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Flashcards in Cardiovascular and Renal Deck (55)
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1
Q

Explain the MOA of digoxin.

A

It is a cardiac glycoside that binds to and inhibits the cardiac Na/K ATPase. This stops Na from exiting the cell and K from entering the cell. Na then exit the cell via Na/Ca ATPase, this increases Ca concentration inside the cardiac cells leading to an increase in inotropy.

2
Q

What is digoxin used for?

A

To treat chronic systolic heart failure, however it is important to know that it is for symptomatic treatment only, digoxin does not reduce mortality, so it often used after ACE inhibitors and diuretics have not worked.

3
Q

What are the effects of digoxin on the heart and how are these effects achieved?

A
  • Increase the inotropy

* Also used to treat certain arrythmias, more specifically atrial fibrillation via direct stimulation of vagas nerver.

4
Q

What are some of the ECG changes seen due to digoxin’s adverse effects?

A
  • Premature ventricular contractions are one of the most common rhythym distrubances although any arrythmia can arise.
  • T wave changes, QT shortening, ST depression - Indicate chronic use, does not indicate toxicity
  • Bradycardia due to parasympathetic activity at SA node
  • Heart block due to parasympathetic activity at AV node
  • Contraindicated in heart block patients , be careful when on beta blockers
5
Q

What are other AE of digoxin?How are these side effects treated?

A
  • GI symptoms: Nausea, vomiting, abdominal pain, this is due to digoxin toxicity
  • Neuro - confusion and weakness, disorientation Visual changes - color changes ** BUZZ - xanthopsia= looks yellow, this is the hallmark of digoxin poisoning Patients with increased susceptibility
  • Patients that have CHF are often on loop diuretics such as furesomide, one of the side effects of these ishypokalemia. If hypokalemia develops, digoxin binds more strongly to the Na/K ATPase, which exacerbates digoxin toxicity
  • Patients with renal insufficiency - increases serum half life of digoxin – look at BUN, creatnine and urine output Other drugs can inhibit renal clearance of digoxin, increasing susceptibility to toxicity by aberrantly increasing digoxin serum levels - antiarrhythmic meds
  • Treatment for toxicity: digoxin specific antibody fragments, digoxin-immune Fab
6
Q

Milrinone and Nesiritide.

A
  • Milrinone and Nesirtide can be used for acute HF management and for slowing down long term progression.
    Milrinone - PDE inhibitor (phosphodiesterase inhibitor), positive inotropic - inhibit degradation of cAMP – increase cAMP - arteriolar dilation and decreased afterload - watch out for hypotension

Nesiritide - synthetic BNP, increase cGMP in smooth muscle - leads to venous and arteriolar dilation, reducing afterload and preload - causes natiuresis

7
Q

What is the suffix of ACE inhibitors?What is their significance?

A

“-pril” -Captopril, Enamapril, Lisiniporil.They reduce mortality in patients with cardiovascular morbidities, they are the first line agents for treatment of hypertension and chronic heart failure.

8
Q

MOA of ACE inhibitors.

A
  • Renin is made, stored and released from JGA controlled by beta 1 receptors.
  • Angiotensinogen is converted to Angiotensin I, then ACE converts it to Angiotensin II
  • ACE is present in vascular endothelial cells, especially in the lungs.
  • ACE inhibitors inhibit this process.
9
Q

What are the effects of Angiotensin II?

A

Angiotensin II –>
* vasoconstriction/pressor effect, acts on vascular smooth muscles to cause constriction Increases GFR, one of its many functions is that during low volumes Ang II causes constriction of efferent arteriole to preserve GFR
Efferent arteriole constriction - increased pressure at glomerulus - increased filtration in glomerulus Proximal convoluted tubule - increase sodium reabsorption
Increases aldosterone - release from adrenal cortex –> increase sodium and fluid retention, at expense of K - increased potassium wasting, this happens at the distal tubules and collecting ducts.

10
Q

What are the effets of ACE inhibitors on the body?

