PHARMACOLOGY: CNS STIMULANTS

2 Groups of Drugs that Act Primarily Stimulate the CNS:

1. Psychomotor Stimulants
- Cause excitement and euphoria, decreased feelings of fatigue and increased motor activity

2. Hallucinogens / Psychotomimetic Drugs

- Produce profound changes in thought patterns and mood

I. Psychomotor Stimulants

A. Methylxanthines
o Theophylline (tea), theobromine (cocoa), caffeine (coffee)
o MOA – inhibition of cell surface receptors for adenosine
o Actions:
 CNS
- Caffeine (1-2 cups of coddee = 100mg – 200mg)
o Mental alertness and deferral of fatigue (12-15 cups = 1.5 mg)
o Anxiety and tremors
- very high doses (accidental/suicidal overdose)
o convulsions, death
 CVS
- Increase HR and force of contraction
- Slight BP increase, arrythmias
- Decreases blood viscosity and improve blood flow
 GIT
- Increase in gastric acid secretion and digestive enzymes (avoided in patients with peptic
ulcer)
- Kidney – caffeine – mild diuretic action
- Smooth muscle – bronchodilation
- Skeletal muscle – reverses fatigue of diaphragm in patients with COPD
o Therapeutic uses – theophylline – bronchodilation (asthma)
o Pharmacokinetics
 Well absorbed orally
 Caffeine
- Distributed throughout the body including the brain
- Cross the placenta to fetus
- Secreted into mothers’ milk
 Metabolized in liver
 Excreted in urine

B. Nicotine
o 2nd to caffeine as the most widely used CNS stimulant
o 2nd to alcohol as the most abused drug
o In combination with tars and carbon monoxide in cigarette smoke
 Lung and CV disorder, carcers
o Used in smoking cessation
o MOA
 Low doses – causes ganglionic stimulation
 High doses – causesganglionic blockage
o Actions:
 CNS
- Highly lipid soluble and readily crosses the BBB
o Low doses – euphoria, arousal, relaxation, improves learning, attention,
problem solving
o High doses – central respiratory paralysis, severe hypotension
o Appetite suppressant
o Peripheral effects
 Increase BP, increase HR
 VC -> decrease coronary flow
 Increase motor action
 High doses – decrease BP, activity ceases in GIT and bladder musculature
o Pharmacokinetics

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  Absorption readily occurs via the oral mucosa, lungs, GI mucosa and skin
 Crosses the placenta and secreted in milk
 Metabolized in lung and liver
 Excreted in urine

*Nicotine withdrawal Syndrome

- Nicotine is addictive and physical dependence develops rapidly
- characterized by irritability, anxiety, restlessness, difficulty in concertrating,
headaches and insomnia
- Bupropion – antidepressant, reduces the craving for cigarettes

C. Varenicline
o A partial agonist
o Useful as an adjunct in the management of smoking cessation in patients with nicotine withdrawal syndrome
o Should be monitored for suicidal thoughts, vivid nightmares, and mood changes

D. Cocaine
o Blocks reuptake of monoamines (norepinephrine, serotonin, and dopamine)
o Prolongation of dopaminergic effects in the brain’s pleasure center (limbic system) -> intense euphoria
o Chronic intake of cocaine -> depletes dopamine
o Action:
 Powerful stimulant of cortex and brainstem
 Increase mental awareness and feeling of well being, euphoria
 Hallucinations and delusions of grandiosity
 Increased motor activity
o Sympathetic nervous system
 Produces “fight/flight”
 Tachychardia, HPN, papillary dilation, peripheral VC
o Hyperthermia – impairment of sweating and cutaneous VD
 Perception of thermal discomfort decreased
o Therapeutic uses
 Local anesthetic – eye, ear, nose, throat surgery
*Cocaine is the only local anesthetic that causes VC
*VC is responsible for necrosis and perforation of nasal septum in chronic inhalation of cocaine powder

o Pharmacokinetics:
 Self-administered by chewing, intranasal, snorting, or IV injection
 Peak effect – 15-20 minutes after intranasal administration
 “high” disappears 1-1.5 hours
 Rapidly de-esterified, excreted in urine
 Detection in urine identifies a user

