Stimulant DrugsPart 1

Kim Edward Light, Ph.D.

Professor, College of Pharmacy

University of Arkansas for Medical Sciences

Stimulant Drugs

Objectives1. Identify specific drugs that act as stimulants2. Outline the general physiological alterations produced

by stimulants3. Identify common therapeutic uses4. Identify different pharmacological mechanisms of

stimulant drug action5. Discuss the negative consequences of stimulant drug

use6. Discuss the pharmacology of the most common

stimulant drugs including their actions, mechanisms, common doses, kinetics, and consequences from acute and chronic use.

Drugs ALTER physiological actions rather than create unique effects.

A simple means of classifying drugs of abuse can be devised based on the general nature of the drug’s actions.

The function of the brain, Thinking, Feeling, Behavior.

Classifying Drugs of Abuse

Three categories Stim-ul-ants® – increase thinking,

feeling, and behavior

Classifying Drugs of Abuse

Depress-ants® – decrease thinking, feeling, and behavior

Confuse-ants® – distort or confuse thinking, feeling, and behavior

® University of Arkansas

Overall Actions

Increase central nervous system arousal and activity. cardiovascular activity.

Neurotransmitters involving adrenergic amines (norepinephrine, epinephrine, dopamine), cholinergic, adenosine, and/or serotonin.

Stimulant Drugs

Nicotine Caffeine Ephedrine, pseudoephedrine, and related Amphetamine, Methamphetamine Methylphenidate, phenmetrazine, and others Cocaine Psychostimulant plants – Khat, Betel

Physiological Actions

↑ activity, alertness, sensory awareness, and reflexive responding (e.g. startle reflex).

↑ cardiovascular activity (HR, BP)

Shift blood flow from skin and mesenteric systems to the skeletal muscles (fight or flight).

↑ renal blood flow and diuresis.

↑ in the rate and depth of respiration.

↑ Bronchial dilation.

↓ appetite – by activating satiety.

Therapeutic Uses

Sleep disorders - narcolepsy, hypersomnia, excessive daytime sleepiness.

Attention disorders – ADD or ADHD Weight loss Nicotine dependance Nasal congestion and stuffiness Bronchial asthma and related difficulties Vasoconstriction with local anesthesia

Acute Effects

Alert and sense of well-being Irritable, aggressive, hyperthermic,

hypersexual, nervous, anxious Seizure, stroke Hypertension, cardiac palpitations,

arrhythmia, heart attack

Chronic Effects

Insomnia, paranoia, fearfulness Nervousness, aggressiveness, irrational Nutritional deficits, weight loss,

dehydration

HistoryTobacco / Nicotine

Columbus credited with introducing plant to Europe.

Jean Nicot, the French ambassador to Portugal, provided its name Nicotiana tabacum.

Nicotine was isolated in 1828.

Tobacco / Nicotine Facts

The primary source of nicotine is tobacco. Tobacco is

smoked chewed snuffed

Nicotine Mechanism of Action Acts on a subtype receptors for

acetylcholine. Brain Autonomic ganglia Adrenal medulla

Nicotinic Effects

Adrenal medulla – ↑HR ↑ BP Brain - Reward Pathway Other brain functions

pain relief - analgesia memory cognition - thinking learning.

Therapeutic Uses

Present Patch, gum, lozenge, or inhaler form to

discontinue smoking

Future

Treatment of chronic pain, Alzheimer's disease, schizophrenia

Toxic Effects of Nicotine

Carcinogenic (cancer causing) Diminished respiratory and

cardiovascular function Depression of the immune system. Remember – Nicotine is responsible for

the use of tobacco!!

Nicotine / Pharmacokinetics

Absorbed - rapidly Distributed throughout the body Metabolized in the liver - produces

cotinine as one metabolite. T1/2 of approximately two hours, Excreted in the milk of nursing mothers

who smoke.

History of Caffeine

Oldest drug used by humans Stories of discovery:

Zen Buddhist Chinese emperor Kaldi, the Arabian goat herder

Making Coffee Coffea arabica

Made from seeds of Coffea arabica Seeds encased in berries (or cherries). Fruit pulp is fermented to free the seeds. Roasting and grinding bring out essential

oils for flavor and allow the extraction of caffeine

Coffee History 1615 – introduced to Europe 1700 coffee houses popular in Europe. Late 1700s Dutch East Indies plantations Early 1800s Plantations Caribbean & South

America Today Brazil and Columbia are world’s leading

producers.

Making TeaCamellia Sinensis

From leaves of Camellia sinensis. The leaves are plucked, dried and ground

to allow oxidation of the constituents thus increasing flavor.

History of Tea

The Portuguese Jesuit Father Jasper de Cruz on a missionary trip to China around 1560.

Along with the Dutch, the Portuguese developed the tea trade.

Introduced to England between 1652 and 1654.

Caffeine ContentCommon Products

Drip coffee.....115 mg Tea..................40 mg Cocoa..............13 mg Coca Cola........46 mg Diet Coke.........46 mg Dr. Pepper........40 mg Mr. Pibb............41 mg Mt. Dew............54 mg

Pepsi...............38 mg Surge...............51 mg Jolt Cola...........71 mg Excedrin...........65 mg Anacin..............32 mg NoDoz............100 mg Vivarin............200 mg Midol...............600 mg

Caffeine Acts on the central and peripheral

nervous systems

Member of a group of drugs called methylxanthines

Actions of Methylxanthines

Caffeine - most active as a CNS stimulant. Theophylline - most active outside the CNS. Theobromine - least active

Differences are related primarily by potency and site of action.

Act as antagonists of adenosine receptors. Adenosine is the neurotransmitter/neuromodulator

Actions of Caffeine

CNS stimulation - alertness and wakefulness,

Increased capacity for sustained intellectual effort and clear thinking

Increase in Heart Rate and force Smooth muscle relaxation especially in

respiratory track. Diuresis (increased urine production)

Pharmacokinetics

Absorption is nearly 100% Peak levels at 15-120 minutes. T1/2 of 3-5 hours. Distribution is seen in all sites in the body Metabolized by the liver Excreted in the urine - less than 5% of excreted as the

parent compound

Caffeine

Typical doses from 40 – 150 mg.

With short duration, doses are repeated every 2-4 hours (“coffee breaks”)

Doses >200-250 mg likely to produce extreme agitation.

Caffeine - High Doses

Extreme nervousness, insomnia, restlessness, and tremors

Convulsions Rapid heart rate Increase contractile force of the heart Cardiac arrhythmias Increased blood pressure Diuresis

Long Term Consequences

Nervousness, Irritability, Insomnia Increased heart rate, hypertension Gastric distress and ulcers Increased serum cholesterol

Athletics and Caffeine

No significant effect on athletic performance The NCAA limit for caffeine in urine is 15

micrograms per ml. Example: 2 cups coffee = urine levels of

3-6 micrograms per ml.

Caffeine Abuse

Dependance and withdrawal Caffeine addiction = “caffeinism” Caffeine in very high doses available in

“look-alike” pills - “legal stimulants” Dietary supplement products for

increased energy or appetite suppression.

Summary

General aspects of stimulant drugs. Common physiological actions. Overview of therapeutic usefulness. Adverse effects - acute and chronic. Differing mechanisms of action. Nicotine from tobacco. Caffeine from coffee, tea, other sources.