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Histamine and pharmacological treatment of allergy.
Antiemetics. Antiserotonic drugs.
Anton Kohút
Acute allergic reaction
Allergens
omalizumab
• Histamine is formed from the amino acid histidine by
histidine decarboxylase.
Histamine is a basic amine, stored in mast cells and basophils (lung, skin, GIT, CNS).
R e l e a s eHistamine is released during inflammatory and alergic
reactions. Secretory process is initiated by a rise of intracellular calcium.
• Drugs increasing histamine release: morphine tubocurarin substance P
Actions of histamine
Antihistaminics (H1)
Antihistaminics (H2)
CimetidineFamotidineNizatidineRanitidine
Treatment of gastric ulcer
Serotonin (5-HT)
Serotonin (5-HT)
5-HT neurotransmission
5HT-R Action Agonist Antagonist
1A, B neuronal inhibition, behavioural effects: sleep, feeding, anxiety, thermoregul.
Buspirone, Sertindole
Ergotamine Metiotepine
1D vasoconstriction Sumatriptan Ergotamin Metiotepine
2A neuronal excitation(increase in the number in suicides)
LSD KetanserineCyproheptadineNefazodone
3 neuronal excitation, vomiting, anxiety
-Metyl-5-HT
OndanzetronGranizetronTropizetron
7 not known LSD KetanserineCyproheptadine
5-HT-R classification and function in CNS
Serotonin has been linked to an exhausting list of conditions:
- depression,- eating disorders, - schizophrenia,- premenstrual syndrome,
anxiety, panic disorder,- seasonal affective disorder, - extreme violence,- hostility and aggression,- suicide, migraine,-- addiction, and more.
Actions and functions of 5–HT
Actions• increased GIT motiliti,• smooth muscle (bronchi, uterus)-
contraction• mixture of vascular constriction and
dilatation,• increased microvascular
permeability• platelet aggregation, • stimulation of peripheral
nociceptive nerve endings• excitation/inhibition of CNS
neurons,
Pathophysiological role• in periphery: peristalsis, vomiting,
platelet aggregation, inflammatory mediator, sensitisation of nociceptors and microcirculation control.
• in CNS: control of apetite, sleep, mood, hallucinations, pain perception and vomiting.
Clinical conditions:- migraine, - carcinoid syndromeflushing, diarhoe, bronchoconstriction,
hypotension), - mood disorders (depression) and
anxiety, - vomiting
Drugs influencing serotoninergic function
Antiemetics
Receptors involved in vomiting
Causes of vomiting
I. Drugs• Anticancer drugs,
cardiac glycosides, apomorphine, levodopa, bromocryptine, cholinomimetics, opiates, ergot alkaloids
II. Physiological• Pregnancy, head
motion, weitghlesness
III. Pathophysiological• Uremia,
endocrinopathies, alcoholism, migraine, allergies,
• gastric irritations
IV. Toxic• Food poisons,
industrial poisons, radiations, infections
Grops of antiemetic drugs
Recomended antiemetic treatment
Migraine are recurrent, moderate-to-severe episodes of head
pain that may be induced by a variety of triggers.A migraine headache is a form of vascular headache. Migraine
headache is caused by vasodilatation that causes the release of
chemicals from nerve fibers.
Pathophysiology and treatment of migraine