CNS STIMULANTS

FINAL TERM

Psychomotor stimulants and hallucinogens

are two groups of drugs that act primarily to stimulate the central nervous system (CNS)

psycho motor stimulants

cause excitement and euphoria, decrease feelings of fatigue, and increase motor activity.

hallucinogens

produce profound changes in thought patterns and mood, with little effect on the brainstem and spinal cord

• theophylline

• theobromine

• caffeine

methylxanthines include

theophylline

methylxanthine found in tea

theobromine

methylxanthine found in cocoa

caffeine

methylxanthine that is considered most widely consumed stimulant in the world, is found in highest concentration in certain coffee products (for example, espresso), but it is also present in tea, cola drinks, energy drinks, chocolate candy, and cocoa.

methylxanthine

MOA:

• translocation of extra cellular calcium

• increase in cyclic adenosine monophosphate and cyclic guanosine monophosphate

• blockade of adenosine receptors.

caffeine

contained in one to two cups of coffee (100 to 200 mg) causes a decrease in fatigue and increased mental alertness as a result of stimulating the cortex and other areas of the brain

1.5 g

Consumption of ____ g of caffeine (12 to 15 cups of coffee) produces anxiety and tremors

very high doses (2 to 5 g) of caffeine

The spinal cord is stimulated only by ____ doses of caffeine.

fatigue and sedation.

Tolerance can rapidly develop to the stimulating properties of caffeine, and withdrawal consists of feelings of

high dose

____ dose of caffeine has positive inotropic and chronotropic effects on the heart

[Note: Increased contractility can be harmful to patients with angina pectoris. In others, an accelerated heart rate can trigger premature ventricular contractions.]

caffeine

has a mild diuretic action that increases urinary output of sodium, chloride, and potassium.

methylxanthines

stimulate secretion of gastric acid, individuals with peptic ulcers should avoid foods and beverages containing this

Caffeine and its derivatives

relax the smooth muscles of the bronchioles.

theophylline

Previously the mainstay of asthma therapy, ____ has been largely replaced by other agents, such as β2 agonists and corticosteroids

β2 agonists and corticosteroids

Previously the mainstay of asthma therapy, theophylline has been largely replaced by other agents, such as ___ and ___

caffeine

is also used in combination with the analgesics acetaminophen and aspirin for the management of headaches in both prescription and over-the-counter products

true

methylxanthines are well absorbed orally. TRUE OR FALSE

caffeine

distributes throughout the body, including the brain. These drugs cross the placenta to the fetus and are secreted into the breast milk.

methylxanthines

are metabolized in the liver, generally by the CYP1A2 pathway, and the metabolites are excreted in the urine

moderate doses of caffeine

caffeine in this dose can cause insomnia, anxiety, and agitation.

high doses of caffeine

this dose of caffeine is required for toxicity, which is manifested by emesis and convulsions.

10 g of caffeine

The lethal dose is ___ g of caffeine (about 100 cups of coffee), which induces cardiac arrhythmias.

true

Death from caffeine is highly unlikely. true or false

Lethargy, irritability, and headache

occur in users who routinely consume more than 600 mg of caffeine per day (roughly six cups of coffee per day) and then suddenly stop.

nicotine

is the active ingredient in tobacco

nicotine

not currently used therapeutically (except in smoking cessation therapy

nicotine

second only to caffeine as the most widely used CNS stimulant and it is second only to alcohol as the most abused drug.

nicotine

In combination with the tars and carbon monoxide found in cigarette smoke, ____ represents a serious risk factor for lung and cardiovascular disease, various cancers, and other illnesses

nicotine

Dependency on the drug is not easily overcome.

low doses of nicotine

this dose of nicotine causes ganglionic stimulation by depolarization.

high doses of nicotine

at this dose, nicotine causes ganglionic blockade.

true

Nicotine receptors exist at a number of sites in the CNS, which participate in the stimulant attributes of the drug. TRUE OR FALSE

nicotine

found in cigarette that is highly lipid soluble and readily crosses the blood–brain barrier.

low doses of nicotine

this dose of nicotine produces some degree of euphoria and arousal, as well as relaxation. It improves attention, learning, problem solving, and reaction time.

high doses of nicotine

this dose of nicotine result in central respiratory paralysis and severe hypotension caused by medullary paralysis

nicotine

• produces some degree of euphoria and arousal, as well as relaxation. It improves attention, learning, problem solving, and reaction time.

