cns stimulants ppt for MBBS ug

2. Little clinical use, except methylxanthines
 Can be classified in to:

› Respiratory stimulants ( Analeptics).
› Convulsants
› Psychomotor stimulants
› Psychomimetic drugs

3. Doxapram :
 MOA not clear, may excite central neurons
 Short acting, high margin of safety.
 Low doses selective for respiratory centre
 ↑ Tidal volume & rate of respiration
Uses :
 Post-anaesthetic resp. depression
 COPD i.e. hypoxemic,hypercapnic res.fail
 Apnoea in premature infants

4. Dose- 2-5mg/min(max 4mg/kg) slow i.v
infusion.
Contraindications:
 Hypoxaemic, normocapnic resp.failureasthma
 Resp.fail due to neurological & muscular
diseases.
 Epilepsy
Side effect:
 Restlessness
 Tachycardia
 High doses: convulsions & arrhythmias


5. No clinical use
 Used as research tools
Strychnine:
 Alkaloid, convulsant poison.
 Spinal cord stimulant
 MOA: Blocking the receptors for Glycine
 In poisoning convulsion treated withDiazepam or clonazepam slow i.v


8. Picrotoxin:
 Blocks the Cl- ion channel of GABAA.
Bicuculline:
 Plant alkaloid, GABAA antagonist.
Pentylenetetrazole (PTZ):
 Direct depolarization of central neurons
 Provides useful animal model for testing
anticonvulsant drugs.

9. Amphetamine group:
 Amphetamine
 Dexamphetamine
 Methamphetamine
 Methylenedioxy Methampheta(MDMA)
 Methylphenedate
 Fenfluramine

10. Non-Amphetamine group
 Modafinil
 Atomoxetine
 Sibutramine
 Pemoline
Cocaine
Methylxanthines:
 Caffeine
 Theophylline
 Theobromine

11. MOA: ↑DA conc. In synaptic cleft by
 Enter N endings by active transport
 Displace DA(also NE) from vesicles
 Also inhibits MOA-B, ↓DA metabolism.
Pharmacological effects: (central)
 ↑ motor activity
 Euphoria & excitement
 Anorexia
 Stereotyped & psychotic behaviour

12. ↑ BP, inhibition of GI motility
 Fatigue both physical & mental reduced.
 Amphetamine psychosis on repeated
use- paranoid ideas, A & T hallucinations.
PK:
 Well absorbed orally
 Freely penetrates BBB
 Unmetabolised drug excreted in urine


13. ADHD with minimal brain dysfunction:
 Characterised by› Hyperactivity
› Inability to concentrate
› Impulsive behavior
 Dexamphetamine,
 Methylphenedate,
 Atomoxetine quite effective.

14. Narcolepsy: Characterised by Sleep attacks during day time
 Night mares in awakening state
 Cataplexy-reversible
 Methylphenedate is still used
 Modafinil- devoid of abuse liability

15. Fenfluramine, dexfenfluramine used
earlier to treat obesity
 Discouraged due to: Tolerance
 Insomnia, pul.htn, abuse potential.
Sibutramine new drug used now
 Blocks neuronal uptake of mainly NE &
5HT (also dopamine) at hypothalamic
site that regulates food intake.


16. Use:
 Severe obesity with risk factors like DM.
Adverse effects:
 Dry mouth
 Headache
 Insomnia
 Constipation
 ↑in HR & BP
 CI in CVS diseases, withdrawn from
market

17. Tolerance
 Psychic dependence, rarely physical.
Amphetamine overdose:
 Euphoria, dizziness, tremors, HTN
 Irritability, anorexia, insomnia
 Higher doses- convulsions, psychotic
manifestations, arrhythmias, coma
 Rx –diazepam(slow i.v), haloperidol
 Gastric lavage, acidification of urine
 HTN-nifedipine/labetolol, arry-esmolol


18. Sudden deaths occurred with MDMA.
 Induces heat stroke like conditionrhabdomyolysis & renal failure
 Inappropriate secretion of ADH
Methylenedioxy amphetamine (love drug)
 75mg- psychotomimetic effects
 150 mg-LSD like effects
 300mg- amphetamine like
 SE: tachycardia, HTN, arrhythmias


