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Pharmacology- Test 3 Material > 25- Regulation of Coronary Blood Flow > Flashcards

25- Regulation of Coronary Blood Flow Flashcards

1
Q

acebutolol (Sectral)

A

Cardioselective- B1 selective antagonist

  • blocks B1 receptors on myocardium and sinus node (can also dec. renin secretion)
  • causes dec. HR and contractility
  • used in CAD without signs of acute HF
  • in combo with nitrates
  • prolong survival in compensated HF d/t reduction of MVO2
  • negative inotropic effects may worsen HF
  • start with low dose and titrate slowly; rebound phenomenon if d/c’d abruptly d/t B1 receptor upregulation can cause unstable angina or MI (need to taper dosing)
  • S/Fx: bronchospasm (avoid in asthmatics), poor outcomes: inc. Type II diabetes, hypoglycemia, hyperlipidemia, myocardial depression, bradycardia, reduced exercise tolerance, sleep disturbance and cold extremeties, impotence
  • Contraindicated in: severe asthma, bradycardia, AV blockade, severe PVD, insulin dependent DM, Prinzmetal’s angina (may inc. vasospasm)
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2
Q

atenolol (Tenormin)

A

Cardioselective- B1 selective antagonist

  • blocks B1 receptors on myocardium and sinus node (can also dec. renin secretion)
  • causes dec. HR and contractility
  • used in CAD without signs of acute HF
  • in combo with nitrates
  • prolong survival in compensated HF d/t reduction of MVO2
  • negative inotropic effects may worsen HF
  • start with low dose and titrate slowly; rebound phenomenon if d/c’d abruptly d/t B1 receptor upregulation can cause unstable angina or MI (need to taper dosing)
  • S/Fx: bronchospasm (avoid in asthmatics), poor outcomes: inc. Type II diabetes, hypoglycemia, hyperlipidemia, myocardial depression, bradycardia, reduced exercise tolerance, sleep disturbance and cold extremeties, impotence
  • Contraindicated in: severe asthma, bradycardia, AV blockade, severe PVD, insulin dependent DM, Prinzmetal’s angina (may inc. vasospasm)
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3
Q

metoprolol (Lopressor)

A

Cardioselective- B1 selective antagonist

  • blocks B1 receptors on myocardium and sinus node (can also dec. renin secretion)
  • causes dec. HR and contractility
  • used in CAD without signs of acute HF
  • in combo with nitrates
  • prolong survival in compensated HF d/t reduction of MVO2
  • negative inotropic effects may worsen HF
  • start with low dose and titrate slowly; rebound phenomenon if d/c’d abruptly d/t B1 receptor upregulation can cause unstable angina or MI (need to taper dosing)
  • S/Fx: bronchospasm (avoid in asthmatics), poor outcomes: inc. Type II diabetes, hypoglycemia, hyperlipidemia, myocardial depression, bradycardia, reduced exercise tolerance, sleep disturbance and cold extremeties, impotence
  • Contraindicated in: severe asthma, bradycardia, AV blockade, severe PVD, insulin dependent DM, Prinzmetal’s angina (may inc. vasospasm)
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4
Q

pindolol (Visken)

A

Non-selective Beta Antagonist

  • blocks B1 receptors on myocardium and sinus node (can also dec. renin secretion)
  • blocks B2 receptors leading to vasoconstriction and bronchospasm
  • causes dec. HR and contractility
  • used in CAD without signs of acute HF
  • in combo with nitrates
  • prolong survival in compensated HF d/t reduction of MVO2
  • negative inotropic effects may worsen HF
  • start with low dose and titrate slowly; rebound phenomenon if d/c’d abruptly d/t B1 receptor upregulation can cause unstable angina or MI (need to taper dosing)
  • S/Fx: bronchospasm (avoid in asthmatics), poor outcomes: inc. Type II diabetes, hypoglycemia, hyperlipidemia, myocardial depression, bradycardia, reduced exercise tolerance, sleep disturbance and cold extremeties, impotence
  • Contraindicated in: severe asthma, bradycardia, AV blockade, severe PVD, insulin dependent DM, Prinzmetal’s angina (may inc. vasospasm)
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5
Q

propranolol (Inderal)

