pharm exam 4 (i think idek anymore)

what are the functions of the circulatory system

delivers oxygen, nutrients, etc

removes CO2

removes metabolic waste

what are the divisions of the circulatory system

pulmonary (to oxygenate blood)

systemic “tubes”

what area of the circulatory system has the most amount of blood

veins, venules, etc

• drug that targets this area will have an increased effect

• arteries, arterioles, etc are more selective (less blood)

what direction does the pressure gradient move in a vessel

high to low

• altered by resistance

what is included in the “resistance” that creates a pressure gradient inside a vessel

vessel diameter

vessel length

blood viscosity

what part of the resistance factor is easiest to manipulate and determines pressure the most

the vessel diameter

• determines how much of a drop there will be

explain the basic distribution of pressure through the systemic circulation

aorta (highest= 120)→ large arteries→ arterioles (get smaller, abt 30 here)→ capillaries → venules → muscular veins→ central veins→ right atrium (lowest, between 0 and -5 here)

what is the average cardiac output in an adult

5 L/min

what is the formula for cardiac output

heart rate (how many times) x stroke volume (how much)

what is heart rate controlled by

autonomic nervous system

what is starlings law and how does it relate to all of this

the more the heart muscle is stretched, the more it contracts (heart will pump what is returned to it)

• can overcomes large amounts

• relates to SV (amt of bood ejected) bc increased venous return, increased stretch= increased SV

when there is a systemic pulmonary imbalance, what happens

things start backing up because output of L and R ventricles is not identical

• pressure starts building up into lungs, systemic pressure decreases, cause death fairly quickly (abt 2 days)

k now we are going into drugs that act on the RAAS

yay

what is involved in the RAAS system and how does it work (sorry long)

renal perfusion is determined by the CO (low blood pressure, BV, etc- kidneys sense it and release renin)

renin converts angiotensinogen (from the liver) into angiotensin I

ACE (from pulmonary/renal endothelium) converts angiotensin I into angiotensin II

• raises BP by vasoconstriction, stimulates ADH, aldosterone, increases sympathetic activity, H2O and Na retention to raise blood volume

what are the actions of angiotensin II

vasoconstriction

release aldosterone

alter cardiac/vascular structure (is bad bc causes calcification, etc)

what are the actions of aldosterone

regulates BV and BP- pump more fluid to raise BP

can cause pathologic CV effects

what are the two ways the RAAS system works

constricts renal BVs

acts on kidney to promote sodium and water retention and potassium excretion

what is another way that the RAAS system can be stimulated

there is some tissue (local, non cardiac) angiotensin II production for some reason but idk what it does lol

what are the medications that we will talk about regarding the RAAS system

ACE inhibitors

angiotensin II receptor blockers

aldosterone antagonists

renin blocker (tekturna)

what is the ACE inhibitor we talk about

captopril (capoten)

what are the uses for captopril (capoten)

hypertension and heart failure

acute MI

LV dysfunction

diabetic/nondiabetic nephropathy

prevent MI, stroke, death in high risk pts

• this isn’t preferred bc its older and not as selective

what are the pathways that ACE inhibitors end up blocking

angiotensin II

bradykinin

what are the effects caused by ACE inhibitors blocking bradykinin pathway

cause vasodilation

cough (usually w infection, cough up fluid, etc, but in this case there is nothing to cough up when used (nonproductive)- which is annoying!

angioedema (swelling of throat- rare

what are the effects caused by ACE inhibitors blocking angiotensin II pathway

vasodilation

decrease BV, CV remodeling

potassium retention

fetal injury

what are the overall adverse effects for ACE inhibitors

first dose hypotension

cough

hyperkalemia

fetal injury

renal fail

angioedema (safety alert bc this can affect breathing)

what are the drug interaction for ACE inhibitor

diuretics

antihypertensive agents (more hypotension)

drugs that raise K levels

lithium

anti inflammatory (aspirin)

what is the mechanism of action for angiotensin II receptor blockers

block access of angiotensin II, cause vasodilation and prevent it from inducing pathologic changes in cardiac structure

reduce K excretion and release of aldosterone

increase excretion of sodium

• doesn’t inhibit kinase II→ doesn’t increase bradykinin levels unlike ACE inhibitors

what is the angiotensin II receptor blocker we talk about

losartan (cozaar)

what are the therapeutic uses for losartan

hypertension

heart failure

diabetic neuropathy

MI

stroke prevention

migraine

what are adverse effects for losartan

well tolerated bc more selective!!

