Lecture Delivered to B.Sc (hnrs) Nursing & B.Sc Physiotherapy

1. CNS Stimulants &
Drugs of Abuse
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2. CNS Stimulation??
“Range of behaviors that includes
mild elevation in alertness,
increased nervousness, anxiety &
Convulsions”

3. • Analeptics.
• Psychomotor stimulants.
• Psychotomimetics.

4. • Analeptics
– Respiratory stimulants & Convulsants.
• Psychomotor Stimulant
– Excitement & Euphoria
– Decrease feeling of Fatigue
– Increase Motor activity
• Psychotomimetic Drugs ( Hallucinogens )
– Changes in Thought Patterns & Mood
– Little Effect on Brain stem & Spinal Cord
NO CLINICAL USE
Group of Abused Drugs along with CNS depressants &
Narcotic Drugs.

5. • Hyper excitability:
associated with drug administration
(Desired or Undesired)
– Results from
• Alteration in fine balance normally maintained in CNS
(between excitatory & Inhibitory influences)
1. Potentiation/Enhancement of Excitatory Transmission
2. Depression/Antagonism of Inhibitory Transmission
3. Pre-synaptic control of Neurotransmitter Release

6. Balance
• Excitatory Influences
Excitatory Neurotransmitters
• Inhibitory Influences
GABA …… Inhibitory Neurotransmitter
Glycine ….. Inhibitory Neurotransmitter

7. Classifications

8. On the Basis of Site Of Action
Cerebral Stimulants
Xanthines (PDE Inhibitors ….. cAMP, cGMP
(ADENOSINE Receptor Blockade …. Stimulant action
– Caffeine,
– Theophylline, (Also Bronchodilators)
– Theobromine
(Tonic Uncoordinated Convulsions)
Medullary Stimulants
– Picrotoxin (Close Cl- Channel … GABA)
( Tonic Clonic Coordinated Convulsions )
Spinal cord Stimulants
– Strychnine ( Competitive Antagonist of Glycine)
(Tonic Clonic Uncoordinated Convulsions

9. Classification (on the basis of effects)
• Convulsants & Respiratory Stimulants
– Amiphenazole
– Doxapram
– CONVULSANTS
• Nikethemide
• Strychnine …. (spinal Cord Stimulant )
• Picrotoxin ….( Brain Stem Stimulant )
• Pentylinetetrazole (PTZ)
Cntd;

10. • Psychomotor Stimulants
– Amphetamine
– Cocaine
– Nicotine
– Methlexanthines
• Caffeine ( Cerebral stimulant )
• Theophyline
• Psychomimetic Drugs ( Hallucinogens )
– Lysergic acid ( LSD )
– Tetrahydro Cannabinol (THC )
– Phencyclidine (PCP)
– Mescaline
– Psilocybin

11. Convulsants &
Resiratory stimulants

12. • Brainstem & Spinal cord
• Little effect on mental
function
• Exaggerated Reflexes
• Increased activity of
– Vasomotor Centre
– Respiratory Centre
– Convulsions
(High Dose )
– Amiphenazole
– Doxapram
– CONVULSANTS
• Nikethemide
• Strychnine ….
(spinal Cord Stimulant)
• Picrotoxin ….
(Brain Stem Stimulant )
• Pentylinetetrazole (PTZ)

13. • Clinically used (Bigger safety margin,
(OCCASIONAL )
– Amiphenazole
– Doxapram
– Nikethemide
• Experimental
– Strychnine
– Picrotoxin
– Pentylinetetrazole ( PTZ )

14. Strychnine (spinal cord Stimulant)
• Plant Alkaloid ( Indian Plant )
• Poison …. Vermin, Stray dogs,
• Tonic …. Very low dose ( both weary brain
& debillitated persons )
• Powerful convulsant
– Opisthotonous Position
• Violant Extensor spasm, Trigger With minor sensory stimuli
• MIMMIC Symptoms of TETANUS TOXIN
• Competitively Block receptors for GLYCINE
• TETANUS toxin Block Release of GLYCINE from
inhibitory neurons

