2. ⦿PHARMACOKINETICS: the study of absorption,
distribution,metabolism and excretion of the injected and inhaled
drugs and their metabolites.
⦿PHARMACODYNAMICS: study of the responsiveness of the
body to a drug and the mechanism by which the effects occur.
⦿An induction agent is the one which causes rapid reversible loss
of consciousness.
3.
4.
5.
6.
7. FACTORS AFFECTING THE
INDUCTION DOSE
⦿Route of administration
⦿Age
⦿Lean body mass
⦿Low cardiac output states
⦿Hypo-proteinemia
9. MECHANISM OF ACTION
⦿GABA is the principle inhibitory neuro transmitter in
the brain. Acts by increasing the chloride conductance
causing hyper polarization of post synaptic membrane
and functional inhibition.
⦿Propofol , thiopentone and etomidate acts via the
GABA receptor.
14. METABOLISM
PROPOFOL THIOPENTONE KETAMINE
Hepatic :oxidative
metabolism by cyt p450
into water soluble
sulphate and glucuronic
acid metabolites.
Pulmonary: converted to
di iso propyl quinol.
Renal
No evidence of impaired
elimination in patients
with cirrhosis of liver and
renal dysfunction
(1)oxidation of the aryl,
alkyl, or phenyl moiety at
C5
(2)N-dealkylation
(3) desulfuration of the
thiobarbiturates at C2
(4) destruction of the
barbituric acid ring.
Metabolized by hepatic
microsomal enzymes.
Ketamine to norketamine
to hydroxyl norketamine
Norketamine has 20-30%
activity.
15. PHARMACOKINETICS
⦿volume of distribution: The theoretical volume that
would be necessary to contain the total amount of an
administered drug at the same concentration that it is
observed in the blood plasma.
⦿ The volume of distribution is useful in estimating the
dose required to achieve a given plasma
concentration .
16. ⦿Context-sensitive half-life or context sensitive half-
time is defined as the time taken for blood plasma
concentration of a drug to decline by one half after an
infusion designed to maintain a steady state (i.e. a
constant plasma concentration) has been stopped.
⦿The "context" is the duration of infusion.
( how long does the effects of the drugs last after
stopping the infusion)
17. ⦿Drug clearance is concerned with the rate at which the
active drug is removed from the body.
⦿ Clearance is defined as the rate of drug elimination
divided by the plasma concentration of the drug.
19. VOLUME OF
DISTRIBUTION
4l/kg 2-4l/kg 3l/kg
ELIMINATION
HALF LIFE
4-7 hrs 7-17hrs 2-3hrs
CONTEXT
SENSITIVE HALF
LIFE
8hrs-40min
CLEARANCE 20-30ml/kg/min 3-4 ml/kg/min 12-17ml/kg/min
20. PHARMACODYNAMICS
PROPOFOL THIOPENTONE KETAMINE
CNS •Primary site of action is
beta subunit of GABA
receptor.
•Increases the dopamine
concentration in nucleus
accumbens: sense of well
being.
•Anti emetic effect :
decreases the serotonin level
in area prostema
Decreases
CMRO2,CBF,ICP.
Decreases CPP.
NEUROPROTECTIVE
Attenuation of changes in
ATP, Na+,Ca2+,K+ caused
by hypoxic injury.
Inhibiting lipid peroxidation.
Reduces the
CMRO2,CBP,ICP.
Maintains CPP.
Free radical scavenging
Robinhood phenomenon
Primary site of
action is the
thalamoneocortico
projection system.
Increases
CMRO2,CBP and
ICP.
?antiapoptotic effect
after cerebral
ischemia and
reperfusion.
22. PROPOFOL THIOPENTONE KETAMINE
CVS Decreases the
SBP,DBP,MAP,CO
,SV.
1.Inhibition of smooth
muscle Ca2+
mobilization.
2.Decreases the
angiotensin-2 elicited
Ca2+ entry.
3.Stimulation of nitric
oxide.
4.Activation of K+-
ATP channels.
Inhibits the baroreflex
and prevents
tachycardia to
hypotnsion.
Cardio vascular
depression :
1.Direct negative
inotropic effect by
decreasing the Ca2+
influx.
2.Peripheral
vasodilatation causing
decresed ventricular
filling pressures .
3.Transient decreased
sympathetic outflow
from CNS.
Decreased CO,SVR,HR
1.Systemic
release of
catecholamines
2.Inhibition of
vagal nerve.
3.Inhibition of
NE reuptake at
peripheral nerves
and non neuronal
tissue.
Increases the
SVR,CO,HR.
Decreased
coronary vascular
resistance.
Premedicate with
midazolam and
glyco pyrrolate.
23. PROPOFOL THIOPENTONE KETAMINE
RS APNOEA
Dose dependent
Depresses the ventilatory
response to hypoxia by direct
action on carotid body
receptors.
With infusion TV decreased,
RR incrased.MV maintained.
