cns stimulants and drug abuse.pdf

Stimulants work by acting on the central nervous system (CNS) to increase alertness and cognitive function. Stimulants can be prescription medications or illicit substances, such as Cocaine. Stimulants may be taken orally, snorted, or injected. If you have a Stimulant addiction, seek help today.

1. CNS stimulants
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VIJAY SALVEKAR
DEPT. OF PHARMACOLOGY
GRY INSTITUTE OF PHARMACY

2. DrugsofAbuse
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Drug abuse is the nonmedical, self-
administered use of a drug that is harmful
to the user, generally act on the CNS to
modify the user’s mental state, although
some are used for enhancing physical
performance.
Common abused drugs include:
•CNS stimulants (e.g., cocaine, amphetamines,nicotine),
•hallucinogens (e.g., LSD, mescaline, phencyclidine, andmarijuana).
•general CNS depressants (e.g.,ethanol),
•sedative–hypnotics (e.g., alprazolam,diazepam),
•opioid analgesics (e.g.,heroin),
•inhalants (e.g., toluene, nitrous oxide, amylnitrate).

3. CNS stimulants“sympathomimetics”
Few clinical uses, Important as drugs of abuse. A primarymotivation
for drug abuse appears to be the anticipated feeling of pleasure
derived from the CNS effects of thedrug.
Factors that limit the therapeutic usefulnessinclude:
1.
2.
3.
Physiological “Physical” Dependence:.
Psychological Dependence“Addiction”
Tolerance to the euphoric and anorecticeffects
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4. are classified according to their actioninto:
1.Psychomotor stimulantscause: excitement, euphoria,decrease
feeling of fatigue & Increase motoractivity
Ex., Methylxanthines (caffeine, theobromine, theophylline), nicotine,
cocaine, amphetamine, atomoxetine, modafinil,methylphenidate.
2.Hallucinogens (psychotomimetic):Affect thought, perception,and
mood, thereforeproduce
profound changes in thought patterns &mood,
little effect on the brain stem & spinalcord
Ex., Lysergic acid diethylamide (LSD), Phencyclidine(PCP),
Tetrahydrocannabinol (THC),Rimonabant.
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CNS stimulants“sympathomimetics”

5. Psychomotorstimulants
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Q. What areStimulants?
Chemical structure are similar to monoamine
neurotransmitters. All are indirect-actingsympathomimetics:
1.Many CNS stimulants release catecholamines,
Therefore, their effects are abolished by prior treatment
with reserpine orguanethidine
Ex:amphetamine,dextroamphetamine,methamphetamine,
methylphenidate(Ritalin),ephedrine,pseudoephedrine
(astereoisomerofephedrine),tyramine.
2.OtherCNSstimulantsblockthereuptakeof
catecholamines(NEandDA)andserotonin:
EX.Cocaine,sibutramine(reduct)
®,modafinil

6. 3.Antidepressants drugs with stimulant effects:
Atomoxetine–a relatively selective NE reuptake inhibitor (ADHD),
Bupropion –blocks the reuptake of both NE andDA.
4.The methylxanthines are adenosine receptor
antagonists.Drugs within this class are NOT
generally considered “psychomotor” stimulants, but
they have distinct stimulant effects caffeine,
theophylline.
NB: MAO and COMT inhibitors (indirect-acting adrenergicagonists),
but they are not traditionally considered to bestimulants.
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Psychomotorstimulants

7. Therapeutic Indications of CNSStimulants
Obesity (anorecticagents).
Attention Deficit Hyperactivity Disorder (ADHD); lack
the ability to be involved in any one activity for longer
than a fewminutes.
Narcolepsy: It is a relatively rare sleep disorder, that is
characterized by uncontrollable bouts of sleepiness
during the day. It is sometimes accompanied by
catalepsy, a loss in muscle control, or even paralysis
brought on by strong emotion, such aslaughter.
Contraindications for CNSStimulants:
anorexia, insomnia, asthenia, psychopathic personality, a
history of homicidal or suicidaltendencies.
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8. 1. Psychomotorstimulants
A.methylxanthines
1.Theophylline (found in tea) : long-acting, prescribed for
night-timeasthma
2.Theobromine: found incocoa.
3.Caffeine: (short-acting) the most widelyconsumed
found in coffee (200 mg/cup),
carbonated soft drinks (60mg/can),
cocoa andchocolate
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9. Mechanism of action:include
several mechanism have beenproposed
Mechanism of action ofmethylxanthine
1-It inhibits phosphodiesterase enz. → ↑cAMP
2-Adenosine (A1, A2 and A3) receptors antagonist almostequally,
which explains many of its cardiaceffects
A2 receptors antagonist responsible for CNS stimulation&
smooth musclesrelaxation
↓calcium in Smoothmuscles↑ calcium in CNS &heart
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10. Actions
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a.CNS:
decrease in fatigue, increased alertness: 100-200 mg caffeine in
1 or 2 cups ofcoffees
Anxiety & tremors-1.5 g of caffeine: 12-15 cups ofcoffee
Spinal cord stimulation: 2-5 g (very highdose)
Tolerance can rapidlydevelop
Withdrawal symptoms: feeling of fatigue &sedation.
b.CVS:at high dose of caffeine +ve inotropic andchronotropic
effects on the heart,↑COP
c.Diuretic action:mild ↑ urinary output of Na+, Cl
-andK
+
d.Gastric mucosa:all methylxanthines stimulate secretion of
HCl
e.Respiratory smooth muscle:bronchodilator, Rx asthma
replaced by β-agonists,corticosteroids.

