The autacoid is divided into 3 sections
1) Amino acid decarboxylated
2) Vasoactive peptide
3) Eicosanoids
We have talked about decarboxylated amino acids with all its details, types and drugs, and in this article we will talk about the other two types, which are Vasoactive Peptide and Eicosanoids. Follow us
Vasoactive Peptides
Angiotensin
- Angiotensin is a peptide hormone that causes potent VC.
- It is a part of the renin-angiotensin system (RAS):
1) When blood pressure is decrease the renal blood flow is decrease the kidneys feel ischemia and convert the pro-renin into renin and secrete it directly into the circulation.
2) Plasma renin convert angiotensinogen to angiotensin I.
3) Angiotensin I (ANG I) is converted to angiotensin II (ANG I) by the angiotensin-converting enzyme (ACE).
4) Angiotensin Il acts by binding angiotensin receptors cause; Potent direct VC increase aldosterone, Na+ and water retention, increase sympathetic activity (increase NE release).
Inhibition of the Renin-Angiotensin System
1) Angiotensin-Converting Enzyme (ACE) Inhibitors
Captopril, Lisinopril, Enalapril, Fosinopril, Perindopril, Ramipril, Benazepril, Cilazapril, Imidapril, Zofenopril, Quinapril, Trandolapril
Mechanism of Action
The hypotensive activity of ACEIS, due to; - Blocks the conversion of angiotensin I to angiotensin II. -Inhibits the degradation of bradykinin (vasodilator cause VD via NO).
Uses
1) Hypertension
2) Heart failure
3) after myocardial infarction
4) chronic kidney disease
5) diabetic nephropathy.
Side Effects
1) Hypotension after initial dose
2) Hyperkalemia
3) Acute renal fallure
4) Dry persistence cough; due to levels of bradykinin and other inflammatory mediator. Can be treated by:
I) Iron supplements (inhibitor of NO synthase).
II) NSAIDS (e.g. aspirin 500 mg/day) inhibit PGs synthesis.
Contraindication
ACEIs are contraindicated in pregnancy, increase risk of fetal malformation (lung hypoplasia and skeletal deformities). (ARBS)
2) Angiotensin II Receptor Blockers (ARBS)
Losartan, Valsartan, Candesartan, Irbesartan, Eprosartan, Telmisartan, Olmesartan, Fimasartan, Azilsartan
- ARBs are have no effect on bradykinin metabolism.
- ARBs more selective blockers of angiotensin effect than ACE inhibitors.
- ARBs have a similar uses to those of ACE inhibitors.
- ARBs have a similar adverse effects to ACE inhibitors, but less.
- ARBs have a similar hazard to ACEIS of use during pregnancy.
3) Direct Renin Inhibitors
Aliskiren
It is act by binding to active site of renin cause decrease plasma renin activity thus inhibiting conversion of angiotensinogen to angiotensin I.
It is used in hypertension.
Adverse effects
1) Gl symptoms
2) Rash and cough; but less than ACEIs or ARBs.
Contraindicated (CA)
1) Pregnancy (same as ACEIs).
Kinins (Bradykinin)
Kinins are potent vasodilator peptides.
Kinins on arteries cause dilatation, but, in veins cause Contraction.
Bradykinin produce; four classic symptoms of inflammation
1) Redness
2) Local heat
3) Swelling
4) Pain
Aprotinin, Ecallantide & Icatibant
Act by inhibits bradykinin synthesis (Kallikrein Inhibitors).
Aprotinin used to reduce bleeding during complex surgery.
Ecallantide used in hereditary angioedema (HAE).
Icatibant is a bradykinin B2 receptor blocker.
Uses: Treatment of acute attacks of HAE.
Eicosanoids
Prostaglandins (PGs), Thromboxanes (TXs) and Leukotrienes (LTs)
Eicosanoids are oxygenation products of polyunsaturated long-chain (20 C atom) fatty acids.
Eicosanoids are not stored within cells, but are synthesized as required.
-PGI2: (Prostacyclin) & PGE1: decrease platelet aggregation & VD
-PGE2: VD, uterine contractions & increase platelet aggregation.
-PGD2: inflammatory response, bronchoconstriction & VD.
-PGF2α: VC, bronchoconstriction & uterine contractions.
-TXA2: increase platelet aggregation, VC & bronchoconstriction.
-LTB4: chemotaxis and T-cell proliferation.
-LTC4, LTD4, LTE4: VC and bronchoconstriction.
Inhibition of Eicosanoid Synthesis
-Corticosteroids pathways of eicosanoid synthesis.
-NSAIDS block PGs and TXs formation by inhibiting COX
-5-LOX inhibitor (e.g. Zileuton) and selective antagonists of the CysLT1 receptor for leukotrienes (LTC4, LTD4 and LTE4) (Zafirlukast, Montelukast and Pranlukast), are used clinically in mild to moderate asthma.
Prostaglandin Analogues
Alprostadil
Is a PGE, analogue, used to maintaining a patent ductus arteriosus in newborns and in impotence.
Misoprostol
Is a PGE, analogue, with oxytocic properties.
It is approved for use in the prevention of NSAID
induced gastric ulcers. C/1 during pregnancy.
Off-label uses:
1) Labor induction
2) abortion
3) missed miscarriage
4) postpartum bleeding.
Cause
1) softening of cervix
2) uterine contraction.
Dinoprostone
Is a PGE, analogue, with oxytocic properties.
It administered vaginally (vaginal insert) for labor induction cause softening of cervix & uterine contraction.
Garboprost
Is a PGF2α analogue, with oxytocic properties.
Used in postpartum hemorrhage in the presence of uterine atony that has not responded to usual therapy (oxytocin, uterine massage, ergot alkaloids).
Latanoprost, Bimatoprost, Travoprost, Unoprostone
Used as ophthalmic solution to control the progression of glaucoma or ocular hypertension by reducing IOP.
Bimatoprost is used in treatment of eyelash hypertrichosis.
Epoprostenol
Is a prostacyclin (PGI:), has 2 major effects:
1) direct vasodilation of pulmonary and systemic arterial vascular beds
2) inhibition of platelet aggregation.
Used in treatment pulmonary arterial hypertension.
References
 Amino acid decarboxylated 2) Vasoactive peptide 3) Eicosanoids We have talked about decarboxyl…){kind=link}
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