19. Only caffeine if used as CNS stimulant
PK:
 Oral- rapid but irregular absorption
 PPB:<50%
 Distributed all over the body
 Met: in liver by demethylation & oxid.
 Metabolites excreted in urine
 T1/2: 3-6hrs


20. AE:
 Gastric irritation, N, V
 Nervousness, insomnia, agitation
 Muscule twitch, rigidity
 ↑body temp,delirium, convulsions
 Tachy, extra systoles at high doses
Uses:
 In Analgesic mixture for headache
 Migraine
 Apnoea in premature infants

21. Produce changes in sensory
perceptions, thoughts, behaviour &
mood.
 Actions mimic psychoses- psychedelics
 Lysergic acid diethylamide (LSD)
 Mescaline
 Phencyclidine
 Cannabinoids


22. Derived from cereal fungus ergot
 Hofmann synthesized & experimented on
himself.
 Act as agonist at 5HT2 receptors.
 Excitation threshold of retina ↓-visual
hallucinations
 Excitation threshold of RAS↓-hyper
arousal state
 Experiences may be bad or good trip.


23. Extract of hemp plant-C.sativa, C.indica
 Bhang- paste of powdered dried
leaves, used as drink
 Marijuana- dried leaves & flowering
tops, smoked in pipes or rolled as
cigarettes.
 Charas or hashish- resinous exudates
leaves & flowering tops, potent smoked
inpipe.
 THC content more in hashish


24. Initial CNS stimulation later sedation.
 Stimulatory phaseeuphoria, ↑talkativeness, ↑appetite
 Felling of confidence, relaxation & well
being
 Other- analgesia, antiemetic
 Peripheral effects- tachy, VD, reddening
of conjunctiva


25. 







Two types CB 1& 2 receptors
CB1 in brain CB2 in periphery
Anandamide-endogenous ligand CB1.
Dronabinol, Nabilone- synt.analogues of
THC
Use: CB1 Agonists- ↑appetite in AIDS pts.
Dronabinol-antiemetic in cancer chemo.
Rimonabant : CB1 antagonist, used for
obesity, dose-20mg OD before Breakfast
Smoking cessation

26. Indications:
 AD, multi infarct dementia
 Mild cognitive impairment
 MR, learning defects, ADHD in children
 TIA, CVA, Stroke
 Organic psychosyndromes
 Sequale of head injury
 ECT, brain surgery

27. ↑ global/regional blood flow
 Direct support of neuronal metabolism
 Enhancement of neurotransmission
 Improvement of discrete cerebral
functions


28. Main pathological features:
 Amyloid plaque
 Neurofibrillary tangles
 Marked ↓ in choline acetyltransferase &
loss of cholinergic neurons in brain.


29. ACEs that cross BBB are preferred.
Tacrine:
 Longer acting, reversible ACE
 Palliative for mild to moderate AD
 Orally active
 Improves memory, cognition, well being
 Facilitates Ach release
 AE: hepatotoxicity


30. Newer reversible Anti cholinesterase
 Better penetration in to CNS
 Better tolerated & less toxic than tacrine
 Clinical results modest & temporary
 Donepezil: 5mg OD orally evening ↑ max
10mg after 4 wks
 Rivastigmine:1.5 mg orally BD ↑ to 3mg
BD after 2 wks
 Galantamine:4mg BD orally ↑to 8mg BD
after 2 wks


31. Transdermal Rivastigmine patch –
applied every 24hrs
 SE:diarrhoe, N, V, ↑urination
Acetyl-L-carnitine:
 Structural analogue of Ach
 ↓ signs & symptoms of dementia in AD
 ↑ cholinergic transmission
 Also have antioxidant properties, slows
progression of AD


32. Excitotoxicity due to enhanced
Glutamate transmission via NMDA recp.
 Dose:5mg OD slowly ↑ to 10-20mg/day
 Non-comp. antagonist of NMDA recp.
 Better tolerated, less toxic.
Miscellaneous :
 Nootropics-piracetam, aniracetam
 High doses of vit E(1000 IU B.D)
 Antioxidants-vit
C, A, Zn, Se, bioflavonoids or spirulina ↓
progression even in middle stage AD.


33. ¡gracias
"thank you" in Spanish