Vasodilators Flashcards
Why does increasing K channel opening relax vascular smooth muscle?
K flux sets the membrane; the longer K channels are open, the closer the membrane potential is to the K equilibrium potential; the closer the membrane potential is to the K equilibrium potential, the harder it is to depolarize the membrane enough to open Voltage-Gated Ca Channels = relaxation of smooth muscle
What are the Direct Arterial Vasodilators?
Minoxidil, Diazoxide, Adenosine
What is the Importance of Minoxidil?
-Needs to be used with a Diuretic and a Beta-Blocker
-Has the side effect of Hair Growth [PDE5]
-Dosed ONCE - TID
What is the importance of Hydralazine?
-Needs to be given with a Diuretic and a Beta-Blocker
-Has the side effects to cause Lupus Like Symptoms
-Dosed BID - 4 TIMES DAILY
What is the importance of Diazoxide?
-It inhibits the release of insulin from pancreatic Beta-cells
-Used IV to treat acute HTN
-used orally for hyperglycemia 2nd to hyperinsulinemia
What is the importance of Adenosine?
-It binds to the A1 Receptor [The A1 receptor will have Gby bind to the GIRK receptor allowing K to flow out = causing hyper-polarization and relaxation]
-IV for Coronary stress test and arrhythmias
What causes the formation of NO?
The synthase of L-Arginine to L-Citruline will release NO into the Vascular Smooth Muscle
What does Acetylcholine do within Smooth Muscle?
It will help relax it via NO only in the endothelium, Acetylcholine without the endothelium will do nothing
How does NO actually cause relaxtion?
NO [released from the endothelium] is going to bind to GUANYLATE CYCLASE causing the production of cGMP. cGMP is then going to dephosphorylate the MLC-PO4 to MLC causing the RELAXATION.
How does protein kinase G relax smooth muscle?
-Inhibition fo L-type Ca channels [Ca 1.2]
-Stimulation of Ca-activated K channels [BK]
-Decreased MLC phosphorylation [Myosin Phosphatase 1]
-Enhanced Ca uptake in to ER [Phospholamban]
What are the Organic Nitrates/Nitrites?
The “-nitrates/nitrites”
-Amylnitrite, Gylceryl Tirnitrate [GTN], Pentaerthritol Tetranitrate [PETN], Isosorbide dinitrate, Isosrbide mononitrate, Nitroprusside
What is important about the Organic Nitrates?
-They are given Sublingually for Acute Angina
-Can develop tolerance
How do the Organic Nitrates develop tolerance?
They run out the reducing agents that will reduce ALDH2, ALDH2 is required for the removal of NO from GTN
What is the Importance of Nitroprusside?
Is only given IV for acute management of hypertensive crisis
-Dilates veins and arterioles
-metabolized in erythrocytes to NO, 4 CN- and cyanmethemoglobin [Increase lactic acid]
What is the importance of Hydralazine?
Will dilate the arterioles perferentailly and appears to interfere with the release of Ca from the ER
-May also cause Lupus-like symptoms
-Also prevent oxidation of NO
What is the Human Type B Natriuretic Peptide?
A hormone within the body that will respond to the increase volume and pressure. This will increase natriuresis and decrease CO & BP
How do PDE3 inhibitors affect Smooth Muscle tone?
Normally GCPRs will cause an increase of cAMP which will inhibit the phosphorylation of MLC causing the Relaxation
-PDE3 is going to breakdown cAMP causing a more Contraction affect; so PDE3 inhibitor are going to help with relaxation
What are the PDE3 inhibitors?
Amrinone/Milrinone
What do the PDE3 inhibitors do?
-They are given IV
-Used in CHF
Will stop PDE3 from making AMP = increasing cAMP
What are the PDE5 Inhibitors?
Tadalafil, Vardenafil, Sidenafil
How do the PDE5 inhibitors work?
They work by inhibiting the breakdown of cGMP which ill cause more NO to be produced causing more vasodilation
What is a weird side effect of PDE5 Inhibitors?
Blue vision
*CONTRAINDICATION: any PDE5 with Organic Nitrates
Why are the PDE5 inhibitors contraindicated with Organic Nitrates?
Both are going to cause an increase in cGMP, which will massively increase vasodilation.
