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ACETYLCHOLINE
ACETYLCHOLINE
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Acetylcholine and succinylcholine

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Acetylcholine and succinylcholine

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Acetylcholine and succinylcholine

  1. 1. ACETYLCHOLINE AND SUCCINYLCHOLINE CASE 2
  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. 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. 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. 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. 6. IUPAC Name: 2-Acetoxy-N,N,N- trimethylethanaminium
  7. 7. 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
  8. 8. 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.
  9. 9. ● 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
  10. 10. ● 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
  11. 11. 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’.
  12. 12. 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.
  13. 13. 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.
  14. 14. 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
  15. 15. ● 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.
  16. 16. The Role Of Acetylcholine On Muscle •The role of Acetylcholine as intermediary in the stimulation of muscle cells by nerve cells.
  17. 17. 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
  18. 18. 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.
  19. 19. STRUCTURE OF SUCCINYLCHOLINE
  20. 20. 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
  21. 21. ● 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
  22. 22. 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.
  23. 23. 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
  24. 24. 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.
  25. 25. 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.
  26. 26. 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.
  27. 27. 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
  28. 28. 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
  29. 29. •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.
  30. 30. 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.
  31. 31. •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.
  32. 32. •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.
  33. 33. 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.
  34. 34. SIDE EFFECTS ● Cardiovascular disease. ● Hyperkalemia. ● Increase intracranial pressure and saliva. ● Malignant hyperthermia ● Prolonged paralysis.
  35. 35. 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
  36. 36. HAVE A NICE DAY

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