Part 23: Vasodilators

Question 1

in vascular smooth muscle, the interaction between ___ and ___ causes contraction, resulting in vasoconstriction

Answer 1

myosin and actin

Question 2

during membrane depolarization of vascular smooth muscle cells, large amounts of ____ ions come in through ____ channels

Answer 2

Ca; voltage gated Ca channels

Question 3

Ca can also enter BV smooth muscle cells through the ___- exchanger where ___ is removed from the cytoplasm and ca enters

Answer 3

Na/Ca (NCX); Na

Question 4

compared to the voltage-gated Ca channels, the NCX is a ____ (major/minor) contributor of Ca influx

Answer 4

minor

Question 5

when might there be reduced removal of Na from the cells and entry of Ca by the NCX?

Answer 5

if the patient is taking a diuretic that depletes the body’s Na

Question 6

when diuretics indirectly affect the NCX does it cause a vasodilator or vasoconstrictive effect?

Answer 6

vasodilator

Question 7

the guanylyl cyclase pathway promotes vasodilation by increasing _____ of myosin, which releases the contractile stste of the smooth muscle cell

Answer 7

dephosphorylation

Question 8

organic nitrates like ____ act in this pathway to cause vasodilation in patients with angina

Answer 8

nitroglycerin

Question 9

what drug class does prazosin belong to?

Answer 9

alpha 1 adrenergic receptor antagonist (antihypertensive)

Question 10

what is the MOA of alpha-1 antagonists like prazosin?

Answer 10

competes for binding to the A1 receptor and prevents endogenous action of NE secreted by sympathetic neurons and results in less Ca for contraction

Question 11

activation of the alpha 1 receptor causes a _____coupled signalling cascade

Answer 11

Gq

Question 12

a rise in intracellular Ca results in activation of mysoin ____

Answer 12

light chain kinase

Question 13

while some Ca may come in by the NCX, most of the Ca enters through _____ channels

Answer 13

L-type voltage gated Ca channels

Question 14

if we can block Ca channels, there will be less calcium ____ activation and a reduction in myosin _____ activity

Answer 14

calmodulin; light chain kinase

Question 15

what are the 2 types of Ca channel blockers?

Answer 15

1. dihydropyridine (DHP)

2. non-dihydropyridine

Question 16

what class of drug does nifedipine belong to?

Answer 16

dihydropyridine type Ca channel blockers (vasodilator; antihypertensive)

Question 17

what class of drug does diltiazem belong to?

Answer 17

non-dihydropyridine type Ca channel blocker (vasodilator; antihypertensive)

Question 18

what is the clinical distinction between DHP and non-DHP Ca channel blockers?

Answer 18

DHPs are only effective in blocking Ca channels in smooth muscle cells, but not those in cardiac muscle cells, but non-DHP act in both

Question 19

blocking Ca channels in cardiac muscle cells generally causes a _______ (increase/decrease) in the activity of these cells

Answer 19

decrease

Question 20

why are non-DHPs like diltiaem not typically used?

Answer 20

they can block ca channels in the heart wich reduces activity of heart cells

Question 21

what are some of the common ADRs of vasodilators?

Answer 21

orthostatic hypotension, dizziness, headaches, bradycardia, cardiac suppression, urinary incontinence

Question 22

what is the severity of hypotension, dizziness and headaches ADRs of vasodilators?

Answer 22

usually not serious, typically resolves over time, but if it doesnt resolve some ptaintes may need dose adjustments

Question 23

bradycardia & cardiac suppression as ADRs are typically seen with what types of vasodilators?

Answer 23

non-DHPs like diltiazem

Question 24

urinary incontinence as an ADR is typically not severe and is typically caused by what class of vasodilators?

Answer 24

A1 andronergic blockers also acting in other smooth muscle like prazosin

Question 25

t/f prozosin can be used for the treatment of urinary retnetion

Answer 25

t

Question 26

t/f vasodilators alone are typically not enough to manage hypertension

Answer 26

t

Question 27

when a drop in BP is sensed, the _____ nervous system is activated

Answer 27

sympathetic

Question 28

stimulation of B____ receptors in cardiac tissues increases heart rate and contractility, and cardiac output, resulting in increased BP

Answer 28

1

Question 29

why would it not make much sense to use nifedipine and prazosin togther?

Answer 29

they both act on smooth muscle to reduce contractility and it is typically better to choose agents that have differing MOAs

Question 30

why would it not make sense to use an ACE inhibitor and ARB togther?

Answer 30

bc they act on the same pathway, and we typically want to diversify to get bettwer efficacy

Question 31

what is angina?

