adrenergic antagonists

what are the 3 major cardiovascular disorder/vascular related diseases for adrenergic antagonists?

1. HTN

2. arrythmias

3. angina

T/F: generally, any non-hydroxy substitution will be an antagonist

• true

what is the general backbone for non-selective adrenergic antagonists? (mixed alpha + beta)

• phenethylamine backbone

  • phenyl ring, ethyl group, nitrogen

what type of drug is this? 

• non-selective adrenergic antagonist (labetalol/Normodyne) 

  • only blocks alpha 1, beta 1, beta 2

    • phenethylamine backbone 

what is the use for labetalol? 

• nonselective alpha1 and beta1, beta 2 blocker

  • HTN 

what is a contraindication for labetalol (Normodyne)?

• asthma

  • blocks beta 2 receptors → bronchoconstriction

what is the brand name of Labetalol?

• Normodyne 

what type of drug is this?

non-selective alp[ha antagonist  (tolazoline / Prsicoline)

• imidazoline ring w/carbons/benzene 

what structure is common with non-selective alpha antagonists?

• imidazoline ring 

T/F: phenethylamine backbones have a high affinity for alpha receptors

• false 

  • imidazoline ring = high affinity for alpha receptors 

CH₂ - imidazoline + heavily substituted benzene ring =

a) alpha 1 agonist 

b) alpha 2 agonist 

c) nonselective adrenergic antagonist 

d) nonselective alpha antagonist 

a) alpha 1 agonist 

NH₂ - imidazoline + heavily substituted benzene ring =

a) alpha 1 agonist 

b) alpha 2 agonist 

c) nonselective adrenergic antagonist 

d) nonselective alpha antagonist 

b) alpha 2 agonist 

which of the following structures is an antagonist that is LESS lipophilic than the agonist? 

a) phentolamine 

b) quinazoline 

c) tolazoline 

d) labetalol 

c) tolazoline

what is the indication for tolazoline?

• pulmonary HTN (newborns with increased BP in lungs

• administered IV

if this drug is given IV for injection, what type of salt will it be/used? 

a) hydrochloride 

b) sodium

a) hydrochloride 

• basic drug (imidazoline) = HCl

what nucleus loves alpha receptors? 

a) imidazole 

b) imidazoline 

c) imidazolidine 

d) all of the above

b) imidazoline 

is there a use for selective alpha 2 antagonists?

• no 

  • no required therapeutic uses 

what type of drug is this?

• non-selective alpha antagonist (phentolamine / Oraverse)

  • imidazoline

what is the use for phentolamine / Oraverse?

• pheochromocytoma diagnosis and treatment

are there any electron withdrawing or donating substituents on the benzene?

• no

what is the major use / only use for alpha 1 selective antagonists?

a) arrhythmias

b) cardiac block 

c) angina

d) HTN 

d) HTN 

• dilates blood vessels

what is the name of this functional group? 

• quinazoline 

  • add an extra nitrogen to quinolone 

what are the common structures found in alpha-1 antagonists? 

• quinazoline nucleus 

• piperazine 

• carbonyl

• amino group 

• 6,7 dimethoxy 

T/F: alpha-1 selective antagonists have a phenylethylamine backbone

• false 

  • have a QUINAZOLINE nucleus 

what metabolizes quinazoline?

• CYP in liver

what is the indication for prazosin (Minipress)

• HTN

  • alpha-1 antagonist 

what type of drug is this?

• alpha-1 selective antagonist (prazosin / Minipress)  

  • quinazoline nucleus 

  • piperazine

  • furan

in alpha-1 selective antagonists, the piperazine is always found at what position? 

a) position 1 

b) position 2

c) position 6 

d) position 7 

b) position 2

how do you number this quinazoline found in alpha-1 antagonists? 

what type of drug is this? 

• alpha-1 antagonist ( Terazosin / Hytrin) 

  • quinazoline nucleus 

  • piperazine

what is the indication for Terazosin ?

• HTN 

  • alpha-1 antagonist 

what type of drug is this?

• alpha-1 antagonist (doxazosin / Cardura) 

  • quinazoline nucleus 

  • piperazine 

what is the indication for doxazosin?

• BPH 

• CHF (congestive heart failure) 

• HTN 

what type of drug is this? 

• alpha-1 antagonist ( Trimazosin) 

  • quinazoline nucleus 

  • piperazine 

what is the indications for Trimazosin?

• HTN 

what is the purpose of the -OH group in Trimazosin? 

• makes it short acting 

  • metabolized directly into phase 2-conjugation

most alpha-1 antagonists are metabolized how and where?

• metabolized by O-demethylation 

  • by CYP in the liver (microsomes) 

alpha-1 antagonists are all given as …

• injection for HTN 

what type of drug is this? 

• special alpha-1 antagonists ( Tamsulosin / Flomax)

  • alpha 1A antagonist 

what is the difference between Tamsulosin from other alpha-1 antagonists?

• phenethylamine nucleus instead of quinazoline nucleus

• no affinity to blood vessels

what is the purpose of the sulfur/sulfonnamine group in tamsulosin? 

• liver HATES sulfonamine

  • drug goes directly to kidneys 

what is the indication for Tamsulosin?

• BPH 

  • alpha 1A antagonist 

what type of drug is this?

• alpha 1A antagonist (Alfuzosin/ Uroxatral)

  • quinazoline nucleus

  • NO piperazine

what is different about Alfuzosin compared to other alpha-1 antagonists?

• NO piperazine ring system → less affinity to circulatory = selective to Alpha 1 A

  • alpha 1A antagonist 

what is the indication for alfuzosin?

• BPH

what type of drug is this? 

• alpha-2 antagonist (Yohimbine HCl) 

what is the indication for Yohimbine?

