Integrated Pharmacology - HTN Flashcards
Chronic changes in BP cause a change in the set-point so that the firing of baroreceptors now occur at higher pressures. Why is this problematic?
Their baroreceptors can no longer respond to try and lower their BP back down to a normal level. They will only try to respond by increasing or decreasing BP back to this new set point.
Thiazide diuretics are the first-line treatment for newly diagnosed HTN. With regards to these medications:
- Describe the general mechanism of action.
- What is one reason why diuretics may not work for everyone?
- What effect do they have on CO and TPR?
Where do thiazide diuretics act?
Early DCT
Describe on a more cellular level the mechanism of action of thiazide diuretics.
They compete with Cl- for the binding site on the Na+/Cl- symporter on the apical membrane of cells in the early DCT to block Na+ reabsorption.
No - they are not filtered really
If clearance is > GFR, they must be secreted elsewhere along the nephron. This is done through organic anion transporters.
Do thiazide diuretics act in the cortex or medulla?
Cortex
How do thiazide diuretics change the concentration of our urine?
Normally, urine reaching the DCT is hypoosmotic and then the DCT makes it even more so by removing more Na+. However, thiazides block this action so they interfere with the ability of the body to excrete a dilute urine. However, they do not affect the ability of the kidneys to concentrate urine because they don’t act in the medulla which contains segments that are responsible for both diluting and concentrating urine.
What class of drugs would inhibit a patients ability to concentrate urine?
Loop diuretics - act in loop of henle, block Na+/K+/2Cl- co-transporter
When a patient begins a diuretic, they are frequently thirsty. If this patient is on a thiazide diuretic, how would you counsel them regarding water consumption and why?
Diuretics decrease ECF volume. This is an isoosmotic volume contraction. The body can respond by initiating the RAAS system to restore volume (non-responders to diuretics) and if the volume loss is great enough, they can also stimulate ADH secretion. This will increase water reabsorption and can result in hypoosmotic ECF. Decreased volume and osmolality will also trigger thirst. If they act on this thirst with water, they can further dilute their ECF since they’re adding pure water. Because some of their Na+ reabsorption mechanisms are being blocked, they can develop diuretic induced hyponatremia because they can’t restore osmolality fast enough, which can be fatal.
Loop diuretics disrupt the reabsorption of Na+ in the loop of henle, which weakens the interstitial gradient leading to decreased water reabsorption in the loop of henle.
When a person starts a loop diuretic, they still get volume contraction and can respond with ADH and RAAS, but they are less able to reabsorb water in the kidney due to the above mechanisms so the risk of consuming more water is lower.
Why is a combined therapy of ACE inhibitor and thiazide diuretic an effective combined therapy?
Decrease TPR by vasodilating (inhibit degradation of bradykinin block production of antiogensin 2).
Wht is the most common adverse reaction of taking an ACE inhibitor?
What is a potentially more serious adverse reaction that is seen when taking an ACE inhibitor?
Why?
Lisinopril has 4 ionizable groups that span a wide range of pKas. Therefore, it always carries a charge and can’t cross biological membranes easily. It requires a transporter (see image).
If a patient taking an ACE inhibitor is suffering from any undesired or intolerable side effects, what is the next class of drug to recommend?
Angiotensin receptor inhibitors (AT1R) –> all drugs end in “artan”
What do AT1 receptors do to reduce BP?
Why is it important to consider race/ethnicity when treating HTN?
