Exam 4 - Lecture 44, Medical Chemistry Adrenergic Antagonists

binds tightly for prolonged period of time to adrenergic storage vesicles in CNS and PNS decreases storage of NE and DA which leak into cytoplasm, Ne and DA gets metabolized by MAO

acts by inhibiting the release of NE PNS only cause doesn’t cross BBB, drug always charged antihypertensive drug

forms covalent bond with receptor (N-2C-Cl), forms aziridinium intermediate. happens in basic forms New receptors have to be made before effect can be overcome non-selective a antagonist

contains piperazinly quinazoline nucleus up to 1000 times selective for a1 over a2 Terazosin - 18hr, 90% Bio av Doxazosin - 36hr, 50-70% bio avi Prazosin - 7-10hr, 50-70% Bio avi

poor oral bio avail <30% and undergoes extensive first pass

added oxymethylene bridge to molecule and it started working well. angina, antihypertensive, and cardia arrhythmia OH essential for H-bond O involved in H binding too Branching important to fit hydrophobic pocket

Difference between propranolol, has 2 OH on ring making it hydrophilic. high water soluble drugs cleared by kidney more lipophilic drugs cleared by liver

Has 1 ring not 2 like propranolol, and no oxymethyline bridge

hydrophilic, cleared by kidney primarily

exception for para substitution rule which would make it selective for B1 drug is nonselective to b1/b2

COO linkage is where esters chop and make it useless, which is why it has very short duration of action

b blocking is about 1.5 time that of a blocking

b blocking is about 10-100 times that of a blocking