Pharmacology – GENERAL & LOCAL ANESTHETICS (MADE EASY)

Pharmacology – GENERAL & LOCAL ANESTHETICS (MADE EASY)


in this lecture we are going to cover
pharmacology of general and local anesthetics but first things first what
is anesthesia so anesthesia is a reversible condition induced by
anesthetic drugs that cause reduction or complete loss of response to pain or
another sensation such as consciousness and muscle movements during surgery or
other invasive procedures that can be painful there are two main types of
anesthesia first is general anesthesia which makes the whole body lose feeling
movement and consciousness drugs that are used to induce this type of
anesthesia are called general anesthetics the second type is local
anesthesia which numbs only a specific targeted area of the body drugs that are
used to induce local anesthesia are called local anesthetics now anesthesia
performed with general anesthetics occurs in four stages that were first
introduced and described back in 1930s these four stages remained essentially the same over time however updated delivery methods and modern anesthetics have
improved the speed of onset safety and recovery so the first stage is known as
induction it is simply a period during which the patient goes from state of
consciousness to a state of unconsciousness next we have the second
stage known as excitement at this stage depression of inhibitory neurons in the
CNS leads to increased excitement involuntary muscle movement increased
heart rate blood pressure and respiration next we progress to the
third stage known as surgical anesthesia at this stage there is a
gradual loss of muscle tone and reflexes patient is fully unconscious
unresponsive to surgery and has regular breathing this is the ideal stage for
surgery and careful monitoring is necessary to prevent further progression
to stage four known as medullary paralysis or overdose at this stage
respiratory and cardiovascular failure occurs which lead to death if the
patient cannot be revived quickly now let’s move on to discussing how general
anesthetics work so the mechanism of action of general anesthetics is not
entirely clear although early theories focused on a single common path of action
for all anesthetics over time it has become increasingly apparent that
multiple sites and different mechanisms are most likely responsible for the
effects of general anesthetics so at the macroscopic level the action of general
anesthetics on thalamus and reticular activating system leads to reversible
loss of consciousness the action on the hippocampus amygdala and prefrontal
cortex causes amnesia and finally the action on the spinal cord is responsible
for immobility and analgesia now at the molecular level things get a little bit
more complicated so to make it simple we can divide general anesthetics into
three groups based on their relative abilities to produce unconsciousness
immobility and analgesia but before we proceed in order to gain a better
understanding of mechanism of action of anesthetics I think it’s important to
know how nerve impulses are generated therefore for those who need a refresher
I would highly recommend to first watch my video about neuronal action potential
now going back to our grouping of general anesthetics the first group
consists of intravenous agents Etomidate Propofol and Barbiturates these drugs
are much more potent at producing unconsciousness rather than immobility
or analgesia and they are commonly used in the induction phase their effects
appear to be mediated by a subset of gamma-Aminobutyric acid type A
receptors GABA-A for short so GABA-A receptors are located both
postsynaptically and extrasynaptically on the majority of neurons in the
central nervous system they are composed of pentameric arrangements of subunits around
a central ion channel pore when endogenous GABA binds to this receptor
it causes a conformational change which opens central pore allowing chloride
ions to pass down electrochemical gradient this in turn leads to stabilization
or hyperpolarization of the resting potential making it more difficult for
excitatory neurotransmitters to depolarize the neuron and generate an
action potential so when Etomidate Propofol and
Barbiturates bind to specific sites on the GABA-A receptor they prolong opening
of the channel suppress neuronal excitability and thus promote
unconsciousness now when it comes to side effects Etomidate can cause adrenal
suppression and transient skeletal muscle movements including myoclonus
Propofol is known to cause respiratory depression and hypotension lastly
Barbiturates can cause apnea cough bronchospasms and just like Propofol
respiratory depression now let’s move on to the second group of general
anesthetics which consists of intravenous agent Ketamine and
inhalation agents Nitrous Oxide Xenon and Cyclopropane in contrast to group 1
and group 3 agents these drugs produce significant analgesia however their
ability to produce unconsciousness and immobility is relatively weak because of
that these drugs are typically used in the maintenance phase of anesthesia
