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Anaesthetics
Anesthesia is a reversible condition of comfort,
quiescence and physiological stability in a patient
before, during and after performance of a procedure.
need for
unconsciousnes need for analgesia need for
s Loss of sensory and muscle
Amnesia- autonomic reflexes relaxation
hypnosis
These general anaesthetics drugs are often
accompained by sedative benzodiazepine: midazolam,
diazepan and lorazepan
At cellular level, anaesthetics alter the behavior of
neurons, by interacting directly with a small number of
ion channels.
Under normal conditions:
These membrane proteins are actived by chemical
signals or change in the membrane environment
Upon activation:
Channels change the electrical excitability of neurons
by controlling the flow of excitatory or inhibitory ions
across the cell membrane via an ion channel that is
integral with the receptor that senses the intial signal.
GABAA receptors
NMDA receptors
Two-pore K + channels
Ketamine, nitrous oxide
GABAA receptor is a 4-
transmembrane (4-TM)
ion channel
5 subunits arranged
around a central pore: 2
alpha, 2 beta, 1 gamma
Each subunit has N-terminal extracellular chain
which contains the ligand-binding site.
4 hydrophobic sections cross the membrane 4
times: one extracellular and two intracellular
loops connecting these regions, plus an
extracellular C-terminal chain
NMDA receptors
Pharmacokinetic properties
espiratory Effects
Reduce or eliminate both ventilatory drive and the
reflexes that maintain airway patency.
Halothane
Enflurane
Isoflurane
Desflurane
Nitrous oxide
Halogenated
compounds:
Contain
Fluorine
and/or
bromide
Simple,
small
molecules
Pharmacokinetics of inhalation
anaesthetics
General Actions of Inhaled Anesthetics
Respiration
Depressed respiration and response to CO 2
Kidney
Depression of renal blood flow and urine
output
Muscle
High enough concentrations will relax skeletal
muscle
Cardiovascular System
Generalized reduction in arterial
pressure and peripheral vascular
resistance. Isoflurane maintains CO and
coronary function better than other
agents
Cardiovascular System
Is the
dose-dependent reduction in arterial blood pressure result of
direct myocardial
depression leading
to reduced cardiac
output
Halothane does not cause a significant change in systemic
vascular resistance but it does alter the resistance and
autoregulation of specific vascular beds, leading to
redistribution of blood flow
Halothane also has significant effects on cardiac rhythm.
Sinus bradycardia and atrioventricular rhythms occur
frequently during halothane anesthesia but usually are
benign
Respiratory System
Spontaneous respiration is rapid and shallow during
halothane anesthesia
Halothane also inhibits peripheral chemoceptor responses to
arterial hypoxemia
Halothane also is an effective bronchodilator and has been
effectively used as a treatment of last resort in patients with
Nervous System
Muscle
Cardiovascular System
Isoflurane produces vasodilation in most vascular beds, with
particularly pronounced effects in skin and muscle.
Disadvantages:
Can induce seizure
Nitrous Oxide
Nitrous oxide is a colorless, odorless gas at room temperature
Cardiovascular System
The cardiovascular effects of nitrous oxide also are heavily
influenced by the concomitant administration of other anesthetic
agents. When nitrous oxide is co-administered with halogenated
inhalational anesthetics, it generally produces an increase in
heart rate, arterial blood pressure, and cardiac output. In
contrast, when nitrous oxide is co-administered with an opioid, it
generally decreases arterial blood pressure and cardiac output.
Respiratory System
Causes modest increases in respiratory rate and decreases in tidal
volume in spontaneously breathing patients.
Nervous System
When administered alone, nitrous oxide can significantly increase
cerebral blood flow and intracranial pressure.
The combination of N2O and inhaled agents results in greater
vasodilation than the administration of the inhaled agent alone at
equivalent anesthetic depth.
Intravenous anesthetics
They are used to facilitate rapid induction of anesthesia
All drugs used for induction of anesthesia have a similar duration of action
when administered as a single bolus dose despite significant differences in
their metabolism.
