Download Léčiva působící prostř. histaminu, serotoninu a dopaminu

Drugs acting by inhibition or
activation of receptors for
dopamine, serotonine and
histamine
Practice pharmacology,
medical students III.yr.
November 2013
Dopamine and dopamine receptors
Effect of antagonists of dopamine
A/ Antipsychotic effect
1/ Typical antipsychotics (1. generation): chlorpromazin, haloperidol
2/ Atypical antipsychotic agents (2. generation):
a/ clozapin, olanzapin, risperidon, ziprasidon, quetiapine
b/ sulpirid and amisulpirid: D2, D3 antagonists
3/ Dopaminergic „stabilisator“ = presynaptic agonist/postsynaptic
antagonist of D2 receptor and 5-HT2 antagonist aripiprazol
B/ Antiemetic effect
metoclopramid, domperidon, itoprid
Drugs used in the treatment of
Parkinson´s disease
1. Agonists of dopamine receptors:
bromokriptin /D2/, ropinirol, pramipexol,
rotigotine
2. Inhib. of MAO-B: selegilin, cannot be
combined with L-DOPA
3. COMT inhibitors: entacapon
4. L-DOPA
SEROTONIN, (5-HYDROXYTRYPTAMIN, 5-HT)
• Serotonine receptors: 5HT1A, 5-HT2, 5-HT3, 5-HT „xyz“
Clinical effects of activation/inhibition of serotonine receptors
5HT-1A agonist = anxiolytic and antidepressant eff.
5-HT2 antagonist eff. = antipsychotic eff., improvement of
sleep
• 5-HT3 antagonists: antiemetic effects
ondansetron, granisetron, tropisetron etc.
• 5-HT1A agonist: buspiron - anxiolytic drug, approved indication
GAD, can be used also as add-on for alcoholics, with care as
add-on to some antidepressant medication
• 5-HT1D (1B) agonists: antimigrenic effects
sumatriptan, naratriptan, zolmitriptan etc.
Antidepressants blocking serotonine receptors
• 5-HT2
• Agomelatine =
agonist at melatonine
receptors and
antagonist at 5-HT2
rcp.
(should not be
combined with alcohol,
regular control of AST
and ALT is necessary)
• 5-HT-2 and 5-HT-3
• Mirtazapine =
noradrenergic and
specific
serotoninergic
antidepressant
HISTAMINE and histamine receptors
• Histamine receptors H1, H2 and H3
• Antagonists of H1 receptors alleviate
symptoms of alergic reactions, can have
antiemetic, sedative effects
• 1/ Sedative – promethazin, hydroxyzin
(hydroxyzine is biotransformed to cetirizine),
bisulepine etc.
• 2/ Not sedative – cetirizine and levocetirizine,
loratadine and desloratadine
• 3/ Not sedative antihistaminic drug blocking
effect of PAF /platelet activ. factor/ = rupatadin
/rupatadine is metabolised to desloratadine/
Histamine and histamine receptors
• Antagonists of H2 receptors
- ranitidine, famotidine,
(historical example cimetidine)
• Antagonists of H3 receptors = betahistin
for Meniere disease and problems like
tinnitus, hearing loss
Questions
2/ What antihistamine drugs can be considered as
immunomodulatory (= can have antiinflammatory
effect) and why? levocetirizine, desloratadine
1/ Treatment with
and rupatadine: clinically these drugs will have
antagonists of
histamine H1 receptor also some effect on nasal obstruction
is symptomatic or
(levocetirizine inhibits migration of eosinophils to
causal therapy of
the site of allergic reaction, desloratadine inhibits
allergic diseases?
expression of adhesion molecules or inflammatory
cytokines, rupatadine blocks also effect of PAF in
It is symptomatic
addition to ihibitory effects on histamine release)
treatment.
3/ What are possible combinations of antihistaminic
drugs with other drugs for treatment of allergy in
clinical practice?
E.g.: cetirizine+mometasone (local corticosteroid);
desloratadine+montelukast (both p.o.)