Neuropharmacology PDF

Neuropharmacology Created @November 11, 2024 9:01 AM Class Pharmacology 1A Phar1A ANS 24-25 HO-1.pdf Phar1A ANS 24-25 HO-2.pdf Phar1A Course ANS 24-25 HO-3.pdf Phar1A ANS 24-25 HO-4(2).pdf Phar1A ANS Materia...

Neuropharmacology Created @November 11, 2024 9:01 AM Class Pharmacology 1A Phar1A ANS 24-25 HO-1.pdf Phar1A ANS 24-25 HO-2.pdf Phar1A Course ANS 24-25 HO-3.pdf Phar1A ANS 24-25 HO-4(2).pdf Phar1A ANS Materials 24-25 HO-5.pdf Phar1A ANS 24-25 HO-6.pdf Phar1A ANS 24-25 HO-5.pdf Phar1A ANS 24-25 HO-6.pdf Neuropharmacology 1 Neuropharmacology 2 Neuropharmacology 3 Neuropharmacology 4  IONOTROPISM - MUSCLE CONTRACTION DROMOTROPISM - RATE OF CONDUCTANCE VIA AV NODE DRUG TARGETS Voltage-gated Na+ channels Blockers stop electrical transmission:  Local anaesthetics for pain relief (Lignocaine)  Treatment of epilepsy (Phenytoin)  Tetrodotoxin (Toxicology, experimental drug) Voltage-gated Ca2+ channels Blockers inhibit transmitter release Neuropharmacology 5   Ziconotide (-conotoxin; experimental drug; clinical application – neuropathic pain) Exocytosis Blocker inhibits transmitter release - Botulinum toxin A – ‘Botox’:  Balancing muscle tone in cerebral palsy  Treatment of hypersecretory disorders Transmitter synthesis Precursor of transmitter (e.g. dopamine) stimulates production:  Treatment of Parkinsonism (L-DOPA, Carbidopa) Vesicular storage Blockers of vesicular transporters lead to empty vesicles Displacement agents (such as amphetamine) cause initial uncontrolled release Presynaptic transmitter uptake blockers prolong transmitter actions treatment of depression (Fluoxetine) Transmitter breakdown Blockers prolong transmitter actions  Treatment of myasthenia gravis (Neostigmine) Postsynaptic ionotropic receptors (ion channels)  Blockers inhibit transmitter effects, muscle relaxation by nicotinic acetylcholine receptor antagonist (Tubocurarine)  Positive allosteric modulators enhance transmitter effects, e.g. treatment of anxiety, insomnia, epilepsy by enhancing GABAA receptor action (Benzodiazepines such as valium) GPCRs – pre- & postsynaptic  Majority of prescribed and experimentally used drugs  e.g. morphine, potent opioid analgesic Presynaptic transmitter uptake Blockers prolong transmitter actions Neuropharmacology 6   Treatment of depression (Fluoxetine) Acetyltransferase catalyses the reaction of acetyl coA + Choline >ACh rate limiting step in Ach synthesis , transport of choline into neuron by choline carrier, which involves use of sodium Na Synthesis Tyrosine Hydroxylase catalyses the reaction of Tyrosine to DOPA DOPA decarboxylase catalyses the reaction of DOPA to Dopamine Dopamine is transported into synaptic vesicles by Vesicular Monoamine inside vesicles Dopamine b hydroxylase hydrolyses into dopamine to noradrenaline Neuropharmacology 7 Neuropharmacology 8  M1 M3 M2 Gq protein coupled Gq protein coupled Gi/o protein coupled decrease in camp increase in ca2+ signalling increase in ca2+ signalling and ca2+ signalling increased glandular secretion increased glandular secretion and smooth muscle contracting and smooth muscle contracting i.e blood vessels i.e blood vessels Neuropharmacology 9  Parasympathomimetic drugs that mimic effects of parasympathetic nervous system agonists of muscarinic receptors inhibits acetylcholinesterase i.e neostigmine which is used to treat myasthenia gravis or pyridostigmine used to treat Alzheimer's Parasympatholytic block effects of PSNS acts as antagonist of muscarinic receptors atropine used to dilate pupils and treat bradycardia Sympathomimetics drug mimic effects of SNS agonist at adrenergic receptor mimic noradrenaline and adrenaline i.e phenylephrine (a1 agonist used as a decongestant Neuropharmacology 10  albuterol is a a2 agonist used to treat asthma increased release of noradrenaline i.e amphetamine causes enhanced sympathetic activity Sympatholytic blocks effects of SNS antagonist of adrenergic receptor i.e propanol Neuropharmacology 11  NORADERNALINE AND ADERNALINE bind to B1 receptors in cardiac myocytes activates signalling pathway i.e gs PROTEIN,ADENYL CYCLASE, camp, pka - PKA PHOSPHYRYLATES VARIOUS PROTEIN Neuropharmacology 12  PARASYMPATHETIC ACTIVATION OF BLOOD VESSELS ACH activates M3 receptors on vascular endothelial cells stimulates NO production NO diffuses into smooth muscle cell > muscle relaxation and reduced blood pressure SYMPATHETIC ACTIVATION activates a1 receptors in vascular smooth muscle in skin, Gi tract, kidneys - constriction Na ACTIVATES B2 RECEPTORS IN VASCULAR SMOOTH MUSCLE in heart ,brain ,lungs ,skeletal muscle > relaxation Neuropharmacology 13 Neuropharmacology 14  Airways : Parasympathetic activation Ach activates M3 receptors in airways leading to contraction of smooth muscle and bronchoconstriction helps protect and recuperate airways especially during periods of low demand Neuropharmacology 15 Neuropharmacology 16 Neuropharmacology 17  Parasympathetic activation of digestive system : ACh activates M3 muscarinic