General anaesthetics, antiepileptics for more drugs acting on CNS refer on my page according to pharmacology-ii syllabus dental

1. DRUGS ACTING ON
CENTRAL NERVOUS
SYSTEM
Vaheeda Rahman, (PhD),.
Dept of pharmacology,
SPS, VISTAS

2.  Central nervous system :
• Brain
• Brain stem
• Spinal cord

4. GENERAL
ANAESTHETICS

5. INTRODUCTION
DEFINITION:
 General anaesthetics: These are drugs which produce
reversible loss of all sensations
and consciousness.
Anaesthesia means:
an- without
aesthesis- sensation

6. HISTORY
Alcohol, opium
Nitrous oxide
Ether
Chloroform
Cyclopropane
Thiopentone
Halothane
1844
1846
1847
1929
1956
1935
19th
century

7. MECHANISM
 LIPID THEORY:

8.  EFFECTS ON ION CHANNELS:

9. STAGES OF ANAESTHESI
 stage of analgesia
 stage of delirium/excitement
 stage of surgical anaesthesia
 stage of medullary paralysis

10. PROPERTIES OF AN IDEAL ANA

11. TECHNIQUES OF INHALATION O
 Open drop method
 Through anaesthetic machines
a.Open system
b.Closed system
c.Semi closed system

12. CLASSIFICATION
General
anaesthetics
Inhalation
Gases
Volatile
Liquid
Intra venous
Inducing
agents
Slower
acting drugs
Balanced anaesthesia (both inhalational and i.v )

13.  GASES: Nitrous oxide
 VOLATILE LIQUIDS: Ether
Halothane
Enflurane
Isoflurane
Desflurane
Sevoflurane
 INDUCING AGENTS: Thiopentone sodium
Methohexitone sodium
Propofol
Etomidate
 SLOWER ACTING DRUGS:
 BENZODIAZEPINES: Diazepam
Lorazepam
Midazolam
 DISSOCIATIVE ANAESTHESIA: Ketamine
 OPIOID ANALGESIA: Fentanyl

14. INHALATIONAL GENERAL ANA
GASEOUS:NITROUS OXIDE:
Pharmacokinetics:
• Onset of action ------- quick and smooth
•Metabolism ------ does not occur
• Excretion ------ quickly removed by lungs
• MAC ------ 105%
•Recovery ------- rapid
• Second gas effect and diffusion hypoxia occurs
• Dose ------- 70% Nitrous oxide, 25-30% of oxygen,
0.2-2% another potent drug
Advantages:
•Cheap and very commonly used
• Non toxic to lever, kidney, brain
Uses:
• Nitrous oxide(50%) along with oxygen
can be used for obstetric and dental

15. VOLATILE LIQUIDS:
ETHER: (DIETHYL ETHER)
Pharmacokinetics:
• Induction is prolonged and unpleasant with struggling
• Recovery ------ slow
Mechanism:
• Reduces Ach output from motor nerve endings
Advantages:
•Potent drug, produce good analgesia
•Still using in developing countries because it is cheap
• Can be given by open drop method
Adverse effects:
• Post anaesthetic vomit and nausea
•Breath holding, salivation and marked respiratory secretions
•Premedication atropine given

16. HALOTHANE(FLUOTHANE) :
Pharmacokinetics:
•Induction ------ reasonably quite and pleasant
•Metabolism: 20% by liver, remaining exhaled out
• Elimination: 24-48 hrs after prolonged administration
• Recovery: smooth and reasonably quick
• Dose :------ for induction --- 2-4%
for maintenance --- 0.5-1%
•causes direct depression of myocardial contractility by reducing
intracellular calcium concentration and sympathetic activity fails to increase
Adverse effects:
•Malignant hyperthermia
• Metabolite of halothane causes chemical and immunological injury
• Repeated use causes hepatitis(1 in 10,000)
• Cardiac output is reduced with deep anaesthesia
• BP falls
• Vascular bed dilates
• Heart rate reduces, tachyarrhythmia occurs
• Greater depression of respiration, breathing shallow

17. INTRAVENOUS GENERAL
ANAESTHETICSINDUCING AGENTS
THIOPENTONE SODIUM:
• Derivative of thiobarbiturate (ultra short acting)
Pharmacokinetics:
• Highly soluble in water
•Distribution: depends on organ blood flow (brain gets large amount)
•Metabolism: hepatic
• Elimination t1/2 is 7-12 hrs
•Dose: injected I.V (3-5mg/kg) as 2.5%solution
• Must prepare freshly before injection
Pharmacology:
•Produce unconsciousness in 15-20 seconds
•Consciousness is regained in 6-10 min
• t1/2 of distribution phase is 3min
Adverse effects:
•laryngospasm is a main adverse effect
• Recovery with shivering and delirium
• Other uses: control of convulsions

18. PROPOFOL:
Pharmacokinetics:
• I.V given for both induction and maintenance
• Distribution t1/2 2-4 minutes(rapidly)
• Elimination t1/2 (100 min) shorter than thiopentone due to rapid metabolism
• Unconsciousness occurs 15-45 seconds and lasts 5-10 min
• Suitable for outpatient surgery
Advantages:
• Post operative nausea and vomiting –low
• Patient acceptability is very good
Adverse effects:
• Excitatory effects and involuntary movements noted for some patients
• Fall in BP- due to vasodilation
• Bradicardia is frequent
• Dose dependent respiratory depression
• Pain during injection is also frequent- can be
minimized by combining with lidocaine
• Dose: 2mg/kg i.v bolus --- for induction
9mg/kg/hr -----------for maintenance

