1. Antihistamines
This study material is recommended specifically for practical courses from Pharmacology II for students of general medicine and stomatology. These brief notes could be used to prepare for the lesson and as a base for own notes during courses. Addititonal explanations and information are given in single lessons.

2. HISTAMINE
CATEGORIZATION, CLASSIFICATION

3. HISTAMINE occurence: basic roles in the human body
impulses for histamine release:

4. HISTAMINE- metabolism
histidine decarboxylase
imidazol-N-
methyltransferase
Histamine
diaminooxidase
MAO
aldehyd dehydrogenase
methylimidazolacetic acid
imidazolacetic acid

5. endothel, smooth muslces
Histamine receptors
subtypes H1-H4
G protein coupled
H1-receptors
H2-receptors
H3-receptors
H4-receptors
endothel, smooth muslces
(vessels, bronchi,
uterus, GIT),
peripheral nerves,
CNS
gastric mucosa,
heart,
immune system,
vessels, CNS
CNS, PNS
presynaptic neurons)
H3 isoform
(T-lymph., eosinoph.,
basoph., intestine, spleen,
thymus)

6. HISTAMINE - receptors H1 H2

7. HISTAMINE - receptors H3 H4

8. HISTAMINE - effects Histamine effects antagonization Symptomatic
Causal
synthesis inhibition - glucocorticoids
release inhibition– cromoglycate, nedocromil, β-sympatomimetics, glucocorticoids
receptor antagonists
- nonspecific, indirect– epinephrine
- selective H1 H2 H3 antihistamines

9. Histamine therapeutic use
negligible
CI: allergic reactions, AB, pregnancy, HT, glucocorticoids,…
dg. in allergology
oraly not active
Histamine analogue
betahistine
synthetic orogin, weak H1-agonist, strong H3 antagonist on presynaptic rcp.→ increase histamine turnover
I: Menier‘s disease, vertigo, tinnitus, weak internal ear perfusion

10. Antihistamines – allergic reactions
Hypersensitivity
incidence
development theories

11. Mechanism of allergic reaction

12. Signs of allergic reactions
senzory nerves irritation
vessel permeability increase
smooth muscle contraction
glandular hypersecretion

13. H1 - antihistamines ethanolamines alkylamines phenothiazines
piperazines
piperidines
others R1
X – C – C - N R2

14. H1 – antihistamines: mode of action
reversible competetive antagonism on H1 receptors

15. H1 – antihistamines: effects
antagonize allergic symptomes induced by histamine:
older agents penetrate BBB and gets into CNS

16. H1 – antihistamines- pharmacokinetics
easy and fast GIT absorption
equally sistributed in the body
CNS penetration– presence of central symptoms:
- „classic“ antihistamines get to CNS,
do have suppressive and other effects on CNS
- modern drugs of 2nd generation does not!!
intensive metabolisation in liver with microsomal enzymes
duration of effect:
short acting 4 – 6hrs: most of classical H1 antihistamines
long acting 12 – 24hrs: most of 2nd generation drugs
routes of administration:

17. H1 – antihistamines: indications
symptomatic treatment of hypersensitivity
allergic rhinitis
urticaria, drug and food allergies
adjuvans in the treatment of anaphylaxis
pruritus of different ethiology
e.g.. allergic and non allergic itching dermatoses
insect bites
tinnitus, Menier‘s disease
migraine
nausea and vomitus
kinetosis (moxastine, embramine)
vertigo
insomnia
- when intolerance to hypnotics is present
anxiety (hydroxyzine)
- weak anxiolytic effect

18. H1 - antihistamines 1st generation older drugs
generally lower selectivity to H1 subtype
cross BBB
effect app 4-6 hrs
higher incidence of AE

19. H1 - antihistamines 1st generation clemastine dimetindene promethazine
bisulepine
cyproheptadine
antazoline
diphenhydramine
ketotifen
chlorphenamine
azelastine
embramine theoclate (=mebrofenhydrinate)
moxastine theoclate (=mefenhydrinate)
diphenhydramine theoclate (=difenhydrinate)

20. H1 anitihistamines Adverse effects
CNS – sedation up to hypnotic effect
paradoxical stimulation
CI:
GIT
nausea, vomiting, diarhhoex constipation

21. H1 – antihistamines 2nd generation
minimal penetration to CNS – minimal sedation
more favorable – higher H1 selectivity, stroger binding to receptors
administered once or twice a day

22. H1 – antihistamines 2nd generation Adverse effects
arhytmogenic effect
QT interval prolongation
less in fexofenadin
astemizole – withdrawn from
market
sedation after overdosing (cetirizine)
Interactions: CYP3A4 inhibitors

23. H1 - antihistamines II. generation cetirizine levocetirizine
loratadine
desloratadin e
terfenadine
fexofenadine
acrivastine
ebastine
rupatadine
mizolastine

24. KONTRAINDIKACE H1 ANTIHISTAMINIK