unlike the drugs in group 1 the group 2 drugs have little to no effect on GABA-A
receptors and instead their effects appear to be mediated primarily by N-methyl-D-aspartate receptors NMDA for short NMDA receptors are located in a
spinal cord and are crucial in pain modulation and processing when
neurotransmitter glutamate binds to NMDA receptor it causes inflow of
extracellular calcium into the postsynaptic neuron which then activates
a series of signaling molecules causing the pain signal to increase and fire
more frequently now Ketamine Nitrous Oxide Xenon and Cyclopropane selectively
inhibit NMDA receptors which ultimately prevents or decreases neurotransmission
of pain group 2 general anesthetics also affect members of the 2-pore-domain
potassium channel family which regulate the resting membrane potential of
neurons specifically they promote the opening of these channels leading to
increased potassium efflux producing a reduction in neuronal excitability that
contributes to their sedative effects now when it comes to
adverse effects Ketamine can cause hypertension tachycardia and
hypersalivation as well as emergence phenomena ranging
from vivid dreams to hallucinations and delirium that may continue for 24
hours after treatment next Nitrous Oxide and Cyclopropane are known to cause
dizziness nausea and vomiting lastly we have Xenon which has many
characteristics of the ideal anesthetic and has virtually no significant
side effects now let’s move on to the third group of
general anesthetics which consists of halogenated volatile anesthetics
Halothane Enflurane Isoflurane Sevoflurane and Desflurane in contrast
to group 1 and 2 drugs group 3 drugs have more diverse
mechanism of action and are more potent at producing immobility studies suggest
that volatile anesthetics produce unconsciousness via different GABA-A
receptor subunits than those targeted by the group 1 drugs also many 2-pore-domain potassium channels that are activated by group 3 anesthetics appear
to highly affect immobility rather than anesthesia
just like group 2 drugs volatile anesthetics also inhibit NMDA receptors
a wide variety of other ion channels are also sensitive to volatile anesthetics
including neuronal nicotinic acetylcholine receptors serotonin type 3 receptors sodium channels mitochondrial ATP-sensitive potassium channels and hyperpolarization-activated cyclic nucleotide-gated channels now when it comes to side effects all of the agents in this group produce a dose-dependent
reduction in blood pressure and cardiac output
additionally Halothane in particular may cause cardiac arrhythmias and
hepatotoxicity while Sevoflurane may cause renal toxicity now before we
move on there is one more agent that’s worth mentioning here which doesn’t
belong to any of the three groups that we discussed so far and that is Dexmedetomidine unlike the other commonly used general
anesthetics Dexmedetomidine has a unique
ability to produce sedation and analgesia without the risk of
respiratory depression these effects result from its binding to the
presynaptic alpha-2 adrenergic receptors of the subtype 2A which are located in a
brain and spinal cord the action on these receptors inhibits the release of
norepinephrine terminating the propagation of pain signals and inducing
light sedation when it comes to side effects of Dexmedetomidine
the most common ones are bradycardia and hypotension as well as transient
hypertension due to weak peripheral alpha-1 receptor agonist activity now
let’s switch gears and let’s move on to brief discussion of the pharmacology of
local anesthetics unlike general anesthetics local anesthetics produce
transient loss of sensory perception especially of pain in a localized area
of the body without producing unconsciousness so how do these drugs
work due to their distinct chemical properties local anesthetics are able to
pass through the neuronal membrane and bind to a specific receptor at the
opening of the voltage-gated sodium channel thus preventing sodium influx
this in turn prevents the initiation and conduction of action potentials which
ultimately leads to loss of sensation in the area supplied by the nerve
examples of the most widely used local anesthetics are Bupivacaine Lidocaine Mepivacaine Procaine Ropivacaine and Tetracaine when used properly local
anesthetics are generally very safe and serious reactions are rare
however when systemic toxicity occurs patients may experience symptoms ranging
from blurry vision and lightheadedness to seizures and cardiac arrhythmias and
with that I wanted to thank you for watching I hope you enjoyed this video
and as always stay tuned for more

36 Replies to “Pharmacology – GENERAL & LOCAL ANESTHETICS (MADE EASY)”

  1. your videos are really good,but you mixed between the stages of anesthesia and depth of anesthesia which are two different thngs

  2. i jus love your videos totally mind-blowing sir… please sir kindly upload some videos on Antimicrobial agents.. you are such a blessing itself 💖

Leave a Reply

Your email address will not be published. Required fields are marked *