principles of pharmacology Flashcards
what is a general anaesthetic
loss of consciousness and global lack of awareness
achieved using general anaesthetic agents
what is a regional anaesthetic
producing insensibility in an area or region of the body
local anaesthetics applies to nerves supplying relevant area
e.g. nerve and plexus blocks incl. central neuraxial block (spinal and epidural)
effect is remote from the injection
what is local anaesthetic
insensibility in only the relevant area of the boy
applied directly to the tissues
effect is at the site of inkection
GA vs sedation
GA - patient is completely unaware of what is occurring
sedation - some awareness but not necessarily recall
regional anaesthesia vs analgesia
regional anaesthesia - little to no sensation of any sort from the blocked area
regional analgesia - only pain sensation need be removed or reduced, other sensations may be retained to varying extents
functions of modern anaesthetic machine
regulation of fresh gases and mixing to deliver precise concentrations of gaseous agents
addition of precise concentrations of inhaled anaesthetic gases
CO2 removal to allow recirculation of inhaled gases
mechanical ventilation
monitoring is integrated
safety of anaesthesia
overall operative mortality 4% - includes all anaesthetic and surgical mortality from all emergency and elective surgery and all patient groups, includes all deaths within 30 days of surgery
anaesthetic mortality 0.00024%
ASA system - mortality is concentrated in ASA groups 3-5
3 components of anaesthesia
hypnosis
analgesia
relaxation
an individual anaesthetic may consist of varying contributions from all 3 but doesn’t require all 3
different drugs do different jobs, some do more than one:
GA agents - relaxation, hypnosis (analgesia)
opiates - hypnosis, analgesia
muscle relaxants - muscle relaxants
LA agents - analgesia, relaxation
3 components of anaesthesia - hypnosis
unconsciousness
necessary component of any GA
3 components of anaesthesia - analgesia
removal of pain and perception of unpleasant stimulus
if patient is unconscious and unaware of pain, still required to suppress reflex autonomic responses to painful stimulus
3 components of anaesthesia - relaxation
skeletal muscle relaxation
necessary to provide immobility for certain procedures, allow access to body cavities and permit artificial ventilation
what is balanced anaesthesia and what are the benefits
different drugs do different jobs
great degree of control over the individual components of the triad
titrate doses separately and therefore more accurately to meet individual requirements
avoid over dosage of individual drugs
enormous flexibility
problems with balanced anaesthesia
polypharmacy - drug interactions, reactions, allergies
muscle relaxation - requirement for artificial ventilation and airway control
separation of relaxation and hypnosis - awareness (possibility of being awake and paralysed and unable to communicate)
general anaesthetic agents - what do they do
inhaled and IV
provide unconsciousness as well as a small degree of muscle relaxation
may to differing extents provide analgesia - negligible for all except ketamine
potent drugs - separates them from sedatives - low doses of a potent agent e.g. propofol may be used to provide sedation
how do general anaesthetic agents work
suppress neuronal activity in a dose dependent fashion
open chloride channels which hyperpolarise the neurons - suppresses excitatory synaptic activity
neurons become reversibly hyperpolarised and therefore less able to likely to reach their threshold potential and fire
–> globally suppressed neuronal activity
how do IV and inhalational GA agents work
inhalational agents - dissolve in membranes, direct physical effects
IV agents - allosteric binding, GABA receptors - open chloride channels
loss of function with GA
cerebral function lot from top down
- most complex processes interrupted first
- LOC early, hearing later
- more primitive functions lost later
spinal reflexes relatively spared - primitive and small number of synapses
allows unconscioussness while preserving some autonomic and automatic functions e.g. respiration and BP homeostasis (impaired in dose dependent fashion)
management of a patient under GA
ABC - long drawn out resuscitation mandates airway management impairment of resp function and control of breathing CV impact care of the unconscious patient
management of a patient under GA
ABC - long drawn out resuscitation mandates airway management impairment of resp function and control of breathing CV impact care of the unconscious patient
IV anaesthesia - unconsciousness and recovery
rapid onset unconsciousness
1 arm - brain circulation time
rapid recovery - due to disappearance of drug from circulation, redistribution V’s metabolism
how do IV anaesthetic agents work so rapidly
highly fat soluble drugs and cross basement membranes extremely quickly
cross the blood brain barrier rapidly and get into neural tissues very quickly
leave the circulation very quickly - a bolus only causes temporary unconsciousness
metabolism contributes very little to the immediate termination of action when given as a bolus
examples of IV GA agents
thiopentone
propofol
IV anaesthetics - blood concentration over time
brain concentration (effect of the drug) follows blood concentration very closely
blood level is very high initially but falls quickly as drug moves into highly perfused tissues
Muscle picks up the drug more slowly but the effect is large because of the relative high mass of skeletal muscle in the body.
