Central nerves system

1. SKELETAL MUSCLE
RELAXANTS

2. Effect of some conditions on muscle:
parkinsons disease.
Tetanus Infection:
Birth injury,
Cerebral vascular disease.
Rigidity :
Spasm
Spasticity :
•Which are due to increased mucle tone,
• can be painfull & disabling.

3. SKELETAL MUSCLE RELAXANTS
 ..
 Periferily/
 centally
↓muscle
tone
 ?
tubocurarine

4. Classification
 Centrally acting
 Peripherally acting

5. Centrally acting
Benzodiazepines : Diazepam
GABA derivaives : Baclofen
Central α2 agonists: Tizanidine
Barbiturates : Phenobarbitone
Mephenesin group: Mephensin,
Chlorzoxazone

6. Peripherily acting
Competitive blockers: d- tubocurarine,
Alcuronium, Gallamine, Metocurine,
Pancuronium, Vecuronium, Atracuronium.
Depoarising blockers: Succinylcholine
Decamethonium

7. Directly acting: Dantrolene
Dual blockers: Benzoquinonium
Miscellaneous: Aminoglycosides, Polypeptides.
Inhibiting release of Ach: Botulinum toxin type A
β- Bungarotoxin
Hemicholinium

8. Pharmacokinetics - PA
 Quartenary compounds – iv/im
 Absorp, metb, excretion.
 Ammonio steroids – hydrolysed in liver
 Atracurium – Hoffmann’s elimination (liver & renal)
 Succinylcholine & mivacurium – butyrylChE- short acting

9. MOA - Centrally acting
Benzodiazepines: diazepam
- Facilitating action of GABA in CNS.
- Acts at all GABAA synapses.
Baclofen: orally active GABA mimetic- GABAB
↑K+ conductance
hyperpolarise
↓Ca influx
At presyn
↓excitatory NT

10. MOA – peripherally acting agents
Non depolarising :- d-tubocurarine (dtc)
dtc  Nicotinic R (α)  competing with ACh
Also block Na Ch  inh release of Ach prejn.
Pore of ion ch
Intense motor blockade
Reduce frequency of ch opening

11. Depolarising blockade
Succinylcholine:SCh
Binds to Ach R
NA ch inactvn (-50mV)
Failure of propogation of AP
Flaccid paralysis
prolonged partial depolarization
(fasciculations)

12. Dual Block
Phase I : rapid onset, persistant depolarisation
no repolarisation
unresponsive to subsequent impulses
augmented by Anti ChE
Phase II: slow, desensitization of Ach rec.
ion ch prolonged closed state
resembles competitive block
reversed by Anti ChE.

13. MOA: Directly acting - Dantrolene
Ryanoid rec  interferes with Ca release from
sarcoplasmic reticulum
Rapid contracting Motor unit

14. Pharmacological actions
Competitive blockers- sequence of paralysis
 Small rapidly moving muscles, eyes, jaws, finger
 Limbs
 Trunk, neck
 Intercostal muscle
 Diaphragm

15. Pharmacological actions
Depolarising blockers:
 Fasciculation: chest & abdomen – 5min(max)
 Neck,limb
 Face, jaw, eye
 Trunk
Transient apnea  at max effect.

16. Pharmacological actions
Competitive
-No action
- partial blockade
Aut G- ↓ BP
Adr Med- ↑HR
Pancuronium:vagal Bl,Gang+
Depolarising
-No action
Vagal +n  Bradycardia
Aut Gang +  HTN,
tachycardia
Autonomic ganglia:
CNS:

17. Competitive
d-tc mast cell
Mivacurium,doxacurium -
+
Pancuronium,
pipecuronium,
Vancuronium
Cisatracurium
rocuronium
Depolarising
SCh  +
Histamine release
}+/--
} –