Propofol decreases cerebral blood flow and the cerebral metabolic rate
for oxygen (CMRO 2 ), which decreases intracranial pressure (ICP) and
intraocular pressure; the magnitude of these changes is comparable to
that of thiopental.
ardiovascular Effects
Produces the most pronounced decrease in systemic blood pressure
Respiratory Effects
Propofol is a potent respiratory depressant and generally produces apnea
after an induction dose
Barbiturates
Thiopental and Methohexital
CNS Effects
Barbiturates produce dose-dependent CNS depression ranging from
sedation to general anesthesia when administered as bolus injections.
CNS
Effects
benzodiazepines decrease cerebral blood flow.
These drugs are potent anticonvulsants used in the treatment of status
epilepticus, alcohol withdrawal, and local anesthetic-induced seizures
Cardiovascular Effects
Midazolam produces a greater decrease in systemic blood pressure
than comparable doses of Diazepam
Respiratory Effects
Benzodiazepines produce minimal depression of ventilation
CNS Effects
ketamine is considered to be a cerebral vasodilator that increases
cerebral blood flow
ketamine is considered an anticonvulsant and may be recommended for
treatment
of status epilepticus when more conventional drugs are ineffective.
Cardiovascular Effects
Ketamine can produce transient but significant increases in systemic blood
pressure, heart rate, and cardiac output, presumably by centrally mediated
sympathetic stimulation
increased cardiac workload and myocardial oxygen consumption, are not
always desirable and can be blunted by coadministration of
benzodiazepines, opioids, or inhaled anesthetics.
Respiratory Effects
Ketamine is not thought to produce significant respiratory depression
LOCAL ANESTETHICS
Loss of sensation in a limited region of the body.
Cocaine Lignocaine
Procaine Mepivicaine
Tetracaine Prilocaine
Chlorprocaine Bupivacaine
More intense and
Benzocaine longer lasting
Less intense analgesia anaesthesia
Esters vs Amides
The ester linkage is more easily broken so the
ester drugs are less stable in solution and
cannot be stored for as long as amides.
Amide anaesthetics are also heat-stable.
The metabolism of most esters results in the
production of para-aminobenzoate (PABA)
which is associated with allergic reaction.
Amides, in contrast, very rarely cause allergic
phenomena. For these reasons amides are
now more commonly used than esters.
Absorption
Determined by several factors:
Dosage, site of injection, drug-tissue binding, local tissue blood
flow, use of a vasoconstrictor (eg, epinephrine), and the
physicochemical properties of the drug itself.
Anesthetics that are more lipid soluble are generally more potent
and have a longer duration of action
Distribution
1. Localized As local anesthetic is usually injected directly at the
site of the target organ, distribution within this compartment plays
an essential role with respect to achievement of clinical effect.
2. Systemic The peak blood levels achieved during major
conduction anesthesia will be minimally affected by the
concentration of anesthetic or the speed of injection.
To do this the
anaesthetic
molecules must
actually enter
through the cell
membrane of the
nerve.
Small nerve fibres are more sensitive than
large nerve fibres
EPIDURAL (infusion)
Sympathetic nerve block
hypotension
Spinal anesthesia
Here, the local
anesthetic is
injected into the
subarachnoid
space of the spinal
cord
SPINAL (one-shot)
No sympathetic nerve
block
No hypotension
ARTICAINE
Approved for use in the USA as a dental anesthetic in 2000, articaine is
unique among the amino-amide anesthetics in having a thiophene,
rather than a benzene ring, as well as an
additional ester group that is subject to metabolism by plasma
esterases .
Elevated levels can be due to inborn errors, or can occur with exposure
to an oxidizing agent, and such is the case with significant exposure to
benzocaine.
COCAINE
Current clinical use of cocaine is largely restricted to topical anesthesia
for ear, nose, and throat procedures, where its intense vasoconstriction
can serve to reduce bleeding.