Antihypertensive Part II Flashcards
Dr. Roane EXAM 2
Intracellular vs. extracellular Calcium concentration
much higher extracellular (10.000x) than intracellular
-> osmotic drive to get into the cells through channels
How are the Ca channels regulated?
-cell signaling
-membrane-voltage (voltage-dependent Ca channels VDCC: L, N, T, R)
-f.e. (T) transient Ca channels, (L) long-lasting Ca channels
Which Ca2+ channels are targeted by Calcium channel blockers?
mostly the L channels
How are smooth muscles unique in terms of contraction?
They can contract and stay contracted
-pyloric sphincter, bladder, or anal sphincter -> stay contracted and prevent leakage involuntarily
MLCK phosphorylates the myosin light chain -> CONTRACTION
can stay contracted until dephosphorylation by the MLCP (phosphatase)
Where does the cell get Ca2+ from?
-Extracellular (through Ca2+ channels)
-Sarcoplasmic reticulum
Which molecules cause VASODILATION?
-ß2-agonists (Albuterol)
-ANP
-Nitric oxide
-> activation MCLP - removes phosphorylation from myosin light chain -> RELAXATION
-> Inhibition of MCLK
How is contractility and HR in the heart regulated?
-Contractility: amount of Ca2+ -> the more the harder the contraction
-heart rate: Na permeability into the SA node
How do Calcium channel blockers reduce BP?
lowering Ca2+ input reduces vascular smooth muscular contraction -> lowering CO
What are the types of CC-blocker?
-Dihydropyridines:
Amlodipine, Nifedipine, Felodipine
-Non-dihydropyridines (more for cardiac diseases):
Verapamil (Calan)
Diltiazem (Cardizem)
Different effects of Dihydropyridines vs. Non-dihydropyridines
Dihydropyridines: greater vascular effect (Vasodilation -> BP)
Non-dihydropyridines: mostly cardiac also vascular -> Arrhythmias
ionotropy (how strong does the heart beat)
chronotropic (how fast does the heart beat, HR)
dromotropy (how fast the AP move from the SA node to the Purkinje fibers)
Which patient population benefits from chronotropic drugs?
patients with arrhythmia -> the heart is too excitable
-Non-dihydropyridine CC-blockers
Why might Amlodipine be the best CC-blocker?
bc its pharmacokinetic profile
-long half-life -> less fluctuations -> less frequently dosed
All CC-blockers are subject to first-pass effect due to CYP 3A4
T or F
True
interaction with CYP3A4 inducer and CYP3A4 substrates
Side effects of CC blocker
Non-dihydropyridines: constipation, worsening cardiac output, and bradycardia
Dihydropyridines: light-headedness, flushing, headaches, peripheral edema
Effects of lowering body fluid volume through diuretics
-lower blood volume
-lowers venous return
-reduces cardiac output
-lowers blood pressure and heart work
MOA for diuretics
Thiazides: Inhibit Na/Cl symporter in the distal convoluted tube
Loops: inhibit Na/K/2Cl symporter in the ascending loop of Henle
K-sparing diuretics (Mineral corticoid receptor antagonists (MRAs): block aldosterone from binding to its receptor in the collecting ducts
-> reduce in Na reabsorption -> more water excretion
MOA of Carbon anhydrase inhibitor
-blockage of the CA transporter, preventing H2CO3 reabsorption
-not so often used as a diuretic
-Off-label: glaucoma
MOA of K-sparing diuretics
-blocking aldosterone receptor
-blocking gene transcription responsible for upregulating Na-channels on the lumen side and Na-K-ATPase pump on the blood side
MOA of thiazides
Inhibiting the Na-Cl Symporter in the distal convoluted tube
K-sparing diuretics
Mineral corticoid receptor antagonists (MRAs):
-Spironolactone
-Eplerenone
Na-channel inhibitor:
-Triamterene
-Amiloride
Which OTC drug might be prescribed with Loop diuretics?
Potassium supplements due to loss of K+
Thiazide diuretics
-Chlorthalidone
-Hydrochlorothiazide (HCTZ)
-Indapamide
-Metolazone
Loop diuretics
-Furosemide (Lasix)
-Torsemide (Demadex)
What stimulates Aldosterone?
-Angiotensin II
-high K+ -> more Angiotensin II -> Aldesterone -> Na+ -> K+ exchange in the collecting duct -> K+ rxcretion
How do alpha-2-agonists reduce BP?
-predominantly in the CNS
-> reduce sympathetic tone -> decrease Vasoconstriction -> decrease CO -> lower BP
-also have peripheral actions -
alpha-2 agonist binds to receptors on presynaptic nerve cells, when blocked there is no NE release
Alpha-2-agonists
-Clonidine (prototype): sedation, withdrawal addictive substances, migraine, PTSD, RSD
-Guanfacine: more alpha-2-selective, ADHD
-Methyldopa: alpha-methyldopa -> alpha-dopamine -> alpha-NE
-not a first-line drug for BP anymore
Direct acting Vasodilators
Hydralazine (oldest oral antihypertensive)
-vasodilates arterioles, not veins
-causes strong reflex tachycardia
Minoxidil
-restore hair loss
-opens ATP-sensitive K+ channel
-in arterioles the hyperpolarization of SM cells -> Vasodilation