• result in central respiratory paralysis and severe hypotension caused by medullary paralysis

• appetite suppressant

nicotine

peripheral effects of ___are complex. Stimulation of sympathetic ganglia as well as of the adrenal medulla increases blood pressure and heart rate.

tobacco

is particularly harmful in hypertensive patients.

exacerbation of symptoms

Many patients with peripheral vascular disease experience an ____of symptoms with smoking.

nicotine induced vasoconstriction

can decrease coronary blood flow, adversely affecting a patient with angina

nicotine

At higher doses, blood pressure falls and activity ceases in both the gastrointestinal (GI) tract and bladder musculature as a result of a nicotine-induced block of parasympathetic ganglia

Nicotine

is highly lipid soluble, absorption readily occurs via the oral mucosa, lungs, GI mucosa, and skin. crosses the placental membrane and is secreted in the breast milk.

60 mg

The acute lethal dose of nicotine is

nicotine

The CNS effects of ___ include irritability and tremors. may also cause intestinal cramps, diarrhea, and increased heart rate and blood pressure. In addition, it increases the rate of metabolism for a number of drugs.

nicotine

Withdrawal is characterized by irritability, anxiety, restlessness, difficulty concentrating, headaches, and insomnia. Appetite is affected, and GI upset often occurs.

pharmacologic and behavioral therapy

Smoking cessation programs that combine ___ and ___ are the most successful in helping individuals to stop smoking.

transdermal patch and chewing gum containing nicotine

have been shown to reduce nicotine withdrawal symptoms and to help smokers stop smoking

inhaler, nasal spray, and lozenges.

nicotine replacement used for smoking cessation include the

bupropion

an antidepressant, can reduce the craving for cigarettes.

nicotine

is a full agonist at neuronal nicotinic acetylcholine receptors in the CNS

varenicline

is a partial agonist at neuronal nicotinic acetylcholine receptors in the CNS.

varenicline

produces less euphoric effects than nicotine

varenicline

is useful as an adjunct in the management of smoking cessation in patients with nicotine withdrawal symptoms.

varenicline

attenuate the rewarding effects of nicotine

varenicline

Patients taking ___should be monitored for:

• suicidal thoughts

• vivid nightmares,

• mood changes.

cocaine

is a widely available and highly addictive drug. Because of its abuse potential, cocaine is classified as a Schedule II drug by the U.S. Drug Enforcement Agency.

cocaine

MOA is blockade of reuptake of the monoamines (norepinephrine, serotonin, and dopamine) into the presynaptic terminals.

This potentiates and prolongs the CNS and peripheral actions of these monoamines. In particular, the prolongation of dopaminergic effects in the brain’s pleasure system (limbic system) produces the intense euphoria that this drug initially causes.

cocaine

Chronic intake of ___ depletes dopamine. This depletion triggers the vicious cycle of craving for this drug that temporarily relieves severe depression

amphetamine

is a sympathetic amine that shows neurologic and clinical effects quite similar to those of cocaine.

Dextroamphetamine

is the major member of this class of amphetamine

methamphetamine

also known as “speed”

methamphetamine

is a derivative of amphetamine available for prescription use. It can also be smoked and is preferred by many abusers.

3,4-Methylenedioxymethamphetamine (also known as MDMA, or Ecstasy)

is a synthetic derivative of meth amphetamine with both stimulant and hallucinogenic properties

amphetamine

effect on the CNS and peripheral nervous system are indirect. That is, both depend upon an elevation of the level of catecholamine neurotransmitters in synaptic spaces. this achieves this effect by releasing intracellular stores of catecholamines

amphetamine

• releasing intracellular stores of catecholamines

• inhibits monoamine oxi dase (MAO)

• weak reuptake transport inhibitor, high levels of catecholamines are readily released into synaptic spaces

amphetamine

stimulates the entire cerebrospinal axis, cortex, brainstem, and medulla. This leads to increased alertness, decreased fatigue, depressed appetite, and insomnia.

amphetamine

The CNS stimulant effects of ____ and its derivatives have led to their use in therapy for hyperactivity in children, for narcolepsy, and for appetite control.

amphetamine

At high doses, psychosis and convulsions can ensue

amphetamine

acts on the adrenergic system, indirectly stimulating the receptors through norepinephrine release.

amphetamine

Factors that limit the therapeutic usefulness of ___ include psychological and physiologic dependence similar to those with cocaine and, with chronic use, the development of tolerance to the euphoric and anorectic effects.

amphetamine

therapeutic use include:

• ADHD

• narcolepsy

• appetite suppression

is completely absorbed from the GI tract, metabolized by the liver, and excreted in the urine.

