Cardiac/Renal Pharm 1

通報

問題一覧

Define Elevated Blood Pressure

Systolic pressure >130 and/or Diastolic pressure >80 on at least 2 occasions

Elevated Blood Pressure is caused as a result of?

From increased peripheral vascular resistance and reduced ability of the ions and electron potentials of the venous system—cause of the increased vascular tone

Essential (primary) hypertension

Occurs when you have abnormally high blood pressure that's not the result of a medical condition and the cause is usually unknown

Affects 30 percent of US adults—important risk factor in CKD and HF

Essential (primary) Hypertension

Define Normal BP

SBP <120 AND DBP <80

Define Elevated BP

SBP <120-129 OR DBP <80

Define Stage I HTN

SBP 130-139 OR DBP 80-89

Define Stage II HTN

SBP >/= 140 OR DBP >/= 90

What individuals are at greater risk for developing HTN?

Those with a family history, non-Hispanic African Americans, low education and income, DM, obese, disabled, high stress lifestyle, high Na+ intake, and smoking

Arterial BP is directly proportional to?

CO and PVR

CO and PVR are controlled by?

Baroreflexes and the renin-angiotensin-aldosterone system [RAAS]

Most pressors work by decreasing?

CO and/or PVR

Baroreflexes control?

Rapid moment-to-moment regulation of BP

Baroreceptors in the kidney

Decrease arterial pressure by releasing renin

How does Na+ control Renin?

Low Na+ intake and Na+ loss increase renin

Renin converts angiotensinogen to _______, which is then converted by angiotensin converting enzyme (ACE) to ______(potent vasoconstrictor)

angiotensin I; angiotensin II

Angiotensin II prefers to vasoconstrict the _______ of the kidney (increasing GFR)

Efferent arterioles

Angiotensin II stimulates ______release, causing the kidney to resorb ____ and thus increase the blood volume—which causes the BP to elevate

aldosterone; Na+

The effects of angiotensin II are mediated by stimulation of __________

angiotensin II type 1 (AT1) receptors

What BP needs two drugs to start from the get go?

>/= 160/90 (SBP >20 or DBP > 10 above goal)

Great options for the patient who also has CAD or HF and also used to prevent headaches

Beta Blockers

How do Beta Blockers lower BP?

Decrease CO and sympathetic output from CNS that decreases HR and BP, and inhibit release of renin which decreases production of Angiotensin II and aldosterone secretion decreasing BP even more

Name the Beta Blocker drugs

Propranolol (prototype), Metoprolol, Atenolol, and Nebivolol

Acts on both B1 and B2 receptors

Propranolol. Sotalol, Nadolol, and Timolol

Selective BBs—act on B1 receptors

Metoprolol, Atenolol, and Nebivolol

Only Selective BB that increases Nitric Oxide—which causes vasodilation

Nebivolol

These drugs are CI with asthma

Non-selective BB

They are DOC in those with HTN and heart disease—previous MI, supraventricular tachyarrythmias, stable ischemic heart disease, chronic HF

Beta Blockers

Are never DOC to treat BP [assuming no heart disease], in those with asthma, 2nd degree heart block, 3rd degree heart block, diabetes or severe peripheral arterial occlusive disease

Beta Blockers

Beta Blockers available in IV form

Esmolol, Metoprolol, and Propranolol

The oral route of these drugs takes several weeks to develop full effects

Beta Blockers

Will decrease HDL and increase triglycerides

Non-cardioselective BB

ADEs of Beta Blockers

Lower BP and bradycardia; Lipid Altercations (non-selective BB); fatigue, insomnia and sexual dysfunction (non-selective BB)

Can cause withdrawl symptoms (HTN, angina, acute MI, and sudden death-ischemic heart disease), so must be tapered for several weeks

Beta Blockers

DOC for high BP in those with DM, CKD, MI, HF, high risk of CAD and those with proteinuria

ACE Inhibitors

MOA ACE Inhibitors

Reduce PVR and Afterload without increasing CO, HR or contractibility; ACEI block ACE—which converts angiotensin I to angiotensin II

Prevents the breakdown of bradykinin, which increases NO and prostacyclin from the vessels

ACEI

Are potent vasodilators of the arterioles and veins

NO and prostacyclin

By reducing levels of ________, aldosterone levels are decreased, as is Na+ and water retention

angiotensin II

ACEI reduce cardiac _________—important reason we use these drugs in folks with CAD

preload and afterload

Slow the progression of diabetic nephropathy and albuminuria—they have a compelling indication for those with diabetic nephropathy—they decrease intraglomerular pressures

