Cardiovascular therapeutics Flashcards
What are the definitions for stage 1 2 and 3 HTN?
Stage 1- 140/90 or ABPM 135/85
Stage 2 160/100 or ABPM 150/95
Stage 3 180/110
What is the algorithm for determining hypertensive therapy?
If the patient is younger than 55 start on an ACEI, then add CCB then add a diuretic.
If the patient is over 55 or afrocaribbean then start on a CCB, then add and ACEI then add a diuretic
What is the most diuretic used in HTN?
Thiazide like diuretic
What is the mechanism of action of ACEIs?
Block conversion of angiotensin I to angiotensin II in the lungs
What is the mechanism of action of CCBs? What are the two main types and how do they differ?
Cause vasodilation by blocking entry of calcium ions through L-type calcium channels.
Dihydropyridines- act preferentially on vascular smooth muscle (amlodipine)
Non-dihydropyridine- Acts on heart and blood vessels (verapamil), can cause bradycardia.
What is the mechanism of action of thiazide diuretics? What are the side effects?
Blocks Na-Cl channels in the DCT. They require excretion into the renal tubule and so are less effective in impaired renal function. Gout and ED.
What is the mechanism of action of loop diuretics?
What are the side effects?
Block the sodium-potassium-chloride pump in the thick ascending limb of the loop of Henle.
Electrolyte dusturbance
What is the mechanism of action of amiloride diuretics?
What are the side effects?
Amiloride works by directly blocking the epithelial sodium channel (ENaC) with an IC50 around 0.1 μM, indicating potent blockade. Antagonism of ENaC thereby inhibits sodium reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the nephron. This promotes the loss of sodium and water from the body, and reduces potassium excretion. The drug is often used in conjunction with a thiazide diuretic to counteract the potassium-losing effect. Due to its potassium-sparing capacities, hyperkalemia (elevated potassium concentration in the blood) can occur. The risk of developing hyperkalemia is increased in patients who are also taking ACE inhibitors, angiotensin II receptor antagonists, other potassium-sparing diuretics, or any potassium-containing supplements.
Other than amiloride what is the other significant potassium sparing diuretic and how does it work?
Spironolactone.
Aldosterone antagonism.
What is the mechanism of action of alpha adrenoreceptor antagonist diuretics?
What is an example?
What are the side effects?
Vasodilation by blocking alpha mediated vasoconstriction Doxasozin
Can cause postural hypotension
What is the mechanism of action of b-blockers?
What are the two types?
What are the side effects?
Beta-blockers are drugs that bind to beta-adrenoceptors and thereby block the binding of norepinephrine and epinephrine to these receptors. This inhibits normal sympathetic effects that act through these receptors. Therefore, beta-blockers are sympatholytic drugs. Some beta-blockers, when they bind to the beta-adrenoceptor, partially activate the receptor while preventing norepinephrine from binding to the receptor. These partial agonists therefore provide some “background” of sympathetic activity while preventing normal and enhanced sympathetic activity. These particular beta-blockers (partial agonists) are said to possess intrinsic sympathomimetic activity (ISA). Some beta-blockers also possess what is referred to as membrane stabilizing activity (MSA). This effect is similar to the membrane stabilizing activity of sodium-channels blockers that represent Class I antiarrhythmics.
The first generation of beta-blockers were non-selective, meaning that they blocked both beta-1 (β1) and beta-1 (β2) adrenoceptors (propranolol). Second generation beta-blockers are more cardioselective in that they are relatively selective for β1 adrenoceptors (Bisoprolol). Note that this relative selectivity can be lost at higher drug doses. Finally, the third generation beta-blockers are drugs that also possess vasodilator actions through blockade of vascular alpha-adrenoceptors.
What are the 4 main medications given to patients with HF with reduced EF?
ACEI/ARB- reduce preload and afterload
B-blockers- Reduce sympathetic activity
Aldosterone antagonists
Digoxin
What is the mechanism of action of digoxin?
Digitalis compounds are potent inhibitors of cellular Na+/K+-ATPase. This ion transport system moves sodium ions out of the cell and brings potassium ions into the cell. This transport function is necessary for cell survival because sodium diffusion into the cell and potassium diffusion out of the cell down their concentration gradients would reduce their concentration differences (gradients) across the cell membrane over time. Loss of these ion gradients would lead to cellular depolarization and loss of the negative membrane potential that is required for normal cell function. The Na+/K+-ATPase also plays an active role in the membrane potential. this pump is electrogenic because it transports 3 sodium ions out of the cell for every 2 potassium ions that enter the cell. This can add several negative millivolts to the membrane potential depending on the activity of the pump.
By inhibiting the Na+/K+-ATPase, cardiac glycosides cause intracellular sodium concentration to increase. This then leads to an accumulation of intracellular calcium via the Na+-Ca++ exchange system. In the heart, increased intracellular calcium causes more calcium to be released by the sarcoplasmic reticulum, thereby making more calcium available to bind to troponin-C, which increases contractility (inotropy). Inhibition of the Na+/K+-ATPase in vascular smooth muscle causes depolarization, which causes smooth muscle contraction and vasoconstriction.
What is the Vaughan-Williams Classification?
Class 1- drugs that block sodium ion voltage gated channels. 1A (intermediate dissociation), 1B (fast dissociation), 1C (slow dissociation)
Class 2: B blockers (block sympathetic dependent AVN conduction)
Class 3: Drugs that substantially prolong the cardiac action potential (amiodarone)
Class 4: CCB
What is the mechanism of action of warfarin? What is the ideal INR in AF and metallic valve replacement?
Inhibits synthesis of clotting factors 2, 7, 9 and 10.
AF- 2-3
Metallic valve replacement- 3-4
