chapter 20- pharm of volume regulation Flashcards
where are low pressure volume sensors located
atria and pulmonary vasculature
where are high pressure volume sensors located
specialized baroreceptors in the aortic arch, carotid sinus, JG apparatus
what is the result of renin
vasoconstriction and sodium retention
what cells in the cortical thick ascending limb respond to increased luminal NaCl
macula densa cells
what is type A natriuretic peptides released by
atria
what is type B natriuretic peptides released by
ventricles
what is type C natriuretic peptides released by
vascular endothelial cells
what is uroguanylin released by
enterocytes
what is uroguanylin (UGN) released in response to
dietary ingestion of salt
what do ANP and BNP bind with high affinity to
NRP-A
what binds to NRP-B
CNP
what is the role of ADH
constricts the peripheral vasculature and promotes water reabsorption in the renal collecting duct
what do V1 ADH receptors do
stimulate vasoconstriction through Gq-mediated mechanism
where are V1 ADH receptors located
in vascular smooth muscle cells
where are V2 ADH receptors located
collecting duct principal cells
what do V2 ADH receptors do
stimulates water reabsorption by Gs-mediated mechanism
what is the first reabsorptive site in the nephron
proximal tubule
where does paracellular reabsorption of luminal Ca++ and Mg++ ions across cation-selective channels occur
thick ascending limb of loop of hence
what does right heart failure lead initially to
peripheral edema
what does left heart failure lea initially to
pulmonary edema
what is nephrotic syndrome characterized by
proteinuria, edema, hypoalbuminemia, and often hypercholesterolemia
what is the primary cause of nephrotic syndrome
glomerular dysfunction
what does the massive proteinuria in nephrotic syndrome lead to
decreased plasma oncotic pressure
what is the mechanism of action of aliskiren
inhibits renin, leading to decreased conversion of angiotensinogen 2 to angiotensin 1, thereby reducing the substrate for ACE and decreasing arteriolar vasoconstriction, aldosterone synthesis, renal proximal tubule NaCl reabsorption, and ADH release
what is the primary clinical application for aliskiren
hypertension (especially those with renal insufficiency)
what are the major adverse effects of aliskiren
hypotension, acute renal failure, angioedema, rash, diarrhea, cough
what are the contraindications for aliskiren
pregnancy, hyperkalemia, cyclosporine therapy
how can aliskiren effect protein aria in chronic kidney disease
may reduce it
what do the ACE inhibitors end with
-pril
what are the clinical applications of ACE inhibitors
HTN, heart failure, diabetic nephropathy, MI
what are the common adverse effects with ACE inhibitors
cough, edema, hypotension, rash, hyperkalemia, altered taste
what are the contraindications for ACE inhibitor use
bilateral renal artery stenosis, renal failure, pregnancy
what pattern of metabolism does captopril have
administered as active drug and processed as active metabolite
what pattern of metabolism does enalapril and ramipril have
ester prodrugs converted to active metabolites in plasma
what pattern of metabolism does lisinopril have
administered as active drug and excreted unchanged
what is the cough and angioedema side effects of ACE inhibitors caused by
bradykinin action
what can co-administration of ACE inhibitors and allopurinol may predispose for
hypersensitivity reactions including stevens-johnson syndrome and anaphylaxis
what do the angiotensin II receptor antagonists end in
-artan
why do angiotensin II receptor antagonists not cause dry cough, as the ACE inhibitors do
because they have no effect on bradykinin
what are the clinical applications of angiotensin II receptor antagonists
HTN, diabetic nephropathy, heart failure, MI, prevention of stroke
what are the common adverse effects of angiotensin II receptor antagonists
rhabdomyolysis, Hypotension, diarrhea, asthenia, dizziness
what are the contraindications for angiotensin II receptor antagonists
bilateral renal artery stenosis, pregnancy
what grade of contraindication are angiotensin II receptor antagonists
category C in first trimester; category D in 2nd and 3rd
what is the mechanism of action of B-type natriuretic peptide (BNP)
increase intracellular concentrations of cGMP by binding to the particulate guanylyl cyclase receptor NPR-A of vascular smooth muscle and endothelial cells, resulting in school muscle relaxation
what is the clinical application of BNPs
acutely decompensated heart failure
what is nesiritide no effect if given orally
