• Smoked

Short Term Side Effects

• Excessive Talking

• Increased Activity

• Nervousness

• Decreased Fatigue

• Anxiety / Panic Attacks

• Hallucinations

• Nervousness

• Excessive Sweating

• Skin Welts

• Violent / Suicidal Behavior

Long Term Side Effects

Methamphetamine use can cause serious long term side effects that can affect the user for the rest of their life:

• Immune System Damage

• Psychological Problems

• Severe Brain Damage

• Fatal Kidney Disorders• Fatal Lung Disorders• Birth Defects• Stroke• Death

Ritalin(methylphenidate)

• Prescribed to ADD and ADHD patients under the brand names, Ritalin, and Aderall.

• ADD /ADHD is thought to be caused by under functioning of the parts of the brain associated with impulse control and executive functions.

• The stimulant nature of aderall, ritalin, etc. speed up the neural transmission to a “normal” level of function

2- Cocaine

•Derived from the leaves of the Erythroxylum coca plant

Historical Overview

• Indigenous Peruvians once considered the coca plant to be divine

• They named it “khoka” which means “the plant”• Europeans changed the name to “coca”• 1859-1860, German scientist,Albert Niemann,

isolated and named cocaine.• 1856, Samuel Percy was the first to suggest that

coca leaves could be used as an anesthetic• 1884 used in clinical practice

Chewing: with an-alkaloid material (South America)Sniffing: hydrochloride salt -absorption: nasal mucous membranes –local vasoconstriction slows absorption and prolongs effect

Routes of Administration:

Oral: large doses are needed for effect rapid onsetSmoking: cocaine is converted to alkaloid (freebase or "crack") which is readily volatilized undegraded at lower temperature. I.V. and smoking: reaches CNS in seconds in high concentration produces more immediate and intense effects.

Routes of Administration:

Effects of Cocaine

Rapid and intensely euphoric sensation commonly called a “rush”Increased heart rateChest painCardiac arrestTremorsBreathing irregularitiesHyperthermia

Intense sweatingPanicAgitationParanoiaHallucinationsDeliriumSeizures

Cocaine Toxicity

Chest painHypertensionTachycardiaMyocardial ischemia and/or infarctionPulmonary edemaAortic rupture

Cardiac dysrhythmiaHemorrhagic strokeEndocarditisMyocarditisCardiomyopathySudden death

Common Street Names

Blow CokeCharliePearl flakeDevil’s dandruff

RockSnowTootPeruvian marching power

Street Names continued…

The crystal form of cocaine is also known as: • Crack • Base • Free base • French fries • Ready rock • Rock

Compare the behavioral effects and toxicity of amphetamine and cocaine.

Activity 1

Nicotine (tobacco) Second after caffeine as the most widely used

CNS stimulant Second after alcohol as the most abused drug.

CNS Effects: Lower doses produce: Powerful CNS stimulant Large doses produce : convulsion, then depress CNS, Stimulates respiration, Produces

emesis . Tolerance to central actions with chronic use

3- Nicotine

Nicotine causes excitation followed by inhibition of all synaptic and parasynaptic ganglia.

At low doses → ganglionic stimulation by depolarization of the postganglionic membrane.

At high doses →ganglionic blockade

Mode of Action

TachycardiaIncreased blood pressureGanglionic blockade and arrhythmias Fatalities: Due to respiratory failure

Cardiovascular effects

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• Nicotine is an addictive substance and produce both physical & psychological dependence.

• Withdrawal from nicotine "quite smoking" → irritability, anxiety, restlessness, difficulty in concentration, headache, insomnia, increase appetite and GIT pain.

• Withdrawal symptoms ↓ by: tans dermal patches

Toxicity

Natural drugs with amphetamine-like action (Ephedra and khat)

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Ephedrine

Norpseudoephedrine (Cathine)

•Common names: Ma Huang; Brigham tea;

Natural Ecstasy…etc.

•Scientific name: Ephedra sinica and other spp.

•Part used: The stems

•Active constituents: Alkaloids (0.5-2.5%),

ephedrine:major one (pseudoepherdrine,

norephedrine, …others).

Ephedra

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Ephedrine is structurally related to

amphetamine and causes CNS stimulation in a

similar way to amphetamines through

increasing the availability of endogenous

neurotransmitters.

Dosage: quantity of ephedra equivalent to

24mg ephedrine/day.

Preparation: Crude powdered drug,

tinctures; fluid extr.

Actions and uses

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•Contraindications and precautions:

• In pregnancy → risk of uterine stimulation

• In diabetic patients → hypoglycemic effects.

• In patients with cardiac arrhythmias, angina,

with history of cerebral disease.

•Concomitant use with beta blockers and

MAO inhibitors →risk of GI and CNS

adverse effects

Actions and uses

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Cathinone

•Scientific name: Catha edulis Forsk. (Fam.

Celastraceae).•Part used: Fresh leaves and twigs.

•Constituents: •Cathinone1%, Norepseudoephedrine;

•Ephedrine…etc.•Tannins, vol. oil.

Khat

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Actions and uses:

The CNS stimulation of khat is manly due to

cathinone and norepseudoephedrine.

(It shows amphetamine –like actions).

Khat is manly used as a social drug through

chewing or taken as an infusion.

Khat is used in Germany to counter obesity.

Cathinone

Khat

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NATURAL DRUGS CONTAINING COCAINE

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•Scientific name: Erythroxylom coca, and other e. spp, (Fam. Erythroxylaceae)

•Part used: The leaves.•Constituents: •Alkaloids cocaine (0.7-1.5%), together with

cinnamyl cocaine, and α- and β- truxillines.•Vol. oil, Flavonoids, Tannins, Vit. A and B2 and

minerals.

Coca

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Natural drugs conaining tobaco

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Nicotine

•Scientific name: Nicotiana tabaccum (Fam. Solanaceae).

•The Part used: The leaves.•Constituents: Alkaloids (nicotine is the most important)

•Actions and Uses:• It is a psychomotor CNS stimulant (some degree

of euphoria, and arousal, as well as relaxation, and improves learning, problem solving and reaction time).

Tobaco

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Nicotine

It is grown mainly produce smoking or smokeless tobacco.Dried leaves make a good insecticide.It is no longer used medicinally.

Smokeless tobacco:Prepared from the same botanical source,

and usually flavored with sugar or artificial sweeteners.

Tobaco

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Which is more toxic in terms of health and economic expenses, tobacco, khat or Coffe and tea

Activity 2

1- Compare the behavioral effects and toxicity of coca, ephedra and khat.2- How amphetamine and cocaine addiction can be treated?3- Explain the different treatment approaches for the amohetamine and cocaine toxicities.

Review questions

Catha edulis (Celestraceae), “Khat”

Datura spp. (Solanaceae)

Erythroxylon coca (Erythroxylaceae)

Nicotiana tobaccum (Solanaceae), “Tobacco”

Tetra hydro Cannabinol (THC)Cathinone

Humulone Cocaine