General anesthetic

1. Present as liquids at room temperature and
pressure –Vaporized into gases for
administration

2. Mechanism: Various ion channels in the CNS involved in synaptic
transmission (including GABA A, glycine, and glutamate receptors) may
play a role.
Metabolism: hepatic.
CNS :
–Unconsciousness and amnesia.
–↑ cerebral blood flow (CBF).
Cardiovascular system: –
–Myocardial depression and systemic vasodilation.
–HR tends to be unchanged, except desflurane
– Sensitize the myocardium to the arrhythmogenic effects of
catecholamines.

3. Neuromuscular system:
- Dose-dependent ↓ in skeletal muscle tone.
May precipitate malignant hyperthermia. a dramatic increase in body
temperature, acidosis, electrolyte imbalance and shock
Hepatic system: Hepatic system: ↓ hepatic perfusion. Rarely, (“halothane
hepatitis”).
Renal system: ↓ renal blood flow.
Respiratory system:
–Dose-dependent respiratory depression .
–Airway irritation and, during light levels of anesthesia, may precipitate
coughing, laryngospasm, or bronchospasm (sevoflurane makes it more
suitable )
–Bronchodilator, (with the exception of desflurane).
–Inhibit hypoxic pulmonary vasoconstriction.

4. A nonflammable, halogenated, hydrocarbon
anesthetic that provides relatively rapid
induction with little or no excitement.
Analgesia may not be adequate. nitrous oxide
is often given concomitantly. Because
halothane may not produce sufficient muscle
relaxation, supplemental neuromuscular
blocking agents may be required.
1-Bromo-1-chloro-2,2,
2-trifluoroethane

5. Pharmacodynamics :
Halothane is a general inhalation anesthetic used for induction and
maintenance of general anesthesia. It reduces the blood pressure and
frequently decreases the pulse rate and depresses respiration. It induces
muscle relaxation and reduces pains sensitivity by altering tissue
excitability. It does so by decreasing the extent of gap junction mediated
cell-cell coupling and altering the activity of the channels that underlie the
action potential.
Metabolism: Halothane is metabolized in the liver, primarily by CYP2E1,
and to a lesser extent by CYP3A4 and CYP2A6.
Toxicity : Toxic effects of halothane include malignant hyperthermia and
hepatitis.

6. Mechanism of action:
Halothane causes general anaesthesia due to its actions on multiple ion
channels, which ultimately depresses nerve conduction, breathing, cardiac
contractility. Its immobilizing effects have been attributed to its binding to
potassium channels in cholinergic neurons. Halothane's effect are also
likely due to binding to NMDA and calcium channels, causing
hyperpolarization.
Advantages:
Induction is rapid.
Surgical anaesthesia produced within 2-5 minutes.
Fast induction .
Highly potent inhalational anaesthetic agent.
Postoperative nausea and vomiting is low.

7. Disadvantages:
Highly lipid soluble.
Causes cardiac arrhythmia.
Causes hypotension.
Severe hepatitis may develop.

8. First public demonstration of ether anesthesia on October 16, 1846 at the
Ether Dome in Boston.
It is a highly volatile liquid, produces irritating vapours which are
inflammable and explosive. Ether is a potent anaesthetic, produces good
analgesia and marked muscle relaxation.
Diethyl ether

9. Mechanism of Action:
The mechanism of action by which ethyl ether produces reversible loss of
consciousness is still unclear. Anesthesia can be produced by a wide
variety of chemical agents, ranging from inert rare gases to steroidal
molecules. Most theories concern interaction of anesthetics with either
membrane lipids or hydrophobic regions of specific membrane-bound
proteins. One hypothesis is that the anesthetic changes the function of an
ion channel protein by modifying the conformation of the protein. Some
investigators suggest that the GABA receptor may be the ion channel
protein that is affected by inhalation of anesthetic agents .The most
appropriate concept for the mechanism of general anesthesia may be the
heterogenous site of anesthetic action, including both lipid and protein
membrane components linked with neuronal function.