15. Opisthotonous Position

16. Pentylenetetrazole (PTZ)
• Mechanism of action Unknown
(GABA mediated Cl- conductance By BZPs
is antagonised)
USES
– In Epilepsy Research Work
– PTZ induced convulsions EEG wave pattern
resembles Absence siezures ...
– To Check for Epileptic Tendency

17. Amiphenazole & Doxapram
(Medullary Stimulant )
• Bigger safety margin (Resp. Stimulation to convulsion)
• Occasionally used in pt. with acute Resp.
Failure.
• Doxapram cause
– Nausea
– Coughing
– Restlessness

18. Picrotoxin (Medullary Stimulant)
• Fish berry
• Block action of GABA …. Blocks Cl- Conductance
• Convulsions

19. Psychomotor Stimulants
Marked effect on mental
functions & Behaviour
• Produce Excitement, Euphoria
Reduce Sensation of Fatigue
Increase motor Activity
– Amphetamine
– Cocaine
– Nicotine
– Methylexanthines
• Caffeine ( Cerebral
stimulant )
• Theophyline

20. • Amphetamine
– Dextroamphetamine
– Methamphetamine
– Methylephenidate
• Methylene Dioxy MethAmphetamine
(EDMA …. ECSTASY )
STREET DRUG

21. Pharmacokinetics
• GIT,
• Nasal mucosa (Snoring)
• Cross BBB
• Unchanged in Urine. .. Excretion increase
when Urine is Acidic
• Plasma half life 5 -20 – 30 hrs
( Urine Flow & pH )

22. Mechanism of action
• Release Monoamines
– Noradrenaline, Dopamine, Serotonine (Fenfluramine)
Effect on Brian
• Locomotor stimulation
• Euphoria & Excitement
• Anorexia.
• Stereo typed behavior.
• Alertness. Grooming, Aggressive activity
• Peripheral Effect : increase B.P, Decrease GIT
motility.

23. Clinical Uses
• ADHD … ( Attention Deficit /Hyperactivity Disorder
– Methamphetamine
– Dexamphetamine
• Norcolepsy
– Disabling Condition … resemble Epilepsy
– Sudden, Unpredicted Fall asleep at frequent
intervals during a day …. Amphetamine HELPFUL
• Appetite Suppressant

24. Toxicity
• Amphetamine Psychosis, Schizopherinic attacks
• Repetitive attacks of Stereotyped behavior
• Tolerance/ Tachyphylaxis … to Peripheral Effects
• Sudden Death in “Ecstasy Users” ( single dose)
– Symptoms like Heat Stroke ( High Temp. Dehydration)
– Muscle damage
– Renal Failure
Water intoxication
Inappropriate secretion of Anti-diuretic Hormone
Increased thirst Increase in Water intake
Overhydration & Hyponatremia

25. COCAINE
• Coca … ( S. American Shrub )
• Reduce Fatigue during work ( at high altitude)
• INHIBIT NOR-ADRENALINE REUPTAKE I
• Peripheral Effects
– Sympathetic Effects
• Effects on Brain
– Euphoria
– Garrulousness
– Increase motor activity

26. Pharmackinetics
• Nasal route ….. ( many others )
• Perforation of nasal septem
• CRACK (oral)…. A street drug (smoked)
• Topical L/A in ophthalmology in
• Experimental Tool for study of Catecholamine release/
uptake I
TOXICITY
• Cardiac dysrhythmia
• Coronary Thrombosis, Cerebral Thrombosis
• Slowly developing damage to Myocardium… Failure

27. If Used in Pregnancy
• Impair brain development
• Brain size decreases in utero.
• Neurological & Limb malformation.
• Sudden infant death.