A

Non-selective Beta Antagonist

  • blocks B1 receptors on myocardium and sinus node (can also dec. renin secretion)
  • blocks B2 receptors leading to vasoconstriction and bronchospasm
  • causes dec. HR and contractility
  • used in CAD without signs of acute HF
  • in combo with nitrates
  • prolong survival in compensated HF d/t reduction of MVO2
  • negative inotropic effects may worsen HF
  • start with low dose and titrate slowly; rebound phenomenon if d/c’d abruptly d/t B1 receptor upregulation can cause unstable angina or MI (need to taper dosing)
  • S/Fx: bronchospasm (avoid in asthmatics), poor outcomes: inc. Type II diabetes, hypoglycemia, hyperlipidemia, myocardial depression, bradycardia, reduced exercise tolerance, sleep disturbance and cold extremeties, impotence
  • Contraindicated in: severe asthma, bradycardia, AV blockade, severe PVD, insulin dependent DM, Prinzmetal’s angina (may inc. vasospasm)
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6
Q

avanafil (Stendra)

A

Phosphodiesterase 5 Inhibitor (PDE-5)Phosphodiesterase 5 inhibitors (PDE-5)

  • inc. levels of cGMP (prevents cGMP conversion to GMP) and promotes modest drop in BP
  • used in erectile dysfunction
  • Onset: 15 min, Half-Life: 5-10 hr, nitrovasodilators contraindicated within 24 hrs
  • S/Fx: can cause hypotension when used in combo with nitrates or alpha receptor blockers (excess cGMP and BP drop of >25 mmHg), HA, rhinitis, flushing, back pain, sudden loss of hearing, inc. loss of vision, blurred vision or loss of blue-green color discrimination
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7
Q

45-46 sildenafil (Viagra)

A

Phosphodiesterase 5 inhibitor (PDE-5)

  • inc. levels of cGMP (prevents cGMP conversion to GMP) and promotes modest drop in BP
  • used in erectile dysfunction and primary PHTN
  • Onset: 1 hr, Half-Life: 3.7 hr, nitrovasodilators contraindicated within 24 hrs
  • S/Fx: can cause hypotension when used in combo with nitrates or alpha receptor blockers (excess cGMP and BP drop of >25 mmHg), HA, rhinitis, flushing, back pain, sudden loss of hearing, inc. loss of vision, blurred vision or loss of blue-green color discrimination
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8
Q

tadalafil (Cialis)

A

Phosphodiesterase 5 inhibitor (PDE-5)

  • inc. levels of cGMP (prevents cGMP conversion to GMP) and promotes modest drop in BP
  • used in erectile dysfunction
  • Onset: 15-30 min, Half-Life: 17.5 hr, nitrovasodilators contraindicated within 48 hrs
  • S/Fx: can cause hypotension when used in combo with nitrates or alpha receptor blockers (excess cGMP and BP drop of >25 mmHg), HA, rhinitis, flushing, back pain, sudden loss of hearing, inc. loss of vision, blurred vision or loss of blue-green color discrimination
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9
Q

vardenafil (Levitra)

A

Phosphodiesterase 5 inhibitor (PDE-5)

  • inc. levels of cGMP (prevents cGMP conversion to GMP) and promotes modest drop in BP
  • used in erectile dysfunction
  • Onset: 30-60 min, Half-Life: 3.3-3.9 hr, nitrovasodilators contraindicated within 24 hrs
  • S/Fx: can cause hypotension when used in combo with nitrates or alpha receptor blockers (excess cGMP and BP drop of >25 mmHg), HA, rhinitis, flushing, back pain, sudden loss of hearing, inc. loss of vision, blurred vision or loss of blue-green color discrimination
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10
Q

isosorbide dinitrate

A

Nitrovasodilator
-increase cGMP
-reduce oxygen demand and increase oxygen supply
- 1st pass metabolism
-duration of action 3-5 hours, administered 3-4 times daily
-tolerance/tachphylaxis
-side effects: headache, orthostatic hypotension, dizziness, flushing, syncope, reflex tachycardia, GI distress, skin irritation (patch)
contraindicated with PDE-5 inhibitors