• sexual dysfunction ( impetus) 

what is contraindicated with nonselective beta antagonists?

• asthma + diabetes 

what are the uses for B1 antagonists/ nonselective beta antagonists?

• HTN

• arrythmia (treat/correct) 

• angina  

how is the structure of beta antagonists similar to NE?

• take OH away from NE structure = antagonist

  • non-hydroxyl substitution 

what are the common structures found in non-selective beta antagonists?

• O-CH₂ between ethylamine and phenyl ring 

what type of drug is this? 

• nonselective beta antagonist (propranolol / Inderal) 

  • O-CH₂ between ethylamine + phenyl ring 

how is propranolol metabolized? `

• aromatic hydroxylation by CYP in liver 

• some goes directly → phase II conjugation 

why should propranolol not be given to a patient with liver (cirrhosis)? 

• propranolol is metabolized by liver (aromatic hydroxylation) 

  • can lead to toxicity

what structure is essential for beta antagonists?

• O separating benzene + ethyl group 

what is the indication for propranolol

• angina

• HTN 

• arrhythmia 

what type of drug is this? 

• non-selective beta antagonists ( Pindolol / Visken) 

  • O-CH2 separates ethylamine and phenyl ring 

what is the indication for pindolol?

• angina

• HTN 

• arrhythmia 

what is the nucleus for pindolol? 

• indole 

why should pindolol not be given to patients with liver failure (cirrhosis) 

• drug is metabolized by liver 

  • can cause toxicity 

what type of drug is this? 

• nonselective beta antagonists (nadolol / Corgard)

  • O-CH2 separates ethylamine + phenyl ring 

what is the indication for nadolol?

• angina 

• HTN 

• arrhythmia 

why should nadolol not be given to a patient with liver failure?

• conjugated in phase II reactions in liver and kidney

  • polar group (secondary nitrogen, secondary alcohol) w/ glucuronic acid 

does nadolol have a catechol group? 

• NO 

  • 3,5 hydroxyl group but it is not on a benzene ring 

what type of drug is this? 

• nonselective beta antagonist ( Timolol Maleate) 

  • O-CH2 separates thiadiazole and ethylamine 

what is the indication for Timolol 

• glaucoma eye drops (more polar with hydrophilic side chain (hetero atoms) 

  • opens canal of Schlemm

T/F: the N-substitutions in nonselective beta antagonists are always bigger than methyl and ethyls

• true (isopropyl or butyl)

what are the common structures found in selective beta1 antagonists? 

• isopropyl N-substiution 

• O-CH2 spacer between ethyl and benzene 

• single benzene ring with 1 substitution at position 4 (para) 

if a drug structure has a single benzene ring with 1 substitution at positon 4/ para, it is most indicative of a 

a) nonselective alpha antagonist 

b) selective alpha-1 antagonist 

c) nonselective beta antagonist 

d) selective beta 1 antagonist 

d) selective beta 1 antagonist 

what type of drug is this?

• selective beta-1 antagonists (atenolol / Tenormin) 

  • only 1 benzene ring w/ substituent at position 4 

  • OCH2 spacer 

what is the indication for Atenolol ? 

• angina 

• arrhythmia 

• HTN

how is atenolol metabolized? 

• metabolized by amidases in liver 

  • produces ammonia + carboxylic group 

what type of drug is this? 

• selective beta1 antagonist (esmolol / Brevibloe) 

  • 1 benzene ring w/ substituent at position 4 

  • OCH2 spacer

what is the indication for esmolol

• INJECTION for acute MI, HTN, arrhythmia 

how is esmolol metabolized? where? 

• ester substituent → esterases in GIT

  • fast metabolism

what type of salt is esmolol given for injection? 

a) Hydrochloride 

b) sodium

• a) Hydrochloride 

  • basic secondary Nitrogen

can you give esmolol orally? 

• no 

  • fast metabolism by esterases in GIT = will inactive drug before absorption 

what type of drug is? 

• beta-1 antagonist (metoprolol succinate / Toprol XL) (metoprolol tartrate/ Lopressor)

  • 1 benzene ring w/ substituent at position 4 

  • OCH2 spacer

how is metoprolol metabolized? 

• O-demethylation by CYP in liver 

what is the indication for metoprolol? 

• angina

• arrhythmia

• HTN

what type of drug is this? 

• beta-1 antagonist (bisoprolol fumarate / Zebeta) 

  • 1 benzene ring w/ substituent at position 4 

  • OCH2 spacer 

is metoptolol or bisoprolol more long-acting? 

• bisoprolol 

  • Isopropyl in ether = less likely to undergo O-demethylation by CYP in liver 

what is the indication for bisoprolol fumarate?

• HTN 

• CHF (congestive heart failure) 

what type of drug is this? 

• b1 antagonist (betaxolol / Beptic S; Kerlone) 

  • single benzene w/ substituent at postion 4 

  • OCH2 spacer 

does betaxolol or metoprolol have longer action of duration?

• betaxolol

  • less likely undergo O-demethylation by CYP in liver = longer duration of action than metoprolol

what is the indication for betaxolol ?

• glaucoma 

• HTN 

• angina 

SATA: which of the following drugs have a longer action of duration than metoprolol?

a) esmolol 

b) bisoprolol 

c) betaxolol 

d) atenolol 

b) bisoprolol 

c) betaxolol 

which of the following is metabolized by esterase? 

a) atenolol 

b) esmolol 

c) metoprolol 

d) bisoprolol 

b) esmolol 

which of the following is metabolized by amidases? 

a) atenolol 

b) esmolol 

c) metoprolol 

d) bisoprolol 

a) atenolol 

which of the following is most likely to be metabolized by CYP for o-demthylation? 

a) atenolol 

b) betaxolol 

c) metoprolol 

d) bisoprolol 

c) metoprolol