Intravenous Anesthetic Agents

by Miss Maidah Mehtab

Mechanism of action
All IV anesthetics except ketamine potentiate GABA
type A receptors to inhibit CNS neurotransmission.
Propofol and barbiturates also potentiates the inhibitory
effects of glycine at glycine receptors in brain and spinal
cord.
Ketamine’s hypnotic effects appear to be largely
mediated by blockade of NMDA receptors
Uses
1. Induction of anesthesia (smother and more rapid than
inhalational agents)
2. Maintenance (alone or with inhalational agents)
3. Sedation during regional anesthesia
4. Sedation in intensive care unit
5. Treatment of status epilepticus
Properties of ideal IV anesthetic agent:
1. Rapid onset
2. Rapid recovery
3. Sedation during regional anesthesia
4. Analgesia at sub anesthetic doses
5. Minimal CV and respiratory depression
6. No emetic effects
7. No excitatory phenomena
8. No emergence phenomena
9. No interaction with NMB
10. No pain on injection
11. Safe if injected inadvertently into an artery
12. No toxic effects on other organs
 Properties of ideal IV anesthetic agent

No release of histamine
No hypersensitivity reactions
Water soluble formulation
No venous sequelae
Long shelf life
No stimulation of porphyria
Classification
Rapidly acting (primary induction) agents

Slower acting (basal narcotic) agents

 Rapidly acting (primary induction)
agents

 Barbiturates
 Methohexital
 Thiobarbiturates
 Thiopental
 Thiamilal
 Imidazole compounds
 Etomidate
 Alkyl phenols
Propofol
Slower acting (basal narcotic) agents
Ketamine
Benzodiazepines
 Diazepam
 Medazolam
Opioids
Fentanyl
Alfentanyl
Sufentanyl
Propofol
Chemical Structure
2,6-Di-isopropylphenol
Chemical Structure
Physical Properties
Lipid soluble
Almost insoluble in water
Initially it was formulated in Cremophor EL
Reformulated in white aqueous emulsion containing
soybean oil and purified egg Phosphatide
1% and 2% solutions are available
Recently 0.5% solution has been made available,
intended to use in children
Organ System Effects
1. Central nervous system
Anesthesia is induced within 20-40s. Transfer from
blood to the sites of action in brain is slower than with
thiopental and there is delay in disappearance of eyelash
reflex. Loss of verbal contact is better end point. There
have been reports of convulsions following its use.
Cerebral metabolic rate, CBF and ICP are reduced.
Organ System Effects
2. Cardiovascular system
Arterial pressure decreases greater than that of
thiopental.
There is slight negative inotropic effect.
HR may increase slightly after induction of anesthesia.
There have been occasional reports of severe
bradycardia.
Organ System Effects
3. Respiratory system
After induction apnea occur more commonly and
for longer duration than after thiopental.
During infusion tidal volume is lower and
respiratory rate higher than in conscious state.
No effect on bronchial muscle tone and
laryngospasm is uncommon
Regarded as drug of choice for induction of
anesthesia when supraglottic airway device is to be
used
Organ System Effects
3.Skeletal muscle system
 Tone is reduced but movements may occur in
response to surgical stimulation
4. Uterus and placenta
Used extensively in patients undergoing
gynaecological surgery and has no effect on uterine tone.
It crosses placenta.
Organ System Effects
5.Hepatorenal system
 There is decrease in renal function
Hepatic blood flow is decreased
liver function tests are not deranged after its infusion
for 24 h
6. Endocrine system
Plasma concentrations of cortisol are decreased.
Pharmacokinetics
 It is distributed rapidly
Not metabolized only in liver but extra hepatic sites of
metabolism also exist
Excretion mainly through kidneys.0.3% is excreted
unchanged
Terminal elimination half life is 3-4.8h but effective
half life is much shorter i.e. 30-60min
Dosage
 For induction a dose of 1.5-2.5mg/kg is required.
Dose should be reduced in elderly and increased in
children
Cardiovascular side effects are reduced if drug is
injected slowly
Propofol
Indications:
 Induction of anesthesia when rapid early recovery of
consciousness is required
 Sedation during regional anesthesia and endoscopy
 Sedation in ICU
 Total intravenous anesthesia
Adverse effects:
 Cardiovascular depression
 Respiratory depression
 Excitatory phenomena (convulsion, myoclonus)
 Pain on injection
 Allergic reaction
Contra indication:
 Airway obstruction
 Hypersensitivity
Thiopental Sodium
Chemical Structure
Sodium 5-ethyl-5-(1-methylbutyl)-2-thiobarbiturate.
Physical Properties
It is yellowish powder with bitter taste and faint smell of
garlic.
Stored in nitrogen to prevent chemical reaction with
atmospheric carbon dioxide.
Mixed with 6% anhydrous sodium carbonate to increase its
solubility in water.
Available in single dose ampoule of 500mg and dissolved in
distilled water to form 2.5% solution
Freshly prepared solution may be kept for 24 h
pH is 10.8
Oil/water partition coefficient is 4.7.
pKa is 7.6.
Thiopental Sodium
Indications:
1. Induction of anesthesia
2. Maintenance of anesthesia (but has cumulative
effects)
3. Treatment of status epilepticus
4. Reduction of intra-cranial pressure (ICP)
Contraindications:
 Airway obstruction
 Hypersensitivity
 Porphyria