18. Competitive
B.P. - ↓
Ganglion blockade
Histamine release
↓ venous return
HR - ↑
Vagal ganglionic blockade
Depolarising
Bradycardia tachycardia
↓ BP- vasodilatation-musc.
↑BP – aut gang +n
Prolonged administration-
cardiac arrhythmias arrest
Cardiovasular system

19. Competitive
• Enhance post operative
paralytic ileus
Bronchosasm -
atracurium
Depolarising
Increases:
• Intragastric pressure
• Salivation
• Gastric secretion
• peristalsis
G I T
Respiratory system

20. Adverse effects:
 Tachycardia, arrhythmias – pancuronium
 Sever hypotention
 Sever bronchospasm
 Anaphylaxis
 Convusions – at high dose Atracurium (metb)
 Hyperkalemia
 Muscle pain
 ↑ IOP,ICP,IGP
 Malignant hyperthermia(RyR)
}d-tubocurarine
}SCh

21. Interactions (impair NM trans)
 Antibiotics –Aminoglycosides, Tetracyclines, Polymyxin
 Anti arrhythmic drugs – Quinidine, Procainamide
 β- blockers : propranolol, timolol.
 Others : CCB’s, Lithium, Mg, Methoxyflurane,
Phenothiazines, Trimethoprim, Quinine.

22. Therapeutic uses
Adjuvants to general anaesthesia:
- Endotracheal intubation
- Bronchoscopy
- Orthopedic manipulation
- During anaesthesia - maintain ventilation
succinylcholine
- Rocuronium
ECT: convulsion, trauma

23. Drug of choice during surgery for
patients with:
Cardiac patients : - vecuronium
Hepatic &
renal compromised:
Myesthenia gravis - Atracurium
(10%)

24. Centrally acting muscle relaxants
Muscle spasms
Tetanus
Spastic neurological : cerebral palsy, spinal injury
Closed reductions & dislocations
- iv diazepam
- Diazepam

25. Contraindications
for SCh:
 Hyperkalemia
 Head injury
 Glaucoma, eye injury
 Trauma, burns, hemiplegia
(– upto 6 mon.)
 Duchenne muscle dystrophy
 Dystrophia myotonica.
Comp blockers
Biliary obstruction
- vecuronium
- rocuronium
Renal failure:
- Metocurine

27. CNS Stimulants
DR. NANDITH

28. Neurotransmitters CNS
 They can be classified into :
 1. Exitatory:
 - Ach, glutamate, aspartate , serotonin and NE.
 2. Inhibitory:-
 - GABA , glycin .

29. CNS Stimulants
 Definition:
“Stimulants are a substance which tends to increase
behavioral activity when administered”

30. Signs and symptoms
 Elevate Mood
 Increase Motor Activity
 Increase Alertness
 Decrease need for Sleep
 In case of overdose lead to convulsion and death

31. MOA of CNS Stimulants
 Block neurotransmitters reuptake (Most reuptake
inhibitors affect either NE or 5-HT(Serotonin) :
Cocaine
 Promote neurotransmitters release : Amphetamine
 Block Metabolism - MAO inhibitors (monoamine
oxidase):ex. Phenelzine
 Antagonize the effect of inhibitory neurotransmitter:
Picrotoxin & Strychnine

32. CNS Stimulants
 They can be divided based on their site of
action
Cerebral stimulants (amphetamines)
Medullary stimulants (Picrotoxin)
Spinal stimulants (strychnine)

33. Amphetamine
 MOA:
 Block the reuptake of norepinephrine and
dopamine into the presynaptic neuron and
increase the release of these monoamines into the
extraneuronal space.

34. Clinical use:
 Narcolepsy.
 Attention-deficit hyperactivity disorder

35. Adverse effects
 Cardiovascular: Hypertension
 Endocrine metabolic: Weight loss
 Gastrointestinal: Abdominal pain, Loss of appetite,
Xerostomia
 Neurologic: Headache, Insomnia
 Psychiatric: Feeling nervous

36. Thank you