receptors in Gi smooth muscle, leading to contraction and increased peristalsis (the movement of food through the digestive tract). ACh also activates M1 and M3 receptors in GI tract glands, stimulating the secretion of saliva, stomach acid, and intestinal fluids. This process aids in the breakdown of food and the absorption of nutrients. The vagus nerve, a major component of the PSNS, plays a role in stimulating M3 receptors. This activation increases calcium signalling, leading to the contraction of smooth muscle in the digestive tract. Neuropharmacology 18  Sympathetic Activation of digestive system Reduced Peristalsis: NA activates β2 receptors in the G) tract, leading to the relaxation of smooth muscle and decreased peristalsis. This slows down the movement of food through the digestive system. Decreased Secretions: the SNS reduces digestive secretions, due to the overall suppression of digestive activity during the "Fight or Flight" response atropine, a parasympatholytic drug, to reduce secretions as a premedication for anaesthesia. Neuropharmacology 19  inhibiting parasympathetic activity, which normally stimulates secretions, is a way to achieve reduced secretions. Vasoconstriction: While not directly acting on the digestive organs themselves, the SNS causes vasoconstriction in the GI tract, reducing blood flow to this area 8This further limits digestive activity by decreasing the supply of oxygen and nutrients. Prioritization of Other Systems: The SNS prioritizes blood flow to the heart, brain, lungs, and skeletal muscles during "Fight or Flight."This is achieved through vasodilation in these areas, which is facilitated by the activation of β2 receptors in the vascular smooth muscle. This redirection of blood flow further reduces the resources available for digestion. Neuropharmacology 20  Parasympathetic Activation of the bladder ach is released from parasympathetic postganglionic neurone activate M3 receptor in detrusor muscle of bladder promotes bladder emptying by detrusor contraction Neuropharmacology 21  Sympathetic activation of the bladder SNS activation generally inhibits bladder emptying. through the coordinated action of NA on different receptors in the bladder: ○ Detrusor Muscle Relaxation: NA activates β2 receptors on the detrusor muscle, the smooth muscle responsible for bladder contraction and emptying. Activation of these receptors leads to muscle relaxation, which reduces the urge to urinate. ○ Sphincter Constriction: Simultaneously, NA activates α1 receptors on the bladder sphincter, the muscular valve that controls urine flow. This activation causes sphincter constriction, further preventing urine leakage Neuropharmacology 22  These actions prevent urination and allow the body to focus on the perceived threat. It is worth noting that the sources acknowledge the complexity of bladder control beyond a simple "Fight or Flight" response, implying that other factors might influence bladder function in real-life situations. ○ Darifenacin, an M3 antagonist, is used to treat urinary frequency, urgency, and incontinence. By blocking the effects of ACh on M3 receptors, darifenacin inhibits detrusor muscle contraction, reducing the urge to urinate. ○ Bethanechol, an M3 agonist, can be used to assist with bladder emptying in cases of urinary retention. It mimics the action of ACh, promoting detrusor muscle contraction. ○ Prazosin, an α1 antagonist, is used to increase urinary flow in benign prostatic hyperplasia. By blocking the effects of NA on α1 receptors, prazosin relaxes the bladder sphincter, allowing for easier urine flow. Neuropharmacology 23  pupil dilation (mydriasis) Na ACTIVATE A1 RECEPTORS Located IN RADIAL DILDATOR PUPILLAE muscle of iris Neuropharmacology 24  muscle contracts more light enters eye, enhancing visual sensitivity and widening field of vision , advantageous ion fight or flight pupil constriction ( MIOSIS) ACH binds to M3 muscarinic receptors intracellular circular iris muscle contracts decrease in pupil size - mitosis reduces amount of light entering eye aids in fluid drainage from eye by thinning the iris which reduces intralocular pressure important for treatment of glaucoma intraocular fluid is produced by epithelium at the ciliary body and drains through the Canal of Schlemm (trabecular meshwork) Accommodation for near vision Ach activates M3 receptors in ciliary muscle ciliary muscle is a sphincter when contracted, pulls the ciliary body inwards this relaxers zonular fibre tension and lens bulge more and focal length decreases change n lends shape allow eye to focus more Neuropharmacology 25  Sympathetic Activation pupil dilation ( mydriasis ) NA activates a1 receptors located in radial dilator pupillae muscle of iris muscle contracts more light enters eye enhancing visual sensitivity and widening field of vision , advantageous in fight or flight Neuropharmacology 26 Neuropharmacology 27 Neuropharmacology 28 Neuropharmacology 29 Neuropharmacology 30 Neuropharmacology 31