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 TimingDiazepam 5-15 mg oral 1-2 hrLorazepam 1-3 mg oral preop.

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

Pathedine 50-100mg IM preopPromethazine 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

Promethazine2-5yr 10-20mg oral 1hr preop5-10 yr 20-25 mg 1\2dose for IMMorphine 0.1-0.2mg\kg IMHyoscine 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 opiatesDrugs 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.

Recovery Hang over clean headed Emerg.

Delir.

PONV + - Antiemetic +

antipruritic

Duration 10 min 10 min < 10min

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

Thiopent. Propofol Ketamine

Commul. ++ - -

• 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 - - + - -

Block

Sux Dtc. Panc. Vecur. Atrac

Symp. - - + - -

HR or +_ +_

BP ? +_ +_ +_

Elim. Ps. Ch Es. ----kidney\liver- –liver-- Hoff + esterNotes; 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 ( Atropine, Scopolamine,

Glycopyrrolate)

• 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