Cardiovascular and Renal Flashcards
Explain the MOA of digoxin.
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.
What is digoxin used for?
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.
What are the effects of digoxin on the heart and how are these effects achieved?
- Increase the inotropy
* Also used to treat certain arrythmias, more specifically atrial fibrillation via direct stimulation of vagas nerver.
What are some of the ECG changes seen due to digoxin’s adverse effects?
- 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
What are other AE of digoxin?How are these side effects treated?
- 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
Milrinone and Nesiritide.
- 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
What is the suffix of ACE inhibitors?What is their significance?
“-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.
MOA of ACE inhibitors.
- 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.
What are the effects of Angiotensin II?
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.
What are the effets of ACE inhibitors on the body?
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
What are the side effects of ACE inhibitors?
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
Describe the association between ACE inhibitors and diabetes.
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.
What drugs should be used to treat HTN and avoid cough caused by ACE inhibitors?Explain their MOA.What are their side effects?
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.
Aliskerin.
Direct renin inhibitor; prevents conversion of angiotensinogen to angiotensin I; similar side effects to ACE inhibitors.
Explain the mechanism by which bicarb ions are absorbed in the proximal convoluted tubule.
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.
Explain MOA of Acetazolamide.What are its uses.
- 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
What are the side effects of Acetazolamide?
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
What is the MOA, indications and side effects of Mannitol?
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!
What is common between Mannitol and Acetazolamide?
Both act on PCR to induce diuresis.
What are some examples of loop diuretics.
Furesomide and ethacrynic acid.Furesomide is a sulfa drug, ethacrynic acid is not a sulfa drug.
Explain the MOA of loop diuretics.
- 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
How does loop diuretics decrease positive lumen potential in the kidneys?
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.
