Acetylcholine and succinylcholine

1. ACETYLCHOLINE
AND
SUCCINYLCHOLINE
CASE 2

2. OUTLINE
● Definition of Acetylcholine
● Chemical structure of Acetylcholine
● Synthesis of Acetylcholine
● Mechanism of Acetylcholine
● Roles of Acetylcholine on muscles
● Definition of Succinylcholine
● Chemical structure of Succinylcholine
● Mechanism of Succinylcholine
● Roles of Succinylcholine on muscles
● Location and effects of Acetylcholine and Succinylcholine

3. DEFINITION OF ACETYLCHOLINE
Acetylcholine was the first neurotransmitter scientists
discovered, as well as the most abundant neurotransmitter in
the body. A neurotransmitter is a chemical that is released by
a neuron, or nerve cell, that sends a signal to another neuron
across a synapse

4. Think of acetylcholine as a mailperson;
residents cannot receive their mail until he or she comes and
delivers it to the mailbox. Like mail persons who deliver the
mail and move on to the next house, acetylcholine acts
quickly and does not hang around. As a result, acetylcholine
is rapidly broken down by another chemical substance called
cholinesterase.

5. THE STRUCTURE OF ACETYLCHOLINE
Present both in the central and peripheral nervous systems (CNS & PNS)
Synthesized by the combination of Acetyl CoA, which is a product of the
Krebs cycle in the mitochondria, and choline, which is obtained
from food (egg yolk, legumes).
In the PNS, it is the transmitter of the neuromuscular junction between
neurons and all types of muscle (cardiac,smooth and skeletal) and thus is
responsible for muscle contraction.

6. IUPAC Name: 2-Acetoxy-N,N,N-
trimethylethanaminium

8. METABOLISM OF ACETYLCHOLINE
● A receptor is cholinergic if it uses acetylcholine as its
neurotransmitter.
● Neurons that synthesize and release ACh are termed
cholinergic neurons.
● A synapse is cholinergic if it uses acetylcholine as its
neurotransmitter

9. SYNTHESIS OF ACETYLCHOLINE
● Acetylcholine is synthesized from choline and acetyl CoA
through the action of choline acetyltransferase in the
cytoplasm of the presynaptic axon .
● It is stored in synaptic vesicles.
● Choline is metabolised into acetylcholine; the acetyl group is
donated by acetyl-CoA.
● The choline acyltransferase enzyme is responsible for catalyzing
this process.

11. ● Upon arrival of action potential on the presynaptic
membrane, ACh is released via exocytosis into the
synaptic cleft.
● ACh travels by diffusion to the receptors on the
postsynaptic membrane.
● Once released, ACh must be removed rapidly.
BREAKDOWN OF ACETYLCHOLINE

12. ● Hydrolysis of ACh to acetate and choline immediately
starts in the synaptic cleft, catalyzed by
acetylcholinesterase.
● The cleavage product choline is are taken up again
by the presynaptic neuron and reused for
acetylcholine synthesis
● The re-uptake is the rate determining step in
acetylcholine synthesis

15. MECHANISM OF ACETYLCHOLINE
When a nerve action potential reaches and invades the nerve terminal,
a shower of acetylcholine vesicles is released into the junction
(synapse) between the nerve terminal and the ‘effector’ cell which the
nerve activates. This may be another nerve cell or a muscle or gland
cell. Thus electrical signals are converted to chemical signals, allowing
messages to be passed between nerve cells or between nerve cells
and non-nerve cells. Chemical transmission involving acetylcholine is
known as ‘cholinergic’.

16. Acetylcholine acts as a transmitter
between motor nerves and the
fibres of skeletal muscle at all
neuromuscular junctions. At this
type of synapse, the nerve terminal
is closely apposed to the cell
membrane of a muscle fibre at the
so-called motor end plate. On
release, acetylcholine acts almost
instantly, to cause a sequence of
chemical and physical events
(starting with depolarization of the
motor endplate) which cause
contraction of the muscle fibre.

