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22 Cards in this Set
- Front
- Back
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Where do K-sparing diuretics act?
Why are they K-sparing? |
Collecting Ducts
They do not promote the loss of potassium into the urine. |
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What are the 2 MOA's exhibited by K-sparing diuretics?
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1) Competitive inhibition of of epithelial Na channel (ENac)
2) Competitive inhibition of mineralocorticoid receptor (MR) This leads to decreased Na reabsorption but increased K reabsorption |
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What is an example of drugs for each mechanism?
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Amiloride
Spirinolactone |
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Explain why each of the 2 mechanisms is effective?
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The first mechanism blocks the ENac receptor, which Na passes through in passing through the apical membrane.
The second mechanism is effective because it blocks aldosterone from binding to the mineralocorticoid receptor. If aldosterone binds the MR receptor, it transverses the nuclear membrane and stimulates transcription of ENac. |
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Name the therapeutic uses of K-sparing diuretics.
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1) Hypokalemia (Increased K absorption)
2) Combination therapy with other diuretics (prevention of hypokalemia) 3) Hyperaldosteronism (Blocks elevated aldosterone effects in various disease states such as HF, adrenal adenoma) |
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What are the 2 side effects of K-sparing Diuretics?
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Hyperkalemia (decreased K secretion)
Male Impotence and gynecomastia (spirinolactone off target effect on androgen receptor |
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What endogenous compound increases Na and H20 excretion into the urine?
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Natriuretic Peptide
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What do the SNS, ADH, and RAAS all have in common?
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They all decrease the amount of Na and H20 excreted.
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How is low pressure sensed?
What is the mechanism in place to increase low pressure? |
Low pressure sensors exist in the large systemic veins and right atria.
They are involved in the regulation of blood pressure. Decreased volume is sensed in the atria, CNS to PNS and the result is increased sympathetic tone and ADH release. - Increased volume sensed in the atria leads to heart cell release of NP and increased Na excretion. |
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How is high pressure sensed?
What is the mechanism in place to lower pressure? |
High pressure sensors exist in the aortic arch, carotid sinus and juxtaglomerular apparatus. Low volume leads to ADH release, renin secretion and increased sympathetic tone. Increased volume leads to decreased ADH release, and decreased sympathetic tone.
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What is the effect of decreased blood volume in the renal arterioles?
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The SNS constricts the afferent more than the efferent and induces renin secretion from the JG cells.
The result is decreased GFR and decreased Na excretion. |
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Describe the path ADH.
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Water loss stimulates mechano/baroreceptors that increase ADH secretion, vasoconstriction and renin release. In addition, high osmotic pressure is sensed by the hypothalamus which signals the posterior pituitary to secret ADH. ADH then works on the kidney to retain water.
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What are ADH's two mechanisms of action?
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1) In the peripheral circulation, it causes vasoconstriction via V1 receptors (GPCR linked to Ca signaling)
2) Renal CD - H20 reabsorption via V2 receptors (GCPR linked to PKA signaling) Vasopression - AC - cAMP - PKA - aquaporin recruited to lumen of CD. |
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What are ADH antagonists referred do as?
What is their mechanism of action? |
Vaptans
They competitively inhibit the V2R receptor on the basolateral membrane therefore inhibiting the effect of vasopressin |
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What are 3 examples of these drugs and their selectivity's?
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Conivaptan - V1/V2
Tolvaptan, Lixivaptan - V2 |
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What are the therapeutic uses of Vaptan's?
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-Euvolemic hyponatremia (Water>>Na)
-SIADH (Syndromes of inappropriate AHD secretion) -Conditions associated with ADH-induced water retention (HF, cirrhotic ascites) |
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What are the side effects of Vaptan's?
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V1 receptor antagonist activity
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Natriuretic Peptides are secreted from the heart in response to increased blood volume. What are the two types of NP? Where are they released from in the heart? What type of receptor senses this change in volume?
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ANP - atria
BNP - ventricles Mechanoreceptors |
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What is the intracellular response to NP binding?
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NP receptors are guanlylyl cyclases Increased cGMP formation and natriuresis (Na excretion)
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What 3 main sites does NP effect?
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Periphery - vasodilation (cGMP induces VSMC relaxation and increases, increased EC permeability to reduce plasma volume)
Kidney - Increased GFR (more efferent constriction) and Natriuresis (cGMP dependent phosphorylation/inhibition of ENac in distal nephron) Brain - decreased thirst, decreased ADH, decreased SNS (decreased renin and aldosterone secretion) |
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What is the drug name for recombinant BNP?
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Nesiritide
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What is its benefit in comparison to other standard HF treatments?
What is the side effect of this drug? |
Lower incidence of arrhythmias
Hypotension due to vasorelaxation effects |
