This document provides an overview of intravenous and inhalational anesthetic agents. It discusses the goals of anesthesia, routes of drug administration, and the pharmacodynamics and pharmacokinetics of various anesthetic drugs. Key intravenous agents described include thiopentone, propofol, etomidate, ketamine, benzodiazepines, and opioids. Inhalational agents discussed include nitrous oxide, halothane, isoflurane, sevoflurane, and desflurane. The document compares the properties, dosages, effects, advantages, and disadvantages of different anesthetic drugs.

1. INTRAVENOUS AND
INHALATIONAL AGENTS
By-
RAHUL SHARMA

2. SURGERY BEFORE ANESTHESIA

3. ANESTHESIA
Allow surgical and diagnostic procedure to be
performed in a manner which is painless to
the patient
Allow control of factors such as
– Physiological functions
– Patient movement

4. ROUTES OF DRUGS
ADMINISTRATION
■ Oral
■ Rectal
■ Transdermal
■ Inhalation
■ Subcutaneous
■ Intramuscular
■ Intravenous

5. Pharmacological
Principles
■ PHARMACODYNAMICS –What the drug
does to the body
Effects of drug
eg-adrenaline=interaction with
adrenoreceptor
■ PHARMACOKINETICS-What the body does
to the drug

6. Intravenous anesthetics
are used in anesthesia for-
Induction
Analgesia
Amnesia
Sedation
Maintenance of anesthesia for longer
duration

7. IDEAL ANESTHETIC
PROPERTIES Rapid onset and offset
 Analgesia at subanesthetic dose
 Minimal cardiorespiratory depression
 No emetic effect
 No excitatory and emergence phenomenon
 No pain on injection
 No release of histamine(bronchospasm)
 No hypersensitivity
 No adrenocortical suppression

8. CLASSIFICATION
Barbiturate Non
barbiturate
Thiopentone
ketamine
Methohexitone
Propofol
Etomidate
Opioid

9. BARBITURATE
THIOPENTONE
METHOHEXITONE
Pentobarbita

10. THIOPENTONE
 Thiopentone was the first intravenous anesthetic
used in clinical practice by Water and Lundy in 1934
 Ultra short acting
 Yellow amorphous powder in 0.5g and 1g vial
 Highly alkaline ph=10.5
 Decrease in alkalinity cause ppt of solution
 Mechanism of action-act on GABAa receptor
cl-
influx
hyperpolarization

11. Pharmacokinetics
Unconsciousness is produced in 15 sec
Elimination half life 10.4 hrs
Consciousness is regained after 15-20
min(redistribution)
Hepatically metabolized and metabolic
products eliminated through kidneys

12. DOSES
Thiopentone = 3-6 mg/kgwt for
induction
Methohexitone =1-2mg/kgwt for
induction

13. Effects
Central nervous system
 CMO2,CMR,ICT all are decreased
 Anticonvulsant(phenyl grp)
 Antanalgesic at low dose
 Narcoanalysis
Cardiovascular system
 Hypotension(vasodilation)
 Tachycardia(baroreceptors)
 Cardiac output decrease
 Cardiovascular depression

14. Respiratory system
Respiratory depression (higher doses)
Apnea-transient apnea(20sec)
Laryngospasm and broncospasm
because airway reflexes preserved

15. Contraindications
Porphyria
Previous hypersensitivity
Hypotensive patient
Hepatic and renal disease
Asthmatics

16. Non Barbiturates
ketamine
 Synthesized by Stevens in1962 and first used in
human by Domino and Corson in 1965
 Available as solution of 10g/ml and 50gm/ml
 Water soluble solution
 Produce dissociative anesthesia because patient may
not appear asleep (eyes open,reflexes intact)
 Complete Iv anesthetic

17. Pharmacokinetics
Onset of action in 30-60sec
Regain of consciousness after 15-20min
Elimination half life 2-3 hrs
Metabolised in liver and products are
excreted in urine

18. Pharmacodynamics
Primary site of action is thalamo-neocortical
projection means dissociates the thalamus
from limbic cortex
Inhibits cortex(unconsciousness)and
thalamus(analgesia)
Receptors
– N Methyl D Aspartate antagonist
– Opioid receptor

19. Effects
Central nervous system
CMO2,CMR,and ICP increases
Analgesia
Emergence reaction-vivid dreaming,floating
of body,excitement,confusion
Hallucination
*hallucination and emergence reaction
decreased by giving benzodiazepines

20. Cardiovascular system
 Sympathomimetic action –inc BP,HR,CO
so choice of anesthesia for shock
 Increase systemic vascular resistance
 Increase pulmonary artery pressure
Respiratory system
 Respiratory depression in higher doses
 Bronchodilation
 Pharyngeal and laryngeal reflexes preserved
 Tracheobronchial and salivary secretions are incresed

