Pharmacology 1

(PHO332)

Lecture 7
Interactive teaching methods

• Mid term exam model answer

discussion.

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mail to the link, a course will be added to your e learning, named as AI-900.

The course contains the required info. To prepare well for Microsoft exam.

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cost.

Any questions in regards this issue ( I am available weekly TUS 8-9 at H204).

Assoc. Prof. Dr. Sameh S. Gad

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Assignment support
Those who selected to take the chance to be Microsoft certified; after you wrote your MSA e

mail to the link,

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 Reminder
#The support you will find in the e learning course (AI
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Reminder

7
 Autacoids
I- Atrial Natriuretic Peptide "Factor" (ANP or ANF):
• Polypeptide released from atrium of the heart in response to atrial stretch from hypervolemia
as well as in response to hypertension.

• The discovery of ANP was followed by that of the B-type natriuretic peptide (BNP)
• ANP and BNP have demonstrated properties leading to vasodilation, increase in natriuresis,
diuresis, and antifibrotic and antihypertrophic effects within the heart.
• They increase G.F.R → ↑ Na+ excretion in urine and inhibit the renin release & ↓
Aldosterone.

• The measurement of BNP is used for the diagnosis and management of heart failure.
 Autacoids

• II- Vaso-Active-Intestinal Polypeptide (VIP):

1- Chemical transmitter in C.N.S. & Periphery.
2- Smooth muscle relaxation → V.D., Relax G.I.T. & Bronchodilatation.

• III- Substance-P:
1- V.D., ↑ Intestinal motility & Bronchospasm.
4- Pain transmitter at Substania Gelatinosa in Spinal Cord.
5- Opioids (e.g. Morphine), and Endorphins & Enkephalins → Opiate receptors →
↓ Release of Substance-P → Analgesia.
 Autacoids (cont.)
IV- Kinins and Angiotensins:

Kinins: Bradykinin
*Powerful Arteriolar V.D. Reflex Tachycardia:
*Edema formation.
*Stimulate Sensory Nerve Endings Pain.
*Important mediator of Inflammation & Anaphylaxis
*Spasmogenic on smooth muscle Bronchospasm.

Renin:
secreted by Juxta-Glomerular Cells.

Angiotensin: Angiotensin I, II
Angiotensin-I: Inactive
Angiotensin-II: Very Active
 Autacoids (cont.)
• V- Eicosanoids
• They have very short duration of action.
• They are synthesized & released as required. Not stored in body.
• Synthesized by All cells from Arachidonic acid.

* Leukotrienes
Synthesized by Lipo-Oxygenase enzymes
• Cysteinyl-Leukotrienes Bronchospasm, Bronchial secretions & Exudation of plasma Bronchial Asthma

* Prostaglandins
• Synthesized by Cyclo-oxygenase (COX) Cyclic endoperoxides (PGG2 & PGH2) are further metabolized by
: a- Prostaglandin synthetase PGD, PGE & PGF.
b- Endothelial Prostacyclin synthetase Prostacyclin (PGI2).
c- Platelet Thromboxane synthetase Thromboxane A2 (TXA2).

• Types of COX: a- COX-1: Physiological constitutive) Renal VD & Gastric HCl.

b- COX-2: Pathological (Inducible) Inflammation, fever, pain and edema.
 Histamine

Biological amine

• Found in Lung, GIT, Skin & Brain:

Present in Mast cells, Basophils & nerve endings.
• Mechanism of action of histamine:

Histamine stimulates specific H-receptors coupled to G-protein:

1- H1-receptors G PLC IP3 & DAG Ca2+ & Protein kinases:
a- Smooth muscle Spasmogenic.
b- Endothelium Nitric oxide Guanylate cyclase cGMP
V.D.

2- H2-receptors Gs Adenylate cyclase cAMP Heart, HCl & V.D.

3- H3-receptors Gi Adenylate cyclase cAMP.

* Actions Of Histamine:
A) H1-Actions:
1- Spasmogenic on Smooth muscles e.g. Bronchi, GIT & Uterus.

2- Increase exocrine secretions especially Nasal & Bronchial.

3- V.D. (H1 > H2) of small vessels. Headache, Hypotension

4- Capillary permeability via & Anaphylactic shock
Shrinking of endothelial cells
Exposing basement membrane Permeable.

5- Skin Itching, Pain & Triple response.

6- Adrenal Medulla Release of Adrenaline.