17. rapid response to a command is required. The action of
acetylcholine is terminated rapidly, in around 10 milliseconds; an
enzyme (cholinesterase) breaks the transmitter down into
choline and an acetate ion. The choline is then available for
re-uptake into the nerve terminal.

18. FUNCTIONS OF ACETYLCHOLINE
● Acetylcholine performs a transmitter at all
neuromuscular connections.
● Acetylcholine is a transmitter in various brain regions
● In the peripheral nervous system, it causes skeletal
muscle to contract

19. ● In the central nervous system, it inhibits the
activation of the cholinergic system
● Acetylcholine plays an important role in the
signal of muscle movement, sensation of pain,
learning and memory formation, the
regulation of the endocrine system and rapid
eye movement (R.E.M.) sleep cycles.

20. The Role Of Acetylcholine On Muscle
•The role of Acetylcholine as intermediary in the
stimulation of muscle cells by nerve cells.

21. SUCCINYLCHOLINE
It is a neuromuscular paralytic drug. This means that it works at the
junction of the nerves and muscles and causes muscular paralysis.
Also resulting in life-threatening heart rhythms, cardiac arrest, and
death in children. For that it should only be used in an emergency
situation

22. STRUCTURE OF SUCCINYLCHOLINE
● It is composed of 2 molecules of acetylcholine.
● They are linked back to back through acetate methyl groups.
● Its molecular formula is C14
H30
N2
O4
● its Molecular Weight is 290.404 g/mol
● Its is a crystalline compound, formed by esterification of succinic
acid with choline.
● It is a depolarizing neuromuscular blocking agent to
acetylcholine.

23. STRUCTURE OF SUCCINYLCHOLINE

24. METABOLISM OF SUCCINYLCHOLINE
● Succinylcholine is what is known as a depolarizing agent.
● It works by binding to acetylcholine receptors in the
neuromuscular junction at the sites where acetylcholine would
normally bind to.
● the acetylcholine receptors treat a molecule of succinylcholine as if
it were a molecule of acetylcholine and open their channels

25. ● When succinylcholine binds to the acetylcholine receptors, the
acetylcholine receptors open as if acetylcholine had bound to them,
allowing sodium ions to rush into the muscle cells and potassium to rush
out.
● The action of these positively charged sodium ions rushing in changes
the voltage level in the muscle cells, causing depolarization and causing
the action potential to travel into the muscle cells.
it causes an initial muscle contraction (called a fasciculation).
METABOLISM OF SUCCINYLCHOLINE

26. succinylcholine is broken down slowly by plasma pseudocholinesterase
a concentration gradient between sodium and potassium
cannot form the muscle cell cannot repolarize
an action potential, which relies on the change of voltage to occur, cannot be generated.
No action potential = no neuromuscular transmission = no movement.
This phase where the ACh receptors are open and the muscle cells are
depolarized is called Phase I block.

27. succinylcholine acts on the Nicotinic receptors of the muscles, stimulates them
and ultimately cause their relaxation.
This process occur in two phases:
Phase I: During Phase I (depolarizing phase), they cause muscular fasciculations
while they are depolarizing the muscle fibers.
Phase II: After sufficient depolarization has occurred,phase II (desensitized
phase) sets and the muscle is no longer responsive to Ach released by the nerve
endings.
METABOLISM OF SUCCINYLCHOLINE

29. ROLE OF SUCCINYLCHOLINE ON MUSCLES
● Succinylcholine, commonly used in anesthesia, paralyzes
normal skeletal muscles by blocking transmission at the
myoneural junction.
● Succinylcholine first bind to postsynaptic nicotinic
acetylcholine (protein that respond to neurotransmitter)
receptors then it causes depolarization muscles.

30. The initial binding leads to muscle
fasciculation(twitching) which could be seen during
induction in paralysis of rapid sequence intubation.
The normal dose for succinylcholine is 1_1.5mg/kg but for
rapid sequence intubation is 70-105mg.
The dose set-action is from 45-60 seconds and the
duration for paralysis is 10-15 minutes.