21. Dose
Induction
– IV 1-2mg/kg
– IM 3-5mg/kg
Sedation
– IV 2.5 -15mcg/kg/min

22. Advantages and uses
Induction,pain management and
sedation
Asthemitcs –bronchodilation
Shock
Depressed patient
Right to left shunt(hypertension)
Sole agent for minor procedures

23. Contraindications
 Head injury-ICT increases
Ocular surgeries
 Ischemic heart diseases-myocardial oxygen
demand increases
Patients with psychiatric diseases
 Hypertensives
 Pheochromocytoma

24. PROPOFOL
Most frequently use IV anesthetic drug today
Its chemical name is 2’6 di isopropylphenol
Milky white, available as 1% and 2% solution
Water insoluble ,pH-7-8.5
Dilution-5%dextrose with water(DNS)
Shorter half life
Early and smooth recovery

25.  Soyabean oil making the injection painful
 Egg is a good media for bacterial growth
 Antimicrobial agents disodium edetate and sodium
metabisulphite
 After the vial, it is mendatory to discard the propofol
vial within 6hrs

26. Pharmacokinetics
 Unconsciousness produced in 15-45sec
 Consciousness is regained in 2-8 minutes
 Elimination half life is 2-4 hrs
 Mainly metabolised in liver and extrahepatic metabolism occur
in kidney and lungs

27. Effects
Central nervous system
 CMO2,CMR,ICT all are decreased
 Anticonvulsant property
 Increased dopamine concentration(nucleus accumbence)
 Antiemetic
Cardiovascular system
 Decreased BP due to decreased CO and SVR
 heart rate decreased(baroreceptor reflex inhibit)
 vasodilation

28. Respiratory system
Apnea
Respiratory depression
Bronchodilation
Depression of upper airway reflexes(LMA)
Decreased ventilatory response to hypoxia

29. DOSES
Induction –IV
– 1-2.5mg/kg
Maintenance(infusion)-IV
– 50-200mcg/kg/min
Sedation(infusion)-IV
– 25-100mcg/kg/min

30. Advantages and uses
Induction
Maintenance
Sedation
Antiemetic
Total intravenous anesthesia
Bronchodilator
Antipruritic

31. Contraindications
Patients with soy allergy
Patient with egg allergy
Children less than 3 yrs(propofol infusion
syndrome)
Hypotensives
Drug addictors(dopamine)

32. Etomidate
■ It is a imidazole derivative
 Short acting
 Brief duration of action than thiopentone
■ Fat emulsion
Pharmacokinetics and
pharmacodynamics
 Act through GABA receptors
 Onset of action 30-60sec
 Duration of action 4-8 min
 Metabolised in liver and products are eliminated through kidney

33. Effects
Central nervous system
 ICT,CMO2,CMR decreased
 Myoclonus(spontaneous movements)
Cardiovascular system
 Cardiovascular stability(minimal change in HR,SV)
Respiratory system
 Ventilatory response to co2 depressed
 Less apnea

34. Dose
 Induction IV
– 0.2-0.5mg/kg
Advantages
 Cardiovascular stable
Minimal respiratory depression
 No histamine release

35. Disadvantages
 Adrenocortical suppression(inhibits enzymes
involved in cortisol and aldosterone synthesis)
 Nausea and vomiting
 Injection is painful
 No analgesia
 Thrombophlebitis
 Inhibition of platelet function

36. Benzodiazepines
 Diazepam
 Lorazepam
 Midazolam
 Flumazenil(benzodiazepine antagonist)
*diazepam and lorazepam hardly used because
– Preparation is oil based
– Elimination half life are prolonged therefore
chances of postoperative respiratory depression
are higher

37. Uses
 Premedication-to reduce anxiety
 Amnesia –
 Used in small procedures like
bronchoscopy,gastroscopy
 Induction-rarely
 To prevent hallucination by kitamine
 To control convulsions

38. Pharmacokinetics and
pharmacodynamics
 Benzodiazepines act through GABAa receptor ,increasing
membrane permeability to cl- causing hyperpolarisation
 Midazolam
– Rapid onset<1min
– Distribution half life 6-15min
– Elimination half life 2-3hrs
 Lorazepam
– Elimination half life 15 hrs
 Oil based preparation
 Bzs are metabolised in liver and metabolic products are
excreted in gut and urine

39. Effects
Central nervous system
 Act on reticular activating system and amygdela producing
sedation,anxiolysis and amnesia
 ICT,CMO2,CBF decresed
 Act on medulla producing muscle relaxation(at spinal cord level)
Cardiovascular system
 Minimal cardiovascular depression
 CO,BP,PVR decreases
 Slight increase in HR

40. Respiratory system
 Respiratory depression at higher doses
 Reduce hypoxic response
 Reduce muscular tone in upper airway leading to risk for
obstruction
DOSES
 Midazolam
■ Premedication(IM)- 0.07-0.15mg/kg
■ Sedation(IV)- 0.01-0.1mg/kg
■ Induction(IV)- 0.1-0.4mg/kg
 Diazepam
– Sedation(IV)- 0.04-0.2mg/kg