Indications for ACE Inhibitors

ACE Inhibitors decrease intraglomerular pressures by dilating _______ arterioles

efferent

Standard of care in those who have had a MI, and 1st line in those with systolic dysfunction, HF, high BP, CKD and those at risk for CAD

ACE Inhibitors

Chronic use of _____ keep BP low, cause LVH to regress and prevent ventricular remodeling in those who have had and MI or those with HF

ACEIs

Pharmacokinetics of ACEIs

-Oral bioavailable as drug or prodrug -All but Captopril and Lisinopril undergo hepatic conversion to active metabolites—so these 2 are preferred in those with live compromise -Fisinopril is only ACEI not renally eliminated—so no dose adjustments with this drug in those with CKD -Enalapril is available IV

ADEs of ACEIs

-Cough (more frequent in women, seen in 10%, thought to be from increased bradykinin and substance P) -Elevation of serum creatinine up 30% from baseline [this is acceptable] -Low BP -Altered taste

Serious ADEs of ACEIs

-Skin rash -Angioedema—elevated bradykinin levels -Retain K+ -Fetal malformations—CI in pregnant woman

Prototype drug for ARBs

Losartan

-These drugs block the AT1 receptor, decreasing activation of AT1 receptors by angiotensin II -Do not increase bradykinin levels

ARBs

-ADEs are similar to ACEIs (except the cough and angioedema), but cannot be combined with ACEIs -CI in pregnant women

ARBs

1st line agents for DM, HF, CKD

ARBs

Prototype drug is Aliskeren—Tekturna

Renin Inhibitors

-This drug inhibits renin and acts earlier in the RAAS system than ACEIs or ARBs -Cannot be given with an ACEI or an ARB

Renin Inhibitors

-Metabolized by CYP34A—many drug-drug interactions -Can cause diarrhea in high doses—can cause cough and angioedema, but less often than ACEIs -CI in pregnancy

Renin Inhibitors

-1st line for BP in Aortic Aneurysms -Can also be useful in treating BP in those who have DM, stable ischemic heart disease

Calcium Channel Blockers

Avoid high doses of short-acting _____ because of increased risk of MI from excess dilatation and reflex tachycardia

Calcium Channel Blockers

Three Chemical Classes of Calcium Channel Blockers

Diphenylalkylamines, Benzothiazepines, and Dihydropyridines

-Works on cardiac & vascular smooth muscle -Can be used to treat angina and SVT and to prevent migraine and cluster HA

Non-dihydropyridines—Verapamil is the prototype

Affects cardiac & vascular smooth muscle, and more effective vasodilator than Verapamil but a better anti-hypertensive

Non-dihydropyridines—Diltiazem is the prototype

-All of these agents have a great affinity for vascular CCs in the heart; don’t interact with other cardiac agents -Useful in treating HTN—very potent pressors

Dihydropyridines—Nifedipine and Amlodipine (prototypes) along with Felodipine and Nicardipine

-Block the inward movement of Ca++ by binding to L-type Ca++ channels in the heart and smooth muscle in the coronary and peripheral arteriolar vasculature -They cause smooth muscle relaxation, and dilation of the arterioles -Used to treat HTN, often as add on therapy -Useful in those who cannot take BBs—asthmatics, diabetics, those with peripheral arterial occlusive disease -All of them can be used to treat angina [after BBs, ACEIs/ARBs]

Calcium Channel Blockers

Calcium Channel Blockers often used to rate control A-Fib

Diltiazem and Verapamil

Pharmacokinetics of Calcium Channel Blockers

-Short 1⁄2 lives—3 to 8 hours -Amlodipine has a very long 1⁄2 life and does not require a sustained release preparation

Common ACEs of Calcium Channel Blockers

-Lower BP, constipation, peripheral edema [dose related; treated by lowering dose OR adding an ACEI -Flushing, dizziness, headache

Serious ADEs of Calcium Channel Blockers

-1st degree AV block—avoid Verapamil and Diltiazem in those with HF or AV block from their negative inotropic and dromotropic [rate of conduction] effects -Gingival hyperplasia

Prototype drug is Prazosin, and also include Doxazosin and Terazosin (treat BPH)

Alpha Blockers

-These agents competitively block alpha-1 adrenoceptors -They decrease PVR and lower BP by causing relaxation of arterial and venous smooth muscle -These agents only minimally change CO, renal blood flow and GFR -No long-term tachycardia occurs, but salt and water retention does

