pulmonary hypertension drugs - IP receptor agonists

prostacyclin is synthesized from ______? and released from what cells

arachidonic acid ; vascular endothelial cells

prostacyclin effects and what cell in this context is it affecting

relaxant and anti-proliferative on the vascular smooth muscle cells

what group of pulmonary hypertension makes less prostacyclin

group 1

prostacyclins receptor/pathway for vasodilator effects

IP receptors; AC activation —> higher cAMP —> lower intracellular Ca

prostacyclin analogues treat what class PH

severe so class III and IV PH

IP receptor agonist drugs (4)

epoprostenol sodium, iloprost, treprostinil, selexipag

epoprostenol sodium dosage form and therapeutic use

IV formulation of prostacyclin (agonist) for the long term tx of group 1 (class III/IV) PH in pt’s who don’t respond to conventional therapy

what line (1st,2nd,3rd?) is epoprostenol sodium for what class of PH and why

first line therapy for class IV - improves pulmonary hemodynamics, symptoms, and mortality over 12 weeks

MOA of epoprostenol sodium

non-selective prostanoid receptor agonist

what receptor activation predominates in epoprostenol sodium and this leads to?

IP receptor activation leading to arterial vasodilation and inhibits platelet aggregation

half life of epoprostenol sodium and what that entails

short (2-3 min) so needs IV infusion via venous catheter

epoprostenol sodium at room temp

Clinically unstable, needs to be stored in the fridge

how to administer epoprostenol sodium

with careful, frequent monitoring

also slow up titration necessary for pt’s to establish tolerance to adverse effects

epoprostenol sodium adverse effects

myalgia and pain in extremities, nausea, vomiting, headache, hypotension, and flushing

rapid withdrawal of epoprostenol can lead to

rebound of PH symptoms

epoprostenol has how many metabolites and what are they

2; both inactive in preclinical (not completely just not clinically relevant bc sm less activity/potency than parent drug)

iloprost dosage form and therapeutic use for what pt pop.

Inhalation formulation for nebulizer administration for the treatment of Group I (Class III & IV) PH

iloprost has an added benefit when co-administered with

endothelin receptor antagonists for severe PH

iloprost moa

selective IP receptor agonist

iloprost is an analogue of _____? and what modification was made to create the drug

endogenous prostacyclin; remove O so instead of furan (no double bonds) —→ cyclopentane

iloprost designed to target

pulmonary vasculature to minimize systemic side effects

iloprost dose frequency

Inhalation doses generally administered >2 h apart due to half-life (t1/2 = 20-30 min), but patient compliance can be challenging

common side effects of iloprost

cough, throat irritation, and other milder than, but similar to those for epoprostenol

treprostinil 3 brand names

remodulin, tyvaso, orenitram

remodulin therapeutic use/ dosage form / what pt.pop

olution formulation amenable for intravenous or subcutaneous infusion for the treatment of Group I (Class II, III & IV) PH

tyvaso and orenitram dosage forms

Inhaled formulation for nebulizer administration (can be used in combination therapy)

Extended- release, oral formulation (monotherapy in tx of naive pt’s)

treprostinil moa / is an analogue of what

Selective IP receptor agonist

Analog of endogenous prostacyclin

treprostinil: what modifications added from og prostacyclin

red stuff (this is normal prostacyclin)

treprostinil is more what compared to prostacyclin/epoprstenol

chemically stable

treprostinil half life and elimination

4 hours; excreted by liver as inactive metabolites

treprostinil contraindicated to what CYP drug and other adverse effects are similar to …

Contraindicated to CYP2C8 inducers or inhibitors

Other adverse effects are similar to those for epoprostenol

selexipag dosage form and therapeutic use

Oral formulation for the treatment of Group I (Class II & III) PH

selexipag moa

Selective IP receptor agonist (structurally distinct from prostacyclin analogs)

selexipag is what kind of drug

prodrug

selexipag adme points (potency/bioavail?)

very potent and 50% bioavail

selexipag contracindlcated to what CYP drug and adverse effects

Contraindicated to CYP2C8 inducers or inhibitors

Adverse effects are similar to those for prostacyclin analogs

(this info same for treprostinil as well)

epoprostenol sodium

iloprost

treprostinil

selexipag

active metabolite of selexipag what changes