Module 13 - Part 2 Flashcards
______ are the mainstay of therapy for HTN.
diuretics
What are the three main classes of diuretics?
Loop diuretics
Thiazide diuretics
potassium sparing diuretics/aldosterone antagonists
Diuretics work by blocking ______ and ________ ion reabsorption from the nephron of the kidney.
sodium
chloride
By preventing the reabsorption of Na+ and Cl-, diuretics make an osmotic pressure within the tubule that prevents the _____ of _______.
reabsorption of water
Diuretics produce more _______ decreases in BP at sites of ____ sodium reabsorption.
effective
high
______ diuretics produce the largest decrease in BP since 20% of sodium is reabsorbed at its site of action.
Loop diuretics (the most effective diuretics available
Mechanism of action of loop diuretics?
They act by blocking sodium and chloride ion reabsorption in the thick ascending limb of the LoH
Loop diuretics are usually reserved for situations that required rapid loss of fluid such as? (3)
Edema
Severe HTN that does not respond to milder diuretics
Severe renal failure
What are the adverse effects of Loop diuretics?
Hypokalemia
Hyponatremia
Dehydration
Hypotension
Low potassium levels in the blood, may also cause fatal ______ ________.
Hypokalemia
may cause fatal cardiac dysrhythmias
Why does hypokalemia occur as an adverse effect when taking loop diuretics if they decrease sodium reabsorption?
The transporter responsible for reabsorbing Na+ and Cl- also transports K+ into the blood, which is why hypokalemia occurs
Most commonly used class of drugs to treat HTN
Thiazide diuretics
Thiazide diuretics act by two main mechanisms, what are these?
Blocking sodium chloride ion reabsoprtion in the distal tubule
Decreasing vascular resistance (unknown mechanism)
For many hypertensive patients, thiazide diuretics alone _____ enough to control BP.
are
Adverse effects of thiazide diuretics?
Hypokalemia - may cause fatal cardiac dysrhythmias
Dehydration
Hyponatremia
Potassium sparring diuretics are also called this.
Aldosterone antagonists
Aldosterone Antagonists/Potassium sparing diuretics mechanism of action?
Act by inhibiting aldosterone receptors in the collecting duct
Blocking these receptors causes increased sodium excretion and potassium retention
What is the main use of potassium sparing diuretics?
Main use is in combination with thiazide and loop diuretics to counteract hypokalemia side effect
Potassium sparring diuretics should not be used with these.
Ace inhibitors or renin in inhibitors
What is the primary side effect of potassium sparring diuretics?
Hyperkalemia - may result in fatal dysrhythmias
Beta blockers are effective at treating HTN and they do this through two distinct mechanisms, what are these?
Blocking cardiac beta 1 receptors
Blocking beta 1 receptors on juxtaglomerular cells
What does blocking beta 1 receptors do?
Blocks catecholamine (e.g. epinephrine) binding to beta 1 receptors, decreasing CO and thus BP
What does blocking beta 1 receptors on juxtaglomerular cells do?
Beta blockers decrease renin release and therefore decrease RAAS mediated vasoconstriction
Beta blockers all have this suffix.
“olol”
What are the beta blocker classes?
1st generation (non-selective) and 2nd generation beta blockers (selective)
Inhibit both beta 1 (heart and juxtaglomerular cells) and beta 2 (lung) receptors
1st generation beta blockers
1st generation beta blocker use can be problematic in what instances?
If patients have asthma or other lung disorders
Produce selective blockage of beta 1 receptors
2nd generation beta blockers
What are the adverse effects of 2nd generation beta blockers?
Bradycardia, decreased CO, heart failure rare, rebound hypertension/cardiac excitation is withdrawn abruptly
How can rebound hypertension/cardiac excitation be avoided?
By tapering the dose of beta blockers slowly over 10-14 days
What additional adverse effects do non-selective beta blockers have?
Bronchoconstriction
inhibition of hepatic and muscle glycogenolysis
The inhibition of hepatic and muscle glycogenolysis can be dangerous to which types of patients?
Patients with diabetes if they accidentally take too much insulin
How do ACE inhibitors decrease BP?
Decrease angiotensin II production
Inhibit the breakdown of bradykinin
Decreased angiotensin II causes what?
Decreased PVR and total blood volume, thus CO
Inhibiting the breakdown of bradykinin has what effect?
Elevated bradykinin leads to vasodilation
ACE inhibitors have this suffix.
“ipril”
What are the ACE inhibitor side effects related to decreased angiotensin II?
1st dose hypotension
Hyperkalemia
Due to 1st dose hypotension with ACEI’s, what is done?
first few doses should be low
Why is hyperkalemia a side effect of ACE inhibitor use?
Decreased angiotensin II means decreased aldosterone release, thus decreased sodium reabsorption and thus greater potassium reasborption – should avoid use with potassium sparing diuretics
What are the side effects related to increased bradykinin?
Persistent cough
Angioedema
Use of certain _______ may decrease the effects of ACE inhibitors.
NSAIDs
Similar action to ACE inhibitors, but the mechanism differs.
Angiotensin receptor blockers (ARBs)
Mechanism of action of ARBs.
Block the binding of angiotensin II to the AT1 receptor (do not block its synthesis), this causes vasodilation and decreased aldosterone release from the adrenal cortex
ARBs have this suffix.
“sartan”
What are the side effects of ARBs?
Although we would expect the sides to match up with ACE inhibitors, there is no hyperkalemia, or persistent cough, and the incidence of angioedema is much lower
What is the mechanism of action of direct renin inhibitors?
Bind to renin and block the conversion of angiotensinogen to angiotensin I
This is the rate limiting step of the RAAS pathway, and thus the entire pathway is affected.
What are the adverse effects associated with DRIs?
Hyperkalemia
Very low incidence of persistent cough and angioedema
Diarrhea
DRIs should never be used with these.
Potassium sparing diuretics
How do calcium channel blockers decrease BP?
Block the entry of calcium into the heart cells and smooth muscle cells, therefore decreasing contraction
What are the two categories of calcium channel blockers?
Dihydropyridine calcium channel blockers
Non-dihydropyridine calcium channel blockers
At therapdeutic doses, dihydropyridine calcium channel blockers do not affect this.
The heart - effect exclusive to smooth muscle around arteries
What is the suffix of dihydropyridine calcium channel blockers?
“dipine”
What are adverse effects of dihydropyridine calcium channel blockers?
flushing, dizziness, headache, peripheral edema, reflex tachycardia, rash
What is the difference between dihydropyridine calcium channel blockers and non-dihydropyridine calcium channel blockers?
The non-hydridopyrimidine counterparts also block calcium channels in the heart and thus also decrease CO.
What are the adverse effects of non-dihydropyridine calcium channel blockers?
constipation, dizziness, flushing, headache, edema, may compromise cardiac function and should be used with caution in patients with cardiac failure
What is the mechanism of action of centrally acting alpha 2 agonists?
bind to and activate alpha 2 receptors in the brainstem –> activation of these receptors decreases sympathetic outflow to the heart and blood vessels, thereby decreasing CO and peripheral resistance
What are adverse effects of centrally acting alpha 2 agonists?
drowsiness, dry mouth, rebound HTN if withdrawn abruptly
The target BP that most patients should achieve is less than this.
140/90 torr
Patients with diabetes or chronic kidney disease should achieve a blood pressure less than this.
130/80 torr
In patients with severe renal disease, ______ diuretics are ineffective so _____ diuretics should be used.
thiazide
loop
