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drugs acting on Autonomic Nervous system

drugs acting on Autonomic Nervous system. M.K.Soltan. Anatomical classification of ANS: Sympathetic nervous system (thoracic lumber). Parasympathetic nervous system (craniosacral). Sympathomimetics ( adrenergic agents ) ( adrenomimetics ).

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drugs acting on Autonomic Nervous system

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  1. drugs acting on Autonomic Nervous system M.K.Soltan

  2. Anatomical classification of ANS: Sympathetic nervous system (thoracic lumber). Parasympathetic nervous system (craniosacral). Sympathomimetics ( adrenergic agents ) ( adrenomimetics ). they can be further classified according to several strategies: I] due to mode of action: A] directly acting: with intrinsic activity on the adrenoceptors that is more or less than NEP. B] indirectly acting : by induction of release of NEP from adrenergic neurons. C] mixed or dual action: that act by the two mechanisms. II] due to chemical structure and pharmacological activity ( target receptor in the body ):

  3. phenyl ethyl amine derivatives:

  4. Stability of adrenaline: adrenaline is photosensitive, exposed to auto oxidation that is catalyzed by light, SAR. Directly acting phenyl ethyl amines. 1) Concerning length of carbon chain: n = 0, aniline with no pressor activity n = 1, benzylamine, very weak PA n = 2, —CH — weak pressor n = 3, same PA of n = 2, —CH2CH2— but with higher toxicity. n = 4, no pressor activity. 2) concerning R group: R = H, mainly pressor activity upon Stimulation of α-receptors. R = CH3, equal affinity to both α and β receptors, so has both pressor and bronchodilator activity. R = isopropyl or tert-butyl groups give compounds with mainly broncholdilator activity due to β-receptors activation

  5. 3) substitution of α-carbon (near NH2 ) by methyl group leads to the following : A] retard MAO metabolism so increase duration of action. B] decrease pressor activity due to decreased affinity to α-receptors. C] increase lipophilicity so increase CNS stimulant activity. 4) substitution of β carbon atom by OH group in the form of levo (-) isomer is very important: why? As OH in this stereochemistry aid in the drug - α-receptor interaction by H-bond , and this can be proved by the absence of activity of adrenalone where β carbon is in the form of carbonyl group. Also desoxyepinephrine is equal to dextroepinephrine in pressor activity.

  6. 5) concerning the two phenolic hydroxyl groups: dihydroxy derivative is better than monohydroxy in activity, favored position for dihydroxy is 3,4 that gives higher activity but less DOA than 3,5. favoured position for monohydroxy is 3. 6) concerning drug receptor interaction: a-benzene ring is flat surface for van der walls interaction with similar flat surface in the receptor. b- amino group act as cationic site to form ionic bond with anionic site in the receptor that may be carboxyl group of acidic amino acid ( glutamic acid or aspartic acid ). c- OH groups play an important rule in the drug receptor interaction by forming H-bonding with the receptor.

  7. Sketch for (-)-adrenaline- receptor interaction. 2- Immidazolene derivatives Naphazoline = 2-(1-naphthylmethyl)-2-immidazoline. Tetrahydrazoline = 2-( 1,2,3,4-tetrahydro-1-naphthyl)-2-immidazoline.

  8. α-adrenergic blockers. β-adrenergic blockers

  9. Parasympathomimetics directly acting cholinergic agent (2-hydroxyethyl ) trimethyl ammonium chloride acetate. 1) surgical procedure on the anterior eye segment 2) Produce miosis after cataract surgery. (2-hydroxypropyl ) trimethyl ammonium chloride acetate. (2-hydroxypropyl) trimethyl ammonium chloride carbamate.

  10. (2-hydroxypropyl) trimethyl ammonium chloride carbamate. 1) Urinary retention. 2) Reflux oesophagitis. indirectly acting cholinergic agents ( choline esterase inhibitors ). 3-hydroxy-1-methyl pyridinium bromide-N,N-dimethyl carbamate. 1) orally used for Myasthenia Gravis, less toxic than neostigmine. 2) antagonize neuromuscular blockers. 3) treatment of paralytic ileus.

  11. Antimuscarinics (parasympatholytics) (cholinolytics). Chemical classification of antimuscarinics: A] amino alcohol derivatives: A.1) amino alcohol esters: ( ester = amino alcohol + acid ). I] natural solanaceous alkaloids: atropine sulfate, hyoscyamine, scopolamine HBr. II] synthetic analogs of solanaceous alkaloids: synthetic esters of tropine and scopine: homatropine HBr, scopolamine butyl bromide. synthetic esters of other amino alcohols: cyclopentolate HCl, oxyphencyclimine HCl poldine methyl sulfate, oxyphenonium bromide, propanthelin bromide. A.2) amino alcohol ethers: ( ether = amino alcohol + other alcohol ). Benzotropine mesylate, chlorophenoxamine. B]amino alcohols: procyclidine HCl, benzhexol HCl. C] amino amides: isopropamide, tropicamide.

  12. A] amino alcohol derivatives:A.1) amino alcohol esters: 2) synthetic esters of other amino alcohols: 2-hydroxyethyl diisopropyl methyl ammonium bromide xanthene-9-carboxylate.

  13. 2) amino alcohol ethers: amino alcohols:

  14. amino amides:

  15. Neuromuscular blockers. non competitive depolarizing blockers competitive non depolarizing blockers

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