5 - Functional Groups, Acids, Bases, Carbonyls

Functional groups impact which properties of drug action?

pharmacodynamics, pharmacokinetics

Which is most lipophilic and why?

contains two ester groups, which are more lipophilic than the ethyl group on the middle drug and the phenol group on the far left drug

Which has the greatest CNS penetration and why?

the lipophilic esters increase CNS penetration

Which drug has a longer duration of action and why?

the drug on the right because the amide group is more stable against hydrolysis than the ester group; esters will always undergo hydrolysis, amides are more resistant

One of these drugs has high selectivity; which one and which region likely causes this?

Propranolol, it is the only drug with the double ring structure

What functional group lowers CNS penetration on fexofenadine?

carboxylic acid

Diphenhydramine is formulated as the HCl salt. In this form, what additional interaction can it make with water?

ion-dipole

Propranolol is formulated as the HCl salt. On what region does the salt form?

NH

T/F: nitrogen and oxygen containing functional groups can both be acidic

true

What is the acidic functional group on acetaminophen?

the phenol

What is the acidic functional group of losartan?

Which is the major form of ibuprofen in the blood and why?

the structure on the right; blood pH is greater than 2 above the pKa, meaning ibuprofen will be ionized in the blood

What is the major form of acetaminophen in the blood?

the structure on the left; blood pH is not greater than 2 above the pKa, meaning acetaminophen will remain unionized in the blood

Based on ionization in the blood, which likely has a larger VOD?

acetaminophen; the unionized drug will be better absorbed in the tissues

Which is likely to have higher oral bioavailability and why?

Losartan: it is a prodrug, meaning it is in it’s inactive form; it becomes active after administration, when the alcohol undergoes oxidation to become a carboxylic acid once already absorbed

On estradiol, which hydroxy group is ionizable?

phenol

The phosphate head on a cell membrane is ________ charged and repels ionized acids. this results in lower VOD

negative

In plasma, drugs containing carboxylic acids are highly bound to _______, resulting in lower VOD

albumin

In general, will an acidic or basic drug will have higher VOD?

basic because harder to ionize

Which drug would you expect to have a longer half life and why?

imipramine, it is basic

Creating the salt form of a drug typically increases which properties?

aqueous solubility and dissolution rate

Which drug is least likely to be ionized in the blood and why?

the far left; it’s nitrogens are non-basic

In nicotine, which nitrogen is more basic?

the nitrogen on the 5-ring structure

Imipramine is formulated as the HCl salt. On which nitrogen does the salt form?

on the amine

_____ is the term for tissues retaining basic drugs, increasing volume of distribution (VOD)

ion trapping

Which has lowest CNS penetration and why?

the far left structure, it contains an acidic group

Lidocaine is formulated as the HCl salt. At which region does the salt form?

the amine

Oseltamivir undergoes hydrolysis to its active form. Which region is most likely to undergo hydrolysis?

the ester

Oseltamivir carboxylate is the active form of oseltamivir. Which region restricts volume of distirubtion?

Carboxylic acid

Enalapril is an ester prodrug. The ester was added to improve which pharmacodynamic property and why?

absorption, the ester allows the drug to be absorbed more readily than the active carboxylic acid component

Which drug likely has the longest half-life and why?

the far right; the amid group will have greater duration of action compared to the carbamate or ester groups of the other drugs

Why does neostigmine have low oral bioavailability?

it has a permanent charge, meaning it will not distribute

Based on structure of these cholinergic drugs, which would selectively increase peripheral cholinergic activity and why?

the middle, the permanent positive charge will not allow it to penetrate the cns, keeping its action in the periphery

On average, what effect do ureas have on volume of distribution compared to amides?

decrease volume of distribution

Methyl salicylate is an ester prodrug. The ester was most likely added to improve which property?

permeability

How would the following likely impact duration of action and why?

increase; amide has greater duration of action than ester