BRONCHODILATION
(+)
Inhibits the vagal induced
broncho constriction by
inhibition of Ca2+ influx.
Potentiates hypoxic
pulmonary vasoconstriction.
Central
respiratory
depression.
Double apnoea.
Minimal central
respiratory
depression.
Bronchodilation
1.Sympathomime
tic effect.
2.Directly
antagonize the
spasmogenic
effect of
histamine.
24. DOSES-
PROPOFOL THIOPENTONE KETAMINE
INDUCTION 1.5-2.5mg/kg. 3-5mg/kg 1-2mg/kg i.v
4-8mg/kg i.m
MAINTAINENC
E
100-
300mcg/kg/min
50-100mg every
10min
0.5-1mg/kg with
50%N2o
SEDATION 25-
100mcg/kg/min.
0.2-0.8mg/kg i.v
2-4mg/kg i.m
25. PROPOFOL
⦿USES
⦿ANTIEMETIC-
10mg i.v bolus followed by 10mcg/kg/min infusion.
⦿Used in chemotherapy induced and post operative nausea
vomiting.
⦿Inhibition of the sub cortical pathway.
⦿ANTIPRURITIC
⦿ANTICONVULSANT
⦿ATTENUATION OF BRONCHO CONSTRICTION
26. SIDE EFFECTS
⦿Allergic reactions.
⦿Abuse potential
⦿Bacterial growth
⦿Antioxidant properties.
⦿Pain on injection.
⦿Inhibits phagocytosis and killing of
Staphylococcus aureus and Escherichia coli.
27. PROPOFOL INFUSION SYNDROME
⦿ Infusion of propofol at 4 mg/kg/hour or more for 48 hours
or longer.
⦿ Impaired fatty acid metabolism, such as medium-chain
acyl coenzyme A (MCAD) deficiency and low
carbohydrate supply.
⦿ The symptoms and signs are the result of muscle injury
and the release of intracellular toxic contents.
⦿ Acute refractory bradycardia leading to asystole in the
presence of one or more of the following
⦿ Metabolic acidosis (base deficit >10 mmol/L),
⦿ Rhabdomyolysis,
⦿ Hyperlipidemia
⦿ Enlarged or fatty liver.
⦿ Cardiomyopathy with acute cardiac failure, skeletal
myopathy.
28. BARBITURATES
⦿USES
⦿Induction and
maintenance of
anaesthesia.
⦿Metho hexital –drug of
choice for electro
convulsive therapy
⦿Methohexital can be
used as a
premedication in
paediatrics.
⦿SIDE EFFECTS
⦿Allergic reaction
⦿Urticarial rash and tissue
necrosis
⦿Cough,hiccoughs,tremors
⦿Inducer of cyt p-450
29. KETAMINE
USES-
⦿Induction in hypovolemic patient
⦿Cardiac tamponade, restrictive pericarditis
,congenital heart disease
⦿ANALGESIA
⦿Change of burn dressing
⦿Debridements
⦿Skin grafting.
⦿Status asthamaticus
⦿Reversal of opioid tolerance
⦿Improvement of post operative depressed state.
30. SIDE EFFECTS
⦿Intact sympathetic system
⦿Direct myocardial depressant.
⦿EMERGENCE REACTION:
-Secondary to ketamine induced depression of auditory
and visual relay nuclei, leading to misperception and
misinterpretation of stimuli.
31. ETOMIDATE
⦿ Carboxylated imidazole .
⦿ Mechanism of action: used as a single isomer R(+)
isomer. Selective modulator of gaba A receptor.
⦿ Pharmacokinetics: large Vd. Present in unionised form
at physiologic ph. Crosses the blood brain barrier .70%
of the drug bound to albumin independent of plasma
drug concentration.
⦿ Metabolism :hepatic microsomal enzymes and plasma
estarases causes hydrolysis of ethyl ester side chain.
Elimination half life 2-5 hrs.
32. PHARMACOKINETIC-
⦿Ph - 4.2
⦿Pka - 8.2
⦿Elimination half life:2-5 hrs.
DOSE-
⦿The induction dose of etomidate is 0.2 to 0.6
mg/kg
33. PHARMACO DYNAMICS
⦿CNS
Decreases CMRO2,CBF AND ICP.
⦿CVS-
lack of effect on the sympathetic nervous system and
on the function of the baroreceptor.
Minimal changes in HR, stroke volume, cardiac output.
Fall in SVR by 15%
⦿RS-
Decreased TV, increased RR.
Stimulates ventilation independent of hypercapnoiec
drive
34. USES
⦿ Etomidate has been used for induction in patients with
a compromised cardiovascular system
⦿ coronary artery bypass surgery
⦿ valve surgery
⦿ percutaneous transluminal coronary angioplasty
⦿ aortic aneurysm repair
⦿ Thoracic surgery.
⦿ cardioversion.
⦿ neurosurgical procedures such
⦿ as giant aneurysm clipping