28. Xanthines
• PDE inhibitors ….. Bronchodilation
• Adenosine Receptor Blockade ….. Stimulant effect
• 100-200mg ( 1 cup Coffe) ….. Alert, Decrease Fatigue
• 1.5 Gm (13 cups) ….. Tremor, Anxiety
• 2-to-5 Gm ……………… Spinal Cord Stimulation
• Tolerance develop quickly to Stimulant Action
• Withdrawal causes fatigue & Sedation
• Increase HR & Contractility ….. Angina?? Dysrhythmia
• Diuretic Action
• Increase HCl in & Gastric secretions
• Insomnia, Anxiety, Agitation, CONVULSIONS (Lethal 10Gm)

29. Nicotine
• Tobacco, 2nd most used CNS stimulant after CAFFEINE
• Used to smoking cessation therapy
– Euphoria, arousal, Relaxation, Improve attention
• Toxicity
– Respiratory paralysis, Hypotension (High Dose)..Medulla
• Peripheral effects are mixed ….. GANGLION BLOCK
• Decrease Coronary flow …. Angina?? …Raynaud …
• Absorbs through skin …. Poison
• Cross BBB
• Irritability, Tremors, Intestinal Cramps, Diarrhea Lung
Cancer
• Ganglion Stimulation …. Depolarizing Block

30. Nicotine WITHDRAWAL
• Due to Physical Dependence
• Irritability, Anxiety, Restlessness, Difficulty in
Concentration, Intestinal Cramps, Appetite is
affected, Headache, Insomnia,
• Smoking cessation Programme
– Electric/Battery Operated Ciggrates
– Transdermal Patch
– Chewing Gum
– Behavioural Therapy
– BUPROPION (antidepressant) decrease craving

31. Psycotomimetics (Hallucinogens)
• Induce Perceptual sense
• Colorful changes in
enviornament, changes in
shapes & color
• Incapable of decision
making as thought process
is affected
– Lysergic acid ( LSD )
– Tetrahydro
Cannabinol (THC )
– Phencyclidine (PCP)
– Mescaline
– Psilocybin

32. Lysergic Acid Diethylamide (LSD)
• 5-HT agonist at pre synaptic receptors in CNS
• Activation of Sympathetic NS
• Hallucination with Brilliant Colors
• Mood alteration
• Tolerance &Physical dependence occurs
• No True dependence
• S/E … Hyper reflexia.
• Nausea, Muscle weakness, Psychotic changes

33. Tetrahydrocannabinol (THC)
• Alkalod in Marijuana Endcannabinoid are identified
• Euphoria, Drowsiness, Relaxation
• Decrease Muscle strength & high skilled motor acvtivity
• APPETITE stimulant
• Visual Hallucinations Delusions
• Enhancement of Sensory activity
• THC receptors (CB1)… G-Protein coupled
• Immediate effect when smoked …. 2-3 hrsLasts “6” hrs
• P450 metabolize …. Elimination through Bile
• Indicated in AID pts ….Loosing weight

34. • Adverse effects
– Increase HR &B.P
– Reddening of Conjuctiva
– Tolerance & Mild dependence with frequent use
• RIMONABANT (CB1 receptor antagonist) in
clinical trials for treatment of OBESITY

35. Drugs of Abuse

36. Drug Abuse
• Use of an illicit drug
• Excessive/nonmedical use of licit drug
• Deliberate use of chemicals (Not considered as drugs by lay
public)
Why used:
Anticipated felling of pleasure due to CNS effects
(Strong feeling of EUPHORIA or ALTERD
Perception)

37. Repetitive use …. WIDESPREAD Adaptive changes in
Brain …… Compulsive Use ……. ADDICTION
• Dependence (physical/physiological dependence)
( NOT ALWAYS CORRELATED WITH DRUG ABUSE
e.g. Bronchodilators, Organic Nitrates, Nonpsychactive drugs)
• Addiction (Psychological dependence)
Compulsive, Relapsing drug use despite Negative consequences
– Chronic exposure
– Habbit formed
– Lose self control
– Triggered by craving
• OPIOIDS (analgesic) …… few desire due to withdrawal
• COCAINE …. One person out of Six become addicted within 10
yrs of 1st Exposure to the drug

38. Each Drug has its on Acute Effects
BUT
Strong feeling of Euphoria & Reward is
Common to ALL drugs of Abuse

39. Dopamine Theory of ADDICTION
• Mesolimbic dopamine system is the primary target
of addictive drugs.
– VAT …. Ventral Tegmental Area
(A tiny structure at the tip of brain stem which projects Nucleus Accumbens)
• The Amygdala,
• Hippocampus,
• Prefrontal Cortex)
All addictive drugs activate mesolimbic dopamine
system