10. Advantages:
Can be used without complicated apparatus
Potent anaesthetic and good analgesic
Muscle relaxation
Respiratory stimulation and bronchodilatation
Does not sensitize the heart to adrenaline
No cardiac arrhythmias
Disadvantages:
 Inflammable and explosive
 Slow & unpleasant induction
 Slow recovery nausea & vomiting
 Convulsion in children
 Cross tolerance – ethyl alcohol

11. An extremely stable inhalation anesthetic that
allows rapid adjustments of anesthesia depth
with little change in pulse or respiratory rate.
2-chloro-1,1,2-trifluoro
ethyl difluoromethyl et
her
Physical Characteristics and Uses:
 Non irritating
 Non inflammable liquid with mild
odour

12. Enflurane induces a reduction in junctional conductance by decreasing
gap junction channel opening times and increasing gap junction channel
closing times. Enflurane also activates calcium dependent ATPase in the
sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. It
also appears to bind the D subunit of ATP synthase
and NADH dehydogenase. Enflurane also binds to and angonizes
the GABA receptor, the large conductance Ca2+
activated potassium channel, the glycine receptor, and antagonizes
the glutamate receptor receptor. These yield a decreased depolarization
and therefore, tissue excitability which results in anesthesia.
Mechanism of action:

13. Advantages:
Like halothane it decreases heart rate, cardiac output and B.P
Uterine relaxation is also similar to halothane
Unlike halothane it does not sensitize heart to catecholamines.
It is a better skeletal muscle relaxant than halothane.
It has rapid induction and recovery than halothane.
Disadvantages and adverse effect:
Greater respiratory depression.
May cause polyuric renal failure.
Can cause jaundice and hepatotoxicity.
Contraindications:
 In epileptic patients.
 In renal failure.

14. A stable, non-explosive inhalation anesthetic, relatively free from
significant side effects.
1-chloro-2,2,2-trifluoroethyl
difluoromethyl ether
Physical Characteristics and uses:
Structural analogue of enflurane
Non inflammable liquid
Pungent odour
Exhibits rapid induction and recovery
than halothane
One and half time more potent than
enflurane

15. Mechanism of action:
Isoflurane induces a reduction in junctional conductance by decreasing
gap junction channel opening times and increasing gap junction channel
closing times. Isoflurane also activates calcium dependent ATPase in the
sarcoplasmic reticulum by increasing the fluidity of the lipid membrane.
Also appears to bind the D subunit of ATP synthase and NADH
dehydogenase. Isoflurane also binds to the GABA receptor, the large
conductance Ca2+ activated potassium channel, the glutamate receptor
and the glycine receptor.

16. Advantages:
Undergoes minimal metabolism as result less fluoride is produced, hence
chance of organ toxicity is rare.
Unlike halothane it does not sensitize myocardium to action of
catecholamines.
Depresses cortical EEG activity and is preferred for neurosurgery.
Also a muscle relaxant and potent coronary vasodilator.
Potent Bronchodilator .
Disadvantage and adverse effect:
Pungent odour and causes bronchial irritation.
Exhibit phenomena of coronary steal which may precipitate regional
myocardial ischemia.
Causes hypotension and reflex tachycardia.

17. —Structurally similar to isoflurane.
—Has anaesthetic actions similar to isoflurane
Physical Characteristics and Uses:
Non inflammable
Non explosive
Irritant
Volatile Liquid
Rapid induction and recovery.
(+-)-2-Difluoromethyl 1,2,2,2-t
etrafluoroethyl ether

18. Advantages:
 Used for outpatient surgery as patient can be discharged few hours
after surgery.
 Less risk of organ toxicity.
 Sensitizes myocardium to catecholamines to a lesser extent than
halothane or enflurane.
 Good muscle relaxant.
 Seizure provoking potential is negligible.
Disadvantage and adverse effect:
Irritant to airways, may provoke breathholding, apnea, coughing,
increased salivation and laryngospasm.
Not suitable for induction in children.
Causes respiratory depression.

19. —Physical properties and uses:
Anaesthetic properties between
isoflurane and desflurane
Non pungent
Non inflammable
Volatile liquid
Induction is rapid and smooth
Recovery is faster than halothane
1,1,1,3,3,3-Hexafluoro-
2-(fluoromethoxy)prop
ane

20. Advantages:
Does not cause respiratory irritation.
Acceptability better by children.
Induction and emergence from anaesthesia are as fast as desflurane.
Good muscle relaxant property.
Cardiovascular effect similar to those of isoflurane but does not produce
“coronary steal”
Sensitizes myocardium to catecholamines to a lesser extent than
halothane or enflurane.
Disadvantage and adverse effect:
Not a bronchodilator.
May trigger malignant hyperthermia in susceptible patient.
Shivering, nausea and vomiting are reported in post operative period.