Cv System Exam 2_7: Treatment Of Peripheral Vascular Dz

Front 1

peripheral artery Dz (PAD)

Back 1

-casued by atherosclerosis
-causes intermittent claudication
-increase risk of CV M/M

Front 2

PAD agents

Back 2

-antiplatelets: aspirin, clopidogrel
-Lipid Lowering agents
-ACE inhibitors

Front 3

what happens in PAD

Back 3

plaque causes downstream decrease in pressure and flow distal to atheroma; endothelial dysfnx causes reduced NO production; RBCs deform and align in planar manner, reducing viscosity and allowing them to pass through

Front 4

what happens in PAD summary

Back 4

chronic tissue ischemia and hypoxia cause decreased ability of RBCs to deform and increased platelet aggregation and activation of clotting factors
-these events increase viscosity and further inhibit blood flow and O2 delivery... giving a vasodilator won't help

Front 5

PAD drugs

Back 5

Cilostazol
Pentoxifylline

Front 6

Cilostazol MOA

Back 6

Inhiit PDE 3 →
↑cAMP in platelets= ↓aggregation
↑cAMP in vessels= vasodilation
-- decreased intermittent claudication

Front 7

where does cilastozal primarily dilate vessels?

Back 7

Femoral AA.

Front 8

why is cilostazol contraindicated in HF?

Back 8

Milrinone PDE Inhibitor decreaes survival with chronic use in HF… translates to cilostazol, even though no one is going to volunteer for that study

Front 9

Pentoxifylline MOA

Back 9

*↑RBC flexibility*
↓plasma fibrinogen
-- ↑blood flow and tissue oxygenation

Front 10

Cilostazol clinical use

Back 10

-more effective than pentoxifylline
-first line in absence of HF

Front 11

Raynaud's Dz

Back 11

vasospasm of small arteries in skin of hands and feet with intermittment pallor and cyanosis
Tx: vasodilators:
-CCBs
-a antagonists
-direct vasodilators (nitrates)
-ACE Is
-- prazosin, amlodipine, nitroglycerine, lisinopril

Front 12

pulmonary arterial hypertension (PAH, Group 1)

Back 12

Right HF... essential HTN is Left HF

Front 13

Which would you use for stage 1 HTN and Raynaud's: prazosin, propanolol, amlodipine, nitroglycerine or hydrochlorothiazed?

Back 13

amlopdipine; used for both... prazosin also, but not a first line drug

Front 14

ultimate cause of increased pulmonary vascular resistance

Back 14

neurohumoral imbalance

Front 15

endothelin

Back 15

vasoconstriction, increased muscle proliferation

Front 16

Prostacyclin & NO

Back 16

vasodilation, decreased muscle proliferation, aggregation inhibition

Front 17

PAH mechanism: Endothelial Dysfnx

Back 17

--overproduction of endothelin
-too much vasoconstriction
-too much proliferation

--underproduction of prostacyclin & NO
-not enough vasodilation
-not enough platelet aggregation inhibiion
-no enough antiproliferation

Front 18

PAH mechanism: Abnormal Ca2++ handling

Back 18

--increased Ca2++ in smooth muscle cells
-too much vasoconstriciton
-too much proliferation

Front 19

PAH summary

Back 19

-proliferation of intima, media and adventitia
-excess smooth muscle tone (vasoconstriction)
-thrombosis in situ

Front 20

PAH Tx goals

Back 20

-prevent thromboembolism= anticoags
-reduce peripheral edema= diuretics (from HF)
-reduce pulmonary vascular resistance remodeling of the pulmonary arteries to increase CO, exercise capacity and reduce mortality

Front 21

vasodilators for PAH?

Back 21

most ineffective in chronic reduction of pulmonary vascular resistance

Front 22

PAH: to much Ca in cell

Back 22

CCB

Front 23

PAH: too much endothelin

Back 23

endothelin antagonist

Front 24

PAH: not enough PGI2

Back 24

PGI2

Front 25

PAH: not enough NO

Back 25

PDE-5i (cGMP)

**remember, PDE-3i → cAMP (Cilostazol)

Front 26

CCBs for PAH

Back 26

-Nifedipine, verapamil, diltiazem
-decrease pulmonary vascular resistance in 10-15% (sucks)
-doses 2-3x higher than use for systemic HTN
-people that do respond may have longer survival

Front 27

remember, inotropic effect of verapamil, diltiazem and amlopidine

Back 27

negative inotropic effect of verapimil > diltiazem >>> amlodpine

Front 28

How can u be sure a person will respond to a CCB?

