Anaesthetics Flashcards
general anasthesia is given ??? and exerts main effects on the CNS
systemically
Local and Regional Anaesthesia block the conduction of impulses in ??? nerves
peripheral sensory
Stage one of general anaesthetics is ??? when you’re still conscious
Analgesia/Amnesia
STAGE II is ??? but it is avoided by a short‐acting IV anaesthetic before
inhalation anaesthetics
Excitement
what occurs at Stage II of general anaesthetics?
Loss of consciousness but responsive to painful stimuli; may move, have incoherent speech, vomiting, and irregular breath
STAGE III General anaesthesia is ??? where reflexes disappear. Respiration initially more regular but depression develops with increasing depth of anaesthesia; muscle relaxation
Surgical anaesthesia
STAGE IV ??? respiratory arrest and cardiovascular collapse; death
Medullary Depression
??? i.e. diazepam, fentanyl
‐ Relieve anxiety
‐ Produce sedation & amnesia
‐ Relieve pain
‐ Reduce secretions
‐ Reduce post operative‐nausea & vomiting
‐ Reduce volume & acidity of gastric contents
‐ Modify the automatic response
‐ Reduce pain during venipuncture
pre-medication
Premedication Agents are Benzodiazepines such as diazepam, Lorazepam, Midazolam. These are taken as oral or IV, and are for ???
For sedation & to decrease anxiety
Anxiolytic, amnesic and hypnotic
Benzodiazepines mechanism of action is: enhance ??? mediated inhibition in CNS
GABA
??? is the second phase of general anaesthesia procedure. It is defined as the period of time from onset of administration to the
development of effective surgical anaesthesia in the patients
Induction
TRUE or FALSE: Intravenous anaesthetics act more rapidly than inhalation as even the fastest‐acting inhalation anaesthetics (e.g. nitrous oxide) takes a few minutes to act and cause a period of excitement before anaesthesia is achieved
true
Intravenous anaesthetics act rapidly, producing unconsciousness in about ~20s; as soon as the drugs reaches the brain. Recovery from intravenous anaesthetics is due to the ??? from sites in CNS
distribution
TRUE or FALSE: opioids are frequently used together with anaesthetics due to their analgesic properties
TRUE
the combination of morphine and ??? provides good anaesthesia for cardiac surgery
nitrous oxide
??? can cause hypotension, respiratory depression and muscle rigidity as well as post‐anaesthetic nausea and vomiting
Opioids
Phase 3: Maintenance is the period during which the patient is ???
surgically anaesthetised
nitrous oxide, halogenated hydrocarbons are examples of anaesthetic drugs used for ??? phase
maintenance
Elimination of ??? is predominantly through exhalation of the unchanged gas
nitrous oxide, halogenated
Phase 4: Recovery is the reverse of induction, dependant on how fast the ??? diffuses from the brain (rather than metabolism of the drug)
anaesthetic drug
3 main neurophysiological changes occur during anaesthesia:
‐ unconsciousness
‐ loss of pain response
‐ loss of motor & autonomic reflexes
All can cause death at ??? doses
supra anaesthetic
Most anaesthetics cause cardiovascular depression by effects on myocardium and blood vessels as well as NS. ??? anaesthetics likely to cause dysrhythmias.
Halogenated
All agents apart from ??? produce similar neurophysiological effects but have different pharmacokinetics/toxicity.
apart from ketamine, NO and
xenon
The Meyer‐Overton hypothesis suggests a hydrophobic site of action, as it was shown there was a close correlation between
anaesthetic ??? and lipid solubility (oil:gas partition coefficient).
potency
It was postulated the anaesthetic drug distorted the lipid component of the cell membrane and caused:
a) volume expansion or
b) altered ???
membrane fluidity
Evidence against the lipid theory is provided by the fact that not all
general anaesthetics are particularly ???
lipid soluble
Anaesthetics are thought to potentate inhibitory ??? receptors such as:
* ??? receptors
* Glycine receptors
ligand‐gated ion channel
GABAA
Anaesthetics thought to inhibit
excitatory ligand gated ion channel
receptors such as:
* NMDA
* 5‐HT3
* ???
Nicotinic acetylcholine
The ??? receptor is a pentamer usually consisting of 2x α, 2x β and 1x γ subunit
GABAA
each subunit of the GABAA receptor has many variants that cause different ???
binding properties
The presence of a particular domain, or binding site on ??? receptor is necessary for potentiating effects of a given anaesthetic agent.
GABAA
The isoform of ??? receptor containing the β3 variant subunit may mediate loss of consciousness, while isoforms containing the β2 variant subunit mediate sedation.
GABAA
Binding to GABAA receptors INCREASES or DECREASES (?) concentration of agonist required to achieve a maximal response =
prolonged synaptic current.
decreases
GABAA receptors: Volatile or IV anaesthetics bind at interface of α‐ β‐subunits?
volatile
GABAA receptors: Volatile or IV bind only at β‐subunit?
IV
Glutamate is major excitatory neurotransmitter in the CNS and has 3 classes of ionotropic receptor, ???, AMPA and Kainate.
NMDA
NMDA is an important site of action for anaesthetics including, nitrous oxide, xenon and ???
ketamine
Ketamine or xenon (?) blocks the pore of the NMDA channel
ketamine
Xenon or ketamine (?) inhibits NMDA receptors by competing with glycine for its regulatory site
xenon
What is the most common form of general anaesthetic for induction of anaesthesia, followed by an inhalation agent?
intravenous general anaesthesia agents
IV general anaesthesia agents are not ideal for maintenance due to their ???
slow rates of elimination
propofol: Facilitates inhibitory neurotransmission mediated by ???
