Circulatory
For pharmacology: what is the mot important determinant of resistance in the circulatory system?
Vessel diameter
if constricted = greater resistance
if dilated = lesser resistance
What 2 enzymes cause formation of angiotensin II?
1. renin (an enzyme produced by the kidneys that helps regulate blood pressure)
2. angiotensin-converting enzyme (kinase II also referred to as ACE) (converts angiotensin I [inactive] to angiotensin II [highly active]
What are the 3 actions of angiotensin II?
1. vasoconstriction (increases BP)
2. release of aldosterone (increases BP)
3. alteration of cardiac and vascular structure (hypertrophy and remodeling)
What system helps to regulate BP in the presence of hemorrhage, dehydration, or sodium depletion?
Renin-angiotensin-aldosterone system (RAAS)
*it constricts renal blood vessels (minutes to hours)
*acts on the kidney to promote retention of sodium and water and excretes potassium (days, weeks, months)
*factors that decrease BP turn ON RAAS
*factors that increase BP turn OFF RAAS
What is Sterling's Law of the heart?
The heart's ability to contract increases as the volume of blood in the heart increases, before it contracts
Cardiac output is determined by what two factors? What is the equation?
Heart rate (controlled by ANS) and Stroke Volume
CO = HR x SV
What suffix do medications in this class have and give an example?
"pril"
lisinopril
What suffix are drugs in this class? Give an example
"sartan"
losartan, valsartan
What are the two therapeutic actions?
treat high blood pressure and heart failure
What is the most important factor in pharmacology (affected by drugs) that determines venous return?
systemic filling pressure (force that returns blood to the heart) (can be lowered by venodilation or decreased blood volume)
Stoke volume is determined by what 3 factors?
1. myocardial contractility (force ventricles contract)
2. cardiac afterload (load against which a muscle exerts its force; AP that the left ventricle must overcome to eject blood) *if AP is increased = SV will decrease = due to more resistance; if AP is decreased = SV will increase = due to less resistance
3. cardiac preload (amt. of tension [stretch] applied to the muscle before contraction; end diastolic volume
What are the 2 MOA?
1. reduce levels of angiotensin II (dilates blood vessels [decreases blood volume and cardiac/vascular remodeling]; retains potassium
2. increase levels of bradykinin (peptide that dilates blood vessels and can cause angioedema when not able to be broken down [lead to fluid extravasation into deep tissues and swelling])
Give 3 therapeutic uses
HTN, HF, myocardial infarction
Diabetic nephropathy
Pts unable to tolerate ACE inhibitors
What is the MOA of spironolactone?
Blocks aldosterone receptors (nonselective)
Binds with receptors for other steroid hormones
What is a rapid negative feedback loop that helps the body maintain a normal blood pressure by maintaining AP (arterial pressure) at a predetermined level?
Baroreceptor reflex (pressure sensors)
*can be reset in 1-2 days to a new level because it has a rapid action not a sustained reaction.
*drugs the decrease AP will trigger baroreceptor reflex
How does the steady state control by the ANS (autonomic nervous system) regulate AP (arterial pressure)? What is the equation?
It adjusts to the CO (cardiac output) and PR (peripheral resistance)
AP = PR x CO
so if there is increase in PR or CO = an increase in AP
Give two therapeutic uses and 3 side effects of ACE inhibitors.
1. HTN, HF, MI, diabetic and nondiabetic neuropathy, prevention of MI, stroke, and death in pts at high CV risk.
2. dizziness, orthostatic hypotension, HA, GI distress, cough (due to increase of bradykinin), first dose hypotension (due to decrease in angiotensin II), fetal injury, angioedema (increase of bradykinin), hyperkalemia (decrease in angiotensin II); renal failure, neutropenia (rare)
Why would a patient be prescribed an ARB over an ACE inhibitor?
ARB is used in patients who could not tolerate an ACE inhibitor d/t cough as ARBs do not tend to cause this SE. (ARBs do not promote accumulation of bradykinin in the lung)
What adverse effect is capable with both Eplerenone and Spironolactone?
hyperkalemia
What 2 things does the RAAS system cause?
1. constriction of arterioles and veins (angiotensin II hormone) (hours response)
2. Retention of water by the kidney (aldosterone release) through the retention of sodium (days response)
Arterial pressure is regulated by what 3 things and how quickly does each respond?
1. Autonomic nervous system (ANS): responds to BP changes; responds in seconds to minutes
2. Renin-angiotensin-aldosterone system (RAAS): responds slowly (hours to days)
3. Kidneys: responsible for long term control; days to weeks
1. Give two drug interactions
2. What is the pharmacokinetics?
1. diuretics (intensify first dose hypotension), antihypertensive agents (increase hypotensive effects), drugs that raise potassium levels (increase K+ serum levels), lithium (increase levels of lithium), NSAIDS (inhibit ACE inhibitors)
2. Administered orally; administer all with food (except captopril and moexipril); given 1-2 x/d; all are prodrug (converted to active in liver or sm. intestine; except lisinopril); all excreted by kidneys so caution to pts with kidney disease
What two labs should patients monitor?
serum potassium and creatinine levels (can cause adverse effects like hyperkalemia and kidney injury)
What foods/drugs should be avoided in patients taking these medications?
foods high in potassium and salt (increased amt of water make it harder for medication to work)
do not take with ACE inhibitors or ARBS (raise K+ levels), NSAIDS (reduce spironolactone effects), digoxin (increased dig levels), lithium (increase lithium toxicity)
alcohol
*You may take this medicine with or without food, but it should be taken the same way (with or without food) each day
Preload is increased in what 3 situations?
Afterload is increased in what 2 situations?
preload:
1. hypervolemia
2. regurgitation of cardiac valves
3. heart failure
afterload: (increased afterload = increased cardiac workload)
1. HTN
2. vasoconstriction