A

Decrease GFR - increased creatinine within first few days of ACE inhib

  • Dilate the efferent arteriole
  • Decrease sodium reabsorption at the PCT
  • Decrease aldosterone release
  • Due to these effect they reduce preload and afterload so the heart doesn’t have to push around so much
  • ACE inhibitors reduce mortality since they inhibit chronic angiotensin II mediated left ventricular hypertrophy and remodeling
11
Q

What are the side effects of ACE inhibitors?

A

Side effects:
* Hypotension and syncope in patients with high renin levels (heart failure patients)
Hyperkalemia due to decrease aldosterone levels, since ACE inhibitors promote natriuresis
* Increase levels of angiotensin 1 and renin
Dry cough - important to know how this happens, there is an increased bradykinin causing lung irritation This is important in patients with hereditary angioedema, contraindicated in hereditary angioedema (C1 esterase deficiency)–> excessive vasodilation
Teratogenic , can causehypotention and kidney failure

Coadministration of ACE inhibitors with NSAIDs can precipitate acute kidney injury by decreasing GFR, NSAIDs normally inhibit the release of prostaglandins which are responsible for dilation of afferent arteriole to preserve GFR during low volumes. NSAIDS inhibit this. Contraindicated in bilateral renal artery stenosissince kidney function in these patients is solely maintained via Angiotensin mediated pathway

12
Q

Describe the association between ACE inhibitors and diabetes.

A

Patients with poorly controlled diabetes may exhibit proteinurea, which singifies glomerular sclerosis. ACE inhibitors can be used to treat HTN as well as slow down the progression of renal disease in diabetic patients.

13
Q

What drugs should be used to treat HTN and avoid cough caused by ACE inhibitors?Explain their MOA.What are their side effects?

A

ARBs, Angiotensin Receptor Blockers, competitively block AT1 receptors, these can be used to treat heart failure diabetic nephropathy and HTN in diabetic patients as well.ARBs have similar side effects as ACE inhibitors except for the cough.

14
Q

Aliskerin.

A

Direct renin inhibitor; prevents conversion of angiotensinogen to angiotensin I; similar side effects to ACE inhibitors.

15
Q

Explain the mechanism by which bicarb ions are absorbed in the proximal convoluted tubule.

A

There is a Na-H+ exchanger on the apical membrane and Na-K ATPase on the basal membrane. For every Na absorbed, a proton is secreted out into the lumen. This proton combines with bicarb to form H2CO3 catalyzed by lumnal carbonic anhydrase. H2CO3dissociates into H2O and CO2, CO2 diffuses into the cell. Intracellular carbonic anhydrase converts CO2 and H2Ois converted into H+ ions and bicarb.

  • Protons are then secreted out to the lumen again and this cycle continues.
  • Intracellular bicarb is absorbed via apical transported.
16
Q

Explain MOA of Acetazolamide.What are its uses.

A
  • It inhibits luminal carbonic anhydrase, leading to excretion of bicarb and Na, this leads to diuresis.
  • Causes alkylation of urine (urine pH increases). Used for: Decreased production of aqueous humor - useful for glaucoma
    Decreased prod of CSF - useful in management for idiopathic intracranial hypertension/pseudotumor cerebri

Mountain sickness (cerebral edema and hypoxia) happens above 3000m Increase pH of urine - prevent uric acid stone formation, and gout

17
Q

What are the side effects of Acetazolamide?

A

Type 2 renal tubular acidosis
Normal anion gap metabolic acidosis, it’s a hypochloremic anion metabolic acidosis
K+ wasting–> hypokalemia

Calcium phosphate stones (insoluble high pH), so it can enhance stone formation as well
Sulfa drugs! Hypersensitivity reaction - fever, rash, BM sup, interstitial nephritis, this is because acetazolamide is a sulfa drug

18
Q

What is the MOA, indications and side effects of Mannitol?

A

Mannitol - osmotic diuretic at the PCT and descending limb of the loop of Henle
Uses Reduces brain volume- draws free water out of CNS - used for treating elevated intracranial pressure
Decreases intraocular pressure
Causes: Mannitol induced expanded extracellular volume can cause pulmonary edema and hypernatremia (due to excessive water loss) - Can exacerbate heart failure

Dehydration - mannitol induced water depletion - need to be well hydratedwhen taking in this med!

