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Autocoids & Antagonists - Histamine aerosol : provocative test of bronchial hyper-reactivity+ control for

1) Autocoids: subs produced by variety of cells that act locally (local hormone) allergy skin test.
- Amine: histamine,serotonin - Allergic reaction: urticarial(H1 antagonist),atopic
- Lipid : prostaglandins, leukotrienes, platelet activating factor dermatitis(diphenhydramine),anaphylactic shock(chlorpheniramineIV), allergic
- Peptide: Bradykinin, angiotensin, kallidin rhinitis&chronic urticarial(2nd generation agents)
2) Histamin Source - Prevention of motion sickness
- plant,animal tissue,component in venoms &stinging secretions, - Vertigo: cinnarizinesuppress labyrinthine reflexes,reduced Ca influx from
neoplasm(eg:systemic mastocytosis) endolymph to vestibular cells
3) Histamin storage - Morning sickness: Doxylamine
- As granules(vesicles)in mast cells & basophils - Common Cold
- Non mast cell source: brain (as neurotransmitter) - Parkinson: Promethazine(block cholinergic action)
- ECL cell (enterochromaffin like cells in GIT) - Appetite stimulant : cyperohepatidine (due to anti-seronin action)
4) Receptors: 9) Adverse Efffect of Histamine
- H1: Smooth muscle, endothelium & brain - Sedation (CNS depression): 1st generation agents(block H1,muscularic,alpha
- H2: Gastric mucosa, cardiac, mast cell, brain receptor)
- H3: Brain - Orthostatic hypotension : promethazine(alpa 1 blackage action)-vasoconnstriction
- H4: Eosinophil, neutrophil, CD4 T cells not occur
5) Physiological action of Histamine - Urine retention &blurred vision : anticholinergic effect
- Allergic action(urtacaria): tissue oedema (vasodilation transudation of fluid - CNS excitation & conculsion in children
into tissue, - Allergy to Antihistamine
triple respond (red spot-flush,edema, flare respond) - Cardiac arrhythmia (terfenadine&astemizole)
- Anaphylactic shock: bronchoconstriction by H1 receptor 10) Second generation antihistamine
H1 activationrelease NOvasodilationdecrease blood - Do not cross BBB less sedation (lesser CNS adverse effects)
pressure - No anticholinergic effects (higher H1 selectivity)
- Gastric acid secretion: contraction of intestinal smooth muscle, stimulant of - Mechanisms of anti-allergic action (inhibit release of histamine from mast cells)
gastric acid secretion - No psychomotor impairment
- Chemotaxis 11) Drug interaction of H1 antagonists
- Neurotransmitter (CVS control,thermal&body weight - Terfenadine & Astemizole (metabolised by CYP3A4)
regulation,sleep&aurosal o Co-administered with CYP3A4 inhibitors (erythromycin, ketoconazole)
- Neurotransmitter: increase HR(by H2/reflex tachycardia&hypotension) fatal ventricular tachycardia, Withdrawn due to arrhythmogenic potential
: Metabolic effect(increase wakefulness,decrease appetite,body - 1st generation agents (with sedation-anticholinergic action) + other CNS
temp control) depressants excessive, SE
:Local stimulation of peripheral pain nerve ending via H3&H1 - Autonomic blocking effects of older (1st generation) antihistamines +
receptors other antimuscarinic or -block
6) Classification additive effect (Eg. Orthostatic hypotension or urine retention/blurred vision)
- First generation antihistamines : 12) Serotonin ( 5-hydroxytryptamine/5HT)
o Ethanolamines : Diphenhydramine (Benadryl), Dimenhydrinate - Source: mainly in EC cells of gut,fromplatelet,found in nerve endings & CVS
(Dramamine) - Metabolism: stored in vesicles after synthesis / inactivated by Monoamine
o Piperazine derivative: Hydroxyzine , Cyclizine , Meclizine Oxidase(MAO)
o Alkylamines : Brompheniramine ,Chlorpheniramine - Subunits:
o Phenothiazine derivatives: Promethazine 13) Serotonin physiological effects
o Miscellaneous : Cyproheptadine - CNS : control mood,sleep,hallucination,appetite,pain perception,precursor of
