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