Back 28

Acute Vasoreactivity Test: super short 1/2 life ... IV epoprostenol, IV adenosine or inhaled NO
[mPAP= main pulmonary arterial pressure]

Front 29

Acute Vasoreactivity Test - Summary

Back 29

-Administer a very short acting vasodilator, either IV epoprostenol, IV adenosine, or inhaled NO
-Measure mean pulmonary arterial pressure (mPAP) and CO
-If mPAP falls to an acceptable level AND CO is unchanged or increased, then…
-Try a CCB
-If they exhibit a sustained response on a CCB, then…
-Long term treatment with CCB

Front 30

Prostacyclin Analogues

Back 30

-Epoprostenol (Flolan) – IV
-Treprostinil (Remodulin) – subcutaneous, IV
-Treprostinil (Tyvaso) - inhalation
-Iloprost (Ventavis) – inhalation

Front 31

Prostacyclin Analogues MOA

Back 31

Prostacyclin (PGI2)
-Dilates pulmonary vessels
-Decrease pulmonary vascular resistance
-Probably a small degree of systemic vasodilation
-Inhibits platelet aggregation
-Antiproliferative effects

Front 32

Epoprostenol- end result

Back 32

-improve hemodynamics
-relieve symtpoms
-increase exercise capacity
-improve quality of life and survival

Front 33

Epoprostenol AEs

Back 33

**Jaw Pain**
nausea, diarrhea
hypotension
headache
flushing
thrombocytopenia
leukocytic classic vasculitis
leg/foot pain

Front 34

What is the difference between epoprostenol, treprostinil and iloprost?

Back 34

pharmicokinetics

Front 35

prostacycln analogue 1/2 lives

Back 35

Epoprostanol- 6min
Iloprost- 20-30 min
Treprostinil- 4hr

Front 36

Epoprostenol admin/comps

Back 36

central venous catheter (CVC)
-must be cold
-once on Ep, must continue or die
-infections at catheter site
-increase mortality

Front 37

Iloprostenol admin/comps

Back 37

SQ infusion or CVC or Inhalation
-SQ injection site pain
-Inhalation 2-3min/4x/day

Front 38

Treprostinil admin/comps

Back 38

Inhalation
10-12min/6-9x/day

Front 39

have clinical trial shown increased mortality for prostacyclin analogues?

Back 39

Epoprostenol only

Front 40

Endothelin Receptor antagonists

Back 40

Bosentan
Ambrisentan
-- both oral

Front 41

Endothelin Receptor antagonists: MOA

Back 41

-Plasma endothelin increased in patients with pulmonary HTN and correlates with Dz severity
-Bosentan blocks both Endothelin A & B receptors
-Ambrisentan blocks Endothelin A receptor only
-- block endothelin-induced vasoconstriction, fibrosis, hypertrophy, hyperplasia and vascular permeability

Front 42

Endothelin Receptor antagonists: end result

Back 42

-improve pulmonary hemodynamics
-increase exercise capacity
-decrease exercise dyspnea
-decrease time/rate of clinical worsening
-- patients showed improved survival at 2 years

Front 43

Endothelin Receptor antagonists:
AEs

Back 43

--Bosentan
-↑ liver aminotransferases (11% incidence)
-enzymes must be checked monthly
--Ambrisentan
-FDA removed liver enzyme check recommendation

Front 44

Endothelin receptor antagonist AEs

Back 44

-decrease in Hb and hematocrit
-teratogenic in some animals
-induces CYP3A4, 2C9 and 2C19
-decrease concentration of some drugs such as hormonal contraceptives... recommend two forms of contraception
**Cat X contraindication: pregnant women**

Front 45

PDE 5 inhibitors

Back 45

Sildenafil
Tadalafil

Front 46

L-arginine to cGMP pathway

Back 46

Front 47

In PAH, endothelial dysfnx causes a reduction in ______

Back 47

NO synthase... end up with more pulmonary vasoconstricton

Front 48

what does inhibiting PDE 5 do?

Back 48

raises concentration of cGMP in pulmonary arterial smooth muscle cells to enhance dilation of the pulmonary vasculature, decreased platelet aggregation and decrease smooth muscle proliferation

Front 49

PDE 5i end result

Back 49

-increase exercise tolerance
-improve mPAP (mean pulmonary arterial pressure, cardiac index and pulmonary vascular resistance

Front 50

PDE 5 AEs

Back 50

-headache
-flushing
-IBD
-epistaxis
-nonarteritic ischemic optic neuropathy

Front 51

PAH Tx summary

Back 51

-CCB in patients that respond to vasoreactivity test
*for other PAH drugs:
-use oral drugs in less severe patients
-use parenteral drugs in more severe patients
-Epoprostenol: first line for the worst patients