Anti-hypertensives Flashcards
How does the RAAS system work?
What are the ultimate functions of Angiotensin II?
- Low renal perfusion causes release of Renin
- Renin activates angiotensinogen to angiotensin I
- ACE activated angiotensin I into angiotensin II
- Angiotensin II causes:
- increased sympathetic activity
- tubule Na and Cl reabsorption and K excretion; H2O retention
- Adrenal glad to secrete aldosterone
- arterial vasoconstriction, increasing BP
- pituitary gland to secrete ADH
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ACE inhibitors are the first line therapy for what diseases?
They also delay the progression of what disease?
- First line therapy:
- HTN
- CHF (post MI wil reduce progression of CHF)
- Migral regurgitation
- Delay progression of renal desease
- Most effective in diabetic patients
What is the MOA of ACE Inhibitors?
- MOA- block the conversion of angiotensin I to angiotensin II in the vascular endothelium
- this is done by an interaction with the zinc ion of angiotensin converting enzyme (peptidyl- dipeptidase)
- Causes a fall in arterial pressure and reduces the cardiac workload of the heart
What role do Bradykinins play in relation to BP and ACE?
- ACE inhibitors increase the amount of bradykinin
- This helps ACE inhibitors be more effective in decreasing BP than ARBS because the bradykinin is a vasodilator, further lowering the BP
- Increase in Bradykinin causes:
- vasodilation
- cough
- Angioedema
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What effects does the decrease in Angiotensin II (caused by ACE inhibitors) have?
- Decreased Ang II causes:
- vasodilation
- decreased blood volume
- decreased cardiac and vascular remodeling
- potassium retention
- fetal injury
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What receptor does Angiotensin II mostly interact with?
What are the effects of this receptor?
- Angiotensin II mostly interactics with AT-1 (GCPR)
- it signals increased Ca++ release from the SR
- AT-1 receptor effects:
- generalized vasoconstriction- especially in the afferent arterioles of renal glomeruli
- increased NE release
- Proximal tubule reabsorption of Na
- Secretion of aldosterone from adrenal cortex
What are the side effects of ACE inhibitors?
- Cough
- hyperkalemia
- Intra-op hypotension (hold am of surgery)
- Granulocytopenia
- Angiodema
- Minimal side effects, so there is usually pretty good patient compliance
What are the different ACE inhibitors available?
How can you easily tell that a drug is an ACEI?
- Drugs that end in -pril are ACE inhibitors
- Captopril
- enalapril
- Ramipril
- benazepril
- lisinopril
- Moexipril
- Quinapril
- Fosinopril
- Trandorapril
What drugs will interact with ACE inhibitors?
- NSAIDS will antagonize the effects because of the decrease in prostaglandins
- Anti-hypertensives will have an additive effect
When are ACE inhibitors contraindicated?
- Pregnancy
- Renal artery stenosis- pts may develop renal failure due to impaired efferent arteriole constriction
- if the efferent arteriole can’t constrict, they will not be able to maintain GFR with low flow
From the Table in the powerpoint, which ACE inhibitors are prodrugs and what are their duration of effects?
Captopril
Enalapril
Lisinopril
Ramipril
Do they have more effect on the Venous system or arterial system?
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Angiotensin II Receptor Blockers (ARBS)
MOA?
Side effects?
Contraindication?
- MOA: Competitive binding to inhibit the action of angiotensin II at its receptor (AT-1)
- blocks the vasoconstrictive actions of Ang II without affecting ACE activity
- Side effects- similar to ACE inhibitors
- NO cough because there is no bradykinin accumulation
- Contraindication
- renal artery stenosis
- pregnancy
How can you know a drug is an ARB?
The drug name ends in -artan
Losartan
Valsartan
Irbesartan
etc…
Hydralazine:
MOA
- Activates guanylate cyclase causing hyperpolarization and vasodilation
- direct relaxant effect of vascular smooth muscles, decreasing SVR
- arteries > veins
- alters Ca transport in vascular smooth muscles
Hydralazine Pharmacokinetics:
metabolism
onset
E1/2t
- metabolism:
- Extensive hepatic first pass metabolism
- Acetylated in liver and excreted in urine (15% unchanged)
- Onset: 15 minutes- give slowly, wait for effect
- E1/2t- 4 hours