Leblanc > Pulmonary HTN drugs Flashcards
what are the 5 forms of pulmonary HTN?
- PAH
- PH assoc w/ L heart dz
- PH assoc w/ lung dz &/or hypoxia
- thromboembolic PH
- misc
T/F: PAH has a good prognosis
FALSE
very low prognosis for survival
what are the subclassifications for PAH?
- idiopathic
- familial/heritable
- drug/toxin induced
- atypical
- persistent PH of the newborn
what types of drugs can cause PAH?
anorexigens
what types of things can cause atypical PAH?
HIV portal HTN congenital heart dz CT dz Schistosomiasis chronic hemolytic anemia
what receptor is implicated in familial PAH?
type 2 bone morphogenic receptor
BMPR2
what % of familial PAH pts have downregulation of BMPR2 compared to iPAH pts?
hPAH = 80% iPAH = 10-20%
what does stimulation of the BMPR2 receptor do?
decreases proliferation & enhances apoptosis
besides BMPR2, what 3 other things can cause heritable PAH?
- ACVRL1/ALK1
- 5-HT transporter polymorphism
- microRNAs controlling gene expression
what is ACVRL1/ALK1?
activin A receptor type II-like kinase
how do local control mechanisms try to keep ventilation & perfusion matched?
by diverting blood flow to better-ventilated alveoli
what causes high altitude sickness?
hypoxic pulmonary vasoconstriction
what are the 3 postulated mechanisms for hypoxic pulmonary vasoconstriction (generally)?
- redox
- ROS
- energy state/AMPK
what 3 factors contribute to elevating pulmonary arterial pressure in PAH pts?
- enhanced vasoconstriction
- luminal obstruction
- propensity for thrombosis
how does the lumen get obstructed in PAH pts?
extensive remodeling of intimal, medial, & adventitial layers of the prox & distal pulm arteries
T/F: it is easy to diagnose PAH
FALSE!
diagnosis of PAH is notoriously difficult
what things can you do to estimate pulmonary artery pressure?
R heart cath
pulmonary artery cath
echocardiography
what are the diagnostic criteria for PAH for pulmonary artery pressure?
> 25mmHg at rest
>30mmHg during exercise
what are the diagnostic criteria for PAH for capillary wedge pressure?
< or = 15mmHg
what are the diagnostic criteria for PAH for PVR?
> or = 3 wood units
what does PVR =?
(mean PAP - PA wedge pressure) / CO
what are the 5 main categories of therapies for PAH?
- prostanoids
- endothelin receptor blockers
- PDE5 blockers
- L-type Ca channel blockers
- NO & cGMP-targeting drugs
what is the main target of all current clinical trials for PAH drugs?
vasoactive properties of the small PA
limited benefit wrt survival & morbidity rates
T/F: PAH is very common
FALSE
very rare
what are the 4 main ways we can try to tackle PAH?
- preclinical animal studies
- studies w/ human PA tissues & lungs
- clinical multi-center trials
- new hypotheses that target BOTH pulmonary arterial remodeling AND right heart failure
T/F: there is a perfect animal model of PAH
FALSE!
how can you induce PAH in a rat?
monocrotaline (induces RVH)
what model gives plexiform lesions?
chronic hypoxia + Sugen
what is Sugen?
VEGF receptor inhibitor
what rats are spontaneously pulmonary hypertensive?
fawn-hooded rats
what gene is a molecular candidate for Ca-activated Cl channels in various cell types, including VSMCs?
TMEM16 genes or anoctamins
what is TMEM16?
a major component of the pore-forming subunit of Ca-activated Cl channels of PASMCs
where is TMEM16 expressed in PASMCs?
at or near the plasma membrane