11. Pharmacokinetics
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Themethylxanthinesarewellabsorbedorally.
Caffeinedistributesthroughoutthebody,includingthe
brain.Thedrugscrosstheplacentatothefetusandis
secretedintothemother'smilk.
Allaremetabolizedintheliver,generallybytheCYP1A2
pathway,themetabolitesarethenexcretedintheurine.
Adverseeffects
Moderate doses: insomnia, anxiety,agitation
High doses: emesis,convulsion
Lethal dose (10 gm of caffeine): cardiacarrhythmia
Suddenly stop: lethargy, irritability,headache

12. B.Nicotine:
Nicotine is the active ingredient intobacco.
Used in smoking cessationtherapy,
Nicotine remains important, because it is 2
nd only to
caffeine as the most widely used CNS stimulant and 2
nd
only to alcohol as the most abuseddrug.
Actions ofNicotine:
Low dose: ganglionicdepolarization
High dose: ganglionicblockade
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13. Actions ofNicotine
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I.CNS:
1.Low dose: euphoria, arousal, relaxation, improves
attention, learning, problem solving and reactiontime.
2.High dose: CNS paralysis, severe hypotension
(medullaryparalysis)
II. Peripheraleffects:
Stimulation of sympathetic ganglia and adrenal
medulla→↑ BP and HR (harmful in HTNpatients)
Stimulation of parasympathetic ganglia→↑ motor
activity of thebowel
At higher doses, BP falls & activating ceases in both
GIT andbladder

14. Pharmacokinetics:
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highly lipid soluble absorbed everywhere (oral mucosa,
lung, GIT,skin).
Crosses the placental membrane, secreted withmilk.
Most cigarettes contain 6-8 mg of nicotine, by inhaling
tobacco smoke, the average smoker takes in 1 to 2mg
of nicotine percigarette.
the acute lethal dose is 60mg,
90% of nicotine inhaled in smoke isabsorbed.
Toleranceto toxic effects of nicotine developsrapidly.

15. Adverseeffects:
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CNS; irritability andtremors
Intestinal cramps,diarrhea
↑HR &BP
Withdrawal syndrome: nicotine is addictivesubstance,
physical dependence on nicotine develops rapidly and can
be severe.
Bupropion: can reduce the craving forcigarettes
Transdermal patch and chewing gum containingnicotine
Varenicline

16. Varenicline(Chantix in the USA and Champix inCanada)

:
partial agonist at Nn receptor inCNS.
It produces less euphoric effects than those produced
by nicotine itself (nicotine is full agonist at these
receptors).
Thus, it is useful as an adjunct in the management of
smoking cessation in patients with nicotine withdrawal
symptom.
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17. C. Cocaine(highly addictivedrug)
1. Mechanism of action:blockade of reuptake
of the monoamines (NE, serotonin and
dopamine)Thus,potentiates and prolongs the
CNS and peripheral actions of these
monoamines.
Initially produces the intense euphoria or “rush” by prolongation of
dopaminergic effects in the brain’s pleasure system (limbic
system).
It is this immediate positive reinforcement, followed rapidly by the
negative reinforcement, that makes the drug, particularly in this
form, soaddictive.
Chronic intake of cocaine depletes dopamine. This depletion
triggers the vicious cycle of craving for cocaine that temporarily
relieves severedepression.
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18. Cocaine
Cocainehasminimalbioavailabilitywhentakenbythe
oralroute.
Instead,thecocainehydrochloridepowderissnorted,or
solubilizedandinjected.Thecocainepowdercannotbe
effectivelysmoked,asitisdestroyeduponheating.
However,crackcocaine,analkaloidalform,canbe
smoked.
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19. 2.Actions:
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a. CNS-behavioral effects result from powerful stimulation
of cortex and brainstem.
Cocaine acutely increase mental awareness and
produces a feeling of wellbeing and euphoria similar to
that produced byamphetamine.
Like amphetamine, cocaine can produce hallucinations
and delusions of paranoia or grandiosity.
Cocaine increases motor activity, and at high doses, it
causes tremors and convulsions, followed by
respiratory and vasomotordepression.