Alpha Blockers

-Reflex tachycardia and postural hypotension occurs when drugs are started and when doses are increased—requiring slow titration -These SE have removed these agents as 1st line drugs to treat BP—can be used as add-ons for refractory HTN

Alpha Blockers

These alpha blockers and other A1 selective alpha blockers are used in the treatment of BPH

Alpha Blockers

Labetalol is the prototype drug, and also includes Carvedilol

3rd Gen Beta Blockers

MOA is block A1, B1 and B2 receptors

Alpha/Beta Blockers

used for HF and HTN—it reduces morbidity and mortality from HF

Carvedilol

Used in gestational HTN and HTN emergencies

Labetalol

Central Acting Pressors

Clonidine and Methyldopa

-Acts centrally as A2 agonist to inhibit sympathetic vasomotor centers, and decrease sympathetic outflow to the periphery—which decreases total peripheral resistance and lower BP -Used in BP that has not adequately responded to two or more drugs -It does not decrease glomerular blood flow or GFR

Clonidine

-Well absorbed orally, and also comes in a patch—renally excreted -ADEs—sedation, dry mouth and constipation

Clonidine

Rebound HTN occurs if this drug is abruptly stopped and must be tapered off

Clonidine

-A2 agonist that is converted to methylnorepinephrine centrally to decrease adrenergic outflow from the CNS -Limited in use because it is sedating—and it requires multiple daily doses

Methyldopa

Used in gestational HTN

Methyldopa

-Act by relaxation of vascular smooth muscle in arteries and arterioles—this causes decreased peripheral resistance and lowers BP -Cause reflex stimulation of the heart—which can prompt angina, MI and/or HF in predisposed individuals [if given alone] -These agents also increase plasma renin—which causes Na+ and water retention—thus are often given with a diuretic and a BB—the combination will decrease CO, plasma volume and PVR

Vasodilators

Direct acting vasodilators used as add-ons for HTN

Hydralazine and Minoxidil

ADEs for Vasodilators (Hydralazine and Minoxidil)

-HA, tachycardia, nausea, sweating, arrhythmia -A lupus like syndrome with high dosages—but reversible

Hypertensive Emergencies

-Severe elevated BP—SBP >180 or DBP >120 with evidence of impending or progressive target organ damage -OR a severe elevated BP without target organ damage

CCBs for Hypertensive Emergencies

Nicardipine or Clevidipine

NO vasodilators for Hypertensive Emergencies

Nitroprusside and Nitroglycerin

Adrenergic receptor blockers for Hypertensive Emergencies

Phentolamine, Esmolol and Labetalol

Vasodilators for Hypertensive Emergencies

Hydralazine

Dopamine agonists for Hypertensive Emergencies

Fenoldopam

BP that remains above goal despite 3 drugs [one of which is a diuretic]

Resistant Hypertension

Common Causes of Resistant Hypertension

-Poor compliance -Pressors not dosed high enough -Excess ETOH -DM -Obesity -OSA -Hyperaldosteronism -Excess salt intake -Metabolic syndrome -Medications—sympathomimetics, NSAIDs, corticosteroids

Positive inotropes increase?

Cardiac contractility and CO

↑ cytoplasmic Ca++ concentration that ↑ the contractibility of the cardiac muscle

Inotropic effect

ALL + inotropes in HFrEF that ↑ intracellular Ca++ have been associated with ______ survival

Reduced

Prototype drug is Digoxin

Positive Inotropes

-It increases the contractility of the heart muscle and used in the treatment of HF -Has a low therapeutic index—only a small difference between the therapeutic dose and a toxic dose

Digoxin

Inhibiting the Na+/K+ ATPase enzyme, this drug decreases ability of the myocyte to actively pump Na+ from the cell—causing a small, but important increase in free Ca++-- leading to increased contractility

Regulation of Cytosolic Ca++ Concentration in Digoxin

-Increases force of cardiac contraction—CO more closely resembles the norm -Vagal tone is also improved—so both HR and myocardial O2 demand decrease -Slows conduction via the AV node—useful in AF

Increased Contractility of the Cardiac Muscle in Digoxin

Low dose digoxin inhibits sympathetic activation with minimum effects on contractility—this effect is why low serum drug levels are targeted in HFrEF

Neurohormonal Inhibition by Digoxin

-HFrEF patients who are still symptomatic on optimal HF therapy -Goal is a drug level of .5 - .8 ng/mL

Uses for Digoxin

100

How would an NP offset hypokalemia in a patient caused by thiazide diuretics?

Order a low sodium diet

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