Lesson 3.4. RAAS Drugs

Renin-Angiotensin-Aldosterone System

acts like a control center in the body that helps regulate blood pressure

Renin

RAAS SYSTEM:

1. starts the system when the body detects that BP is too low.

2. weak vasoconstrictor, is produced when renin interacts with angiotensinogen (from the liver) in the blood.

3. from the lungs that circulates in the blood and converts Angiotensin I to Angiotensin II

4. is a potent vasoconstrictor which increase BP by narrowing the blood vessels

5. an anti-Diuretic Hormone, triggered by Angiotensin II to retain salt and water which further increases the volume of blood to raise BP

1 = ?

Angiotensin I

RAAS SYSTEM:

1. starts the system when the body detects that BP is too low.

2. weak vasoconstrictor, is produced when renin interacts with angiotensinogen (from the liver) in the blood.

3. from the lungs that circulates in the blood and converts Angiotensin I to Angiotensin II

4. is a potent vasoconstrictor which increase BP by narrowing the blood vessels

5. an anti-Diuretic Hormone, triggered by Angiotensin II to retain salt and water which further increases the volume of blood to raise BP

2 = ?

Angiotensin Converting Enzyme

RAAS SYSTEM:

1. starts the system when the body detects that BP is too low.

2. weak vasoconstrictor, is produced when renin interacts with angiotensinogen (from the liver) in the blood.

3. from the lungs that circulates in the blood and converts Angiotensin I to Angiotensin II

4. is a potent vasoconstrictor which increase BP by narrowing the blood vessels

5. an anti-Diuretic Hormone, triggered by Angiotensin II to retain salt and water which further increases the volume of blood to raise BP

3 = ?

Angiotensin II

RAAS SYSTEM:

1. starts the system when the body detects that BP is too low.

2. weak vasoconstrictor, is produced when renin interacts with angiotensinogen (from the liver) in the blood.

3. from the lungs that circulates in the blood and converts Angiotensin I to Angiotensin II

4. is a potent vasoconstrictor which increase BP by narrowing the blood vessels

5. an anti-Diuretic Hormone, triggered by Angiotensin II to retain salt and water which further increases the volume of blood to raise BP

4 = ?

Aldosterone

RAAS SYSTEM:

1. starts the system when the body detects that BP is too low.

2. weak vasoconstrictor, is produced when renin interacts with angiotensinogen (from the liver) in the blood.

3. from the lungs that circulates in the blood and converts Angiotensin I to Angiotensin II

4. is a potent vasoconstrictor which increase BP by narrowing the blood vessels

5. an anti-Diuretic Hormone, triggered by Angiotensin II to retain salt and water which further increases the volume of blood to raise BP

5 = ?

hypertension

The drugs under RAAS can also be used to manage ________________

dry cough

ACE Inhibitors’ side effect is ______________ due to the inhibition of the breakdown of bradykinin

ACE Inhibitors

Blocks the action of ACE and prevents the conversion of Angiotensin I to Angiotensin II

Kallikrein-Kinin system

ACE Inhibitors

• inhibits the RAAS by blocking ACE while stimulating the a._____________ to produce bradykinin (potent vasodilator)

• decreases BP mainly by decreasing b._____ without significant effect of CO and HR – c.__________________________

a = ?

PVR

ACE Inhibitors

• inhibits the RAAS by blocking ACE while stimulating the a._____________ to produce bradykinin (potent vasodilator)

• decreases BP mainly by decreasing b._____ without significant effect of CO and HR – c.__________________________

b = ?

no reflex tachycardia

ACE Inhibitors

• inhibits the RAAS by blocking ACE while stimulating the a._____________ to produce bradykinin (potent vasodilator)

• decreases BP mainly by decreasing b._____ without significant effect of CO and HR – c.__________________________

c = ?

prodrugs

All drugs under ACE Inhibitors are a._______ which are hydrolyzed inside the body into -prilat (active forms) except b.___________________.

a = ?

Captopril and Lisinopril

All drugs under ACE Inhibitors are a._______ which are hydrolyzed inside the body into -prilat (active forms) except b.___________________.

b = ?

Captopril

DRUGS INCLUDED IN THE ACE INHIBITORS:

• prototype drug

• active agent

Lisinopril

DRUGS INCLUDED IN THE ACE INHIBITORS:

• lysine derivative of enalaprilat

• active agent

Benazepril, Fosinopril, Moexipril, Perindopril, Quinapril, Ramipril andTrandolapril

DRUGS INCLUDED IN THE ACE INHIBITORS:

• prodrugs

Angiotensin Receptor Blockers

Directly blocks the angiotensin receptors (AT1), preventing both the vasoconstriction and aldosterone activation to retain salt and water

PVR with no apparent change in CO and HR

Angiotensin Receptor Blockers

a. reduce _______________________________ hence no reflex tachycardia

b. work similarly with ACE inhibitors but has potential for __________________ of angiotensin action

a = ?

complete inhibition

Angiotensin Receptor Blockers

a. reduce _______________________________ hence no reflex tachycardia

b. work similarly with ACE inhibitors but has potential for __________________ of angiotensin action

b = ?

