Clinical Pharmacology of

Anesthetic drugs

Dr. Ahsan K. Siddiqui

 General Anesthesia
• Definition – Induced, Reversible, controlled,
loss of sensation
• Components:
1. Analgesia
2. Muscle relaxation
3. Amnesia
4. Suppression of excessive autonomic
responses
• Practical Conduct :

Pre Anesthetic check up

Just preoperative monitoring

Induction

Maintenance

Recovery

Post operative Care

 Monitoring

Maintenance

Induction Recovery

Pre op. Check Post op. Care

• Anesthesiologist Tools

Drugs : Hypnotics, Analgesics, Muscle

relaxants & others
Gases : Oxygen, Nitrous Oxide
Vapors: Halothane, Isoflurane, Sevoflurane
Equipments : Anesthetic Machine - Breathing
Circuits, Monitors…….
Others: iv access, Infusion fluid, Airway
equipments……..,…..
 Premedication

Reasons for administration of premedications

1. Reduction of fear and anxiety
catecholamine , risks

2. Reduction of saliva secretion

3. Prevention of vagal reflexes (caused by surgical
stimulation like squint op., stretching of anal sphincter,
or associated with medication e.g., B –blockers
4. As part of anesthetic technique e.g. use of narcotics
5. To produce amnesia
- Hyoscine ( Scopolamine)
- Benzodiazepines - anterograde amnesia
- Diazepam -hyoscine – in 75% pts complete
amnesia

6. For specific therapeutic effects

- Transdermal glyceryl nitrate patches for angina
pts,
- Steroids
- B – blockers
(anterograde amnesia- inability to form new memories,
Impairment of memory for events occurring after the onset of
amnesia)
Drugs :
1. Anxiolysis\ Amnesia: BNZ, Hyosc., Antihist.
(H1 Blochers)
2. Analgesia: Opiates

3. Adjuvant to GA : BNZ & Ketamine

4. Anti-emetic : Metoclopramide, Antihist.

5. Antacids : H2 blockers, Antihist., Na Citrate

6. Antihist. : Promethazine,Diphinhydramine
7. Antivagal \ Antisialagogues: Atrop, Hyos.,AntiH

8. Antitromb. / Anticoag.: Heparin, Stockings

9. Antibiotics: Infective Endocarditis Prophylaxis

10: Attention to pre-existing medications:

Continue: unless otherwise

Stop : MAOI, Contraceptive pills
Change : Insulin, oral hypogly., Steroids
 Common Premadications

Drug Dose Route Timing

Diazepam 5-15 mg oral 1-2 hr
Lorazepam 1-3 mg oral preop.

Morphine 5-15 mg IM
Hyoscine 0.2-0.4 mg IM 1hr pre

Pathedine 50-100mg IM preop

Promethazine 12.5-25mg IM

Midazolam 2.5-5 mg IM
 Children

Drug Dose Route Timing

Diazepam Syrup 0.2mg\kg oral 1 hr

Medazolam 70-100 mcg\kg IM preop

Promethazine
2-5yr 10-20mg oral 1hr preop
5-10 yr 20-25 mg 1\2dose
for IM
Morphine 0.1-0.2mg\kg IM
Hyoscine 5mcg\kg IM
 Side effect of premadications :

Delayed recovery and interaction of Specific

drugs
 Opioids

• Act on opioid receptors located through out

CNS
• Identified as mu - mu1 & mu2
keppa (k)
delta (d)
sigma
• Most effective as producing analgesia
• They provide some degree of sedation
 IV opiates
Drugs Dose Onset Duration

Morphine 0.1-0.2mg\kg slowest long

Pathedine 1-2 mg\kg slow long

Fentanyl 1-2mcg\kg rapid short

Alfentanil 10-20mcg\kg v. rapid v. short

Sufentanil 0.2-0.4mcg\kg rapid short

 Induction

Check: pt \ machine\ Monitors

Monitoring:
Basic Monitoring:
Anesthetics, clinical, Air way
EKG,NIBP,SpO2, Capnography
Add.: PNS\Temp.\ CVP
Agent for induction : IV vs. Inhalational
Analgesia: Opiates
 IV Induction Agents

