Autacoids (histamine) Flashcards
What is the action of Histamine in B.Vs
H1 receptor located on B.Vs
1- when activated
2- it activate Endothelial derived relaxing factor (EDRF)
3- EDRF diffuse in Smooth musc. and activates guanylcyclase
4- Guanylcyclase increase the level of cGMP
5- produce smooth musc. relaxation
V.D
in H1 it is rapid onset and short duration
In H2 it is slow in onset and more sustained
What is the effect of histamine on H1 receptors on
a) non vascular smooth muscle
b) the heart
c) the nervous system
a) It produces contraction
b) it slows the A/V conduction
c) it produces itching and pain
H1 receptors are blocked by H1 antagonist as
Chlorpheniramine
It produces sedation as it crosses the BBB
Effect of histamine on H2 receptors on
a) gastric mucosa
b) B.Vs
c) heart
A) increase acidity
B) V.D slow in onset and more sustained
C) positive chronotropic and inotropic
H2 antagonist
Cimetidine
Effect of histamine on H3 on presynaptic neuron of CNS ,CVS , GIT , Bronchial smooth muscles
It reduces the release of histamine from histaminergic neurons
H3 antagonist
Thiperamide
Where histamine receptors locate
H1
on B.Vs ,heart and CNS
H2
on gastric mucosa , B.Vs and heart
H3
Presynaptic neuron
What is the effect of histamine on
a) heart
b) B.Vs
c) non vascular smooth muscles
d) exocrine gland
e) nerve ending
A) positive inotropic and chronotropic .
Negative dromotropic
B) V.D and increase permeability
C) contraction and cause B.C
D) increase secretions and increase acidity of stomach
E) stimulate nerve ending causing itching and pain
Histamine antagonists
1- physiological antagonism — adrenaline
2- pharmacological antagonism — competitive antagonism
3- preventing release — by steroids and cromolyn sodium
H1 antagonists effects
1- affect vascular( V.D) and non vascular(contraction) smooth muscles but its effect on bronchial asthma is minimal because of leukotrienes
2- the first generation drugs cause sedation but the second generation does not penetrate BBB so no sedation
3- treat motion sickness as it has anticholinergic action
4- local anesthetic and antipruritic
H1 drugs not cross BBB and not affect muscarinic receptors
fexofenadine and loratidine
What are the side effects of H1 antagonists
1- Sedation dizziness tennitus lassitude fatigue nervousness insomnia and tremors
2- nousea vomiting and gastric distress
3- atropine like effect ( اعراض زغلولة )
4- overdosage cause excitation , hallucination excitement ataxia and convulsions
5- allergic manifestations when given topically
Therapeutic uses of H1 antagonists
1- allergic disorders . Given with epinephrine
2- in motion sickness and vesitular disturbances as menieres disease
What is more effective in motion sickness
Scopolamine
First generation H1 antagonists and their effect
1- diphenyldramine
2- Dimenhydrinate
3- promethazine
4- chlorpheniramine
Cause sedation and anticholinergic effect
What are second generation H1 antagonists and what are the differences between them and first generation drugs
1- fexofenadine
2- loratadine
No sedation
No anticholinergic effect
What are H2 antagonist drugs and how they work
Ranitidine
Cimetidine
Famotidine
Nizatidine
The block the effect of histamine on gastric mucosa
What are the pharmacokinetics of H2 blockers
H2 blockers are well absorbed when given orally
The bioavailability of all drugs is 50% however the bioavailability of nizatidine is 90%
Why cimetidine is not used today
Cuz of its side effects
1- on CNS : headache , dizziness and confusion
2- it increases serum prolactin leading to antiangrogenic effects . Reduce estrogen catabolism in men may cause gynecomastia , galactorrhea and loss of libido in females .
3- leucopenia and elevated serum creatinine level
4- it inhibits the activity of cytochrome p450 in liver thus prolong other drugs duration as warfarin, phenytoin, propranolol, nifedipine and theophylline and decreases liver blood flow
What are the therapeutic uses of H2 blockers
1- gastric mucosa
2- in esophageal reflux
3- preanesthetic as it rduce aspiration of gastric contents
4- prophylaxis of stress ulcers and it is given IV
