Lipophilic Functional Groups in Chemistry

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Questions and Answers

What is the functional group of alkenes?

Carbon-oxygen single bond

Carbon-carbon double bond (correct)

Carbon-nitrogen single bond

Carbon-carbon triple bond

What is the simplest alkene?

Naloxone

Ethyne

Ethene (correct)

Lidocaine

What is the functional group of esters?

Carbon-carbon double bond

Carbon-nitrogen single bond

Carbon-carbon triple bond

Carbonyl group attached to an alkoxy group (correct)

What is the functional group of amides?

Carbonyl carbon atom singly bonded to a nitrogen atom Signup and view all the answers

What is the simplest alkyne?

Ethyne Signup and view all the answers

What is the structural arrangement of carbon in a carbonyl group?

C=O Signup and view all the answers

Which of the following is a characteristic of the carbonyl group?

It is polar with oxygen being more electrically negative Signup and view all the answers

What is the simplest alkane?

Methane Signup and view all the answers

What is a characteristic of alkanes?

They are not water soluble Signup and view all the answers

Which functional groups contain a carbonyl group?

Aldehydes, ketones, carboxylic acids, esters, and amides Signup and view all the answers

What type of molecules do lipophilic functional groups tend to be drawn to?

Hydrocarbons and other non-polar molecules Signup and view all the answers

What is a common characteristic of amines?

They have a lone pair of electrons on the nitrogen Signup and view all the answers

What is the general formula for alcohols?

ROH Signup and view all the answers

What is a key feature of the hydroxyl group (-OH) in alcohols?

It is highly polar and easily forms hydrogen bonds Signup and view all the answers

What is a characteristic of amines that makes them important in pharmaceuticals?

Their ability to accept a proton from a strong acid Signup and view all the answers

What type of reaction is hydrolysis classified as in Phase I metabolism?

Hydrolysis Signup and view all the answers

What is the result of enzyme induction on the half-life of a drug?

Shortening Signup and view all the answers

What is the main purpose of Phase II metabolism?

To make the compound more water-soluble Signup and view all the answers

What happens to orally given drugs in the first pass metabolism?

They are carried via portal vein circulation to the liver for metabolism Signup and view all the answers

What is the term for the attachment of a sugar group to a molecule in Phase II metabolism?

Glycosylation Signup and view all the answers

What is the effect of hepatic disease on the clearance rate of drugs that are capacity-limited?

It decreases the clearance rate Signup and view all the answers

What is the bioavailability of IV drugs by definition?

1 Signup and view all the answers

What happens to enzymes when there is enzyme inhibition?

Their activity decreases Signup and view all the answers

What is the result of enzyme saturation on the metabolism of a drug?

The metabolism rate decreases Signup and view all the answers

Which phase of metabolism is responsible for making a drug more water-soluble?

Phase II metabolism Signup and view all the answers

Study Notes

Functional Groups

Lipophilic molecules are drawn to hydrocarbons and other non-water-soluble molecules.

Amines

Amines are derivatives of ammonia (NH3) with the general formula NR3, NHR, NRR', and +NRR'R".
All amines have a lone pair of electrons on the nitrogen atom.
Amines can form hydrogen bonds and tend to be more soluble in water than many other functional classes.
A large number of medications are amines.
Amines have a noticeable base strength and will accept a proton from a strong acid to form its conjugate acid (an ammonium salt).

Alcohols

Alcohols have the general formula ROH, where R represents any alkyl group.
The hydroxyl group (-OH) of alcohols is highly polar and easily forms hydrogen bonds with other polar molecules.

Carbonyl Groups

The carbonyl group (=O) is a key component of several functional groups: aldehydes, ketones, carboxylic acids, esters, and amides.
The carbonyl group is polar, with the oxygen being more electrically negative.
The carbonyl group is structurally identified as C=O.