• The ideal intrav. Agent reliably and pleasantly

induces full anesthesia within one arm-brain
circulation time

- is free of side effects

- completely wears off in a few minutes

- it must be capable of infusion to maintain
anesthesia without problems.
• I.V. anesthetic agents may be used for

1. Induction of anesthesia
2. As a sole agent for operation (TIVA)
3. To supplement volatile anesthesia or regional
anesthesia
4. For sedation
 IV Induction Agents

Propofol –
- Mechanism of action – facilitation of inhibitory
neurotransmission mediate by GABA
- Not water soluble
- 1% solution aqueous solution is available for IV
use as an oil-in-water emulsion containing
- soybean oil
- egg lecithin
- glycerol
• Only for IV administration

• Rapid on set ( one arm brain circulation time)

- 1\2 life 2-8 min. ( recovery rapid, no hangover)

- V. high clearance rate( 10 time that of thiopentone)

• Conjugation in liver results in inactive metabolites

• Excretion – in urine

• Can be used in Chr. Renal F, hepatic ds.

 Thiopent. Propofol Ketamine
barbiturate phenol
phencyclidine

Pain -- + --
Phleb. Less more less
Rapid onset ++ +++ +
BP decrease decrease increase
Analgesia -- -- +
Bronch ppt Asthma -- +
Mech. GABA GABA Desociat.
of act.
 Thiopent. Propofol Ketamine

Commul. ++ - -
Recovery Hang over clean headed Emerg.
Delir.
PONV + - Antiemetic +
antipruritic
Duration 10 min 10 min < 10min

Route iv i.v i.v \ i.m

• Life Support During Induction

A. Airway : Support: manual \ Atrif. Airway

B. O2 FM + circuit +- An. Agent
Chest expansion\ bag \ monitor

C. Circulatory Support
D. Definitive Airway : Guedel`s Airway
Laryngeal Mask Airway
ETT MR + Circuit + IPPV
 MAINTENANCE
Anesthesia ( Tetrad) :

Unconsciousness : Inhal. Vs TIVA

Analgesia : N2O + Opioids / LA
Relaxation : M.R.
Autonomic : Pares. : Anticholin.
: Symp. : GA
Opioids
CVS drugs
 Inhalational Anesthetics
• The greater the uptake of anesthetic agent, the
greater the difference b \ w the inspired and
alveolar conc. And slower the rate of induction.

• Three factors affect anesthetic uptake

1. Solubility in the blood
2. Alveolar blood flow
3. partial pressure difference b\w alveolar gas
and venous blood.
• The relative solubility's of an anesthetic in air,
blood, and tissues are expressed as Partition
Coefficients
Partition Coefficients
• N2O 0.47 ( insoluble in blood)
• Halothane 2.4
• Isoflurane 1.4
• Desflurane 0.42
• Sevoflurane 0.65

(Factors that speed induction also speed recovery)

• MAC – the alveolar conc. of an inhalational anesthetic
that prevents movement in 50% in response to
surgical stimulus.
- a measure of potency
MAC%
Nitrous oxide 105
Halothane 0.75
Isoflurane 1.2
Sevoflurane 2.0
Desflurane 6.0
• ISOFURANE – dilates coronary arteries ( but less
potent than nitroglycerine or adenosine).
- Can cause (coronary steal syndrome) regional
myocardial ischemia)

• DESFLURANE – Low solubility of desflurane in

blood and tissues causes a very rapid wash in and
wash out of anesthetic.

