2. PROPERTIES OF THE IDEAL INTRA
VENOUS ANAESTHETIC AGENT{1 OF 3}
1-rapid onset: achieved by an agent that is mainly :
A- un-ionized at blood ph(7.35 – 7.45)
B- highly lipid soluble
** these properties permit penetration of the BBB
2-rapid recovery:
-early recovery of consciousness is usually produced by rapid
redistribution of the drug from brain into other well-perfused tissues
particularly muscles
-plasma conc. Of drug decreases & drug diffuses out of the brain along a
conc. gradient
-quality of the recovery period is more related to the rate of metabolism
of the drug
* Drugs with slow metabolism are with a more prolonged hangover
effect (fatigue, weakness, pain, nuasea vomiting..etc )and accumulate
if used in repeated doses or by infusion for maintenance of anesthesia
2
4. Pharmacokinetics
-with no other drugs ,the anesthetic
state persists for 5-10 mins
Its concentration is low enough in
the brain such that
consciousness returns.
So is most commonly used in the
induction phase of general
anesthesia
As with all lipid soluble anesthetic
drugs, the short duration of action
of Sodium thiopental is almost
entirely due to its redistribution
away from central circulation
towards muscle and fat tissue.
Sodium thiopental (pentothal)
4
5. SODIUM THIOPENTAL
(PENTOTHAL)
Pharmacokinetics
-An IV dose of 3-5 mg/kg results in loss of
consciousness
-time required to render the patient unconscious
is generally
30-60 secs after administration .this is called the
“arm brain” circulation time
-arm brain circulation time
is the time required for the drug to pass from site of
injection to the brain as it passes through the right
heart ,pulmonary circ., and the left heart 5
6. Pharmacokinetics
-sulphur containing drugs , acidosis, NSAIDS may displace
thiopental from albumen
-liver &renal disease may be associated with low albumin levels
so result in an increase in free thiopental which inc. the anesthetic
toxicity and potency
-metabolism occurs primarily in the liver with approximately 10 to
15%of the drug level metabolized per hour
-a desulfuration rxn in liver produces pentobarbital which under goes
oxidative metabolism yielding 2 compounds with no anesthetic
activity
-less than 1% of the drug is excreted unchanged in the urine
Sodium thiopental (pentothal)
6
7. SODIUM THIOPENTAL
(PENTOTHAL)
pharmacodynamics
CNS:barbiturates interact with chloride ion channels by
altering the duration they spend in an open state
-this facilitates inhibitory neurotrasmitters such as gama amino
butyric acid(GABA)
As well as blocking excitatory NTM actions such as glutamic acid
-thiopental will decrease both cerebral electrical & metabolic activity
So it can be used to stop seizures activity in emergency
situations
-to maintain depression of cerebral electrical activity very high dose
are required
-But to maintian seizure control & avoid cv depression from high
dose of thiopental other drugs are used (e.g. benzodiazepines)
7
8. SODIUM THIOPENTAL
(PENTOTHAL)
pharmacodynamics
CNS: Elevated ICP can quickly be reduced by
thiopental BUT The improvement of ICP requires high
dose of thiopental to be maintained
The reduction of ICP is due to cerebral vasoconstriction,
reduced cerb. Metabolism &oxygen requirments
associated with dec.cerebral blood volume
-theopental has an an anti-analgesic effect, since low
dose may decrease pain threshold
-Intraocular pressure decreases
up to 25% with 3-5mg/kg of thiopental and persists for
3 to 5 minutes 8
9. SODIUM THIOPENTAL
(PENTOTHAL)
Pharmacodynamics
CVS:-thiopental causes a dose related depression
of myocardial function as measured by CO,SV, and
blood pressure
-coronary blood flow, heart rate ,&myocardial oxygen
uptake all increase following thiopental administration
-venous tone decreases (decreased preload)
And contributes to the increase in HR and decrease in
BP
-little change in total peripheral resistance
9
10. SODIUM THIOPENTAL
(PENTOTHAL)
Pharmacodynamics
Respiratory:-induction of anesthesia with
thiopental may be associated with 2 or 3 large
breaths followed by apnea for less than 1min
-there is dose related depression of the
respiratory response to hypercarbia and
hypoxia
-laryngospasm and bronchoconstriction may
be associated with light levels of thiopental and
with airway manipulation or intubation
-FRC is reduced by 20% with induction of
anasthesia
>Functional Residual Capacity (FRC) is the volume of air
present in the lungs at the end of passive expiration. 10
11. SODIUM THIOPENTAL
(PENTOTHAL)
Pharmacodynamics
GI: enzyme induction may occur with
prolonged high dose therapy
- Hypoalbuminemia will result in an increase in
unbound (free) thiopental and an increase in
the potency of thiopental
GU/pregnancy/fetus:
- Thiopental has little or no effect on the kidneys
or gravid uterus.