Hydrocarbon Functional Groups

Alkanes (C-C) are also known as paraffins and are the simplest of the organic compounds.
Alkanes are characterized by carbon-carbon single bonds.
Alkanes are the carbon backbone for other functional groups and are not water-soluble.
Alkanes are hydrophobic (water-fearing) and lipophilic (lipid-loving).

Alkenes

Alkenes have a carbon-carbon double bond functional group.
The simplest alkene is ethene (ethylene).
The location of the double bond is given by a locant number that identifies the first carbon in the double bond.
The main functional group always gets the lowest number.
Drugs that have alkenes include Naloxone and Vitamin K.

Alkynes

Alkynes have a carbon-carbon triple bond functional group.
The simplest alkyne is ethyne (acetylene).
Alkynes are relatively rare in medical settings.

Amides

Amides are similar to esters and have a carbonyl carbon atom singly bonded to a nitrogen atom.
Examples of amides include PCN, LSD, and Lidocaine.

Esters

Esters have a carbonyl group attached to an alkoxy group (single bond to an oxygen atom).
Esters have increased lipophilicity, which increases the absorption of the drug.

Hepatic Clearance

Hepatic clearance is the rate of hepatic metabolism by the liver, which is the difference between the drug concentration flowing into the liver and the drug concentration flowing out of the liver, multiplied by the rate of liver blood flow.
Clearance is the amount of blood completely cleared of drug per unit time.

Phase II Enzymes

Special consideration that affects metabolism is the difference between slow and fast acetylators (phase II reaction).
Slow acetylators are more prone to toxicity with amides.
Ethnicity affects acetylator phenotype:
- Caucasians: 50% fast acetylators
- African Americans: 50% slow acetylators
- Asians: 60-100% fast acetylators (e.g. Japanese: 80% fast acetylators)

Metabolism

Phase I metabolism is enzymatic and can be saturated when too much or different drugs that use the same pathway are given in combination.
The liver cannot remove every last drug molecule, and there is always some drug in the effluent plasma.
The fraction of inflowing drug extracted by the liver is the extraction ratio.

CYP-450 System

CYPs are a family of enzymes, with 50 types collectively known as the CYP-450 system.
6 enzymes (CYP1A2, 2C9, 2C19, 2D6, 3A4, and 3A5) metabolize 90% of drugs.

Metabolic Pathways

There are 4 basic pathways of metabolism: phase 1 and phase 2 reactions.
Phase 1 reactions include: oxidation, reduction, and hydrolysis, which increase the drug's polarity.
Phase 2 reactions include conjugation, which increases solubility and renders the conjugate more water-soluble for subsequent excretion.

Sites of Metabolism

Hepatic microsomal enzymes are responsible for the metabolism of most drugs.
Other sites of drug metabolism include the plasma, lungs, kidneys, and gastrointestinal tract, and placenta.

Oxidation and Reduction

Oxidation is the loss of electrons, loss of hydrogen atoms, or gain of oxygen atoms.
Reduction is the gain of electrons, gain of hydrogen atoms, or loss of oxygen atoms.
Oxidation and reduction are complementary processes.

Induction and Inhibition

Some drugs can increase the amounts of available enzymes, known as induction, resulting in shorter half-life.
Some drugs can inhibit these enzymes, resulting in prolongation of half-life.

Phase 2 Reactions

Phase 2 reactions are synthetic reactions that attach polar molecules to the compounds being metabolized.
Most drugs undergo phase 1 reactions and then phase 2 reactions.
Common phase 2 reactions involve the attachment of a sugar group to the molecule, making it water-soluble.

First Pass Metabolism

Orally given drugs are carried via portal vein circulation to the liver, where they get metabolized.
The bioavailability of IV drugs is 1 by definition.

Extraction Ratio

When clearance is flow limited, it is generally unaffected by modest changes in hepatic capacity.
When clearance is capacity limited, changes in liver metabolic capacity produce nearly proportional changes in clearance rate.

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Description

Learn about lipophilic molecules and functional groups that are attracted to hydrocarbons and other non-water soluble molecules. Understand their properties and types.