41. Opioids
 Opium is among the oldest drug in the world
 Used for analgesia
 Produce sedation
 Analgesics are divided into 2 groups
■ opioid-morphine,fentanyl
■ Nonopioid –
diclofenac,aspirin,paracetamol,aceclofenac
ketorolac
 To abolish shivering-pethidine and tramadol

42. Opioid receptor
Present in CNS,spinal cord and GIT
■ Receptors
– Mu-mu1 and mu2
– Kappa
– Delta
– Sigma and epsilon(nociception)

43. Classification
 Naturally occurring
– Morphine
– Codeine
 Semisynthetic
– Heroine
– Dihydromorphone
 Synthetic
– Butorphanol
– Pethidine
– Fentanyl,alfentanil,remifentanil
– tramadol

44. Systemic effects
 Hypotension
 Bradycardia
 Respiratory depression
 Depressed ventilatory response to hypoxia
 Inhibit tracheal and airway reflex
 Analgesia
 Sedation
 Hypothermia-inhibit temperature regulating centres
 Increase synthesis of ADH

45. Fentanyl
 Rapid onset-2-5min and rapid recovery(1-2hr)
 Cardiac stable
Dose
Morphine-0.03-0.15mg/kg(IV)
0.05-0.2mg/kg(IM)
Fentanyl
– Intraoperative-2-50mcg/kg(IV)
– Postoperative-0.5-1.5mcg/kg(IV)
Tramadol- 50-100mg for every 4-6hrs

46. Inhalational anesthetic
agents Inhalational anesthesia refers to the delivery of gases or
vapours to the respiratory system to produce anesthesia
 First anesthetic gas i.e.,nitrous oxide used by Humphry Davy
on himself for toothache
 Ether first used by William T.G Morton in the USA in 1846
 After that halothane,isoflurane,sevoflurane,desflurane etc
discovered
 Used mainly for maintainance of anesthesia
 Induction -children

47. Site of action
 CNS-unconsciousness,amnesia
 Dorsal horn of spinal cord-analgesia and immobility

48. Potency of inhalational
agents
 By minimum alveolar concentration(MAC)
 MAC is defined as minimum concentration of agent required
to produce immobility in 50% of the subjects given noxious
stimulus
 MAC values
Halothane -0.74
Isoflurane-1.15
Sevoflurane -2.05
Desflurane-6.0
Nitrous oxide -104

49. Factors affecting MAC
Factors increasing the MAC
 Hyperthermia >42
 Hypernatremia
 Chronic alcohol abuse and chronic opioid abuse
 Catecholamines ,cocaine

50. Factors decreasing the
MAC
 Hypothermia and hyperthermia(upto42)
 Hyponatremia,hypercalcemia
 Pregnancy
 Hypoxia
 Hypotension
 Drugs –all local anesthetics
 Increasing age
**AGENT WITH MINIMUM MAC WILL BE MOST POTENT

51. UPTAKE AND DISTRIBUTION OF
INHALATIONAL AGENTS
1. Transfer from Inspired Air to Alveoli
i. the inspired gas concentration FI
ii. alveolar concentration
iii. characteristics of the anaesthetic circuit
2. Transfer from Alveoli to Arterial Blood
i. blood:gas partition coefficient τB:G
ii. cardiac output CO
iii. alveoli to venous pressure difference dPA-vGas
3. Transfer from Arterial Blood to Tissues
i. tissue:blood partition coefficient τT:B
ii. tissue blood flow
iii. arterial to tissue pressure difference dPa-tGas

53. HALOTHANE
 Widely used in INDIA
 Colorless ,pleasant smell,non irritant,non inflammable
 Not a good analgesic
 Not used for cardiac patients
 CO,BP,HR decreases
 Myocardial depression
 Bronchodilator
 Depress respiratory centre and hypoxic reflexes
 Muscle relaxant
 Minimal stimulation of salivary and bronchial secretion

54. ISOFLURANE
 It is fluorinated methylethyl ether ,pungent smell
 Rapid induction and recovery
 Muscle relaxation
 Cardiovascular stable(minimum bradycardia)-MI
 CO maintained
 Bronchodilation
 Decrease renal blood flow and GFR
 ICT decreases-choice for neurosurgery
 Hypotension(vasodilation)

55. SEVOFLURANE
 NON pungent,sweet odour,
 Faster pleasant and smooth induction
 CO moderately decreased and depress respiration
 Bronchodilation
 Decrease portal blood flow
 Increase ICT
 With dry sodalime it produce compound A(olefin)-
nephrotoxic
 Produce convulsions

56. DESFLURANE
 Isomer of isoflurane
 Pungent odour ,unpleasant induction-coughing or
laryngospasm
 Produce maximum muscle relaxation
 Minimal metabolism-prolonged duration surgeries
 HR increases,BP decreses
 Depressed ventilatory response to hypercapnia
 Increase ICT
 Hypotension