Losartan

Drugs Included in the Angiotensin Receptor Blockers:

a. prototype

b. other drugs

a = ?

Valsartan, Telmisartan, Irbesartan, Eprosartan, Candesartan, and Olmesartan

Drugs Included in the Angiotensin Receptor Blockers:

a. prototype

b. other drugs

b = ?

Chronic Kidney Disease

CLINICAL USES OF ACE INHIBITORS AND ARBS:

• diminish proteinuria (nephroprotective) and stabilize renal function

Heart Failure and Myocardial Infarction

CLINICAL USES OF ACE INHIBITORS AND ARBS:

• decrease cardiac hypertrophy or “remodeling.”

reducing diabetes incidence

CLINICAL USES OF ACE INHIBITORS AND ARBS:

• ACEi helps in ________________________ among patients with high CV risk

hypertension, heart failure, and myocardial infarction

CLINICAL USES OF ACE INHIBITORS AND ARBS:

• common uses include:

hypotension

ADVERSE EFFECTS OF ACE INHIBITORS AND ARBS:

• Severe _____________ after initial dose

Dry Cough

ADVERSE EFFECTS OF ACE INHIBITORS AND ARBS:

• Major ADR

• maybe associated with bradykinin irritating nerve endings in the lungs

• ACEi > ARBs

Hyperkalemia

ADVERSE EFFECTS OF ACE INHIBITORS AND ARBS:

• More with patients with diabetes or renal insufficiency

• ACEi > ARBs

Potential Teratogenic Risk

ADVERSE EFFECTS OF ACE INHIBITORS AND ARBS:

• may cause fetal hypotension, anuria, renal failure, malformation and death

allergic skin rashes and altered sense of taste

ADVERSE EFFECTS OF ACE INHIBITORS AND ARBS:

• minor adverse effects

Aliskiren

• direct renin antagonist

• Should NOT be combined routinely with an ACEi or ARBs

renin

Aliskiren MOA:

1. Directly inhibits ________

2. Reduces production of a.__________________ (vasoconstrictor) and b.________________ (sodium and water retention)

1 = ?

angiotensin II

Aliskiren MOA:

1. Directly inhibits ________

2. Reduces production of a.__________________ (vasoconstrictor) and b.________________ (sodium and water retention)

2.a. = ?

aldosterone

Aliskiren MOA:

1. Directly inhibits ________

2. Reduces production of a.__________________ (vasoconstrictor) and b.________________ (sodium and water retention)

2.b. = ?

hypertension

Aliskiren Use:

Diarrhea

ADRs of Aliskiren:

• due to higher doses

angioedema

ADRs of Aliskiren:

• occurs less often than other ACEis

cough and drug-drug interactions

ADRs of Aliskiren:

• other effects

starts RAAS

INCREASES BP:

Mechanism: Renin Release

Component Affected: ?

Reason:

conversion to Angiotensin II

INCREASES BP:

Mechanism: Renin Release

Component Affected:

Reason: ?

increase in TPR

INCREASES BP:

Mechanism: Angiotensin II

Component Affected: ?

Reason:

causes vasoconstriction

INCREASES BP:

Mechanism: Angiotensin II

Component Affected:

Reason: ?

increases SV

INCREASES BP:

Mechanism: Aldosterone

Component Affected: ?

Reason:

causes sodium and water retention

INCREASES BP:

Mechanism: Aldosterone

Component Affected:

Reason: ?

increases HR

INCREASES BP:

Mechanism: Cathecolamines

Component Affected: ?

Reason:

stimulates the heart to beat faster

INCREASES BP:

Mechanism: Cathecolamines

Component Affected:

Reason: ?

decrease in Renin activity

DECREASES BP:

Drug: Aliskiren

Component Affected: ?

Reason:

blocks renin

DECREASES BP:

Drug: Aliskiren

Component Affected:

Reason: ?

decrease in TPR and SV

DECREASES BP:

Drug: ACE Inhibitors

Component Affected: ?

Reason:

blocks the production of Angiotensin II and Aldosterone

DECREASES BP:

Drug: ACE Inhibitors

Component Affected:

Reason: ?

decrease in TPR and SV

DECREASES BP:

Drug: ARBs

Component Affected: ?

Reason:

blocks Angiotensin II from binding to its receptor

DECREASES BP:

Drug: ARBs

Component Affected:

Reason: ?

decreases SV

DECREASES BP:

Drug: Diuretics

Component Affected: ?

Reason:

increases sodium and water excretion through urination

DECREASES BP:

Drug: Diuretics

Component Affected:

Reason: ?

decreases HR

DECREASES BP:

Drug: Acetylcholine

Component Affected: ?

Reason:

slows the heart rate down

DECREASES BP:

Drug: Acetylcholine

Component Affected:

Reason: ?