Anesthetics pdf - Drugs Affecting the Central Nervous System

Unit 3: Drugs Affecting the Central Nervous System

Lecture 4+5 - Anesthetics

Local Anesthetics Drugs

Unit 3: Drugs Affecting the Central Nervous System

General anesthetic drugs



Anesthesia: Is a Greek Word meaning lack of

sensation.



Anesthesia is divided into 2 parts:

A. General anesthetic drugs B. Local anesthetic drugs

General anesthetic drugs



Are drugs which produce reversible loss of Sensation and

consciousness.  General anesthetic agents can be
administered by different routes:
  Oral administration
  Subcutaneous
  Rectal suppository
  Intravenous injection anti inhalation



But l.V or inhalational administration is preferred. The

drugs which are given as anesthetics b l.V
administration are used for specific purpose as quickly
acting general anesthetics for few minutes or as a
supplement with  another general anesthetic agents as:
Thiopental (i.v anesthetic agent), (Nitrous oxide, ether
and halothane (Inhalation agent).
As a supplement in order to produce the induction of
anesthesia in a short period, because the inhalational
anesthetic agents need a time about 15-20 minutes for
production of induction.
During this 15—20 minutes, the patients will start into
what we called stages of general anesthesia.

1) Stage I (Analgesia): The subject is conscious but

drowsy. Responses to painful stimuli are reduced. It is
pronounced with ether and nitrous oxide but not with
Halothane.

2) Stage II (Excitement): This stage starts when the patient

is unconscious. The respiratory rate is increased and
irregular. There is a rise and irregularity in B.P. During
this stage the pupils are dilated. This stage may be
prolonged leading to increase risks of sudden death. To
avoid this stage of anesthesia, a short acting barbiturate
such as Pentothal is given l.V before inhalation anesthesia
is administered.

3) Stage III (Surgical anesthesia).

The patients are not responded to surgical stimulation.
Pupils become to dilate again and the eyes are dry.
The skeletal muscle becomes relax.
Corneal and laryngeal reflexes are absent.
Light reflex is lost.

The skeletal muscle becomes marked relax. Surgery may
proceed during this plane.

4) Stage IV (Medullary paralysis):

The medullary center becomes completely paralysis
failure of ventilation and circulation, marked fall in B.P.
Death can rapidly ensue.

General aspects of anesthesia:

The practice of anesthetist has three main parts:



Before surgery (pre-medication):

The principle is to provide:

A. Sedation and amnesia (to reduce anxiety and stress).

-The patient who is going to do operation is normally
afraid, -Sedation and amnesia may produce by a drug like
diazepain.

B. Analgesia.

e.g. of drug produces analgesia pethedine or morphine.

C. Inhibition of para-sympathetic autonomic system

(Antimuscari.nic agent)....
1) To reduce bronchial secrçtion. Mostly happen with the

use of an irritating drug such as ether. Bronchial
secretion may cause bronchospasm.

2) To reduce secretion of salivary glands, because the

saliva may enter the larynx causes laryngospasm.

3) To reduce reflex bradycardia and hypotension. E.g. of

drug produces inhibition of para-sympathetic.
Atropine or 1-lyoscine.
So Typical combination drugs used in premedication
Include:
Morphine    Hyoscine               These combination
or                     +       or }               usually given
lhr.before
pethedine      Atropine                      operation



During surgery:

The most important is to produce sleep, analgesia & muscle
relaxation by using a single drug or more than one drug.



After surgery:

The anesthetist ensures that the effects of hypnotic,
analgesic and muscle relaxant are adequate.
The patient must never be left alone until he is conscious

Unit 3: Drugs Affecting the Central Nervous System

Types of general anesthetic agents

Inhalation agents



Pharmacokinetics:

The level of anesthetic is determined by the tension
(concentration) of anesthetic in the brain tissue. It is
influenced by:

1) Solubility

An anesthetic agent with high solubility in blood as ether
will provide slow induction because blood will act as a
reservoir or store for the drug, so that it does not enter the
brain easily until the reservoir has been filled.