GABAA
propofol has a high lipid solubility = ??? onset of action (cross BBB rapidly)
rapid
t1/2 is short (2‐8 mins), so recovery is also quick and has less hangover (low nausea). this describes propofol, thiopental, or etomidate?
propofol
what agent can be used to induce and/or maintain anaesthesia for example, in day surgery where rapid
recovery is desirable BUT not usually used for maintenance due to slow elimination
propofol
propofol infusion syndrome: severe metabolic acidosis, skeletal muscle
necrosis, hyperkalaemia, lipaemia,
hepatomegaly, renal failure, arrhyrthmia and ???
cardiovascular collapse
what is the only remaining barbiturate in common use as an
anaesthetic and is administered via IV?
thiopental
??? has a higher lipid solubility than propofol and very fast onset of action as a result. given as a sodium salt due to high lipidity and poor water solubility
thiopental
TRUE or FALSE: thiopental has a short duration due to redistribution (mostly to muscle) rather than metabolism/ elimination. It accumulates in body fat, restricting ability to give repeated doses.
TRUE
thipental cause tissue damage if extravascular injection accidentally takes place or injected into ???
artery
??? is similar to thiopental but more rapidly metabolised. Binds to GABAA receptor, especially the R enantiomer. Has greater therapeutic window
Etomidate
Thiopentalm, propofol, or etomidate is structurally unrelated to other anaesthetics due to an imidazole ring that allows water solubility under acidic conditions and lipid solubility under physiological pH
etomidate
ketamine’s mode of action differs from other agents and has been demonstrated to be an ???
receptor antagonist ‐ specific ketamine receptors and interactions with opioid receptors have been postulated. S enantiomer more potent indicates a stereospecific receptor.
NMDA
??? causes a neuroleptic state i.e dissociative anaesthesia where patient appears conscious but amnesic and insensitive to pain. Thalamus dissociated from limbic cortex
ketamine
what drug causes hallucinations, disturbing dreams and delirium, however is a “complete” anaesthetic
in that it produces analgesia, amnesia and unconsciousness. Side effects less in children so sometimes used in paediatrics
ketamine
In contrast to other agents ketamine ??? arterial blood pressure, heart rate and cardiac output. Also causes increased intracranial pressure. Respiration unaffected.
increases
Commonly use inhalation or IV (?) anaesthetic drugs in maintenance (rather than induction) of anaesthesia
inhalation
Isoflurane, sevoflurane and desflurane are typical modern ??? anaesthetics that have excellent pharmacokinetic properties, are non‐flammable and have few side‐effects.
inhalation
what are generally small, lipid‐soluble molecules that readily cross the alveolar membranes.
Isoflurane, sevoflurane and desflurane and Nitric oxide
define an anaesthethics pharmacokinetics
Rate of delivery of the drug to the lungs by inspired air and rate of delivery of drug from the lungs by the bloodstream and then to the tissues
blood:gas parition coefficient = solubility in blood or fat?
blood
oil: gas partition coefficient = solubility in blood or fat?
fat
for rapid control of inhaled anaesthetics, you want the blood concentration to follow as quickly as possible the changes in ??? of the drug in inspired air
partial pressure
which coefficient determines induction rate and recovery?
blood: gas coefficient
TRUE or FALSE: The higher the blood/gas coefficient the greater the anaesthetic’s solubility and the greater the uptake by pulmonary circulation = alveolar pressure rises slower, prolonging induction.
TRUE
alveolar pressure is ??? by the residual lung gas (i.e. oxygen) when anaesthetic first inhaled
reduced
(blood-gas) if an anaesthetic is more soluble, it has a fast or slow onset?
slow onset
(solubility in lipids) More lipophilic anaesthetics have lower or higher potency?
higher
(solubility in lipids = potency) Lipophilic anaesthetics gradually accumulate in ??? = prolonged “hang‐over”
body fat
why is there an issue of giving anaesthetic drugs with high lipophilic nature?
low blood flow to adipose tissue means it takes many hours for drug to enter and exit fat following rapid blood‐gas exchange
what type of anaesthetic inhibits voltage‐dependent Na+‐channels within neuronal cell membrane. Prevents neuronal action potential propagation by penetrating neuronal phospholipid cell membrane in non‐ionised (lipophilic) form, is protonated inside the neuron, and then binds to internal surface of Na+‐ channels in their ionised form
local anaesthetic
Local Anaesthetic preferentially blocks open Na+‐channels = “Use dependence”, ie. degree of
blockade is proportional to the ???
rate of stimulation of the nerve
Local anaesthetic esters: Relatively unstable in solution, inactivated quickly by non‐specific esterases
in plasma and tissue. Metabolism of most esters produces ??? ‐‐ known to
cause allergic reaction
para‐ aminobenzoate (PABA)
local anaesthetic amides: Stronger bond, more stable in solution,
longer shelf‐ life ~2 yrs. Heat stable or instable?
stable
TRUE or FALSE: all Local Anaesthetics are weak bases
TRUE
local anaesthetic potency: Higher lipid solubility = better able to cross cell membranes = ???
more potent
local anaesthetic duration of action: Higher protein binding = less free fraction available for metabolism = ???
longer duration of drug
