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

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……..,…..

Reasons for administration of premedications 1. Reduction of fear and anxiety

catecholamine ,


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
Diazepam Lorazepam Morphine Hyoscine Pathedine Promethazine Midazolam

5-15 mg 1-3 mg 5-15 mg 0.2-0.4 mg 50-100mg 12.5-25mg 2.5-5 mg

oral oral IM IM IM IM IM

1-2 hr preop.

1hr pre preop

Drug Dose Route oral IM Timing 1 hr preop

Diazepam Syrup 0.2mg\kg Medazolam 70-100 mcg\kg Promethazine 2-5yr 5-10 yr Morphine Hyoscine

10-20mg 20-25 mg 0.1-0.2mg\kg 5mcg\kg


1hr preop 1\2dose for IM


Side effect of premadications :
Delayed recovery and interaction of Specific drugs

• 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 Morphine Pathedine Fentanyl Alfentanil Sufentanil Dose 0.1-0.2mg\kg 1-2 mg\kg 1-2mcg\kg 10-20mcg\kg 0.2-0.4mcg\kg Onset slowest slow rapid v. rapid rapid Duration long long short v. short short

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.

barbiturate phencyclidine


Ketamine -less + increase + + Desociat.

Pain -Phleb. Less Rapid onset ++ BP decrease Analgesia -Bronch ppt Asthma Mech. GABA of act.

+ more +++ decrease --GABA



Ketamine Emerg. Delir. + < 10min i.v \ i.m

Commul. ++ Recovery Hang over clean headed PONV Duration Route + 10 min iv - Antiemetic antipruritic 10 min i.v

• 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

Nitrous oxide Halothane Isoflurane
Sevoflurane Desflurane

105 0.75 1.2
2.0 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.)


Isoflurane -1.2%

Sevoflurane +_ 2% No change minimal -minimal -+_ or minimal

-----------halogenated ether-------------

Pleasant Smell MAC HR SVR Contractility BP CO

++ 0.75% arrhythmia +_ -

-minimal -+_ or minimal

Halothane Catachol. sensitisation Bronchi Uterus Hepatic Tox. Renal Tox. +++ Dilatation Relaxation + --

Isoflurane less less --

Sevoflurane less less -+

• Neuromuscular Blocking Agents( Ms relaxants) ( no anesthesia, amnesia or analgesia)
• Depolarizing Acetyl-choline receptor agonist Nondepolarizing competitive antagonist

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 5
( mg\kg)

1 Min. -

0.2-0.4 0.6-0.1 0.05-0.1 0.25-. +++ ++ + + -

Hist. G.B. Vagal

Sux Symp. HR BP or ? +_

Dtc. -

Panc. +

Vecur. +_ +_

Atrac +_ +_

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 Sympathetic & parasympathetic ganglia Skeletal muscle Glands ( Lacrimal
salivary, gastric)

Smooth muscle
(Bronchial, GIT, bladder, bld


Heart(SA node,AV

• Agonists

Acetylcholine Nicotine • Antagonist N D P M relaxants

Acetylcholine Muscarine Antimuscarinics

• RECOVERY : Titrate : Reversal : (Muscle relaxant) Atropine + Neostegmine opiate : Nalaxone Benzodiazepine : flumazinil Extubation \ Airway oxygenation Consciousness

• Pharmacological character of anticholinerg. Dg.
Atropine Tachycardia Bronchodilat. Sedation Antisialagogue effect +++ ++ + ++ Scopolamine + + +++ +++ Glycopyrrolate ++ ++ 0 +++

• Post- Operative Care : R. Room : A. Airway, recovery position B. O2 C. CVS : Consciousness Analgesia


• 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

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