40. Withdrawal
• The state in which adaptive changes become fully
apparent once drug exposure is terminated.
In Human withdrawal symptoms with OPIOIDS is very strong

41. Each drug has specific Molecular target
with distinct cellular mechanism
• THREE classes are Distinguished
– G protein linked (Gio
– Ionotropic receptors OR Ion channels (GABA)
– Dopamine Transporter

42. Calssification

43. • Drugs That activate G protein-coupled Receptors
– Opioids,
– Cannabinoids,
– Hydroxy butyric acid (GHD) (Gio)
– LSD, (Non addictive, 5HT2A
– Mescaline,
– Psilocybin
• Dtrugs that bind to Ionotropic receptors.
– Nicotine,
– Alcohol,
– BZPs,
– Phencyclidine, ( Non addictive, NMDA receptors)
– Ketamine (Non addictive, NMDA receptors)
• Drugs that bind to Transporter of Biogenic Amines
– Cocaine,
– Amphetamine,
– Ectasay

44. Ketamine, Phencyclidine(PCP)
• G/A ….. Dissociative ( Only Ketamine clinically)
– “Club Grug”s
– “AngleDust, Hog, Special K”
• Use Dependent
• Competitive antagonism on NMDA receptors
• Crystalline Powder in pure form
• IN STREET….. Liquid, Cap. Pills to be Snored.
Ingestion, Inj. Or Smoked

45. Contd…….
• Psychedelic effects last for 1 hr
• Increased B.P. Impaired memoery, Visual Alterations
• At high doses Unpleasant Out-of-body & near Death
experiences are on record.
• DO NOT CAUSE DEPENDENCE & ADDICTION
• PCP may lead to long lasting Psychosis resembling
Schizopherenia

46. Inhalants
• Nitrates
• Ketones
• Aromatic Hydrocarbons
• House holds, Industrial Products
• Sniffing, …Inhalation from open container
• Huffing, … Soaking of Cloth in volatile substance
before inhalation.
• Bagging … Breathing in & out of paper or plastic
bag filled with fumes

47. Contd …
• Inhalant use is particular in children & young adults
• Alter function of ionotropic channels.
• Nitrous oxide bind with NMDA Receptors
• Fuel additives bind enhance GABA receptors function
• MOST INHALANTS products cause Euphoria: increase
excitability of VAT …. TOLUENE … Addictive
• Amyl Nitrate (“Popper”) Produce SM relaxation &
enhance Erectile function … But not Addictive
• MANAGEMENT of TOXIC EFFECTS …..
Supportive

48. DEPENDANCE & ADDICTION
TREATMENT
• Addiction is not Irreversible
• Reversal of action of drug is Life Saving
• FDA approved antagonists are only for Opioids &
BZPs
Treatment of opioid WITHDRAWAL
• STRATEGIES
– Alpha2 Antagonis CLONIDIDINE
– Slowing Tappering of long acting Opioids.
– Agonists acting on the same receptor acting on the
same receptors of abused drug (only for Opioids &
Nicotine

49. • Contd ….
For example
– Heroin addicts …… Methadone
– Smoking …. Nicotine Transdermal Patch
• To Reduce Craving:
• FDA approved ….. Naltexone for Opioid & Alcohol
addicts
• For Nicotine Addiction….. Partial agonists …..
– Cytsine (plant extract) Vareniciline (synthetic)
– BUPRIPIONE …. An antidepressant …. FOR NICOTINE
CESSATION THERAPY

50. ALCOHOL (Ethanol)
• Dependance become apparent 6-12 hrs after
cessation of Heavy drinking as WITDRAWAL
• TREATMENT:
• Supportive
• Bzps ….. Oxazepam, Lorazepam .. As no Heaptic
metabolism
• Chlordiazopoxide: … Preffered as long acting…. If
LFTs Normal ….