Pulmonary Arterial Hypertension Flashcards
Pulmonary HTN hemodynamically defined by ?
Mean pulm arterial pressure mPAP > 20 mmHg at rest measured by right heart catherization
Classification of Pulm HTN
Group 1 PH due to ?
Group 2 PH due to ?
Group 3 PH due to ?
Group 4 PH due to ?
Group 5 PH due to ?
- Pulm arterial HTN
- Left heart disease
- Lung diseases and or hypoxia (PH -ILD)
- Pulmonary artery obstructions (CTEPH)
- unclear multifactorial mechanisms
Group 1 PAH :
Can be ___ or ___-
- Associated with other medical conditions such as? (6)
- Drug and toxin induced by ? (3)
Idiopathic, heritable (<10% of cases)
- Connective tissue disease
-HIV infection
-Portal HTN
-congenital Heart diseases
-scleroderma
-lupus - Methamphetamines
-desatinib
-FenPhen
PAH is a disease resulting in ____ through pulmonary arterial circulation resulting in ____ which causes incr ___ of the ___ and ultimately right HF
What are the new hemodynamics of PAH? (3)
mPAP
PAWP
PVR
-restricted blood flow
-incr pulm vascular resistance (PVR)
- workload
-right ventricle
mPAP > 20 mmHG
PAWP <= 15 mmHg
PVR > 2 wood units
Clinical Presentation of PAH :
-F and S
-D or L on E
-P
-Exertional ___ and S
-Chronic ___ –> decr ___ and right to left ___
-Fatigue and SOB
-Dizziness or lightheadedness on exertion
-peripheral edema
-chest pain, syncope
-Hypoxemia , cardiac output, shunt
Goals of TX :
- Improve __ and __
- Objective assessments
-Improve ___ (2)
-Improved ___ (6)
-BNP
-Prolong __
- QOL and sx’s
- Exercise –> 6MW, Cardiopulm
-Hemodynamics –> CO, BP, O2 sat, PVR, mPAP , RR
-Survival
All patients will do vasodilator testing :
- what does this test prove?
- Should not be performed in ?
- Pt is responder if?
- Responders have sustained beneficial response to ?
- presence of pulmonary vasoreactivity
- overt right HF or hemodynamic instability
- Decr in mPAP by at least 10 mmHG; to an absolute value of < 40 mmHg without decr in CO
- Oral calcium channel blockers
CCB’s
- Used in patients that are ____.
-if does not imrpove to ___ or ___ on CCB, an alternative should be prescribed
-Very few do well on ___ - Agents used ? (3) (DAN)
-avoid ___
- responders to vasodilator testing
-functional class1 or 2,
-Long term CCB therapy - Long acting nifedipine
-diltiazem
-amlodipine
-Verapamil (negative inotropic effect)
CCB’s
- Amlodipine
- Diltiazem
- Nifedipine (XL)
FDA approved ?
Doses for each ?
DDI’s ?
Toxicity monitoring ? (6)
None are FDA approved for Pulm hypertension
- amlodipine 2.5 mg PO BID, up to 10 mg BID
DDI : with CYP 3A4 - Diltiazem 30 mg PO TID, up to 480 mg per day.
DDI : CYP3A4 and PGP - Nifed : 30 mg PO daily up to 90 mg per day.
DDI : CYP3A4 and PGP - BP, HR, Peripheral edema, flushing, muscle cramps, gingival hyperplasia (more with Amlodipine)
Endothelin Receptor Antags (ERA’s)
1. Warnings? (3)
For each drug, state the rout of admin and frequency of dosing, then state the necesary requirments for monitoring for each
- Bosentan
- Ambrisentan
- Macitentan
- all are teratogenic
-require monthly preg test - 2 methods of contraception
-REMS - Oral BID –> Monitor LFTS before and monthly during therapy, monthly preg testing, REMS , specialty pharmacy
- Oral QDAILY –> monthly preg testing, REMS , specialty pharmacy
- Oral QDAILY –> monthly preg testing, REMS , specialty pharmacy
ERA’s: For each, state DOSE, DDI’s , and toxicity monitoring
FDA approval?
- Bosentan (6)
- Ambrisentan (4)
- Macitentan ( 5)
If u have a pt on lots of medications, for example HIV meds, which drug would u pick and why?
All are FDA approved for PAH
- 62.5 mg PO BID. Max 125 mg BID.
- DDI : CYP 2C9, 2C19, 3A4
- MAJOR AE : LFTS !!!
