Autonomic Medications Introduction PDF

AUTONOMIC MEDICATIONS  Adrenergic transmission (synthesis) NA is synthesized in the axon of the noradrenergic neurons. Tyrosine (tyrosine hydroxylase) to DOPA DOPA (DOPA decarboxylase) DOPAMINE DOPAMINE (hydroxylase) noradrenaline Then in the adrenal medul...

AUTONOMIC MEDICATIONS  Adrenergic transmission (synthesis) NA is synthesized in the axon of the noradrenergic neurons. Tyrosine (tyrosine hydroxylase) to DOPA DOPA (DOPA decarboxylase) DOPAMINE DOPAMINE (hydroxylase) noradrenaline Then in the adrenal medulla NA will change in to adrenaline by the action of phenylethanolamine N-methyl transferase enzyme  Storage and release The synthesized NA is stored, together with ATP It is released by two ways 1. By exocytosis; influx of Ca to presynaptic neuron will lead to release of NE by exocytosis in to the synaptic cleft 2. Non-exocytosis release: certain drugs like amphetamine replace and release the NE from the vesicles  Noradrenaline: release is mainly regulated by an auto-inhibitory feed back mechanism (the released noradrenaline in the synapse will stimulate α2 receptors in the presynaptic neuron and in turn inhibit the release of NE.  Elimination of catecholamine Catecholamine (NA, adrenaline, isoprenaline) are eliminated by re- uptake and/or metabolic degradation, A. Reuptake: They are removed by one of the mechanisms: 1. Uptake 1: it is uptake to pre synaptic neuron and it is more selective to NA 2. Uptake 2: (extraneuronal reuptake): it is uptake by effector organ like heart and smooth muscle, it is relatively selective to adrenaline B. Metabolism: 1. Monoamine oxidase enzyme (MAO): of the mitochondria in the cells and this enzyme is particularly abundant in neurons 2. Catechol-O-methyl transferase (COMT): found in variety of neuronal and non- neuronal tissues.  Classification of adrenoceptors They are divided in to 2 classes 1. α receptor (α1 and α2) 2. β Receptors (β1, β2 and β3)  Action of adrenergic receptors α1: – Found in the smooth muscle of many organs and they cause contraction of the blood vessels – Relaxation of the GIT. – Contraction of all sphincters(GIT, urinary) – Mydriasis due to contraction of dilator pupillae muscle  α2: – Found in presynaptic neuron ,CNS, blood vessels, it inhibit transmitter release, – In addition they cause platelets aggregation – If found postsynaptically work as α1  Action of adrenergic receptors β1: – Mainly in the heart, stimulation result in an increase contractility and heart rate β2: – Present in the smooth muscle, its stimulation lead to bronchodilation, peripheral vasodilation, relaxation of the visceral smooth muscle and skeletal muscle tremor. – increase aqueous humor secretion. – Increase liver glycogenolysis. Β3:  Action of adrenergic receptors Adrenaline, noradrenaline and isoprenaline act on both α and β receptors but with different potency α receptors stimulated more by noradrenaline and less with isoprenaline, β stimulated more with isoprenaline and less with NE.  ACh synthesis Choline is transported from the extracellular fluid in to the cytoplasm of the cholinergic neuron by an energy dependent carrier system Choline acetyl-transferase catalyzes the reaction of choline with acetyl coenzymeA (CoA) to form acetylcholine. Choline is a quaternary amine and carries a permanent positive charge, and thus, can not diffuse through the membrane  Storage of ACh The ACh is packaged in to the presynaptic vesicles by an active transport process The mature vesicles contain not only Ach but also ATP and proteoglycan Vesamicol blocks the ACh transport in to synaptic vesicles  Release of ACh When an action potential reach the nerve terminal it opens the voltage gated Ca channels, causing an increase concentration of Ca intra- cellularly This will promote the fusion of vesicles with the cell membrane and release of their content in to the synaptic space. Release can be blocked by botulinum toxin  Degradation and recycling of ACh The signal is rapidly terminated, because AChesterase cleaves Ach into choline and acetate in the synaptic cleft. Recycling of choline: choline may be recaptured by high affinity uptake system that transport molecule inside to neuron (used to synthesis new acetylcholine)  Ach receptors There are 2 major classes of Ach receptors in the parasympathetic system 1. Nicotinic receptors 2. Muscarinic receptors  1. Nicotinic receptors Nicotinic receptors are located at A. Neuromuscular junction B. Ganglionic synapse. Ach is their agonist They are divided in to two types (NN and Nm) A. NN found in the postganglionic neurons B. NM found at motor end- plate  2. Muscarinic receptors There are five subclasses of muscarinic receptors (mACHR) are G- protein coupled receptors which mediate the effect of Ach at various effector organs 1. M1: neuronal receptors mainly found in CNS and gastric parietal cells 2. M2: cardiac receptors mainly found in the heart and in presynaptic terminal neurons 3. M3: mainly located at exocrine Good luck