-although thiopental crosses the placenta
It has no significant effect on the fetus when
used for cesarean section (dose used is limited
to 4mg/kg)
11
12. SODIUM THIOPENTAL
(PENTOTHAL)
Dose & administration
-the usual dose is 3-6 mg/kg
- Thiopental should be used with caution
for Patients suffering from shock status
because normal dose may lead to rapid
death
-for a short procedure (e.g.cardioversion) a
dose of 2 mg/kg is generally sufficient
-for frail elderly women with hip fracture .5-
1 mg/kg may induce anesthesia 12
13. SODIUM THIOPENTAL
(PENTOTHAL) INDICATIONS
1- induction of anesthesia
2- maintenance of anesthesia
for short procedures
3- control of convulsive states
4- for supplement of regional
anesthesia or low potency
anesthesia
13
15. SODIUM THIOPENTAL
(PENTOTHAL)
SIDE EFFECTS
1- hypotension :if thiopental is administered to
hypovolemic, shocked or previously hypertensive pt
2- respiratory depression :when excessive doses are
used
3- tissue necrosis : following venous infusion
4- laryngeal spasm
5- bronchospasm :unusual but may be precipitated in
asthmatics pts
6- allergic reaction : from cutanous rashes to severe
anaphylactic shock with cvs collapse
15
16. SODIUM THIOPENTAL
(PENTOTHAL)
SIDE EFFECTS
7- Rarely, intra-arterial injection can occur.
The consequences of accidental arterial injection may be severe.
The degree of injury is related to the concentration of the drug.
Treatment consists of
1. dilution of the drug by the administration of saline into the
artery,
2. heparinization to prevent thrombosis, and
3. brachial plexus block.
Overall, the proper administration of thiopental intravenously is
remarkably free of local toxicity.
16
20. PROPOFOL
PHYSICAL AND CHEMICAL
PROPERTIES
so Propofol is a highly lipid soluble oil that’s combined
with glycerol, egg, and soya bean oil for IV
administration.
It’s appearance is similar to that of a 2% milk.
It has a pH of 7 and is supplied in 20 ml ampoules with
a concentration of 10 mg/ml.
Neither precipitates histamine release nor triggers
malignant hyperthermia.
Has no effects on muscle relaxants.
Associated with low incidence of nausea & vomiting. 20
21. PROPOFOL
DOSAGE
For healthy unpremedicated 2.5-3 mg/kg.
For premedicated 1.5-2 mg/kg.
Elderly patients <= 1 mg/kg.
Maintenance of anesthesia (50-150 mcg/kg/min)
combined with N2O and Opioids (Continuous
Infusion: Total intravenous Anesthesia TIVA)
For IV conscious sedation for operative procedures
with local anaesthesia 25-75 mcg/kg/min.
21
22. PROPOFOL
EFFECTS ON ORGAN SYSTEMS
Cerebral:
decreases cerebral blood flow and intracranial
pressure. Propofol has antiemetic, antipruritic,
and anticonvulsant properties.
