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Pharmacology, image, image, image, image - Coggle Diagram
Pharmacology
Sites where drugs can act to modulate neurotransmission process & mechanism by which they do it
Where
Drugs exert their effects by binding to protein molecules
Enzymes: cyclo-oxygenase (COX1 and COX2)
Transporters
Receptors
Occasionally ion channels
Act everywhere in those steps of synthesis, storage, release and termination
What
neurotransmission is:
synthesis, storage, release, action @ receptors, termination of action
How does neurotransmission work
:
Synthesis
:
transmitter precursor
is pumped into the cell then its acted on by
sympathetic enzyme
to make the
final
transmitter
Storage
: then its stored in synaptic vesicles
Release
:
exocytosis
allows the migration of synaptic vesicles to the end of the membrane, allowing discharge of contents of vesicles(transmitter) then act on receptor & produce response
Termination
: happens in 2 ways. 1st were transmitter is
broken
by enzymes that are found within synapse. 2nd is transmitter=
removed
from synapse by being sucked up & recycled back into the nerve terminal
Exocytosis
Preparation for release
: Neurotransmitters are stored inside synaptic vesicles within the nerve terminal
Activation of nerve terminal
: When the nerve terminal is
activated
by an
AP
, various ions, including
calcium
, enter the cell
Influx of calcium
triggers exocytosis, hence what happens
Migration of vesicles
: The synaptic vesicles containing neurotransmitters move toward the membrane at the nerve terminal
Fusion with membrane
: One of the vesicles fuses with the membrane at the nerve terminal
Release of neurotransmitter
: The contents of the vesicle, which include neurotransmitters, are discharged into the synaptic cleft
Interaction with receptors: Once released, neurotransmitters can then bind to receptors on the target tissue (such as muscle cells or other neurons), initiating a response in the receiving cell
How drugs can bind
Mimic the actions of endogenous factors
(also called neurotransmitters): most common at receptors taargets where drugs
mimic the actions of neurotransmitter
Agents are called
agonists
. Can be called
parasympathoMIMETICS
, or
sympathoMIMETICS
, depnding on which system they target
Inhibit the action of endogenous factors
:
1)
Many drugs are enzyme inhibitors/ transport blockers.
2)
Many drugs can also block receptors preventing the action of neurotransmitters
Agents are called
antagonists
. They remove the effect of 1 arm of ANS, so either called
parasympathoLYTICS
, or
sympathoLYTICS
Drugs affecting sympathetic system
Clinical uses of drugs targetting NA receptors
a adreonceptors (blood vessels)
Agonists
at a receptors cause
vasoconstriction
:
Constrict small blood vessels
in nose & eye(clear up redness) acting as nasal decongestants and ocular decongestants. Given "locally" only
Antagonist
a receptors cause
relaxed
blood vessels in circulatory system.
1) Used in hypertension
2)Access all blood vessels
b receptors
Heart
Agonist
at b receptors:
stimulate the heart
(in heart failure)
Antagonists
at b receptors:
slow
heart (used indirectly to help lower BP) ie blockage of b receptors
bronchi/lungs
Agonists
: relax & open bronchi(asthma)
Antagonist
: contraindicated in asthma (trigger it)
Application:
anaphylaxis
Symptoms
: closing of airway (shortness of breath), heart pumps less blood
Treatment
: give
adrenaline
cause it targets B receptors hence relax & dilate bronchial smooth muscle. And @ heart it would target B receptors hence increase force & rate of heart contraction. And it causes a receptors to vasoconstrict hence raising BP.
Effect of NA
agonists
: activate alpha & beta transmittors
Stimulation of a receptors leads to vasoconstriction(raising BP), slowing gut, mydraisis
Stimulation of b receptors leads to increasing force & rate of heart contraction, slowing gut, relaxing & dilation of bronchial smooth muscle
Effect of NA
antagonist
: block a & b receptors
a blockage leads to: vasodilation, lowering BP, speeding gut, miosis
b blockage leads to: decrease force & rate of heart contraction, speeding gut, constriction of bronchial smooth muscle
Drugs affecting NA neurotransmission
Actions of NA at receptors= terminated by
reuptake
. By the nerve terminal sucking it back up into nerve thru a pump called "uptake-1"
NA reuptake blockers
: used in depressive disorders (effects are in brain rather than ANS)
Effects of
indirectly acting mimetic
: ie
pseudoephedrine
drug, causes vasocinstricition by activating
a receptors
, constrcit small blood vessels in nose & eye acting as nasal decongestants
Review of ANS
Part of peripheral efferent nervous system. Composed of preganlionic & postganglionic
2 arms
Parasympathetic system
Rest & digest
Opposite symptoms to sympathetic. Just addition to increased exocrine secretion
Ach
is released from preganglionic fibres which activates post gaglionic fibre to release
Ach
. Hence the neuro-transmitter at the
neruoeffector junction
is Ach.
