Angiotensin and adrenergic Antagonist pharmacology Flashcards Preview

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Flashcards in Angiotensin and adrenergic Antagonist pharmacology Deck (45):

In HFrEF stage C, what is the baseline treatment strategy (which you would add to in certain circumstances)?

• ACEI or ARB + Beta Blocker


When would you add Aldosterone Antagonist to ACEI/ARB + Beta Blocker treatment?

• Class C disease, complicated by reduced kidney function
• Lower creatinine clearance (less than 30mL/min
• Lower potasssium (less than 5mEq/dL


When would you add Hydral-nitrates to the ACEI/ARB + Beta Blocker treatment?

• Class C disease
• Particulary in persistent symptomatic African Americans


When would you add Loop diuretics to ACEI/ARB + Beta Blocker treatment?

• Class C disease, cases of volume overload


What is the Kinin pathway?

• Bradykininogen
• Converted to bradykinin by kallikrenin
• Kinase II converts bradykinin to inactive fragments


What effects on VASCULAR SMOOTH MUSCLE does Angiotensin II have?

• Increases arterioloar constriction
• Raises arterial blood pressure


What effects on BRAIN does Angiotensin II have?

• Increase ADH secreation
• Increase thirst
• Increase water intake and absorption
• Increase arterial blood pressure


What effects on KIDNEY FUNCTION does Angiotensin II have?

• Increased sodium resorption in the tubules
• Increased filtration fraction in arterioles
• Messes with GFR
• Increases sodium and water retention
• Increases arterial blood pressure


What effects on ADRENAL CORTEX does Angiotensin II have?

• Increases aldosterone secretion
• Increses sodium resorption and water resorption
• Increases arterial blood pressure


What effects on CNS AND PERIPHERAL NERVOUS SYSTEM does Angiotensin II have?

• Increases sympathetic activity
• Increases arteriolar constriciton
• Increases cardiac output by way of heart rate
• Increases arterial blood pressure


What are the three ACEI drugs of extreme importance?

• Captopril
• Enalapril
• lisinopril


What are the initial daily doses for the three important ACEI drugs?

• Captopril
○ 6.25mg 3X
• Enalapril
○ 2.5mg twice
• Lisinopril
○ 2.5 - 5mg once


What are the side effects of ACEI drugs you should be worried about?

• Cough
• Hyperkalemia
• Angioedema
• Renal dysfunction
• Neutropenia
• Hypotension


What is done to monitor patients on ACEI drugs?

• Chemistry-7 with Mg and Ca once every 2 weeks at first (one month)
○ Becomes monthly after that
• CBC once a month
• BP every 2 weeks for one month then monthly


What are the concerning ACEI drug interactions?

• Lithium
• Salt substitutes
• Loop diuretics
• Potassium sparing diuretics


When should you NOT use ACEI drugs?

• Pregnancy
• Bilateral renal artery stenosis
• Angioedema
• hyperkalemia


What is the general, all-told result of the SOLVD prevention trial concerning ACEI use?

• It helps patients live longer
• 45% RR at 6 months, 50% RR at 12 months
○ Cumulative probability of death
• Doesn't help too much in cardiovascular causes of death alone though


What are the three important drugs in the ARB category?

• Candesartan
• Losartan
• Valsartan


The HOPE trial shows what about ARB use?

• Relative risk of 0.77 over placebo for heart failure outcomes


Why can there be angiotensin II "escape"?

• Non ACE conversion of ATI to ATII
○ Chymase
○ Cathepsin G
• Non-Renin conversion of angiotensinogen
○ T-P factor
○ Cathepsin G
○ tonin


What are the non-ACE ATII converters?

• Non ACE conversion of ATI to ATII
○ Chymase
○ Cathepsin G


What are the non-renin angiotensin converters?

• Non-Renin conversion of angiotensinogen
○ T-P factor
○ Cathepsin G
○ tonin


Where are AT1 receptors?

• Lung, smooth muscle, liver, brain, kidney (1a)
• Adrenals (glomerulosa), pituitary (1b)
* these are angiotensin II receptors


What does activation of the AT1 and AT2 receptors do?

• Aldosterone secretion
• Vascular constriction
• Dyspogenic response
• Renal/inotropic response
• Growth promoting (fibroblast, endothelial cells)
• Angiotensinogene gene expression increase
• Antiproliferative effects
• Cell differentialtion


Where are AT2 receptors?