Answer 31

a condition where narrowing of the coronary vessesl causes reduced blood flow and reduced O2

Question 32

angina typically presents as ___

Answer 32

chest pain or pressure upon excretion of exercise

Question 33

angina that worsens with exercise is called ___

Answer 33

effort angina

Question 34

what is the main management for angina?

Answer 34

to balance out O2 supply and demand, which will help to reduce the symptoms ; lowering BP can also help

Question 35

vasodilators increase O2 ____

Answer 35

supply

Question 36

B blockers decrease O2 _____

Answer 36

demand

Question 37

organic nitrates cause ____ to ____increase/decrease O2 supply

Answer 37

vasodilation; increase

Question 38

what agents can be used to reduce cardiac output to reduce O2 demand?

Answer 38

B blockers and non-NHPs like diltiazem

Question 39

organic nitrates act by increasing ____ in the vascular smooth muscle cells

Answer 39

nitric oxide

Question 40

nitric oxide is normally produced by ____ cells surrounding vascular smooth muscle cells in BV

Answer 40

endothelial

Question 41

when nitric oxide is made, it diffuses into the vascular smooth muscle cells where it increases the activity of ____, which promotes more ____

Answer 41

guanylase cyclase; cyclic GMP

Question 42

cyclic GMP activates ____ that dephosphorylate myosin light chains, causing muscle relaxation

Answer 42

phosphatases

Question 43

endogenously, nitric oxide has a very _____ (long/short) half life

Answer 43

short

Question 44

due to its short t1/2, NO is not an effective therapeutic strategy on its own, but we can administer drugs that produce NO once they are inside these cells, these agents are called ____

Answer 44

nitric oxide donors

Question 45

____ are one class of nitric oxide donors that can be used to achieve vasodilation in angina

Answer 45

organic nitrates

Question 46

____ is one of the more familiar nitrate agents used clinically

Answer 46

nitroglycerin

Question 47

nitroglycerin is metabolized in vascular smooth muscle cells by _____ and other enzymes to make NO

Answer 47

glutathione S-transferase

Question 48

organic nitrates are readily metabolized in the ____, giving them _____ (high/low) oral bioavailability

Answer 48

liver; low

Question 49

what are the typical administration routes of nitroglycerin?

Answer 49

parenteral: sublingual, transdermal are most common

Question 50

sublingual nitroglycerin is for ______ (acute PRN or chronic prophylactic) use

Answer 50

acute PRN

Question 51

transdermal nitroglycerin is for ______ (acute PRN or chronic prophylactic) use

Answer 51

chronic prophylactic

Question 52

what type of nitroglycerin should a patient with effort angina take?

Answer 52

sublingual

Question 53

what type of nitroglycerin should a patient with angina at rest take?

Answer 53

transdermal

Question 54

nitrates cause a ______(reduced/increased) preload in the heart and _____ (reduces/increases) the after load

Answer 54

reduced;reduces

Question 55

what is preload?

Answer 55

the filling pressure of the heart

Question 56

what is after load?

Answer 56

the pressure the heart needs to pump against

Question 57

dilation of ____ arteries reduces the after load

Answer 57

coronary

Question 58

dilation of _____ reduces preload

Answer 58

veins

Question 59

nitroglycerin increases O2 ____ and decreases O2 ____

Answer 59

supply; demand

Question 60

when using nitrates, one of the ADRs (aside from orthostatic hypotension, headache, dizziness) is a compensatory increase in ______

Answer 60

heart rate (which can increase BP)

Question 61

wrt to the ADR of compensatory tachycardia, which patients are more likely to require an additional antihypertensive to manage this?

Answer 61

those taking it chronically (usually goes away for PRN users)

Question 62

_____ develops with continual nitrate exposure

Answer 62

tolerance

Question 63

why does nitrate tolerance happen?

Answer 63

saturation of the metabolic pathways required to activate organic nitrate, causing less NO production and reduced vasodilation

Question 64

is a patient has developed nitrate tolerance, will changing the dose restore the effect?

Answer 64

no

Question 65

how can the development of nitrate tolerance be minimized?

Answer 65

have chronic use patients schedule a nitrate-free period , usually overnight for 8 hrs, which will promote restoration of the enzymes and substrates needed for the metabolic pathways in the morning

Question 66

organic nitrates are dangerous when combined with what type of drug?

Answer 66

erectile dysfunction drugs like sildenafil

Question 67

why is it dangerous to combine erectile dysfunction drugs like sildenafil with organic nitrates?

Answer 67

sildenafil inhibits the breakdown cyclic GMP by phosphodiesterase, which promotes vasodilation and blood flow to peripheral areas, when combined with nitrates, this causes a very large increase in cyclic GMP and a very large hypotensive effect that can be extremely dangerous and even fatal