Sympathetic system
Fight or flight
Pupile dilation
Bronchodilation (but lungs are only affected due to the release of adrenaline)
Increased rate & force
Vasoconstriction/vasodilation
Decreased GI motility
Ach
is released from preganglionic fibers then it influences post ganglionic fibers to release
NA
to influence tissues -
Neuroeffector junction
= part where post ganglionic fibers infleunces the tissue. The
transmitter
in this area for this system is
NA
Activates
adrenal gland
to secrete adrenaline into the blood stream and this dilates or relaxes the bronchi
Tissues
are only innervated by 1 side of the ANS
Blood vessels innervated
only
by symapthetic nervous
Bronchi in lungs=innervated only by the parasympathetic nervous system, but bronchi
only responds to adrenaline
Drugs that affect ganlionic neurotransmission
Locations of NAChRs: found in ganglia on adrenal medulla & neuromuscular receptors
When activated: response on skeletal muscle,
release of adrenaline
as the post ganglionic fibers of the sympathetic system and parasymapthetic system. Hence, it is
hard
to predict what it will exactly do
Effect of blockage/activation of nictotinic receptors:
unpredictble effects, as responses are complicated by affecting both the
sympathetic & parasympathetic arms
Receptors of the ANS
Ach receptors
Nicotininc Ach receptors (nAChRs)
Location
: on
ganglia
(start of post ganglionic fibres in both sympathetic & parasympathetic) &
skeletal muscle
(of the somatic efferent system). And on
adrenal medulla
Muscarinic Ach receptors (mAChRs)
Location: on
tissues & responsible for organ effects
. Responds to Ach release in that parasympathetic system. Eg of muscles: smooth(glands, gut) and cardiac muscle
Actions:
DUMBELLS
ie
D
iarrhoea,
U
rination,
M
iosis(constriction of eye),
B
radycardia(slow heart rate),
B
ronchoconstriction,
E
mesis(vomitting),
L
acrimation
L
ethargy,
S
alivation
Parasympathetic system
NA receptors
Associated with
symapthetic system
(sometimes called adregenic)
Alpha receptors
Location
: tissues & responsible for organ effectors. ie eyes, salivary glands, vessels, few in gut.
Function
:
excite & contract
. In GIT they close sphincters stop food from moving.
Beta receptors
Location
: tissues & responsible for organ effectors. ie smooth & cardiac muscles. Found in
heart
, few in gut, bladder,
lungs
Function
:
relax & inhibit
,
except
in the
heart
where they stimulate.
Drugs affecting parasympathetic systems
Muscarinic
What effect will muscarinic
agonists
cause
DUMBBEELS
What effect will muscarinic
antagonists
cause
Anti-DUMBBELLS
ie mydriasis(open up of pupil), dry mouth, speeding of the heart, slowing of GI movement= constipation
Application
:
Mydriasis= examination of the retina via the pupil, help of
atropine
durg derived from belladonna
Decreased bronchial smooth muscles:
asthma
would be treated as the mucous is dried and bronchial smooth muscle contractions are decreased
Decreased motility= treat diarrhoea
Drugs affecting Ach neurotransmission
Actions of
ACh
at receptors is
terminated
by
AChE
(acetylcholinesterase). AChE breaks down ACh into its constituients ie choline and acetate
Durgs that
prevent
the
breakdown
of Ach=
anticholinesterase
. Hence [Ach] would be increased around the
neuroeffector junction
=
increased
tissue responses= further activate parasympathetic system and
more DUMBBELLS
Organophosphate insecticide posining
results in DUMBBELLS & increased activation of
somatic nervous system
followed by paralysis
Application: some types of anti-cholinestaerases can help in
myasthenia gravis
. Which is an auto-immune disorder where there is muscle weakness due to insufficient effects of Ach @ skeletal muscle
Drugs that
interferes
with Ach
release
: ie botulininm(
botox
) toxin=
inhibits release of ACh
. Observe
anti-DUMBBELLS
. And progressive muscle weakness &
paralysis
, observe drooping eyelids, slurre speech, difficulty breathing.
Theraputic uses of botox= mostly related to effects on skeletal muscle neurotransmission. ie
bleopharospasm
= uncontrolled contractions of eyelids, and
cerebral palsy
to reduce muscle rigidity & uncontrolled spasms
