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Block 9 Week 4 > Leblanc > Pulmonary HTN drugs > Flashcards

Leblanc > Pulmonary HTN drugs Flashcards

1
Q

what are the 5 forms of pulmonary HTN?

A
  1. PAH
  2. PH assoc w/ L heart dz
  3. PH assoc w/ lung dz &/or hypoxia
  4. thromboembolic PH
  5. misc
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2
Q

T/F: PAH has a good prognosis

A

FALSE

very low prognosis for survival

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3
Q

what are the subclassifications for PAH?

A
  1. idiopathic
  2. familial/heritable
  3. drug/toxin induced
  4. atypical
  5. persistent PH of the newborn
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4
Q

what types of drugs can cause PAH?

A

anorexigens

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5
Q

what types of things can cause atypical PAH?

A 
HIV
portal HTN
congenital heart dz
CT dz
Schistosomiasis
chronic hemolytic anemia
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6
Q

what receptor is implicated in familial PAH?

A

type 2 bone morphogenic receptor

BMPR2

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7
Q

what % of familial PAH pts have downregulation of BMPR2 compared to iPAH pts?

A 
hPAH = 80%
iPAH = 10-20%
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8
Q

what does stimulation of the BMPR2 receptor do?

A

decreases proliferation & enhances apoptosis

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9
Q

besides BMPR2, what 3 other things can cause heritable PAH?

A
  1. ACVRL1/ALK1
  2. 5-HT transporter polymorphism
  3. microRNAs controlling gene expression
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10
Q

what is ACVRL1/ALK1?

A

activin A receptor type II-like kinase

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11
Q

how do local control mechanisms try to keep ventilation & perfusion matched?

A

by diverting blood flow to better-ventilated alveoli

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12
Q

what causes high altitude sickness?

A

hypoxic pulmonary vasoconstriction

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13
Q

what are the 3 postulated mechanisms for hypoxic pulmonary vasoconstriction (generally)?

A
  1. redox
  2. ROS
  3. energy state/AMPK
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14
Q

what 3 factors contribute to elevating pulmonary arterial pressure in PAH pts?

A
  1. enhanced vasoconstriction
  2. luminal obstruction
  3. propensity for thrombosis
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15
Q

how does the lumen get obstructed in PAH pts?

A

extensive remodeling of intimal, medial, & adventitial layers of the prox & distal pulm arteries

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16
Q

T/F: it is easy to diagnose PAH

A

FALSE!

diagnosis of PAH is notoriously difficult

17
Q

what things can you do to estimate pulmonary artery pressure?

A

R heart cath
pulmonary artery cath
echocardiography

18
Q

what are the diagnostic criteria for PAH for pulmonary artery pressure?

A

> 25mmHg at rest

>30mmHg during exercise

19
Q

what are the diagnostic criteria for PAH for capillary wedge pressure?

A

< or = 15mmHg

20
Q

what are the diagnostic criteria for PAH for PVR?

A

> or = 3 wood units

21
Q

what does PVR =?

A

(mean PAP - PA wedge pressure) / CO

22
Q

what are the 5 main categories of therapies for PAH?

A
  1. prostanoids
  2. endothelin receptor blockers
  3. PDE5 blockers
  4. L-type Ca channel blockers
  5. NO & cGMP-targeting drugs
23
Q

what is the main target of all current clinical trials for PAH drugs?

A

vasoactive properties of the small PA

limited benefit wrt survival & morbidity rates

24
Q

T/F: PAH is very common

A

FALSE

very rare

25
Q

what are the 4 main ways we can try to tackle PAH?

A
  1. preclinical animal studies
  2. studies w/ human PA tissues & lungs
  3. clinical multi-center trials
  4. new hypotheses that target BOTH pulmonary arterial remodeling AND right heart failure
26
Q

T/F: there is a perfect animal model of PAH

A

FALSE!

27
Q

how can you induce PAH in a rat?

A

monocrotaline (induces RVH)

28
Q

what model gives plexiform lesions?

A

chronic hypoxia + Sugen

29
Q

what is Sugen?

A

VEGF receptor inhibitor

30
Q

what rats are spontaneously pulmonary hypertensive?

A

fawn-hooded rats

31
Q

what gene is a molecular candidate for Ca-activated Cl channels in various cell types, including VSMCs?

A

TMEM16 genes or anoctamins

32
Q

what is TMEM16?

A

a major component of the pore-forming subunit of Ca-activated Cl channels of PASMCs

33
Q

where is TMEM16 expressed in PASMCs?

A

at or near the plasma membrane

Block 9 Week 4 (5 decks)

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