Cns stimulants

1. CNS Stimulants
By
Dr. Sajjad Ali
Senior Lecturer Pharmacology

6. Classification
1. Psychomotor Stimulants
 Caffeine
 Cocaine
 Nicotine
 Amphetamine
 Theophylline
2. Hallucinogens
 Dronabinol
 Lysergic acid diethylamide
 Phencyclidine
 Tetrahydocannabinol

7. Psychomotor Stimulants
 These agents produces euphoria
 Cause excitement
 Decrease fatigue

8. Methylxanthines
• Methylxanthines includes;
• theophylline which is found
in tea
• Theobromine found in
cocoa
• Caffeine found mainly in
coffee

9. Mechanism of Action of
Methylxanthine
• Methylxanthines inhibit phosphodiesterase
(PDE), the enzyme that degrades cAMP to AMP
• Thus by inhibiting enzyme PDE , the intracellular
conc. Of cAMP increases as a result
bronchodilation occurs
• Moreover methylxanthine also block adenosine
receptors in CNS, but relation between this action
and the bronchodilating effect is not known

10. Other effects of methylxanthines
• Other effects of methylxanthine which can
occur at therapeutic doses include;
CNS stimulation
Cardiac stimulation
Vasodilation
Slightly increase in B.P.
Diuresis
Increased GIT motility

11. Dose related effects of caffeine
Very high doses of caffeine (2-5 g of
caffeine ) causes stimulation of spinal
cord and more severe CNS as well as
peripheral effects
Tolerance:
 Tolerance can develop rapidly to the
stimulating properties of caffeine
 Withdrawal reactions consist of feeling
fatigue and sedation

12. Dose related effects of caffeine
100-200 mg of caffeine which is contained
in one to two cups of coffee have following
effects;
1. Decrease fatigue
2. Increase mental alertness by stimulating
cortex and other areas of brain
Consumption of 1.5 g of coffee which is
contained in 12-15 cups of coffee causes;
1. Tremors
2. anxiety

13. Clinical uses
1) Aminophylline salt is most commonly used
for the treatment of;
Asthma
COPD
2) Caffeine is commonly used for its diuretic
effects

14. Pharmacokinetics
• Methylxanthines are well absorbed orally
• Distributes throughout the body
including brain
• These drugs can cross placenta to the
fetus and secreted into mother’s milk
• All methylxanthines are metabolized in
liver generally via CYP1A2
• Metabolites are excreted in urine

15. Adverse effects
 Peptic ulcer
Moderate doses cause;
 Insomnia
 Agitation
High doses cause;
 Emesis
 Convulsions
Lethal doses cause(10 g of caffeine/ about 100 cups
of coffee);
 Cardiac arrhythmia
 Death

16. Cocaine
 It is widely available and
highly addictive drug that is
currently abused daily by
more than 3 million people
in US
Mechanism of Action:
 it blocks reuptake of
monoamines
(norepinephrine, serotonin
and dopamine) into
presynaptic nerve endings

17. Actions
CNS:
 It causes stimulation of the cortex and
brainstem
 It increases mental awareness and produces a
feeling of well being and euphoria
 It also produces hallucinations and delusions
 It increases convulsions and tremors

18. Sympathetic Nervous system
 Peripherally it potentiates the action of action
of norepinephrine, and it produces the fight
and flight syndrome
 It causes hyperthermia
Therapeutic Uses:
 It has local anesthetic effects
 It is applied topically

19. Adverse effects
 Anxiety
 Seizures
 Arrhythmias
 Respiratory failure
 Hypertension
 Agitation
 Death (R.I.P)

20. Amphetamine
Mechanism of Action:
 Amphetamine increase the
release of catecholamine in
the synaptic spaces
 It also inhibits the actions of
MAO (monoamine oxidases)
in presynaptic nerve ending
 By doing so more
catecholamine is released
into the synaptic space

21. Therapeutic Uses of Amphetamine
 It is used for the treatment
of following diseases
1. Attention deficit
hyperactivity
disorder(ADHD)
2. Narcolepsy
- Narcolepsy is a sleep disorder
characterized by uncontrolled
bouts of sleepiness during day
time

23. Pharmacokinetics
 It is completely absorbed from the GIT Tract,
metabolized by liver and excreted by urine
 Amphetamine abusers often administer the
drug Via IV route
 Euphoria caused by amphetamine lasts 4-
hours

24. Adverse effects
 Vertigo
 Hypertension
 Insomnia
 Confusion
 Potential for addiction
 Nausea
 Diarrhea

25. Nicotine
 It is the active ingredient in tobacco
 It is not currently used therapeutically
 It is second only to the caffeine as the most
widely used CNS stimulant
 It is second only to alcohol as the most abused
drug

26. Mechanism of Action
 In low doses, it causes ganglionic stimulation by
depolarization
 At high doses, it causes ganglionic blockade
Actions:
CNS:
 It is highly lipid soluble and readily crosses the
blood brain barrier
 At low dosing it produces euphoria and arousal
 It improves attention, learning, problem solving
and reaction time

27.  At high doses it causes respiratory paralysis
and severe hypotension caused by medullary
paralysis
 It is appetite suppressant
Peripheral effects:
 It stimulates sympathetic nervous system as a
result B.P. and H.R. increases
 It also stimulates parasympathetic ganglia as a
result motor activity in GIT increases

28. Pharmacokinetics
 It is highly lipid soluble
 The acute lethal dose is 60mg
 1-2mg of nicotine per cigarette
 It is metabolized in lungs and liver
 It is excreted via urine
 Tolerance develops rapidly

29. Adverse effectsa
 Irritability
 Tremors
 Intestinal cramps
 Diarrhea
 Increased H.R.
 Increased B.P.
 Increased metabolism of a
number of drugs

30. Withdrawal Syndrome
 Nicotine produces physical dependence as it is a
substance having additive potential
 Withdrawal symptoms are;
Irritability
Restlessness
Anxiety
Difficulty in concentrating
Headaches
GIT pain

31. Varenicline
 It is a partial agonist at neuronal nicotinic
receptors in CNS
 It produces less euphoric effects than that by
nicotine
 It is useful in management of smoking
cessation

32. Hallucinogens
Lysergic acid diethylamide:
 It exhibits serotonin agonist activity at presynaptic 5-HT1
receptors in the mid brain it also stimulates 5-HT2
receptors
 It is taken orally
 It causes;
i. Pupillary dilation
ii. Increased B.P.
iii. Increased body temperature
iv. It induces hallucination with brilliant colors
v. It alters mood
vi. Tolerance and physical dependence occurs

33. Adverse effects:
 Hyperreflexia
 Nausea
 Muscular weakness

34. Tetrahydrocannabinol
 The main psychoactive agent contained in
marijuana is tetrahydrocannabinol
 Tetrahydrocannabinol is available as dronabinol
 This product is prescribed to treat emesis and to
stimulate appetite
 Dronabinol can produce euphoria
 Drowsiness
 Relaxation

37.  THC decreases muscle strength and impairs
highly skilled motor activity such as that
required to drive a car
 THC has following side effects;
1. Tachycardia
2. Hypertension
3. Hallucination

38. Phencyclidine (PCP)
 It is also known as angel dust
 It inhibits the reuptake of dopamine, 5-HT and
norepinephrine neurotransmitters into the
presynaptic nerve endings
 It is an analog of ketamine, which produces
dissociative anesthesia (insensitivity to pain
without loss of consciousness) and analgesia

39.  PCP has no therapeutic
importance
 Its manufacturing in USA is
an illegal process

40. THE END