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11
Q

isosorbide monoitrate

A 
Nitrovasodilator
-increase cGMP
-reduce oxygen demand and increase oxygen supply
-minimal 1st pass metabolism
-longer duration of action
-tolerance/tachphylaxis
-side effects: headache, orthostatic hypotension, dizziness, flushing, syncope, reflex tachycardia, GI distress, skin irritation (patch)
contraindicated with PDE-5 inhibitors
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12
Q

nitroglycerin

A

Nitrovasodilator
-increase cGMP
-reduce oxygen demand and increase oxygen supply
- 1st pass metabolism
-duration of action dependent on formulation
-tolerance/tachphylaxis
-side effects: headache, orthostatic hypotension, dizziness, flushing, syncope, reflex tachycardia, GI distress, skin irritation (patch)
contraindicated with PDE-5 inhibitors

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13
Q

nitroprusside sodium

A

direct vasodilator

  • generates NO which activates guanyly cyclase, increase cGMP
  • effect on veins and arteries to reduce preload and afterload
  • use: produce hypotension in surgery and hypertensive emergencies
  • adverse effects- rapid decrease in MAP, cyanide accumulation (infusion >48 hours and/or impaired renal function)
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14
Q

aspirin

A
  • inhibits the synthesis of thromboxane A2 by irreversible acetylation of cyclooxygenase
  • used to help reduce TIA, stroke, MI, ACS
  • side effects- excessive bleeding
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15
Q

clopidogrel

A

thienopyridine

  • ADP antagonists at P2Y-12 receptor
  • block ADP mediated activation of glycoprotein GPIIb/IIIa
  • prevents platelet aggregation
  • use in combination with aspirin in ACS, MI, and stroke
  • side effects- neutropenia
  • genetic variability in metabolism
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16
Q

prasugrel

A

thienopyridine

  • ADP antagonists at P2Y-12 receptor
  • block ADP mediated activation of glycoprotein GPIIb/IIIa
  • prevents platelet aggregation
  • use in combination with aspirin in ACS, MI, and stroke
  • few drug interactions
17
Q

ranolazine

A

PFox inhibitor

  • inhibits late sodium current to reduce sodium and calcium overload in ischemic myocytes
  • no negative chronotropic or inotropic effect
  • minimal effects on heart rate and blood pressure
  • improved exercise tolerance
  • reserved for patients with chronic angina that are refractory to traditional antianginal agents
  • avoid in patients with prolonged QT intervals or hepatic impairment
18
Q

ticagrelor

A

non-thienopyridine

  • reversibily binds to the P2Y-12 sub type receptor
  • prevent platelet aggregation
  • use in combination with aspirin in ACS, MI, and stroke
19
Q

cGMP

A

-levels increased by NO and cause vasodilation through inhibition of actin and myosin crossbridges

20
Q

epicardium I (subendocaridal)

A
  • provides most resistance to coronary blood flow and is primary site for regulation of blood flow to heart muscle
  • most perfusion occurs during diastole and these are essentially closed during systole
21
Q

guanylyl cyclase

A

increases levels of cGMP through action of NO

22
Q

humoral regulation

A

local and other factors that contribute to regulation of coronary BF (catecholamines, thyroid hormones, adrenal hormones, histamine, serotonin, kinins, TXA, adenosine, etc.)

23
Q

microvascular angina

A
  • angina or angina-like discomfort with exercise, ST segment depression, or other signs of ischemia
  • normal coronaries so due to microvascular dysfunction
24
Q

nitrate tolerance

A
  • decreased response to nitrates after prolonged use, tachyphylaxis
  • interrupt therapy for 8-12 hours to get initial effect
  • mechanism unclear at cellular level
25
Q

phosphodiesterase type 5 (PDE-5)

A
  • normally converts cGMP into GMP

- inhibitors prevent this conversion leaving more cGMP to promote vasodilation

26
Q

Prinzmetal angina

A
  • transient vasospasm while resting and often occurs in cycles
  • usually occurs at same time during the day and not d/t exercise or emotional stress
  • supply ischemia
27
Q

stable angina

A
  • effort related angina and relieved with rest/medication
  • usually due to fixed lesion
  • lasts a few minutes
  • demand ischemia
28
Q

unstable angina

A
  • acute coronary syndrome
  • rest/medication does not relieve
  • non-effort dependent
  • myocardial infarct
  • supply ischemia
29
Q

autoregulation of coronary blood flow

A

-global coronary blood flow autoregulated to maintain constant blood flow between coronary perfusion pressures within a CPP of 50-150 mmHg

Pharmacology- Test 3 Material (10 decks)

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