28 - High Blood Pressure II Flashcards
What are calcium channel blockers?
medication that prevents calcium from entering certain cells, especially in the heart and blood vessels
they inhibit the movement of calcium by binding to L-type voltage-gated calcium channel receptors
What are the two classes of calcium channels?
1) Dihydropyridines: primary effect is vasodilation: amlodipine, clevidipine
2) Non-dihydropyridine: primary effect reduce cardiac contractility and heart rate: verapamil, diltiazem
What is the signal for smooth muscle contraction?
increased intracellular Ca2+. This can arise from plasma membrane Ca2+ channels, or activation of a Gq-coupled cascade.
Contraction can be diminished by blockers of voltage-gated Ca2+ channels
What are the two primary classes of drugs targeted by RAAS
angiotensin receptor blocker (ARBs) and angiotensin converting enzyme inhibitors (ACEis)
What happens when a stimulus such as low blood pressure or low serum sodium triggers the RAAS?
Renin: enzyme secreted by the kidney (juxtaglomerular apparatus) that processes angiotensinogen to ATI
ACE: angiotensin converting enzyme that processes ATI to ATII
ATII: powerful vasoactive peptide that causes vascular smooth muscle control, and aldosterone release
Aldosterone: steroid hormone that promotes reabsorption of Na+ and H2O in the kidney (preserves blood volume and increases blood pressure)
What is renin release also stimulated by? What will inhibit renin release?
B adrenergic receptors
inhibition of B1 adrenergic receptors by beta blockers will inhibit renin release
What does ACE do?
Angiotensin converting enzyme that processes ATI to ATII
Exists primarily as a membrane bound glycoprotein in the pulmonary capillary endothelium
What does ATII do? What is it mediated by?
powerful vasoactive peptide that causes vascular smooth muscle control, and aldosterone release
AGII effects primarily mediated by the ATII receptor (type 1): usually called the AT1 receptor
The AT1 receptor activates a classical Gq protein and phospholipase C pathway to produce second messengers, such as inositol trisphosphate (IP3) and diacylglycerol (DAG) which mobilizes the intracellular calcium stores and activates protein kinases C and different downstream signaling pathways. Ca2+ leads to the activation of CaMK with leads to (blank) and PKC and CaMK signals trigger synthesis/release of (blank)
smooth muscle contraction
aldosterone
What is aldosterone?
Steroid hormone that promotes reabsorption of Na+ and H2O in the kidney (preserves blood volume and increases blood pressure)
Lipid soluble, and because of this, is NOT kept in vesicles as NT
Targets of Aldosterone:
Nephron, including the distal convoluted tubule of the nephron
Na+/K+ ATPase pump (on the basolateral membrane): causes Na+ reabsorption (water follows osmotically)
Increased blood volume and blood pressure
How does angiotensin-converting enzyme inhibitors (ACEi) act on the RAAS? Also name 2 examples of drugs
enzyme inhibitor (prevents cleavage of angiotensin I into angiotensin II)
reduces generation of all downstream RAAS signals (ATII, aldosterone)
blocking ACE also reduces the breakdown of bradykinin, a potent vasodilator
Most common side effect is dry cough due to increased bradykinin levels-mediated bronchoconstriction
Common drugs: Captopril, Enalapril
How do ARBs act on the RAAS? Also name 2 examples of drugs
block AT1 receptors in vascular smooth muscle and adrenal cortex, causing vasodilation and decreasing aldosterone secretion.
Better tolerated than ACEi
No dry cough side effect as ACEi
Common drugs: Losartan, Valsartan
How do aldosterone antagonists act of the RAAS? Name 2 drugs:
competitive antagonist of the aldosterone receptor (mineralocorticoid receptor (MR))
diuretic has actions by inhibiting aldosterone effects
Common drugs: Spironolactone and eplerenone