19
Q

What is common between Mannitol and Acetazolamide?

A

Both act on PCR to induce diuresis.

20
Q

What are some examples of loop diuretics.

A

Furesomide and ethacrynic acid.Furesomide is a sulfa drug, ethacrynic acid is not a sulfa drug.

21
Q

Explain the MOA of loop diuretics.

A
  • Selectively blocks NKCC in the thick ascending limb of loop of Henle Reduce lumen positive potential, promoting excretion of Mg2+ and Ca2+
  • Induce expression of COX-2, synthesizing prostaglandins that enhance salt excretion and dilate the afferent arteriole –> increased afferent blood flow
22
Q

How does loop diuretics decrease positive lumen potential in the kidneys?

A

NKCC absorbs Na, K and Cl ions into the cell from the tubules, it allows the K ions to go back to the tubules via facilitated diffusion. This leads to a net positive potential in the lumen of the tubules that pushes Mg and Ca ions out. Due to loop diuretics, there is a reduction in this positive potential leading to excessiveexcretion of Mg and Ca ions as well.

23
Q

How does NSAIDs interfere with loop diuretics MOA.

A

NSIADs decrease prostaglandin production, do not allow dilation of afferent arteriole.

24
Q

Explain how pulmonary edema may develop in CHF patients?

A

In CHF patients, the heart is unable to pump enough blood around the body and into the kidneys this causes the kidneys to release renin which causes an increase in total ECF volume. This improves blood flow into the kidneys but the heart may further deteriorate and this increased volume may start leaking out in the alveoli causing pulmonary edema. Loop diuretics can be used to inhibit this.

25
Q

What are the uses of loop diuretics?

A

1st line for symptomatic treatment of acute decompensated heart failure with fluid overload
Treat symptoms of pulmonary edema in an acute heart failure exacerbation
* 62 yo orthopnea, SOB, history of risk HF (HTN and MI) - crackles on auscultation - need to give this guy loop duretics
Ascities in liver failure
HTN

26
Q

Side effects of loop diuretics.

A

Potassium wasting - hypokalemia

Ototoxic - dose dependent hearing loss.
SULFA drugs - skin rash, eosinophilia, etc Interstitial nephritis
Hyperuricemia—gout, uric acid reabsorption is enhanced during hypovolemia

Metabolic alkalosis -Na/H pump in the distal tubules. Causes severe dehydration

  • Chronic use - Hypomagnesmia and hypocalcemia (rare)
27
Q

How is Na, Ca and Cl absorbed in DCT?

A

At the apical membrane at DCT there is a NaCl cotransporter that actively absorbs and there is a Na-K ATPase at the basal membrane.Ca is actively absorbed via Ca transporter at the apical membrane which is regulated by PTH levels. At the basal membrane there is a Ca-Na antiporter that causes Ca to go into the blood stream.

28
Q

Explain MOA of thiazides.What are the 2 examples of thiazides.

A

Inhibit Na absorption by inhibiting NaCl cotransporter at the apical membrane at DCT.HydrochlorothiazideChlorothalidone

29
Q

How does thiazides enhance Ca absorption?

A

It is important to know how thiazides increase Ca absorption – thiazides work by inhibit NaCl absorption in the DCT by blocking NaCl cotransporter, water follows to the DCT leading to diuresis. Due to the presence of Na-Ca antiport at the basal membrane, Ca absorption is increased due to decreased Na in the cells lining the lumenDCT is impermeable to water and there is no net positive potential

30
Q

Indications for thiazides use.

A

First line for mild or moderate Primary hypertension

  • Can be useful in symptomatic heart failure BUT loop diuretics are first line, thiazide diuretics are used as adjuvant therapy Treating nephrogenic diabetes insipidus (not producing enough ADH, or just not responding to ADH) Idiopathic hypercalciuria - treat pts with risk of stones – there is an increased risk of kidney stones in hyperparathyroid, hyper-vitaminosis D, sarcoidosis

Osteoporosis - increases calcium reabsorption

31
Q

What are the side effects of thiazides.