• SEVOFLURANE – Excellent choice for rapid and

smooth inhalational induction.
( b\c of non pungency and rapid increases in alveolar
anesthetic conc.)
 VOLATILE ANESTHETICS
Halothane Isoflurane Sevoflurane
hydrocarbon -----------halogenated ether-------------

Pleasant ++ -- +_
Smell
MAC 0.75% 1.2% 2%
HR No change
arrhythmia minimal
SVR +_ -- --
Contractility - minimal - minimal
BP - -- --
CO +_ or +_ or
minimal minimal
 Halothane Isoflurane Sevoflurane

Catachol. +++ - -
sensitisation
Bronchi Dilatation less less
Uterus Relaxation less less
Hepatic Tox. + -- --
Renal Tox. -- - +
• Neuromuscular Blocking Agents( Ms
relaxants) ( no anesthesia, amnesia or analgesia)

• Depolarizing Nondepolarizing
Acetyl-choline competitive antagonist
receptor agonist

Nondepolarizing Muscle relaxants are not significantly

metabolized ( except mivacurium metabolized by
pseudocholinestrase & atracurium – metabolized by hofmann
elimination and ester hydrolysis )

Need reversal agents ( Cholinesterase inhibitors) that

inhibit acetylecholinesterase enzyme activity.
 Muscle Relaxants
Sux Dtc. Panc. Vecur. Atrac.
Type Depol ------Non --- Depolarising----------
Onset 30 S. ---3-5 min---- --------2-3 min----
Dur. V. Short ----Long ----- --intermediate ---
(3-5 min) ( 30-60min) ( 20-30min)
Dose 1 0.2-0.4 0.6-0.1 0.05-0.1 0.25-.
5
( mg\kg)

Hist. Min. +++ - - +

G.B. - ++ - - -
Vagal - - + - -
 Sux Dtc. Panc. Vecur. Atrac

Symp. - - + - -

HR or +_ +_

BP ? +_ +_ +_

Elim. Ps. Ch Es. ----kidney\liver- –liver-- Hoff +

ester
Notes; Sux. apnoea, K/ ICL/IOP,
Dysrhythmia,
MH+, Myalgea ( fasciculation)
 Reversal Agents

• Cholinesterase inhibitors ( Anticholinesterse)

• Characteristics of cholinergic receptors
Nicotinic Muscarinic
• Location Autonomic Ganglia Glands ( Lacrimal
Sympathetic & salivary, gastric)
parasympathetic Smooth muscle
ganglia (Bronchial, GIT,
Skeletal muscle bladder, bld
vessels)
Heart(SA node,AV
node)
• Agonists Acetylcholine Acetylcholine
Nicotine Muscarine
• Antagonist N D P M relaxants Antimuscarinics
• RECOVERY :

Titrate : Reversal : (Muscle relaxant)

Atropine + Neostegmine
opiate : Nalaxone
Benzodiazepine : flumazinil
Extubation \ Airway
oxygenation
Consciousness
• Pharmacological character of anticholinerg. Dg.

Atropine Scopolamine Glycopyrrolate

Tachycardia +++ + ++
Bronchodilat. ++ + ++
Sedation + +++ 0
Antisialagogue ++ +++ +++
effect
• Post- Operative Care :
R. Room : A. Airway, recovery position
B. O2
C. CVS : Consciousness

Analgesia
 MONITORING

COMPLECATION IN THE RECOVERY ROOM

HYPOTENTION-HYPERTENSION-ARRHYTHMIA

RESPIRATORY : Airway Obstruction, Hypoxia,

Hypoventilation

Delayed recovery

Pain

PONV
• Complication in recovery room

CVS : Hypotension – hypertension – arrhythmia

Respiratory : Airway obstruction, Hypoxia,

Hypoventilation

Delayed Recovery
Pain
PONV
 RECOVERY :

Stop Anaesthesia

# Titrate : Reversal : MR : Prostig. + Atropine.

Opioids : naloxone

A. Extubation \ Airway
B. O2
C. Consciousness
Thank you