Pharmacokinetics:
75 to 85 % of drug is protein bound
Diffuses rapidly into CNS due to its lipid solubility and
unionized state at body pH
Metabolism occurs in liver and excreted renally
Termination elimination half life is 11.5 hrs
A hangover effect is common.
 Dosage

• For induction a dose of 4mg/kg is required

initially. If loss of eyelash reflex does not
occur within 30s,supplementry doses of 50-
100mg should be given unless
consciousness is lost
•Dose should be reduced in elderly and
increased in children
 Organ System Effects
Central nervous system .1
•Anesthesia is induced in less than 30s.
• causes progressive depression of CNS
•Its hypnotic action is potent but has poor analgesic activity
•There is secondary decrease in CBF,cerebral blood
volume and ICP
•At subanesthetic blood concentrations thiopental has
antanalgesic effect and reduces the pain threshold
• conciousness is regained in 5-10 min.
•Very potent anticonvulsant.
 Organ System Effects
Cardiovascular system .2
•Myocardial contractility is depressed, when
large doses are used or if injection is rapid.
•Arterial pressure decreases.
•HR may decrease but there is often a reflex
tachycardia.
 Organ System Effects
Respiratory system .3
•After induction a short period of apnea is common.
•Respiratory depression is influenced by
premedication
•Laryngeal spasm may be precipitated by surgical
stimulation or the presence of secretions, blood or
foreign bodies in region of pharynx or larynx
•Less satisfactory than tiopental in this respect
•Increase in bronchial muscle tone.
 Organ System Effects
3.Skeletal muscle system
• Tone is reduced at high blood concentrations
•Causes poor muscle relaxation and movements occur in
response to surgical stimulation
•No significant direct effect on NMJ
4. Uterus and placenta
•Little effect on resting uterine tone.
•It crosses placenta readily although fetal blood
concentrations does not reach the same levels as in
mother
 Organ System Effects
5.Hepatorenal system
•Hepatic microsomal enzymes are induced.
•Functions of liver and kidneys are impaired after
its administration
6. Eye
•IOP is reduced by 40%
•Pupil first dilates and then constricts
•The corneal, conjuctival, eyelash and eyelid
reflexes are abolished
Adverse effects:
1. Hypotension(avoided if drug is injected slowly)
2. Respiratory depression
3. Tissue necrosis (if injected extra-vascular)
4. Laryngospasm
5. Bronchospasm (avoid in asthma)
6. Thrombophlibitis (less common in 2.5% conc.)
7. Allergic reactions 1 in 14000-20000
8. Intra-arterial injection (lead to sever vasospasm and
sever pain it may lead to gangrene of the limb,
treatment by keeping the cannula in and inject
papeverine 20 mg, heparin and fluid)
Etomidate
Chemical Structure

