Intravenous anaesthetic agents.

• Development of IV techniques occurred later than for

inhalational anaesthetic agents.
• IV induction agents is usually preferred now because
it is faster with less risk of excitement or laryngospasm.
IV anesthetic agents Used for:-
• 1. Anesthesia induction agents
• 2. Maintenance of anaesthesia, including TIVA,
• 3. Sedation.
• 4. Anticonvulsant.
Some of IV agents have also been given im or rectally
 Classified as general into :
A. ◗ rapid onset:
• - Barbiturates: ------------------thiopental, methohexital.
• - Imidazole compounds: ----- Etomidate.
• - Alkyl phenol: ------------------ Propofol.
B. ◗ slow onset:
• - Ketamine.
• - Benzodiazepines.------------ Midazolam
• - Opioids.----------------------- Fentanyl
•
 Features of the ideal iv anaesthetic agent:-

physical/chemical properties:
• 1 - Chemically stable at room temperature and on
exposure to light; long shelf-life.
• 2 - Water-soluble, not requiring reconstitution
before use, nor any additives.
• 3 - Compatible with iv fluids and other drugs.
• 4- Cheap
 pharmacology:
• 1 - Painless on injection, without causing
thrombophlebitis.
• 2- Harmless if extravasated or injected intra-arterially.
• 3 - Low incidence of adverse drug reactions.
• 4 - Smooth onset of anaesthesia within one arm– brain
circulation time, without unwanted movement,
coughing or hiccups.
• 5 - Anticonvulsant, antiemetic and analgesic properties.
• 6 -No increase in cerebral blood flow, ICP or intraocular
pressure.
• 7 - No respiratory depression. with Bronchodilator
action .
• 8 - No cardiovascular depression or stimulation, or
arrhythmias.
• 9 - Predictable recovery, related to the dose injected.
• 10 - Rapid metabolism to non-active metabolites; i.e.
non-cumulative.
• 11 - No impairment of renal or hepatic function or
corticosteroid synthesis.
• 12- No emergence phenomena.
• 13 - No teratogenicity
 Barbiturates
• Group of IV anesthetic agents synthesized in 1864. derived from barbituric acid,
including thiopental in 1934, and methohexital in 1957.
• ● Divided clinically into:-
• ◗ Long-acting, e.g. phenobarbital.
• ◗ Very short-acting, e.g. thiopental.
•
• Mechanisms of Action
• Barbiturates depress the reticular activating system in the brainstem, which
controls multiple vital functions, including consciousness by binding to the γ-
aminobutyric acid type A (GABA A ) receptor and potentiation of the action of
GABA (inhibitory neurotransmitter )in CNS .
•
•
 Thiopental sodium ( Thiopentone )
• Ultra rapid IV anesthetic agent first used in 1934.
• Physical Properties
• Stored as the sodium salt, is a yellow powder with a
faint garlic smell, with 6% anhydrous sodium carbonate
(preservative) added to prevent formation of
(insoluble) free acid when exposed to atmospheric CO2
.
• Most commonly used as a 2.5% solution (i.e. each ml
contain 25mg), with pH of 10.5 of solution .
• pKa is 7.6; and about 60% is nonionized
 Pharmacokinetics
• A. Absorption
• In clinical anesthesiology, thiopental, use IV only
• Rectal thiopental has been used for induction in children
• B. Distribution
• The duration of sleep doses of thiopental is determined by
redistribution, not by metabolism or elimination.
• Redistribution to the peripheral compartment—specifically, the
muscle group—lowers plasma and brain concentration to 10% of
peak levels within 20–30 min ( Figure below).
• This pharmacokinetic profile correlates with clinical experience—
patients typically lose consciousness within 30 s and awaken within
20 min.
•
• The minimal induction dose of thiopental will
depend on body weight and age.
• In contrast to the rapid initial distribution
half-life of a few minutes, elimination of
thiopental is prolonged (elimination half-life
ranges of 10– 12 h).
 C. Biotransformation
• Barbiturates are principally biotransformed via hepatic oxidation to
inactive water-soluble metabolites.
•
• Effects on Organ Systems A. Cardiovascular 1. Causes dose-related
direct myocardial depression, decreasing cardiac output this lead
to
• 2. causing compensatory tachycardia with increased myocardial O2
demand.
• Cardiovascular depression is related to speed of injection and is
exacerbated by hypovolemia.
• 3. Vasodilation of peripheral capacitance vessels, which increases
peripheral pooling of blood due to depression of the medullary
vasomotor center.
 B. Respiratory :-
• 1. Causes dose-related depression of the respiratory center,
decreasing the responsiveness to CO2 and hypoxia.
• 2. Apnea is common after induction.
• 3. Laryngospasm and bronchospasm readily occurs
following laryngeal stimulation.
• C. CNS :-
• 1. Rapid smooth induction , occurring within one arm–brain
circulation time. 2. Involuntary movements 3. Painful
injection are rare. 4. Recovery within 5–10 min after a
single dose 5. Anticonvulsant. 6. Decreases pain threshold
(antanalgesia). 7. Reduces cerebral perfusion pressure, ICP
and cerebral metabolism.
• D. Immunological :-
• Anaphylactic allergic reactions may occur .
• Other Effects:
• 1. Skeletal muscle relaxation 2. Causes
hepatic enzyme induction 3. Has no effect on
uterine tone
• Complications:
• 1-Extravenous injection causes pain and
erythema.
• 2- Intra-arterial injection causes intense pain,