Cardiovascular:
decrease in arterial blood pressure secondary to a
drop in systemic vascular resistance,
contractility, and preload. Hypotension is more
pronounced than with thiopental. Propofol
markedly impairs the normal arterial baroreflex
response to hypotension.
22
23. PROPOFOL
EFFECTS ON ORGAN SYSTEMS
Respiratory:
propofol causes profound respiratory depression.
Propofol induced depression of upper airway
reflexes exceeds that of thiopental.
Venous irritation:
Pain on injection is more common than with thiopental
esp. if given in a small vein in the hand.
To solve this problem:
1. small doze of lidocaine with propofol.
2. administering propofol through a fast flowing more proximal IV
catheter. 23
24. PROPOFOL
INDICATIONS
indication Approved Patient Population
Initiation and maintenance of
Monitored Anesthesia Care
sedation
Adults only
Combined sedation and regional
anesthesia
Adults only (See PRECAUTIONS
)
Induction of General Anesthesia Patients ≥ 3 years of age
Mainenance of General Anesthesia Patients ≥ 2 months of age
Intensive Care Unit (ICU) sedation
of intubated, mechanically
ventilated patients
Adults only
24
25. PROPOFOL
CONTRAINDICATIONS
1. Egg allergy.
2. Lack of resuscitation equipment or
knowledge of the drug.
3. Inability to maintain a patent airway.
4. Conditions in which reduction in blood
pressure can’t be tolerated. E.g. patients with
fixed cardiac output (severe aortic or mitral
stenosis, IHSS, pericardial tamponade) and
those in shock status.
25
26. KETAMINE
It’s a dissociative anesthetic
agent.
by dissociative we mean that
the patient is unconscious but
appears awake and doesn’t
feel pain.
It has anesthetic and
analgesic effect 26
27. KETAMINE
PHYSICAL & CHEMICAL PROPERTIES
27
chemically related to the psychotropic
drug ( e.g. phencyclidine).
Water soluble, and 10x more lipid
soluble than thiopental.
pH=3.5 - 5.5
29. KETAMINE
PHARMACOKINETICS
DOSAGE
IM 5 – 10 mg/kg. peak plasma level
reach approx 15 minutes
IV 1 – 2 mg/kg. dissociated stage is
noted in 15 seconds. intense analgesia,
amnesia & unconciousness occur within 45-
60 minutes
subsequent IV doses of 1/3 – ½ of the
initial dose maybe required 29
30. KETMINE
METABOLISM
It has a rapid absorption and distribution to the
vessel rich groups like THIOPENTAL
Hepatic metabolism is required for elimination
<5% excreted unchanged in urine
30
31. KETMINE
MECHANISM OF ACTION
There are 3 theories explains the MOA of ketamines :
1 – N-methyl aspartate receptor theory :
NMA receptors may represent a subgroup of the sigma opiate
receptors (the PCP site) that blocks spinal pain reflexes.
2 – Opiate receptor theory :
Ketamine may have some affinity for opiate receptors but it’s
effect can’t be reversed with naloxone.
3- Miscellaneous receptor theory :
It reacts with muscarinic, cholinergic and serotonergic receptors.
Ketamine is a potent analgesic at subanesthetic plasma
concentrations.
It has a wide margin of safety ( up to 10x the usual dose )
31
32. KETMINE
PHARMACODYNAMICS
CNS :
1. ketamine increases cerebral oxygen
consumption, cerebral blood flow, and
intracranial pressure
2- generalized increase in the muscle tone and
purposful movements.
3- Unpleasant dreams, hallucinations or frank delirium
(esp. females & large doze of ketamine).
incidence of dilirium in 15-35 year old pts is approx.
20%
32
33. KETMINE
PHARMACODYNAMICS
Respiratory system:
It preserves laryngeal &pharyngeal airway reflexes.
• Ketamine is a potent bronchodilator.