20. b.SympatheticNS:
peripherally potentiate the action of NE→ fight orflight
c.Hyperthermia:
impair sweating & cutaneousvasodilation
↓Perception of thermaldiscomfort
d.local anestheticaction:
blockade of voltage-activated Na
+
channel.
Cocaine is the only LA that causes vasoconstriction, chronic
inhalation of cocaine powder → necrosis and perforation ofthe
nasalseptum
Cocaine is often self-administered by chewing,intranasal
snorting, smoking, or intravenous (IV)injection.
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2.Actions:

21. Adverseeffects:
Anxiety reaction that includes: hypertension, tachycardia,
sweating, andparanoia.
Because of the irritability, many users take cocaine withalcohol
A product of cocaine metabolites and ethanol is cocaethylene,which
is also psychoactive and causecardiotoxicity.
Depression: Like all stimulant drugs, cocaine stimulation ofthe
CNS is followed by a period of mentaldepression.
Addicts withdrawing from cocaine exhibit physical and emotional
depression as well as agitation. The latter symptom can betreated
with benzodiazepines orphenothiazines.
Toxiceffects:
Seizures RX I.Vdiazepam
fatal cardiac arrhythmias.propranolol
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22. D.Amphetamine
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Is a non catecholamine, (shows neurologic and clinical
effects quite similar to those of cocaine),
dextroamphetamine is the major member of this class
compounds.
methamphetamine (speed) is a derivative of
amphetamine that can be smoked and it is preferredby
many abusers.
Methylenedioxymethamphetamine (also known as
MDMA, or Ecstasy or Molly) is a synthetic derivative of
methamphetamine with both stimulant and
hallucinogenicproperties.

23. 1. Mechanism ofaction:
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Amphetamine, actby
releasing intracellular stores of
catecholamines.
also inhibits MAO, high level CAOs are
readily released into synapticspaces.
2.Actions:
a.CNS:a combination of its dopamine and NE release
enhancingproperties.
Amphetamine stimulates the entire cerebrospinal axis, brainstem,
and medulla.This lead to increase alertness, decrease fatigue,
depressed appetite, andinsomnia.
b.Sympathetic Nervous System: indirectly stimulating the
receptors through NErelease.

24. 4. Adverseeffects:
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addiction, dependence, tolerance, and drug seeking
behavior.
a. CNS:insomnia, irritability, weakness, dizziness, tremor,
hyperactive reflex, confusion, delirium, panic states, and
suicidal tendencies, especially in mentally illpatients.
-Chronic amphetamine use produce a stateof
“amphetamine psychosis” that resembles thepsychotic
episodes associated withschizophrenia.
Overdoses are treated with chlorpromazine or haloperidol,
which relieve the CNS symptoms as well as the HTN
because of their α–blockingeffects.
The anorectic effect of amphetamine is due to its actionin
the lateral hypothalamic feedingcenter.

25. 4. Adverseeffects:
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b.CVS:palpitations,cardiacarrhythmia,HTN,anginal
pain,andcirculatorycollapse.Headache,chills,and
excesssweatingmayalsooccur.
c.GIT:anorexia,nausea,vomiting,abdominalcramps,and
diarrhea.
Contraindications:
HTN, CV diseases, Hyperthyroidism, Glaucoma, Patients
with a history of drugabuse

26. Narcolepsy:
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Amphetamine,methylphenidate.
Recently, a new drug, modafinil and its R-enantiomer
derivative, armodafinil, have become available to treat
narcolepsy.
Modafinil produces fewer psychoactive and euphoric
effects as well as, alterations in mood, perception,
thinking, and feelings typical of other CNSstimulants.

27. Atomoxetine
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approved for ADHD in children andadults.
It is a NE reuptake inhibitor (should not be taken by
individual onMAOI).
It is not habit forming and is not a controlledsubstance.

28. Methylphenidate(Ritalin)®
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It has CNS stimulant properties similar to those of
amphetamine and may also lead to abuse, although its
addictive potential iscontroversial.
Itistakendailyby4-6millionchildrenintheUSA.The
pharmacologicallyactiveisomer,Dexmethylphenidate,
hasbeenapprovedintheUSAfortheRxofADHD.
Methylphenidate is a more potent dopamine transport
inhibitor than cocaine, thus making more dopamine
available.
It has less potential for abuse than cocaine, because it
enters the brain much more slowly than cocaine and,
does not increase dopamine levels asrapidly.

29. 2. Therapeuticuses:
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Methylphenidate has been used for several decades in
the treatment of ADHD in children aged 6 to16.
It is also effective in the treatment of narcolepsy.
Unlike methylphenidate, dexmethylphenidate is not
indicated in the treatment ofnarcolepsy

30. 3. Adversereactions:
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GIT effects are the most common; abdominal pain and
nausea.
Other reactions include anorexia, insomnia, nervousness,
andfever.
Inseizurepatients,methylphenidateseemstoincrease
theseizurefrequency,especiallyifthepatientistaking
antidepressants.
Methylphenidateiscontraindicatedinpatientswith
glaucoma.

31. E. Synthetic Cathinones “bathsalts,”
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Cathinone is the psychoactive component in an evergreen
shrub called Khat. Work in a manner very similar to
cocaine andamphetamines.
Bath salts are generally snorted or ingested, but they may
also be injected.
Ex., Methcathinone, butylone, methylene dioxypyrovalerone,and
naphyrone
These products are packaged and labeled in such a way as
to circumvent detection, prosecution, andenforcement.

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