A

Hypercalcemia
Hyperglycemia – for some reason there is impaired release of insulin from pancreas and impaired utilization, especially in diabetic and pre diabetic patients. Hyperlipidemia Hypokalemia Hyponatremia Hyperuricemia
increase lithium levels by decreasing lithium clearance in the kidneys (make sure you monitor levels in those taking this for bipolar disorder) - Ironically high lithium levels is a common cause of nephrogenic diabetes insipidus
SULFA drugs - thiazides
Contraction alkalosis via hypovolemia induced renin production at the kidneys! More renin –> more aldosterone –> more angiotensin II. Angiotensin II leads to increases bicarb reabsorption at the PCT

32
Q

Explain the mechanism of absorption of Na, K, H+ ions and water at the collecting duct.

A
  • Principal cell- major site of Na, K and water transport. It has ENaC receptor at the apical membrane ENaC reabsorbs Na across luminal membrane - creates a negative luminal potential that facilitates K+ excretion
  • K channels allow excretion of K across luminal membrane
  • Alpha intercalated cells of the collecting duct = major site of H+ secretion
    H+ ATPase on apical membrane of alpha intercalated pumps H+ ions into lumen
33
Q

How does aldosterone affect the cells at the collecting duct and what are its associated effects?

A

Aldosterone upregulates K channels on apical membrane, increasing K excretion Alsosterone upregulates ENaCs on apical membrane - increasing Na reabsorption Aldosterone upregulates Na/K+ ATPase on basolateral membrane Aldosterone upregulates H+ATPase on apical membrane that are present on the alpha intercalated cells, increasing H+ excretion

34
Q

What are the 2 classes of K+ sparing diuretics, what is their MOA and what are they used for?

A

Amiloride andTriamterene- inhibits Na reabsorption by inhibitingENaC, promotes natriuresis.
* Treats Lithium induces nephrogenic diabetes insipidus since it enhances the clearence of lithium
* Liddle syndrome (overactive ENaCs lead to HTN and hypokalemia), can be treated with these agents.
Eplerenone and Spiranolactone -K-diuretics - competitive aldosterone receptor antagonists:
* Treats primary and secondary hyperaldosteronism, vignette would involve patient with HTN with hypokalemia - think hyperaldosteronism. Prevents MC remodeling induced by high levels of aldosterone, decreased mortality in HF
* Can treat diseases with excess androgens such as PCOS etc.

35
Q

What are the side effects of K+ sparing diuretics?

A

Less selective for receptor, antiadrenergic side effects – it can block testerone synthesis for example Spironolactone inhibits 17-alpha hydroxylase - enzyme in the testosterone synthesis pathway
* Causes gynecomastia
* Impotence and decreased libido Causes hyperkalemia - increased risk in renal disease - decreased excretion of potassium or contaminant use of meds that inhibit angiotensin II and renin activity (such as ACE inhibitors and Beta blockers) - Need to balance with K wasting diuretic - give both K diuretic and K wasting diuretic such as thiazide - balance acid base balance K sparing - causes normal anion gap metabolic acidosis (by decreasing the function of the H+ ATPase
K sparing - inhibit the effects of aldosterone in the collecting duct causing a type 4 renal tubular acidosis (RTA)
* This is the only renal tubular acidosis which is associated with hyperkalemia

36
Q

What kind of Ca channels are found in the heart?

A

Voltage gated L type calcium channels

37
Q

What are the 2 types of Ca channel blockers?

A

Dihydropyridines block L type calcium channels in smooth muscleNon-dihydropyridines block L type calcium channels in cardiac muscles

38
Q

Name dihydropyridine Ca channel blockers

A

“-dipine” – nefidipine, amlodipine, nicardipine, felodipine

39
Q

What are the uses of Ca channel blockers?

A
  • Used in hypertension
  • IV dihydropyridines can be used in hypertensive emergencies
  • Angina - CCB if beta blockers or nitrates do not work or contraindicated, use dihydropyridine before other CCB
  • Stable angina
40
Q

State an additional use of nefidapine.