• The CO2 response curve is shifted to the left with its
slope unchanged (similar to opiates).
FRC unchaged.
Minute ventilation unchanged.
Tidal volume unchanged.
Hypoxic pulmonary vasoconstriction unchanged.
Ketamine causes increased secretions but this can be
limited by anti-cholinergic drugs.
33
34. KETMINE
PHARMACODYNAMICS
CVS:
• It produces central sympathetic stimulation,
which increases:
1. arterial blood pressure, heart rate, and cardiac
output.
2. Pulmonary artery pressure.
3. Coronary blood flow.
4. Myocardial oxygen uptake.
It may cause myocardial depression if the
sympathetic nervous sys is exhausted or
blocked. 34
35. KETMINE
PHARMACODYNAMICS
GI
Minimal anorexia, nausea & vomiting.
GU
Placental transfer does occur, but neonatal depression hasn’t
been observed if the doze is limited to < 1 mg/kg.
Muscle system
Generalized increase in skeletal muscle tone.
Increases the effects of muscle relaxants.
Endocrine Sys.
Increased sympathetic stimulation increased blood
glucose, increased plasma cortisol, increased heart rate. 35
36. KETMINE
INDICATIONS
1- sole anesthetic for diagnosis and surgical
procedures
2- induction of anesthesia
3- to supplement regional or local anesthetic
techniques
4- for anesthetic induction in severe asthmatic pts. Or
patients with cardiovascular collapse requiring
emergency surgery
36
37. KETMINE
CONTRAINDICATIONS
1- lack of knowledge of the drug
2- lack of resuscitative equipment
3- inability to maintain a patent airways
4- allergy to ketamine
5- history of psychosis
6- cerebro-vascular disease
7- Patients. For whom hypertention is hazardous
37
38. BENZODIAZEPINES
Features which result in their
popularity as adjuvant IV anaesthetic
agents:
1 – amnesia
2 – minimal cardiarespiretory
depressant effect.
3 – anticonvulsant activity.
4 – low incidence of tolerance and
dependence. 38
39. BENZODIAZEPINES
MODE OF ACTION
1 – They inhibit the actions of glycine (by increasing
the conc. Of a glycine inhibitory neurotransmitter)
which will lead to antianxiety and skeletal muscle
relaxant effects.
2 – They facilitate the actions of the inhibitory
neurotransmitter GABA which results in the
sedative and anticonvulsant effects.
Benzodiazepines are highly lipid soluble.
They are highly protein bound (albumin).
They are metabolized by the liver through conjugation with
glucoronic acid and excreted by the kidneys.
Midazolam and Diazepam are the most commonly used
benzodiazepines during operative procedures. 39
41. BENZODIAZEPINES MIDAZOLAM AND
DIAZEPAM
THE DIFFERENCES BETWEEN THEM
1- Midazolam is 2-3 times more potent than
diazepam:
2- The dose for IV conscious sedation: 0.5 – 3
mg up to 0.1 mg/kg for midazolam, and 1-10
mg for diazepam.
3- The dose for inducing anesthesia: 0.2 – 0.4
mg/kg for midazolam , and 0.15-1.5 mg/kg for
diazepam.
4- Midazolam has a more rapid onset, greater
amnestic effect, less postoperative sedative
effects than diazepam. 41
42. BENZODIAZEPINES MIDAZOLAM AND
DIAZEPAM
THE DIFFERENCES BETWEEN THEM
5- Pain on injection and subsequent
thrombophlebitis is less likely with midazolam
(an emulsion of diazepam)
6- Midazolam is more costly than diazepam).
7- Midazolam’s duration of action is less than
diazepam but almost 3 times that of thiopental.
8- Elimination half time for midazolam range from
1-4 hours, and for diazepam from 21-37 hours.
9- Midazolam is supplied as a clear liquid in
concentrations of 1-5 mg/ml.