ADHD

are hyperkinetic and lack the ability to be involved in any one activity for longer than a few minutes.

• Dextroamphetamine

• methamphetamine

• mixed amphetamine salts

• methylphenidate

can help improve attention span and alleviate many of the behavioral problems associated with this syndrome, in addition to reducing hyperkinesia.

Lisdexamfetamine

is a prodrug that is converted to the active component dextroamphetamine after GI absorption and metabolism.

Atomoxetine

is a nonstimulant drug approved for ADHD in children and adults.

[Note: This drug should not be taken by individuals on MAO inhibitors and by patients with angle closure glaucoma.]

atomoxetine

Unlike methylphenidate, which blocks dopamine reuptake more than norepinephrine reuptake, ___ is more selective for inhibition of norepinephrine reuptake. Therefore, it is not considered habit forming and is not a controlled substance.

methylphenidate

Unlike ___, which blocks dopamine reuptake more than norepinephrine reuptake, atomoxetine is more selective for inhibition of norepinephrine reup take. Therefore, it is not considered habit forming and is not a controlled substance.

narcolepsy

is a relatively rare sleep disorder that is characterized by uncontrollable bouts of sleepiness during the day

• catalepsy

• paralysis

Narcolepsy is a relatively rare sleep disorder that is characterized by uncontrollable bouts of sleepiness during the day. It is sometimes accompanied by ___, a loss in muscle control, and even ___ brought on by strong emotions such as laughter.

mixed amphetamine salts or methylphenidate

sleepiness of narcolepsy can be treated with drugs, such as the

• Modafinil

• armodafinil

___and its R-enantiomer derivative, ___, are considered first-line agents for the treatment of narcolepsy.

may have some potential for abuse and physical dependence, and both are classified as controlled substances

modafinil

• promotes wakefulness, but it produces fewer psychoactive and euphoric effects and fewer alterations in mood, perception, thinking, and feelings typical of other CNS stimulants.

• The mechanism of action remains unclear, but may involve the adrenergic and dopaminergic systems.

• effective orally.

• Headaches, nausea, and nervousness are the primary adverse effects.

• Phentermine

• diethylpropion

are sympathomimetic amines that are related structurally to amphetamine. These agents are used for their appetite-suppressant effects in the management of obesity

sodium bicarbonate

Administration of urinary alkalinizing agents such as ____ will increase the nonionized species of amphetamine and enhance the reabsorption of dextroamphetamine from the renal tubules into the bloodstream.

IV injection and/or by smoking

Amphetamine abusers often administer the drugs by

amphetamine

The euphoria caused by ____ lasts 4 to 6 hours, or four- to eightfold longer than the effects of cocaine.

amphetamine

may cause addiction, leading to dependence, tolerance, and drug-seeking behavior. In addition, they have the following undesirable effects

Amphetamine

Adverse effects of usage include insomnia, irritability, weakness, dizziness, tremor, and hyper active reflexes. can also cause confusion, delirium, panic states, and suicidal tendencies, especially in mentally ill patients.

benzodiazepine (lorazepam)

are often used in the management of agitation and CNS stimulation secondary to amphetamine overdose.

Chronic amphetamine use

produces a state of “amphetamine psychosis” that resembles the psychotic episodes associated with schizophrenia.

long-term amphetamine use

associated with psychic and physical dependence, tolerance to its effects may occur within a few weeks

amphetamine

The anorectic effect of ____ is due to its action in the lateral hypothalamic feeding center

amphetamine

In addition to its CNS effects, __ causes palpitations, cardiac arrhythmias, hypertension, anginal pain, and circulatory collapse. Headache, chills, and excessive sweating may also occur.

acts on the GI system, causing anorexia, nausea, vomiting, abdominal cramps, and diarrhea

amphetamine

Patients with hypertension, cardiovascular disease, hyperthyroidism, glaucoma, or a history of drug abuse or those taking MAO inhibitors should not be treated with

Methylphenidate

has CNS-stimulant properties similar to those of amphetamine and may also lead to abuse, although its addictive potential is controversial. It is a Schedule II drug.

Methylphenidate

is presently one of the most prescribed medications in children. It is estimated that 4 to 6 million children in the United States take this drug daily for ADHD.

Methylphenidate

a Schedule II drug used for the treatment of ADHD