• Midbrain/thalamus, adrenal gland (medulla), embryonic tissue
* these are angiotensin II receptors


What receptors are blocked by ARBs?

• Angiotensin II receptor AT1


What are the side effects of ARB use?

• No cough, which is nice
• Hyperkalemia
• Uricosuric effects
• Less angioedema


What are precautions for ARB use?

• Uric acid overproducers
• Pregnancy
• Volume depletion
• Renal arterial stenosis
• Hyperkalemia
• hypotension


What are the 5 biological responses to Beta-adrenergic receptor activation that we talked about?

• Cardiac myocyte growth
• Positive inotropic response
• Positive chrontropic response
• Myocyte toxicity
• Myocyte apoptosis


What are the first generation beta blockers?

• Propanolol
• Timolol
○ Non-selective for beta1 vs beta2, no ancillary properties


What are the 4th generation beta-blockers?

• Non selective
• Disigner efficacy enhancing or adverse event lowering acillary properties


What are the third generation beta-blockers?

• Selective or nonselective
• Potentially important ancillary property
• Carvedilol
• Bucindolol
• nebivolol


What are the second generation beta blockers?

• Metoprolol
• Atenolol
• Bisoprolol
○ Selective for Beta1 or beta2, no ancillary properties


What drugs have beta1 and alpha1 selectivity?

• Carvedilol
• Bucindiolol
• Labetalol


What drugs work by alpha1 blockade?

• Labetalol
• carvedilol


In whom is it appropriate to use Beta-blockers?

• Mild to moderate symptoms of HF
• Systolic dysfunction of LV (less than 40% EF)
• Receiving treatment with ACEI + diuretic
• No distinction male/female
• CAD or nonischemic dilated cardiomyopathy
• Doesn't matter diabetes
• COPD without reactive airway disease


When should Beta-blocker therapy be initiated?

• When diuretic treatment is started so that patient has minimal evidence of fluid retention
• When treatment with ACEI has been going on for 2 weeks
• No recent use of IV vasodilators or + inotropic agents. Not in ADHF or cardiogenic shock
• Systolic blood pressure above 90mmHg
• No 2nd or 3rd degree heart block
• Heart rate over 60bpm
• Absence of end-organ failure


What is inhibition of Neprilysin doing?

* function/action of newer beta-blockers
• Working in two pathways: Natriuretic peptide system and Renin-angiotensin system
○ Blocks angiotensin II binding AT1 receptor
○ Blocks:
§ Vasoconstriction, increased blood pressure, sympathetic tone, fibrosis/hypertrophy
• Natriuretic peptide system
• Blocks the conversion of BNP to inactive fragments
○ Outcome means vasodilation, decreased blood pressure, decreased sympathetic tone, decreased fibrosis
○ Natriuresis diuresis


What drugs are neprilysin inhibitors?

• Sacubitril is a prodrug metabolized to LBQ657, which inhibits neprilysin, thereby increasing levels of peptides (such as natriuretic peptides). Valsartan is an angiotensin II receptor blocker that selectively blocks the angiotensin II type 1 receptor and inhibits angiotensin II dependent aldosterone release. 
* these are a combination therapy that synergistically tackle the RAAS activation problems


What are the indications of sacubitirl/valsartan use?

• Reducing CV deatha dn HF hospitilization in Chronic HFrEF pts
• Use with HF therapies, but it replaces ACE inhibitor or ARB


What should NOT happen with sacubitril/valsartan use?

• Concomitant ACE inhibitor use
○ Angioedema risk
○ Washout period needed of 36 hours
• History of angioedema to prior ACEI or ARB use
• Concomitant aliskiren in pts with diabetes


What is ivabradine doing?

• Messing with the If or funny current so it purely messes with heart rate
• Reduces heart rate


What are you worried about in ivapradine use?

• It's a bad drug for pregnant women
• Monitor for atrial fibrillation
• Monitor for bradycardia
• Don't use in 2nd degree heart block patients


What are the drug interactions of ivapradine?

• Any CYP3A4 inhibitors or inducers will interact with this drug
• Moderate risk QTc-prolonging agents
○ Enhances QTc prolonging effect
• Any agents that enhance bradychardia


When should you NOT use Ivabradine?

• Acute decompensated HF
• Low BP, under 90/50
• Sick sinus syndrom
• SA block
• 3rd degree AV block
○ Unless pacemaker is present
• Resting heart rate less than 60bpm prior to treatment
• Severe liver disease (CYP cleared)
• Pacemaker dependence