- Other : Infection, HA, fluid retention, edema ,jaundice - 5 MG PO DAILY TITRATE TO 10 MG DAILY IF TOLERATED.
DDI : CYP 3A, 2C19. UGT 1A9S, 2B7S, 1A3S
Major AE : Peripheral Edema
Other : HA, NASAL CONGESTION, ANEMIA - 10 MG PO DAILY
DDI : CYP 3A4, CYP 2C19 MINOR
Major AE : Nasal congestion + UTI
Minor AE : Pharyngitis, HA, Anemia - Ambrisentan bc it has the most MINOR DDI’s
PDE5 I’S and Guanylate Cyclase Stimulators**
- WARNINGS? (2)
For each drug, state route of admin, freq of dosing and considerations
- sildenafil
- tadalafil
- riociguat**
- Hypotension and CI with Nitrates
- oral TID, not to be used with nitrates or guanylate cyclase stimulators
- oral QDAILY, not to be used with nitrates or guanylate cyclase stimulators
- oral TID. Not to be used with Nitrates and or PDE5I’s; REMS;
-Requires nursing visit for titration
PDE5I’s :
1. Sildenafil (Revatio, Viagra)
-Dose?
AE”s? (4)
-IV formulation of Revatio for PAH dose as compared to PO ?
- Tadalafil (Adcirca, Cialis)
-Dose? - drug interactions for all? (3)
- 20 mg po TID
-HA, flushing, dyspepsia, nose bleed
- 10 MG IV = 20 mg PO - 20-40 mg po once daily
- CYP inhibitors + inducers and NITRATES
Soluble Guanylate Cyclase Stimulator
- Riociguat (Adempas)
a.Dose? (initial, incr, target)
b.CI with? (7)
c. Drug interactions?
d.What happens if you smoke?
e.What specific conditions is it indicated for besides pulm art htn?
1a. Initial 0.5-1 mg PO TID
-Every 2 weeks incr by 0.5 mg TID
-Target 2.5 mg PO TID
b. Nitrates, PDE5I’s (Silden, tadal, varden), Dipyridamole, theophylline, aminophylline
c. CYP inhibs and inducers + Antacids
d.Smoking results in 50-60% plasma level reduction
e. PH in CTEPH
- Sildenafil (Revatio)
-Dose
-DDI (2)
-No ___
-Toxic monitoring ? - Tadalafil (Adcirca)
-Dose
-DDI
-No ___, ___ regimen
-AE’s for toxic monitoring ? - Riociguat (ADempas)
-Dosing ?
-DDI’s (CYPS) and 1 drug
-What program needs to be used?
-What drugs should NOT be used in conjunction ? (6)
-Toxic monitoring ? (3)
- 20 mg PO TID . IV dose is half of PO dose
-CYP 3A4, CYP 2C9 MINOR
- NITRATES
Major : HA!!, VIS IMPAIRMENT!,
Minor : N/D, Periph edema, Dyspepsia, flushing - 20-40 mg po daily
-CYP 3A4
-Nitrates, once daily
- Same as above + Pharyngitis! - 1 mg po TID , 2 weeks incr by 0.5 mg TID, if tolerate ur goal is 2.5 mg TID
-CYP 1a1, 3a4, 2C8, 2J2, ACTIVE METABOLITE CYP 1A1 and Antacids (Tums) u can use PPi’s or H2ra’s .
-REMS
-NITRATES, PDE5I’S, DIPYRIDAMOLE, THEOPHYLLINE, AMINOPHYLLINE, SMOKING
major : Dyspepsia, gastritis, HYPOtension
Minor : HA, dizzi, diarrhea, nausea
Prostacyclins :
- warnings? (3)
- Serious side effects
central line infections
risk of abrupt discontinuations
Name the 4 Prostacyclins and their route of admin
- EPOprostenol (IV infusion )
- TREprostinil (Iv infusion, sc infusion, inhalation qid –>nebulization, inhalation QID –> Dry powder inhal, oral –> BID or TID)
- Iloprost (Inhalation QID)
- Selexipag (Oral, BID and IV!)
Epoprostenol (Flolan and Veletri )
-Gold standard for ?
-Route of Admin ?
-Dose starting at ?
-Provided by ? Requires?