B) H2 -Actions:
1- Some V.D. (V.D. is H1 Mainly).
2- Heart +ve Inotropic & Chronotropic. H.R. is due to H2 & Reflex via ¯
Bl.p.
3- Gastric HCl secretion.
4- Specific H2-Blockers e.g. Cimetidine and ranitidine Treat Peptic
ulcer

C) H3-Actions:
1- C.N.S. Arousal, cognition, Memory & Pathophysiology of Epilepsy.
2- Presynaptic Release of histamine (Autoregulation) & other mediators.
3- Peripheral actions.
4- Specific H3-Blockers e.g. Thioperamide & Clobenpropit.
 Anti-Histaminics = H-1 Blockers
* Classification :
A) First Generation Anti-histaminics Sedatives & Atropine like.
B) Second Generation Anti-histaminics
No BBB No Sedation, No Atropine-like, No Anti-Emetic, No Anti-Serotonin & Long
Duration (12 Hs)

12- Terfenadine (Triludan): Obsolete

Cardio-Toxic Prodrug CYP 450 Fexofenadine (Safe Active Metabolite).
13- Fexofenadine (Telfast): 60 – 180 mg od po.
Safe active carboxylated metabolite of Terfenadine.
14- Astemizole (Hismanal): 5 – 10 mg od po.
15- Mequitazine (Primalan): 2.5 – 5 mg bid po.
16- Loratadine (Claritine): 5 – 10 mg bid po.
17- Desloratadine (Clarinex): 5m po
18- Cetirizine (Zyrtec): 5 – 10 mg od po.
19- Acrivastin (Semprex): 8 mg od po
• Pharmacokinetics of Antihistaminics:

1- Absorbed orally.

2- Pass BBB (EXCEPT Second Generation).

Pass placental barrier e.g. Meclizine & Cyclizine à Teratogenic.

3- Metabolized in liver: Most of them are enzyme inducers.

Terfenadine & Astemizole (Cardio-Toxic prodrug) à Non-toxic active metabolites

4- Excreted in urine & milk à Sedate suckling baby.

• Pharmacodynamics of Anti-histaminics:

1- Competitive antagonists at H1-receptors of histamine:

*Block COMPLETELY the Spasmogenic, á Capillary permeability & Skin actions.
*Block Most the V.D. & Hypotension.
*NO effect on á Heart or á Gastric acidity.

2- Some have Anticholinergic = Atropine-like effect à Dry mouth.

3- Some have Antiserotonin effect.
4- Some have Na+-Channel block = Membrane stabilizer Local anesthetic & Direct
myocardial depressant effect = Quinidine-like action e.g. Antazoline.

5- CNS (EXCEPT Second Generation):

a- Mainly CNS depression à Sedation & drowsiness.
b- Anti-emetic & Anti-motion sickness (Block H1- & M-receptors in Vomiting center).
c- Anti-Parkinsonism (Block of M-receptors in basal ganglia).
d- Toxic dose à Convulsions specially in children.
* Therapeutic uses of Anti-histaminics:

1- Allergic manifestations : Conjunctivitis, rhinitis, urticaria & insect

stings.
a- In life-threatening anaphylactic shock & angio-edema à
Use Adrenaline.
b- NOT very effective in bronchial asthma:
- Asthma is due to other mediators e.g. SRS-A & PAF.
- Atropine-like effect à Dry bronchial secretions.
2- Motion sickness e.g. sea sickness e.g. Dimenhydrinate.
3- Vestibular disturbances (Meniere’s disease) e.g. Dimenhydrinate.
4- Parkinsonism e.g. Diphenhydramine.
5- As sedative & hypnotic e.g. Promethazine.
6- Common cold e.g. Chlorpheneramine à Sedation & dries the
secretions.
7- Cardiac arrhythmias e.g. Antazoline.
• Side Effects of Antihistaminics:

1- Drowsiness & sedation (EXCEPT Second

2- Dry mouth & avoid in glaucoma & enlarged prostate. generation).
3- Hypersensitivity reactions.
4- Teratogenic e.g. Meclizine & Cyclizine.
5- Toxic dose à Convulsions especially in children.
6- Drug Interactions:
a- Enzyme inhibitors e.g. Grapefruit, Macrolide antibiotics (Erythromycin)
&
Antifungal (Ketoconazole) inhibit metabolism of Terfenadine &
Astemizole à Long Q-T interval in ECG → Cardiac arrhythmias.
b- Sedative Anti-histaminics potentiate other sedatives e.g. Alcohol.
Faculty of
Pharmacy