ACE Inhibitors + AT1 Receptor blockers

1. ACE-INHIBITORS / ARBs
Cardiovascular system (CVS)
(Pharmacology & Therapeutics-1)
Lecture by
Dr. Syed Baqir Raza Naqvi
(BSc, Pharm-D, M. Phil-Pharmacology)
Nazar College of Pharmacy
DAKSON Institute of Health Sciences, Islamabad
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2. Pathophysiology of RAS
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3. RAAS
• When there is renal ischemia (Less blood supply
to kidney) there is secretion of renin (Proteolytic
enzyme) from juxta-medullary cells of kidney.
• Renin act on angiotensinogen (protein) and
converts angiotensin-I to angiotensin-II, in the
presences of angiotensin converting enzyme
(ACE).
• Angiotensin-II is the powerful vasoconstrictor
agent that is 40 times more potent then nor-
adrenaline.
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4. Parindopril
Forinopril
Ramipril
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5. Pharmacology of ACE Inhibitors
• Captopril was first introduced in 1977. it is useful in cases of
hypertension, where renin secretion is high.
Mechanism of Action
• Renin acts on angiotensinogen and converts it into angiotensin-I. The
angiotensin-I is then converted to angiotensin-II by the action of an
enzyme ACE.
• Angiotensin-II causes hypertension by two mechanisms;
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6. • 1. Angiotensin-II is a powerful vasoconstrictor and causes
vasoconstriction of blood vessels all over the body. There is increased
peripheral resistance that causes hypertension.
• 2. Angiotensin-II also causes increased secretion of aldosterone
which in turns causes sodium and water retention and leads to
increased blood volume which causes an increase in cardiac output &
blood pressure.
• ACE Inhibitors inhibits the ACE and prevents formation of
angiotensin-II, thus reduces its hypertensive action. They cause
vasodilation and may reduce Na+ retention.
Mechanism of Action; cont.
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7. Note
Effects of ACE Inhibitors;
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8. Indications
Congestive Heart failure
• Captopril is used in the treatment of CHF. It decreases the afterload
(Resistance of arterial system to left ventricular contraction)
• It also decreases pre load (the volume of blood which enters the heart &
causes its stretching) by decreasing fluid retention and by causing dilation
of vessels.
Dyspnea
• Captopril is considered as single agent therapy in patients who presents
with mild dyspnea but don’t show symptoms.
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9. Hypertension
• ACE Inhibitors are extremely important remedy for the treatment of
hypertension. Now a days they are considered to be the first line drugs in
the treatment of extensive hypertension, especially incase of sugar
patients.
• They are preferred b/c of following properties;
1. No postural hypotension
2. No rebound hypertension
3. Safe in diabetics
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10. Diabetic Nephropathy
• The disease of kidney that includes
degenerative lesions of tubules and commonly
accompanies larger stages of diabetes mellitus.
• Captopril have particularly useful role in
treating patients with diabetic nephropathy b/c
they diminish proteinuria (Excretion of Proteins
in urine) and stabilize renal functions.
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Adverse Affects of ACE Inhibitors
• CNS: Dizziness, Headache, Insomnia.
• CVS: 1st dose hypotension, palpitation.
• GIT: Nausea, diarrhea, taste disturbance.
• Allergic reactions: Rashes, edema, hemolytic anemia.
• Resp. System: Laryngeal edema, Cough (due to release
of bradykinins from mast cells and so it is called allergic
cough).

12. 8. Increased Serum K+
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13. 13

14. Different Brands of ACE Inhibitors
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15. 15
Angiotensin-II Receptor
Blockers (ARBs)

16. Angiotensin-II Receptor Blockers
• Angiotensin-II receptor blockers
are non peptide orally active
compounds.
• These are extremely potent
competitive antagonist of the
angiotensin-II type 1 (AT1)
receptors.
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Losartan
Valsartan
Condensetron
Eprosetron
Telmosetron
Irbesetron
Drugs

17. Losartan
Losartan was the first marked blocker of angiotensin-II Type 1
receptors.
Mechanism of Action
Angiotensin-II Receptor blockers (Losartan) are the drugs which act at
the receptor site by blocking the effect of angiotensin-II at its
peripheral site.
There are two types of Angiotensin-II receptors;
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Angiotensin-II type 1
(AT₁) Receptors
Angiotensin-II type 2
(AT₂) Receptors

18. • AT1 Receptors are located in the kidney, arterioles, smooth muscles
and adrenal glands.
• AT2 Receptors are present in brain and kidneys.
• The vasopressor effects of angiotensin-II are mediated when it binds
with AT1 Receptors.
• Losartan act by competing with Angiotensin-II at the peripheral AT1
receptors. Thus, angiotensin is unable to produce its vasopressor
effect and the drug thus shows antihypertensive effect.
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Mechanism of Action

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Mechanism
of
Action

20. 20

21. Clinical Uses of losartan
Hypertension
• Approved for the treatment of essential hypertension by lowering
the blood pressure and reducing the morbidity and mortality
associated with hypertension.
Congestive Cardiac Failure
• Angiotensin-II receptor blockers are used in CHF as a substitute for
ACE inhibitors in the patient with severe cough and edema.
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22. Adverse Affects
• CNS: Headache, Dizziness,
Insomnia.
• CVS: Hypotension,
Tachycardia.
• Allergic: Skin rashes,
Urticaria etc.
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Contraindications
Angiotensin-II receptor blockers
are contraindicated in;
i. Pregnancy.
ii. Renal Failure.