D-Ethyl-1-imidazole-5-carboxylate
Physical Properties
It is presented as clear aqueous solution containing 35%
propylene glycol or in an emulsion with triglycerides and
soya-bean oil.
Soluble but unstable in water.
Available in ampoule of 20mg in 10ml.
pH is 8.1.
Etomidate
Indications:
 Used in patient with cardiovascular disease (cardiovascular
stable)
 Suitable for out patient anesthesia
Adverse effects:
 Excitatory phenomena (involuntary movements, hiccups,
cough)
 Pain on injection
 Nausea and vomiting
 Venous thrombosis
Contraindications:
 Airway obstruction
 Porphyria
 Adrenal insufficiency
 Long term duration
Dosage:
Dose of 0.3mg/kg IV

Pharmacokinetics:
76% of drug is protein bound
Metabolism occurs in plasma and liver and metabolites
are excreted in urine
Termination elimination half life is 2.4-5 hrs.
Short acting agent with duration of action 2-3 min
Ketamine Hydrochloride
Chemical Structure

2-( 0-chlorophynyl)-2-(methylamino)-cyclohexanone
hydrochloride.
 Physical Properties
It is presented as solutions of 10mg/ml containing NaCl
to produce isotonicity and 50 or 100mg/ml in multi dose
vials which contain benzothonium chloride as
preservative.
Soluble in water.
Available in ampoule of 20mg in 10ml.
pH is 3.5-5.5
pKa is 7.5
Ketamine hydrochloride:
Indications:
 Shocked patient
 Paediatric anesthesia
 Difficult locations (at accident site, wars)
 Analgesia And sedation (wound dressing change)
 In ICU
 In developing countries (where anesthesia equipments and
trained staff are in short supply)
Adverse effects:
 Emergence delirium, nightmares and hallucinations
 Hypertension and tachycardia
 Prolong recovery
 Salivation
 Increase intra-cranial pressure
Dosage:
Dose of 2mg/kg IV and 8-10mg/kg IM

Pharmacokinetics:
Only 12% of drug is protein bound
Metabolism occurs occurs predominantly in liver.
Among metabolites is norketamine which is
pharmacologically active
Termination elimination half life is 2.5 hrs.
Organ System Effects
1. Central nervous system
Anesthesia is induced in 30-60s and has duration of
action10-15 min.
Also effective within 3-4 min after IM injection and has
DOA of 15-25 min.
 causes progressive depression of CNS
It is a potent analgesic at subanesthetic blood
concentrations.
Induction is smooth but delirium may occur with
restlessness and agitation
There is increase in CBF, cerebral blood volume and ICP.
Organ System Effects
2. Cardiovascular system
There is increased myocardial contractility to
adrenaline.
Arterial pressure increases by up to 25% and HR by
20%.
Cardiac output and myocardial oxygen consumption
increases.
Organ System Effects
3. Respiratory system
After IV induction transient apnea may occur.
Respiratory depression is influenced by
premedication
Laryngeal and pharyngeal reflexes are maintained
well as compare to other IV anesthetics.
bronchial muscle muscle is dilated.
Organ System Effects
3.Skeletal muscle system
 Toneis usually increased.
Spontaneous movement may occur but reflex
movement in response to surgical stimulation is
uncommon.
4. Uterus and placenta
It crosses placenta readily.
Fetel concentrations are equal to those in mother
Organ System Effects
5.Gestrointestinal
Salivation is increased

6. Eye
IOP increases
Eye movement often persist during surgical anesthesia.