42
43. BENZODIAZEPINE ANTAGONISTS
(FLUMAZENIL)
It’s an imidazobenzodiazepine.
It specifically antagonizes benzodiazepine’s central
effects by copetative inhibition.
It’s elimination half-time is one hour, considerably less
than most benzodiazepines; therefore we will need
repeated administrations of flumazenil to antagonize a
benzodiazepine with a longer half-time.
43
44. BENZODIAZEPINE ANTAGONISTS
(FLUMAZENIL)
Flumazenil is supplied as a colourless liquid in a
concentration of 0.1 mg/ml.
The usual initial dose is 0.2 mg over 15 seconds,
if the desired level of consiousness is not
obtained within one minute of administration we
can give repeated doses of 0.1 mg every minute
up to the maximum of 2 mg, and if sedation
recurs we can use infusions of 0.1-0.4 mg/hour.
Flumazenil is well tolerated.
The most common side is nausea (4% of
patients). 44
48. NARCOTIC AGONISTS
PHARMACODYNAMICS
CNS:
Opioids sedate through interfering with
sensory perception of painful stimuli.
large doses produce unconsciousness but
they are generally incapable of producing
anesthesia and it can’t guarantee total
amnesia.
It may produce nausea & emesis through
stimulation of the chemoreceptor trigger
zone.
48
49. NARCOTIC AGONISTS
PHARMACODYNAMICS
Respiratory
They result in dose related depression
of respiratory rate and minute
ventilation and increase the tidal
volume which will lead to a slow deep
respiration. Reversed by naloxone
administration.
49
50. NARCOTIC AGONISTS
PHARMACODYNAMICS
CVS
Opioids have little myocardial depressant effect even
when administered in high doses.
Supplementation with either N2O or benzodiazepines
may depress cardiac output.
They decrease systemic vascular resistance either by
decreasing sympathetic outflow or by releasing
histamine (as morphine) which produces vasodilation
& decrease SVR.
Synthetic opioids are less likely to release histamine.
They produce bradycardia by stimulation vagal
nucleus in the brain stem. 50
51. NARCOTIC AGONISTS
PHARMACODYNAMICS
GIT
Narcotics slow GI mobility and may result in
constipation or post operative ileus.
All narcotics increase biliary tract tone which
may lead to biliary colic with patients with bile
stones.
Others
Increases the bladder sphincter’s tone urine
retention.
Anaphylactic reactions, bronchospasm, chest
wall rigidity and pruritis.
51
52. NARCOTIC AGONISTS
FENTANYL AND MORPHINE
Fentanyl is the most narcotic agent used
during induction of anaesthesia due to its
rapid onset (highly lipid soluble) and
predictable duration of action (30
minutes).
Morphine is used in the perioperative
period to provide long lasting analgesia.
And it should be administered slowly at a
rate < 5 mg/min to avoid excessive
histamine release.
52
53. NARCOTIC AGONISTS
FENTANYL AND MORPHINE
Potency Ratio Analgesic dose Low dose
Morphine 1 10
mg 0.05 - 0.2 mg/kg
Fentanyl 100 100
mcg 0.5
–
3
mic g/kg
53
54. NARCOTIC ANTAGONISTS
(NALOXONE)
Naloxone competes with opioids at the mu, delta,
kappa and sigma receptors.
Ampules of 0.02, 0.4 and 1 mg/ml.
Peak effect 1-2 min.
Duration of action 30-60 min.
Used in perioperative surgical patients with excessive
sedation or respiratory sedation secondary to
opioids.
54
55. NARCOTIC ANTAGONISTS (NALOXONE)
Given in small incremental doses.
High doses of naloxone will result in sudden
reversal of analgesic effects leading to abrupt
return of pain resulting in hypertension,
tachycardia, pulmonary edema, ventricular
dysrhythmias and cardiac arrests.
If sedation or respiratory depression recurs,
continuous infusion of 3-10 micg/kg/hour of
naloxone is required.
55