Fatty tissue picks up drug even more slowly but given lengthy enough exposure can store large amounts due to the high fat solubility - large amounts stored after a length procedure, leaches out slowly over a long time period
what is a TCI pump system
target controlled infusion pump system
with total IV anaesthesia (TIVA) we can’t measure the drug conc in real time so use calculations to make estimates
allows very accurate infusion to achieve specific blood or brain concentrations of agents - calculations and assumptions about physiology based on age, sex and size
what are inhalational anaesthetics
halogenated hydrocarbons
uptake and excretion of inhalational anaesthetics
uptake and excretion via lungs
partial pressure gradient - lungs > blood > brain (patient given a relatively high concentration of the agent at induction to breath in, gas moves down pressure gradient to produce unconsciousness)
cross alveolar BM easily
arterial PP equates closely to alveolar PP
what is MAC
minimum alveolar concentration
the concentration of the drug required in the alveoli to produce anaesthesia with any particular agent i.e. measure of potency
low MAC value = potent agent
e.g. halothane (MAC 0.8%) is more potent than desflurane (6%) because it takes less concentration of the agent to produce the same effect
process of inhalational anaesthetics
induction - slow, can be good when this is desirable
maintenance of anaesthesia - prolong duration, very flexible
awakening - stop inhalational admin, washout - reversal of conc grad
when can a slow induction with inhalational anaesthesia be desirable
e.g. potentially obstructing airway
what is the main role of inhalational agents
extension or continuation of anaesthesia
patient breathes gas mixture containing inhalational agent for duration of procedure and will remain unconscious for as long as the anaesthetic is administered
metabolism of inhalational agents
undergo very little actual metabolism in the bdoy
breathed back out again almost completely unchanged
sequence of GA
induction - IV/inhalational
maintenance - inhalational
more modern agents allow IV maintenance (propofol, opiate - remifentanil) - better recovery
+/- additional regional anaesthesia/analgesia
physiology of GA: CVS - central effects
adverse effects are almost universally depressant (ketamine is the exception)
central effects arise due to depressant effects of the agent on CV centres and nuclei in brainstem
reduced symp nerve activity
direct -ve chronotropic and inotropic effects on the heart
reduced vasoconstrictor tone –> venous and arterial vasodilation
physiology of GA: CVS - direct effects
direct effects of anaesthetic on vascular smooth muscle and myocardium - compounds the effects of the reduced symp activity
vasodilation –> decreased peripheral resistance
venodilation - decreased venous return, decreased CO
-vely inotropic - worsen the fall in CO
physiology of GA: resp
all anaesthetic agents are resp depressants (excl ketamine) - reduce hypoxic and hypercarbic drive (depression of brainstem resp centres), decreased tidal volume and increase rate
paralyse cilia
decrease FRC - lower lung vol, VQ mismatch
opiate resp depression
preserves tidal vol
low resp rate
why is post-op oxygen often required
fall in lung vol due to anaesthetic and VQ mismatch persists into post-op period
can persist for several days so patients can require post-op O2 for several days
what are muscle relaxants and what is required at the same time
paralyse skeletal muscle
indiscriminate - resp and airway muscles are also affected
unconsciousness must also be provided with systemic muscle relaxants
indications for muscle relaxants
ventilation and intubation
when immobility is essential e.g. microscopic surgery, neurosurgery
body cavity surgery - access
problems with muscle relaxants
awareness - due to the separation of unconsciousness from relaxation in the triad
incomplete reversal - airway obstruction, ventilatory insufficiency in immediate post-op period, unlikely to persist
apnoea - dependence on airway and ventilatory support
analgesia in anaesthesia - what is used alongside it
if analgesia is good enough then there is no need for unconsciousness e.g. regional anaesthesia which can be used alone or part of a combined technique
most commonly used in conjunction w/ unconsciousness as part of a balanced GA technique w/ or w/o relaxation
Regional techniques usually provide reasonable muscle relaxation by blocking motor nerves so spinal or epidural analgesia may not require additional muscle relaxation.
why is intra-operative analgesia used
prevention of arousal from pain of surgery
opiates contribute to hypnotic effect of GA
suppression of reflex responses to painful stimuli
e.g. tachycardia, HT, gross movement
regional anaesthesia has no direct sedative effect but can allow lighter levels of GA to be used
examples of opiate analgesics
fentanyl
morphine, oxycodone
remifentanil
fentanyl uses
short acting
potent
intra-operative analgesia
morphine, oxycodone and conventional opiate uses
intra-operative analgesia which we want to continue into the post-op period
remifentanil uses
very highly potent and extremely short acting
has to be given by infusion
high potency - allows use as a very potent adjunct to inhalation and IV agents, allowing them to be used in lower doses - faster recovery
doesn’t provide any post-op analgesia
examples of local anaesthetics
lignocaine
bupivacaine
ropivacaine
how do local anaesthetics work
analgesia w/o hypnosis
block Na+ channels and prevent axonal AP from propagating
effects on every tissue, toxic if delivered wrong (e.g. IV)
effects of local and regional anaesthesia
retain awareness/consciousness
lack of global effects of GA
derangement of CVS physiology - proportional to site of anaesthetised area
relative sparing of resp function - preferred technique in pts w/ concomitant resp problems
US guided regional anaesthesia
US used to guide needle placement
safer and more effective delivery of LA drug w/ less likelihood of going intravenously or direct nerve/vascular injury