- Second generation antihistamines melatonin
o Fexofenadine , Loratadine ,Desloratadine ,Cetirizine - CNS : vomit centre has 5HT receptors,activation-vomit
- GIT : 5-HT3 reeceptor in gastrointestinal tract&involve in vomiting reflex, GI
7) Histamine receptor antagonists (Mechanism of action) :
-
mortility,smooth muscle
Resp : serotonin cause bronchoconstriction
- H1-receptor antagonists (1st gen)
- CVS : platelet aggregation (activate 5-HT receptors),vasoconstrictor
A) block histamine action : by reversible competitive binding to the
14) Serotonin pharmacological action
H1 receptors.
- Enhance: anxiolytic, vasoconstrictor agent, prokinetic agent
B) block muscarinic receptor, alpha adreno receptor,serotonin & local
- Block: anti-emetic, control of apetitte
anesthetic receptor sites
15) Serotonin agonists ( Therapeutic uses)
*2nd generation is better
- Anxiolytic : Buspirone,5-HT1A agonist, effective anxiolytic
- Pharmacological actions: sedation,anti-nausea,anti-parkinson, inhibit adrenergic
- Prokinetic action: Cisapride,5-HT4 agonist,treatment of oesophageal reflux
receptor,serotonin receptor, local anaesthetic action, anti-cholinergic action
disease&motility disorder
8) Histamine : therapeutic uses
- Control Of Apetite: Dexfenfluramine,selective 5-HT agonist (appetite suppresent) 1. Vascular PGI2 and PGE2 maintain patency of
- Prokinetic action: Tegaserod,5-HT4 partial agonist(for irritable bowel syndrome with 2. Non vascular (Vasodilator) ductus arteriosus,
constipation)
- Vasoconstrictor Action: 5-HTD/1B agonist,for migraine GI smooth PGI2, PGF2, Increased GI motility
16) Serotonin Antagonists ( Theraupeutic Uses) muscle thromboxanes, (Adverse effect) of
- Control appetite:Cyproheptadine: potent H1-receptor & 5-HT blocking action leukotrienes prostaglandins
- Anti-emetic: Ondansetron5-HT3 antagonist-prevetn nausea& vomit (activate GI smooth
- Antipsychotic: Clozapine:antipsychotic(5HT2A antagonist) muscle contraction)
17) Serotonin syndrome: overdose with a single drug, or concurrent use of several
drugs resulting excess serotonergic activity in the central nervous system Respiratory smooth PGE2 (relaxation of resp PGE2 : bronchodilator
muscle smooth muscle)
Precipitating drugs Clinincal presentation Therapy PGD2, TXA2, and PGF2
SSRI (selective serotonin Hypertensoin, Sedation(benzodiapens), (contraction)
reuptake inhibitor) tremor, Paralysia
Antidepressents hyperthermia, Intubation
MAOI(mono amine hyperactive bowel sounds, Ventilation Reproductive PGF2 (uterine smooth Alprostadil: (PGE1)
oxidase inhibitor diarrhea, 5HT block with drug muscle contraction)* treatment of erectile
agitation, (cyproheptadine/chlorpromazi PGE1 (relaxing the smooth dysfunction
coma ne) muscle of the corpora
cavernosa enhance
- erection)
18) Ergot Alkaloids:
- produced from fungus, contain>active subsances, Platelets PGD2, PGI2 inhibit Eoprostenol: (PGI2)
- affect alpha aadrenoreceptors, dopamine receptors, 5-HT receptor aggregation vasodilator and
TXA2 enhance platelet antithrombotic action,
aggregation used in pulmonary
hypertension TXA2
synthesis inhibitors or
COX inhibitors are used to
inhibit platelet
aggregation.

Kidney PGE2 & PGI2 maintain Long term use of PG


renal blood flow and synthesis inhibitors (e.g
glomerular filtration rate NSAIDs (COX inhibitors)
through their local renal damage)
vasodilating effects.

Protection of GI PGE2 & PGI2 enhance Misoprostol: (PGE1)


mucosa mucus and bicarb suppresses gastric acid
secretion, inhibit gastric secretion, used with
acid secretion. NSAID

19) Eicosanoids:
- 20carbon unsat FA from arachidonic acid(AA)from cell membranes,syhthesised by
all tissue
- Product: prostaglandins, thromboxanes, leukotrienes, lipoxins
Organ Pharmocological action Name of drugwith
use/adverse effect
Smooth TXA2 & PGF2 (potent Alprostadil: (PGE1)
muscle vasoconstrictor) analogue, given iv to