2) Elimination

It depends mainly on the lungs

3) Metabolism and toxicity.

Some of the inhalation anesthetics are metabolized to
certain toxic effects as:

 Chloroform: produces hepatotoxicity associated with free

radical formation in liver cells.

 Methoxyflurane: is now very rarely used because 5O%

of Methoxyflurane is metabolized, generating fluoride and
oxalate which cause renal toxicity.

 Enflurane: also generates fluoride but at much lower

level (non-toxic).

 Halothane: is metabolized (about 30%) to bromide,

trifluoracetic acid and other metabolites which may be
responsible for the rare occurrence of liver toxicity.

Halothane (Fluothane):



Advantages:

 Potent and nonflammable.
 Induction is smooth and rapid. The surgical anesthesia

is produced within 2-5 minute.

 No effect on bronchial and salivary secretion.
 recovery is rapid and incidence of post-operative

nausea and vomiting is low.



Disadvantages:

  Muscle relaxation is not enough.
  Potent respiratory depressant.
  Induces cardiac arrhythmia.
  Sever hepatitis which may be fetal.
  Expensive.



Drug interaction:

 Potentiate the response to antihypertensive drugs.
 Sensitizes the heart to adrenaline (when adrenaline is

used to obtain bloodless filed of surgery).

Isoflurane



Is an isomer of Enflurane. It is a new non-flammable

agent.



Its intermediate in potency with Halogenated agents and

the heart rhythm is stable during its use.



It has a good muscle relaxation effect.



It has low blood/gas solubility.

Nitrous oxide



It is non-flammable agent



It is mixed with oxygen 50% for surgical anesthesia; this

mixture is added to another inhalation agent to reduce the
requirement of the inhalation agent by 50%.



Anoxia may occur if mixed with less than 20% oxygen



Euphoria and hallucination during induction called

laughing gas.



Advantages:

  It has strong analgesic action.
  induction is rapid.
  Produces light anesthesia without depressing the

respiratory or vasomotor center.

 Recovery time rarely exceeds 4 mm even after

prolonged administration.



Disadvantage:

It must be used with more effective anesthesia and muscle
relaxants to produce a state of full surgical anesthesia.



Adverse effects

 Nausea and vomiting.
 Bone marrow depression with repeated uses and

teratogenic risk.

Unit 3: Drugs Affecting the Central Nervous System

Intravenous anesthetic agents:



Produce rapid induction, because the blood

concentration can be raised rapidly.



Are used in short minor operation or as a supplement with

inhalational anesthetic to produce the induction for the
major operation.

The I.V Anesthetic agents are mainly the:

1) Very short acting barbiturate: like



Thiopental



Methohexital



Thiamylal



Thiopental in a single dose exerts its effect within 30

second and it remains for about 4-7 mm. It is quickly
take up from the plasma into the fat depots of the
body. After many injection have been given. The fat
depots become saturated and a further dose produces a
prolonged effect.



Great care is necessary to avoid over dose which results in

depression of respiratory activity



Laryngospasm and increased bronchial secretion are

common.
Insignificant analgesic effect and the muscle
relaxation is too short.

2) Ketamine



It is hallucinogen drug. In anesthetic doses, it produces a

trance-like state known as dissociation anesthesia
(sedation, amnesia and analgesia). The effect of ketamine
is on the superficial pain but not on visceral pain. So for
this reason ketamine uses to induce anesthesia for the
patient who has superficial pain as a minor operation.



Advantages:

 Anesthesia remains for up to 15 mm. after a single I.V

injection & is characterized by a good analgesic action

 It does not induce bronchospasm, so it is used to

anesthetist patient suffering from asthma.



Disadvantages:

 It lacks of muscle relaxation.
 It raises heart rate, intracranial & intraocular

Pressure.

 Its recovery is very slow and may be a companied by

hallucination.