and may cause distal blistering, oedema and
gangrene, because of crystallization of
thiopental within arterioles and capillaries,
with local noradrenaline release and
vasospasm.
 Treatment:-
• Leaving the needle/cannula in the artery, the
following may be injected:
• A. Saline, to dilute the drug. B. Vasodilators,
traditionally papaverine 40 mg, phentolamine 2–
5 mg, to reduce arterial spasm. C. Local
anaesthetic, traditionally procaine 50–100 mg
(also a vasodilator), to reduce pain. D. Heparin, to
reduce subsequent thrombosis E. Postponement
of surgery has been suggested
• 3-Respiratory/cardiovascular depression as above.
• 4-Adverse drug reactions. Severe anaphylaxis is rare
(1:14 000–35 000), typically occurring after several
previous exposures.
• Contraindicated :-
• 1. Porphyria. 2. Heart failure. 3. Asthma. 4.
Hypovolemia.
• ● Dosage:
• 3–6 mg/kg IV . Requirements are reduced in:-
• 1. Hypoproteinaemia, 2. Hypovolemia, 3. The elderly
4. critically ill patients.
• Injection should be over 10–15 s, with a
pause after the expected adequate dose
before further administration
has also been given rectally: 40–50 mg/kg as
5–10%solution
 Propofol (Diprivan)
• IV anaesthetic agent, ( is 2,6-Diisopropylphenol .) first
used in 1986.
• Produce anaesthesia by binding to GABAA receptors
and potentiating the action of endogenous GABA.
• It's not water soluble, presented as an oil–water
emulsion:
• 1% form (presented in 20 ml ampoules, 50,100 ml
vials and 50 ml prefilled syringes) or 2% (for infusion
only and presented in 50 ml vials and 50 ml prefilled
syringes)
• Each ampule containing 10% soya bean oil, 1.2%
egg phosphatide and 2.25% glycerol as
preservative lead to pain during injection,
bacterial growth and anaphylactic reaction .
• A new formulation containing mediumchain
triglycerides causes less pain on injection;
• Propofol should be administered within 6 h of
opening the ampule.
• Fospropofol is the phosphate prodrug of
Propofol and as such has a slower onset of
action; it is licensed in the USA for ‗light sedation
 Pharmacokinetics
• A. Absorption
• Propofol is available only for intravenous administration
only for the
• 1. Induction of general anesthesia , 2. Maintenance of
anesthesia. 3. TIVA .(total intravenous anesthesia) 4.
Moderate to deep sedation.
• B. Distribution
• Propofol has a rapid onset of action. , recovery from
Propofol is more rapid (2–8 min) and is accompanied by
less ―hangover‖ than recovery from thiopental, ketamine,
or Etomidate. This makes it a good agent for outpatient
anesthesia.
• C. Biotransformation:- Metabolised in the liver as rapid
metabolism ( 1st order kinetic ). Extrahepatic
metabolism is suggested by a plasma .no active
metabolite.
• D. Excretion:-
• Metabolites of Propofol are primarily excreted in the
urine,
• There are no active metabolites.
• Because of rapid recovery with minimal residual
effects, making it a popular agent in short cases, e.g. in
day-case surgery.and suitable for TIVA and IV sedation.
•
 Effects on Organ Systems:
• ◗ CNS
• 1. Induction is smooth and rapid, with only occasional movements. 2. Pain
on injection is common; it may be reduced by prior administration of
opioid analgesic drugs, injecting into a large vein, and prior injection of ,or
mixing with, lidocaine. (2 mL of 1% lidocaine in 18 mL Propofol). 3. NO
analgesia effect reported. 4. Has an antiemetic effect. Increased appetite
5. Reduces cerebral blood flow, ICP.
• ◗ CVS:
• 1. Hypotension is common, Factors associated with Propofol- induced
hypotension include large doses, rapid injection, and old age. 2. Normo- or
bradycardia is common; because of resetting of the baroreceptor reflex
has been suggested. It may be severe in patients at the extremes of age,
those receiving β-adrenergic blockers, or those with impaired ventricular
function
 RS
• 1. Respiratory depression is profound or marked.
2. Propofol inhibits hypoxic ventilator drive and
depresses the normal response to Hypercarpia .
3. It tends to obtund upper airway reflexes, thus
allowing manipulation /instrumentation more
readily than thiopental. Thus particularly useful
when placing the LMA.
• ◗ Other:
• - Allergic phenomena have been reported
 Dosage:
• ◗ 1.5–2.5 mg/kg for induction (increased to 2.5–5 mg/ kg in
children).
• ◗ for maintenance, several regimens have been suggested, based
on pharmacokinetic studies, including the Bristol regimen
• ◗ for sedation .. 1.0–4.0 mg/kg/h (licensed for up to 3 days).
• ● precautions :-
• A history of egg allergy does not necessarily contraindicate the
use of Propofol because most egg allergies involve a reaction to egg
white (egg albumin), whereas egg lecithin is extracted from egg
yolk. Which cause pain during injection
• Propofol formulations can support the growth
of bacteria, so sterile technique must be
observed in preparation and handling.
Contamination during preparation for infusion
has led to iatrogenic bacteremia.
• Myocardial failure and acidosis have been
reported after prolonged infusion of high doses in
adults, leading to the description of a distinct
metabolic syndrome, the Propofol infusion
syndrome
• Contraindicated:-
• 1. Hypovolemia.
• 2. Heart failure.
• 3. History of allergy.
• 4. Heart block.