19. SLOWER ACTING DRUGS
BENZODIAZEPINES:
Pharmacokinetics:
• Distribution: t1/2 of diazepam is 15 min
•This is a premedication product
• Now frequently using for inducing, maintenance, and supplement anaesthesia as well
as conscious sedation
• Dose: 0.2-0.3mg/kg or equivalent diazepam
•Unconsciousness in 5-10 min
• Amnesia persists------ 2-3 hrs
• Sedation persists------ 6hrs or more
•Post operative nausea and vomiting is absence
Adverse effects:
• Injected i.v produce sedation and amnesia
• If large doses given recovery delays
• BZD’s are poor analgesics
• An opioid or nitrous oxide is added if produced pain
• Involuntary movements are not stimulated
• Requires neuromuscular blockers
• Uses: now preferred for endoscopies, angiographies, fracture setting etc

20. COMPLICATIONS OF
GENERAL ANAESTHESIA• Respiratory depression
• Cardiac arrhythmias, asystole, fall in BP
• Aspiration of gastric contents
• Laryngospasm and asphyxia
• Fire and explosion (rare)
• Delirium, convulsions, excitatory effects
• Recall of events during surgery
During
anaesthesia
• Nausea and vomiting
• Persisting sedation
• Pneumonia, atelectasis
• Organ toxicities
• Nerve palsies
• Emergency delirium
• Cognitive defects
After
anaesthesia

21. DRUG
INTERACTIO
NS
• Antihypertensive's-general anaesthetics: BP fall
• Corticosteroid-anaesthetics: cardiovascular collapse
Treatment: give 100mg of hydrocortisone
• Insulin need of a diabetic is increased
during general anaesthetics
• Neuroleptics, opioids, clonidine and
monoamine oxidase inhibitors potentiate
anaesthetic effect
• Halothane sensitizes heart to Adr

22. PREANAESTHETIC
MEDICATION Preanaesthesia: agents which show synergic effect on the
anaesthetic drugs
 Advantages of preanaesthetics:
 Decrease acidity and volume of gastric juice: less damages if aspirated
 Anti emetic effect extending to the postoperative period
 Decrease secretions and vagal stimulation
 Supplement analgesic action of anaesthetics and potentiate them: less
anaesthetic is needed
 Amnesia for pre and postoperative events
 Relief of anxiety and apprehension preoperatively
and to facilitate smooth induction

23.  Examples:
 Sedatives-anti anxiety drugs
 Opioids
 Anticholinergics
 Neuroleptics
 H2 blockers
 Antiemetics

24. ANTI-
EPILEPTIC
DRUGS

25. INTRODUCTION
DEFINITION:
 EPILEPSY: group of disorders of CNS characterized by
paroxysmal cerebral dysrhythmia, manifesting as brief
episodes(seizures) of loss or disturbances of consciousness
with/without characterized body movements(convulsions)
sensory or psychiatric phenomena
 ANTIEPILEPTICS: drugs which reduces
epilepsy (mainly seizures) in
human body

26. TYPES OF SEIZURES
GTCS
Absence
seizures
Atonic
seizures
Myoclonic
seizures
Infantile
spasms
Generalized
seizures SPS
CPS
SPS/CPS
Partial
seizures

27. CLASSIFICATION
• Barbiturates
• Deoxybarbiturates
• Hydantoin
• Iminostilbene
• Succinamides
• Aliphatic carboxylic acid
• Benzodiazepines
• Phenyltriazine
• Cyclic GABA analogue
• Newer drugs
• Prolongation of sod
channel inactivation
• Facilitation of GABA
mediated chlorine channel
opening
• Inhibition of T type
calcium current
Based
on
chemical
structure
Based
on
mechanism
of action

28. • Barbiturates: phenobarbitone
• Deoxybarbiturates: primidone
• Hydantoin: phenytoin, fosphenytoin
• Iminostilbene: carbamazepine, oxcarbazepine
• Succinamides: ethosuximide
• Aliphatic carboxylic acid: valproic acid, divalproex
• Benzodiazepines: clonazepam, diazepam, lorazepam
• Phenyl triazine: lomatrigine
• Cyclic GABA analogue: gabapentin
• Newer drugs: vigabatrin, topiramate,
tiagabine, zonisamide,
BASED ON CHEMICAL NATURE:

29. BASED ON MECHANISM OF ACTION:
 Prolongation of sod channel inactivation:
• Phenytoin
• Carbamazepine
• Valproate
• Lomatrigine
• Topiramate
• Zonisamide
 Facilitation of GABA mediated chlorine channel opening:
• Barbiturate
• Benzodiazepine
• Vigabatrin
• Valproate
• Gabapentine
• Tiagabine
 Inhibition of T type calcium current:
• Ethosuximide
• Trimethadione
• Valproate

30. PHENYTOIN
 PHARMACOKINETICS:
 Absorption:
• oral route
• 80-90% bound to plasma protein
 Metabolism:
• Hepatic
• t1/2 is 12-24 hrs
 Excretion:
• 5% unchanged in urine

31.  PHARMACOLOGY:
 Mechanism:
•Therapeutic level:
• Prolongation of sodium channel inactivation
•At high concentration:
•Reduction in calcium influx
•Inhibition of glutamate and facilitation of GABA responses
Action of phenytoin:
• On Tonic clonic epilepsy

32.  ADVERSE EFFECTS:
 At therapeutic level:
• Hypersensitivity
• Megaloblastic anemia
• Osteomalacia
• Hyperglycemia
• Foetal hydantoin syndrome
• Hirsutism
• Gum hypertrophy
 At high plasma levels:
• Fall in BP, cardiac arrhythmias---when i.v injected
• Nausea, vomiting
• Drowsiness, hallucination, mental confusion