angioedema

fetal harm

renal failure

what is the renin blocker we talk about

aliskiren (tekturna)

what is the MOA for tekturna

binds to renin, inhibits rate limiting 1st step

what are theraputic uses of tekturna

hypertension, only direct renin inhibitor

alone or combo with other antihpyertensives

what are adverse effects of tekturna

angioedema and cough, GI effects

hyperkalemia

fetal injury

• its oral absorption is low, even lower w high fat diet

what is the aldosterone inhibitor we talk about

eplerenone (inspra)

what is the mechanism of action for eplerenone (inspra)

selective blockade of aldosterone receptors

what are adverse effects of aldosterone antagonist

hyperkalemia (high blood potassium)

what is the other aldosterone antagonist we talk about

spironolactone (aldactone)

• also treats hypertension/ heart failure

• blocks aldosterone receptors, bind w receptors for other steroid hormones

what are adverse effects of spironolactone (aldactone)

hyperkalemia

gynecomastia (affects seggs hormones)

hirsutism (growing hair)

deepening of voice

now we are getting into calcium channel blockers

yay

what do calcium channel blockers do

prevent calcium ions from entering cells (which usually trigger cell death)

what organs do the ca channel blockers effect

vascular smooth muscle (regulate contraction, no effect on veins)

heart (affect myocardium and pacemakers- SA and AV node)

what else do ca channel blockers effect in regards to the heart

coupling of cardiac calcium channels to beta adrenergic receptors

explain the coupling of cardiac ca channels with B1 receptors

when B1 receptor activates, it activates the 2nd messenger system (increases levels of cAMP), which activates PKA, which phosphorylates ca channels, causing more Ca to enter, triggering a stronger contraction, increases HR

what type of calcium channel blocker does not affect this pathway and why?

DHPs- bc they only act on blood vessels (arterioles), not the heart

what are the different classifications of ca channel blockers and their associated med

DHP (dihydropyridines): nifedipine

phenylalamine: verapamil

benzothiazepine: diltiazem

what is the site of action for DHPs

arterioles

what is the site of action for verapamil and diltiazem (non DHPs)

arterioles and on the heart

what are the hemodynamic effects of verapamil

vasodilation

reduced arterial pressure

increased coronary perfusion

what are the therapeutic effects of verapamil

angina

primary hypertension

cardiac dysrhythmias

migraine

what are the adverse effects of verapamil

constipation

dizziness

facial flush

headache

edema

gingival hyperplasia

heart block

what are the drug interactions of verapamil

digoxin

b adrenergic blockers (cause too much blocking)

what does toxicity of verapamil cause

severe hypotension

bradycardia/ AV block

V tach- dysrhythmias

what are the action/uses for diltiazem

blocks ca channels in heart/ BV

lowers BP

• used for angina, hypertension, dysrhythmias

• used more widely than verapamil

what does nifedipine do

its a DHP (leaves heart alone!)

cause vasodilation by blocking ca channels

causes lowered BP, increased HR and contractile force due to reflex effect (baroreceptor?)

what are therapeutic uses for nifedipine

MI

angina- avoid IR formulation?

hypertension

might relieve migraine/suppress preterm labor

what are adverse effects of nifedipine

flushing

dizziness

headache

peripheral edema

gingival hyperplasia

reflex tachycardia

what can be used to treat reflex tachycardia from nifedipine

beta blocker because it doesn’t hit the smooth muscle in GI tract and cause constipation??
- come back to this

k now we are getting into vasodilators

yay