because it is a peptide
what are the major adverse effects of BNPs
hypotension, headache, confusion, tremor, pruritis
what are the contraindications for BNPs
cariogenic shock, systolic pressure less than 90
how does nesiritide effect capillary wedge pressure
decreases it
what drug, administered in co-administration with nesiritide, cause increase risk of hypotension
ACE inhibitors
what hormones in the body does nesiritide lower the plasma levels of
aldosterone and endothelin-1
what are the vasopressin receptor 2 antagonists
conivaptan and tonivaptan
how is conivaptan administered
IV
how is tolvaptan administered
orally
what are the contraindications for V2 antagonists
concurrent use of potent CYP 3A4 inhibitors, hypovolemic hyponatremia
what are the clinical applications of conivaptan and tolvaptan
SIADH, euvolemia hyponatremia, heart failure, cirrhotic ascites, autosomal dominant polycystic kidney disease
what are common side effects of conivaptan and tolvaptan
atrial fibrillation, orthostatic hypotension, HTN, dyspepsia
what tetracycline analogue can treat SIADH
demeclocycline
what is the clinical application of acetazolamide
high altitude sickness, glaucoma, heart failure, epilepsy
what are common side effects of acetazolamide
metabolic acidosis, diarrhea, weight and appetite loss
what are the contraindications for acetazolamide
adrenal gland failure, cirrhosis, hyperchloremic acidosis, hyponatremia/hypokalemia
what volume regulating drug can be used for treatment of acute mountain sickness
acetazolamide
how does aspirin effect acetazolamide
increases its plasma concentration, potential leading to CNS toxicity
what is the mechanism of action of mannitol
acts as ormolu, filtered at the glomerulus but not subsequently reabsorbed in the nephron; exert an intraluminal osmotic force and limit reabsorption of water across water-permeable nephron segments
what are the clinical applications of mannitol
cerebral edema, increased intraocular pressure, prophylaxis of oliguria in acute renal failure
what are the contraindications of mannitol
anuria, severe dehydration, heart failure
why does mannitol require careful monitoring of volume status
because it promotes vigorous natriuresis
what co-transporter do loop diuretics inhibit
NKCC2
what are the loop diuretics
furosemide, bumetanide, torsemide, ethacrynic acid
what are the clinical applications for loop diuretics
hypercalcemia, hyperkalemia, HTN
what does coadministration of sulfonamides with loop diuretics increase
ototoxicity and nephrotoxicity
what loop diuretic can be given to individuals who are allergic to sulfonamides
ethacrynic acid
what loop diuretic is most ototoxic
ethacrynic acid
what part of the kidney do thiazide diuretics effect
distal convoluted tubule cells
what do thiazide diuretics promote the reabsorption of
transcellular calcium reabsorption
what are the contraindications for thiazide diuretic use
anuria, hypersensitivity to sulfonamides, co-adminsitration with agents that prolong QT interval
what volume regulating drug can be used to decrease urinary calcium wasting in osteoporosis
thiazide diuretics
what is hydrochlorothiazide’s effect on glucose
decreases glucose tolerance and amy unmask diabetes in patients at risk for impaired glucose metabolism
what effect can thiazide diuretics have on patients with nephrotic diabetes insipidus
paradoxically produces a modest decrease in urine flow
what is the mechanism of action of spironolactone and eplerenone
inhibit aldosterone action by binding to and prevent nuclear translocation of the mineralocorticoid receptor
what is the mechanism of action of amiloride and triamterene
competitive inhibitors of the principal cell apical membrane ENaC sodium channel
what are the clinical applications of spironolactone and eplerenone
HTN, CHF, hypokalemia, primary aldosteronism
what volume regulator can be used to treat acne vulgaris
spironolactone
what volume regulator can be used to treat female hirsutism
spironolactone
what are the common side effects of spironolactone and eplerenone
hyperkalemia metabolic acidosis, GI hemorrhage, breast cancer, gynecomastia, abnormal menstruation
what are the contraindications for spironolactone and eplerenone
anuria, hyperkalemia, acute renal insufficiency
what are the clinical applications for amiloride and tramterene
HTN, liddle’s syndrome
what are the side effects of amiloride and triamterene
diseases of hematopoietic stem, nephrotoxicity (tramterene), hyperkalemia metabolic acidosis
what is effected in liddle’s syndrome
ENaC sodium channel
