Vasoconstrictors/Vasodilators Flashcards
What receptors are the molecular basis that causes vascoconstriction?
GPCRs coupled to vasoconstriction: a1 adrenergic
what drugs are alpha1 receptor agonists?
- epinepherine
- phenylephrine
- midodrine
- droxidopa
what do we use for an adjunct to local anesthetics that can help reduce blood flow to injection site?
epinepherine
what drug do we use for homeostasis during surgery?
epinepherine
what are the direct-acting a1 receptors ?
phenylepherine
what is an indirect acting agent for a1?
peudoephederine
what are the partial agonists for a1 receptors?
naphazoline, oxymetazoline, tetrahydrozoline
why does increasing K+ channel openings relax vascular smooth muscle?
- K+ sets membrane potential
- longer channels open the closer to equilibrium
- The closer to equilibrium the harder it is to depolarize enough to open VOLTAGE_GATED Ca2+ Channels
what is minoxidil? What does it do?
K+ Channel agonist/open
- promotes hair growth (hypertrichosis)
what drug classes are vasodilators?
- Cyclic GMP Modulators
- K+ Channel agonists
- Endothelin receptor Agonist
- PGI2 analogs - IP receptor agonist
what is diazoxide? what is its use and moa?
- K+ channel agonist/opener
- inhibit release of insulin from Pancreatic B-cells
- orally for hypoglycemia to hyperinsulinemia
what is adenosine? What is it used for?
- binds to A1 (GPCR)
- given IV - coronary stress test
- also supraventricular arrhythmias
how does adenosine hyperpolarize vascular smooth muscle?
GIRK
1. Gby binds and activates GIRK–> conducts K+ and membrane hyperpolarization
what is the nitric oxide-cyclic GMP pathway?
- eNOs found in vascular endothelium (activated by Ca2+-CAM)
- NO diffuses to vascular smooth muscle
- guanylate cyclase is found in the vascular smooth muscle
what happens after NO moves to smooth muscle and how does it relax it?
- NO binds to heme iron group in guanylate cyclase
- activates protein kinase G (cGKI)
- elevated GMP reduces phosphorylation of myosin LC causing relaxation
how does protein kinase G relax smooth muscle?
- inhibit L-type Ca2+ channel (Cav1.2)
- stim Ca2+ K+ channel (BKca)
- decreased myosin phosphatase 1
- enhance Ca2+ in ER (phospholamban)
what do organic nitrates do?
breakdown to NO (bioactivation)
what are the PK of organic nitrates?
- given sublingual in tx of acute attacks of angina
- tolerance occurs with continuous admin
who had a tolerance to glyceryl trinitrate?
munitions workers
what is the PK for glycerol trinitrate?
likely accounts for the lack of efficacy of GTN in a large percentage of the Asian population
what is the mechanism of cell damage inititated by hyperglycemia?
AGE precursor methylglyoxal inhibits vasorelaxation stimulated by acetylcholine/Nitric Oxide
what does sodium nitroprusside do ?
- dilates veins and arterioles
- limits duration of treatment due to ctructure
what is hydralazine and what does it do?
- dilates arterioles preferentially
- interfere with the release of Ca2+ from the ER
what does the combo of hydralazine and ISDN do for BiDil?
decreased mortality in AA with CHF
what is BNP and what does it do?
- human type B natriuretic peptide
- binds and activates membrane-bound guanylate cyclase
what is sacubitril and when is it not used?
- inhibitor of neprilysin (a protease)
- prevents breakdown of BNP by enhancing its action
- not used with ACE
what are the 2 PDE3 cAMP inhibitors? what do they do?
amirone and milrinone
1. inhibit the breakdown of cGMP/AMP
what fold of difference does cGMP PDE5 have over PDE6?
10 fold selectivity inhibition of PDE6 in retina
what does the inhibition of PDE6 in retina cause?
bluish vision
what is the effect for sildenafil on blood flow in the penis?
predominent in the corpus cavernosum
what is special about levitra compared to other PDE5s?
- shorter time to onset than viagra
- more selective than viagra
what is special about cialis compared to the other PDE5?
- more selective than viagra
- longer duration of action than viagra or levitra
when is a PDE5 contraindicated?
organic nitrates
what are the main vasodilators used in PAH?
actin neutralizers
what are the 3 vasoconstrictor antagonists?
- bosentan
- macitentan
- ambrisentan
what does bosentan and macitentan have in common?
- both block ETa and ETb
- low MW receptor antagonsits
what is special about ambrisentan?
blocks only ETa
what are vasoconstircotr antagonsits approved for and contraindicated for?
- approved for pulmonary arterial HTN
- contraindicated in pregnancy and hepatotoxicity (bosentan only)
what do prostacyclin analogs do? where is it produced?
- relax pulmonary vascular SM
- PGI2 found in endothelium
what are the different drugs in the prostacyclin class and what is their dosage form?
- PGI2 –> IV
- treprostinil –> oral, IV
- lloprost –> inhalation
- selexipag –> oral (bid), IV
what is adempas and its mechansim and metabolism?
- allosteric activator of sGC
- increases cGMP concentration in VSM
- substrate for P-gp, CYP1A1, 3A
what drug is this?
minoxidil
what drug is this?
diazoxide
what drug is this?
SNP
what drug is this?
hydralazine
what drug is this?
sacubitril
what class is this?
PDE3
what drug is this?
tadalafil
what drug is this?
sildenafil
what drug is this?
vardenafil
what drugs is this? what class?
vasoconstricotr antagonsit
- bosentan and macitentan
what drug is this?
ambrisentan
what drug class is this?
prostacyclin analogs
what drug is this?
riociguat