- High risk pt’s
- Continuous IV infusion via central venous catheter - 3 to 6 minute half life
- 2 ng/kg/min then titrate to dose range 25-45 ng/kg/min
- Specialty pharmacies , requires home teaching + daily admin/mixing using powder and diluent
IV Epoprostenol
-Can cause ___
AE’s such as :
H,J, F,N,D,S,M,I
-If there’s an interruption in infusion, this can be ___
-Tachyphylaxis
HA, Jaw pain, FLushing , N/D, Skin rash, Musculoskeletal pain , infections
-life threatening
Treprostinil (Remodulin and Orenitram)
1. Half life ?
2. Sq and IV avail , as well as inhalation and PO
3. Improved ___
4. AE’s similar to ? except ?
5. Oral ER tablet (Orenitram)
-Dose
- AE’s (4)
- 4.5 hrs
- 6MW
- Epoprostenol
-rate of catheter infection higher with regular formulation - Starting dose 0.125 mg TID or 0.25 mg BID
-HA, N/V/D
Treprostinil (Remodulin ) SQ
-Major AE?
-Varies from ?
-Improves after?
-Dose? (For SQ and IV)
Infusion site pain and site reaction
-Site to site and pt to pt
- several months
- 1.25 ng/kg/min
INHALED Prostacyclin Analogs
- Iloprost (Ventavis)
- DOsing ? - Treprostinil nebulizer (Tyvaso Neb)
-Dosing ?
-For PH groups ? (2) - Treprostinil Dry powder (Tyvaso DPI)
-Dosing ?
-PH groups?
- 2.5 mcg via nebulizer 6-9x per day while awake
- 3-9 breaths 4x per day while awake
PH group 1 and PH group 3 - 1 breath 4x per day while awake
-PH Group 1 PAH, PH Group 3 PH ILD***
Selexipag (Uptravi) Oral/IV (Prostacyclin receptor agonist)
- Dose?
-Increase to ??
-Renal adjustment ?
-Avoid in ?
-Moderate hepatic failure dose?
-Administer with or without __ but its recc with ___ to reduce ___
- CYP interactions?
-If patient on Plavix, how would u change the dosing?
-AE’s? (5)
- 200 mcg to 1600 mcg PO BID
-Increase by 200 mcg BID at weekly interval to highest tolerable dose up to 1600 mcg PO BID
-No
- Severe hepatic failure
- initiate at 200 mcg daily
- food, food, GI upset
-CYP 2c8 (Plavix), CYP 3a4
-From BID to Once daily
- HA, N/D, Muscle pain, Jaw pain
For each drug, state dose, DDI’s, and Toxic monitoring paramaters
All fda approved for Pul HTN, Epo also approved for Scleroderma
- Epoprost (FLolan , Veletri)
- Treprostinil (Sq, IV, INH, PO)
- Iloprost (ventavis)
- Selexipag (Uptravi)
- 2 ng/kg/min
- rapid hydrolysis in blood
- HA, vomiting, anorexia, flushing, myalgia, dizzi - SQ or IV 1.25 ng/kg/min
-INH 18 mcg via INH system 4x daily up to 54 mcg 4x daily
-PO 0.25 mg Q12h or 0.125 mg q8h
- CYp 2c8 and 2c9
- HA, cough, inject site pain, N/D, Throat irritation - 2.5 mcg via nebulizer, if tolerated up to 5 mcg 6-9x daily but no more than q2hrs
-Cough, HA, flushing, peripheral vasodilation, lockjaw - 200 mcg PO BID. Up to 1600 mcg BID at weekly interval if tolerated
-CYP 3a4, 2c8, UGT 1a3, UGT 2b7
-HA, N/D/V, Myalgia, flushing
Surgical Intervention
1. Lung transplant can be what 3 different scenarios?
- Chronic Thromboembolic Pulm HTN (CTEPH Group 4)
-What 2 methods to use?
- Singe or double lung, Combined heart and lung
- Pulmonary Thromboendarterectomy (PTE)
-Balloon Pulmonary Angioplasty (BPA)
What should be avoided in PAH pt’s?
Pregnancy
Supportive Therapies for PAH Pt’s
- Diet –>
- Exercise –>
- Appropriate ___
- Avoidance of ___
- Anti___
- D
- O
- Caution in ___
- P
- sodium restriction
- not heavy physical, low level aerobic
- vaccinations (Flu, Pneumo, COVID)
- Pregnancy due to hemodynamic changes
- Anticoag if not CI
- Diuretics (RV overload, peripheral edema)
- Oxygen (keep O2sat > 90%)
- High altitude
- Pyschological support