A

Nefedipine - used in hypertension in pregnancy, this is to signify Ca channel blockers are safe to use in pregnancy

41
Q

State the specific uses of dihydropyridine Ca channel blockers.

A
  • Dilate coronary arteies, so they are used for prinzmetal angina,CCB are the first line therapy for vasospastic angina.
  • CCBs can also be used to treat other vasospastic phenomena such as Raynauds phenomena
  • Dihydropyridines can also be used in the management of subarachnoid hemorrhage, some patients have berry aneursyms that are prone to rupture which can lead to subarachnoid hemorrhage
42
Q

State an additional use of nimodipine

A
  • Nimodipine prevents vasospasm after subarachnoid hemorrhage
  • Berry aneurysms (think polycistic kidney disease)
  • Subarachnoid hemorrage
  • On exam, if see blood in subarachnoid space (subarachnoid hemorrage), most common cause is the rupture of a intracranial aneurysm, might see polycistic kidney disease
43
Q

Name non dihydropyridine Ca channel blockers and state their respective efficacies.

A

Verapamil - strongest cardiac depression effects –decrease HR and cardiac outputDiltiazem - intermediate depression with some vasodilator activity

44
Q

What are the uses of Verapamil and Dilitazem?

A
  • Decrease angina symptoms, Verapamil decrease myocardiac oxygen demand by acting as a negative inotrope and chronotrope and by lowering the systemic resistance.
  • These have Antiarrhythymic properties!
  • Lead to a negative inotropy
45
Q

What are the side effects of CCB?

A
  • Headache
  • Flushing
  • Light headedness Peripheral edema
  • Hypotension leading to tachycardia
46
Q

What are the side effects of nefidipine?

A

Nefidipine has a shorter half life but it haslots of side effects, it can exacerbate MI due to reflex tachycardia, it is contraindiacated in post MI patients and those with unstable angina

47
Q

What are the side effects of verapamil?

A

Constipation and gingival hypertrophy

48
Q

What kind of patients cannot be given verapamil or dilitazem?

A

Both are contraindicated in patients with heart block

49
Q

What is the first line treatment for patients with HTN with comorbidities consisting ofHF, MI and/or diabetes?

A

ACE inhibitors

50
Q

What are the guidelines for treating primary HTN?

A

Primary hypertension - ACE inhibitors or ARBs, thiazide diuretics, calcium channel blockers are first line agents.Use 2 antihypertensives for BP >20/10 mmHg above goal

  • Calcium channel blockers dihydropyridines
  • Thiazide diuretics
  • ACE inhibitors or ARBs
  • Hydrochlorothiazide = first line agent for treating HTN
51
Q

What is the definition of a hypertensive emergency?

A

SBP > 180 or DBP > 120 + end organ damage (the question may state something about blurry vision, lung involvement etc)

52
Q

What is the protocol for treating HTN crisis and what drugs are used in such setting?

A

It is important to know that in hypertensive emergencies pressures should be reduced gradually in order to avoid ischemic injuries to parts of the body that have grown accustomed to the high blood pressure.In this kind of hypertensive emergency beta blockers are the first line treatment option – esmolol and metoprolol, these are given IV in acute setting, following agents can be used.

  • IV Labetalol (alpha and beta antagonist), so it also acts as a vasodilator
  • IV Nicardipine - cause arteriolar dilation, it’s a CCB dihydropyridine
  • IV clevidipine - cause arteriolar dilation, CCB dihydropyridine
53
Q

What drug can be used to HTN crisis in pregnancy and what are its side effect?

A

Hydralazine - direct arteriolar dilation, safe in pregnancy; However it can cause reflexive tachycardia and to avoid this it is given with a beta blocker to minimize reflexive sympathetic activationAE: Hydralazine may cause drug induced lupus

54
Q

What is hydralazine?

A

It is a direct acting smooth muscle relaxant, MOA is unknown

55
Q

Fenoldapam

A

Fenoldopam - dopamine 1 receptor agonists –> increased cAMP - dilated arteriolar beds - also causes coronary dilation; dilation of renal arteries - increased renal perfusion while lowering BP, causes natriuresisFenoldopam is the only agent that reduces blood pressure while increasing renal perfusion