31. Succinylcholine is used when you want the effect of paralysis
to wear off quickly like in the case of a logical exam. With
succinylcholine, you would be able to help you do your
neurological exam much sooner.
Also used when you want to activate a patient quickly after a
procedure.

32. RISKS OF USING SUCCINYLCHOLINE
It increase potassium level leading to:
● Hyperkalemia so it can not be used on:
1.Burn victims
2.Crush victims
3.Rhabdomyolysis
4.End stage renal disease victims
● Intraocular pressure
● Malignant hyperthermia
● Bradycardia

33. Acetylcholine exerts its effects by binding to and
activating receptors located on the surface of cells.
There are two main classes of acetylcholine receptor,
nicotinic and muscarinic.
muscarine is a compound found in the mushroom.
nicotine is found in tobacco.
EFFECTS AND LOCATION OF ACETYLCHOLINE

34. •Nicotinic acetylcholine receptors are ligand-gated
ion channels permeable to sodium, potassium, and
calcium ions.
•capable of switching from a closed to open state
when acetylcholine binds to them; in the open state
they allow ions to pass through.

35. Nicotinic receptors come in two main types, known as
muscle-type and neuronal-type:-
• The muscle-type can be selectively blocked by curare.
• the neuronal-type by hexamethonium.
• The main location of muscle-type receptors is on muscle
cells.
•Neuronal-type receptors are located in autonomic ganglia
(both sympathetic and parasympathetic), and in the central
nervous system.

36. •Muscarinic acetylcholine receptors have a more
complex mechanism, and affect target cells over a
longer time frame.
•In mammals, five subtypes of muscarinic receptors
have been identified, labeled M1 through M5.

37. •The M1, M3, and M5 subtypes; they increase intracellular levels.
Their effect on target cells is usually excitatory.
• The M2 and M4 subtypes; they decrease intracellular levels. Their
effect on target cells is usually inhibitory.
•Muscarinic acetylcholine receptors are found in both the central
nervous system and the peripheral nervous system of the heart,
lungs, upper gastrointestinal tract, and sweat glands.

39. USES SUCCINYLCHOLINE
Succinylcholine is used for:
● Relaxing muscles during surgery or when a tube must be inserted in
the windpipe. It may also be used for other conditions as determined
by your doctor.
● Succinylcholine works by keeping muscles from contracting, which
causes paralysis of the muscles.

40. SIDE EFFECTS
● Cardiovascular disease.
● Hyperkalemia.
● Increase intracranial pressure and saliva.
● Malignant hyperthermia
● Prolonged paralysis.

41. References
➢ "Nicotine to Nicotinoids: 1962 to 1997". In Yamamoto, Izuru; Casida, John. Nicotinoid
Insecticides and the Nicotinic Acetylcholine Receptor. Tokyo: Springer-Verlag. pp.
3–27
➢ Itier V, Bertrand D (August 2001). "Neuronal nicotinic receptors: from protein
structure to function". FEBS Letters. 504 (3): 118–25.
➢ Nutritional Biochemistry Book Second Edition.Tom Brody.P:319
➢ http://bmcanesthesiol.biomedcentral.com/articles/10.1186/1471-2253-14-14
➢ https://www.drugs.com/cdi/succinylcholine.html
➢ https://www.altibbi.com/%D8%A7%D9%84%D8%A7%D8%AF%D9%88%D9%8A%D8
%A9/%D8%B3%D9%88%D9%83%D8%B3%D9%85%D9%8A%D8%AB%D9%88%D9%8
6%D9%8A%D9%88%D9%85-%D8%B9%D9%84%D9%85%D9%8A
➢ https://www.youtube.com/watch?v=cp_CZpCBVpk
➢ http://doctorlib.info/pharmacology/pharmacology/14.html
➢ https://www.youtube.com/watch?v=eKsfoLmoJwE

42. HAVE A NICE DAY