E. Amphetamine
o Noncatecholaminergic sympathetic amine
o MOA
 Indirect-acting
 Inhibits MAO
o Actions:
 CNS
- Major behavioral effects result from combination of its dopamine and norepinephrine
release-enhancing properties
- Stimulates the entire cerebrospinal axis, cortex, brainstem and medulla
o Increase alertness, decrease fatigue, decrease appetite, insomnia
- High doses – phychosis, convulsions
o Therapeutic uses uses
 Therapy for hyperactivity in children, narcolepsy and appetite control
1. Attention Deficit Hyperactivity Disorder (ADHD)
o Child is hyperkinetic and lacks the ability to be involved in one activity for longer than a few minutes

2. Narcolepsy
o A rare sleep disorder characterized by uncontrollable bouts of sleepiness during the day
o Sometimes associated by catalepsy (loss of muscle control) or even paralysis brought about by strong
emotions such as laughter

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 - Pharmacokinetics
o amphetamine is completely absorbed from the GIT, metabolized in the liver, excreted in urine
- Adverse effects:
o Chronic uses - “amphetamine psychosis”
o Confusion, panic state, suicidal tendencies
o Palpitations, arrhythmias, HPN, angina pain
- Contraindications:
o Amphetamine is not given to patients with HPN, history of drug abuse, hyperthyroidism, cardiovascular
diseases, glaucoma

*3,4-methylenedioxymethamphetamine (MDMA)
- “Ecstacy”
- Synthetic derivative of amphetamine

F. Methylphenidate
o MOA
 Blocks dopamine reuptake
*Less potential for abuse than cocaine because it enters the brain more slowly than cocaine, thus, it not increase dopamine rapidly
o Therapeutic uses:
 ADHD in children 6-16 years old
 Narcolepsy
o Pharmacokinetics:
 Rapidly absorbed on oral administration
 The de-esterified product, ritalinic acid, is excreted in the urine
o Interferes in the metabolism of warfarin, diphenylhydantoin, Phenobarbital, primodone, tricyclic
antidepressants
o Contraindicated in patients with glaucoma

II. Hallucinogens / Psychotomimetric Drugs

- Ability to induce altered perceptual states reminiscent of dreams
- Altered states are accompanied by bright, colorful changes in the environment and by plastic of constantly changing
shapes and color
- Interferes with rational thought, thus cannot make a normal decision

1. Lysergic Acid Diethylamide (lSD)

o Low doses – hallucinations with brilliant colors
o Activates the sympathetic nervous system – papillary dilation, increase BP, piloerection, increase
temperature

2. Tetrahydrocannabinol (THC)
o Main phychoactive alkaloid in marijuana
o Produces euphoria, followed by drowsiness and relaxation
o Stimulates appetite, produces, enhancement of sensory activity, impairs highly skilled motor activity
o Effects appear immediately after the drug is smoked but maxillary effects are seen 20 minutes after; by 3
hours the effects disappear
o Highly lipid soluble
o Elimination largely through biliary route
o Adverse effects:
o Increase HR, decrease BP, reddening of conjunctiva, toxic psychosis
*Dronabinol
 Appetite stimulant in patients with AIDS who are losing weight
 Given for severe emesis caused by some cancer chemptherapeutic agents
*Rimonabant – used to treat obesity – decreases appetite and body weight

3. Phencyclidine PCP / “angel dust”)

o Inhibits reuptake of dopamine, serotonin, norepinephrine
o Major Action
 Blocks ion channel regulated by NMDA subtype of glutamate receptor
o Produces hypersalivation, dissociative anesthesia, analgesia