Drug+Action

**__Preface__**
Drug action or Pharmacology, is the study of the effect of different chemical compounds on the biochemical reactions of living organisms. Pharmacology is often branched into two paired studies: Pharmacokinetics and Pharmacodynamics. The former looks into the biochemical reactions done to the drug by the organism, while the latter refers to the biochemical reactions in the organism due to the drug.

Drugs are classified into two types:


 * **Agonists** - they stimulate and activate the receptors
 * **Antagonists** - they stop the agonists from stimulating the receptors

Although Pharmacology is a huge topic that can stand on its own, we will only focus on the ways that stereochemistry plays a role in drug action.

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Drug Enantiomers
Enantiomers of a chiral drug have identical physical and chemical properties in an achiral environment. In a chiral environment however, different enantiomers could display different chemical and pharmocological (biochemical reactions) behaviors. Since living systems are, in fact, chiral environments, chiral drug enantionmers will behave differently to one another. Ergo, for any given chiral drug, it is imperative to consider both enantiomers as separate drugs, as their chemical and physical behaviors will vary in a chiral environment.

When dealing with the molecular shapes of drugs, scientists are concerned with their 3D conformation. Different enantiomers will have different key characteristics thanks to their 3D form. The range of drug characteristics include **potency**, **efficacy**, **specificity**, and **affinity.**

A reminder regarding chiral isomerism:

"The absolute configuration at a chiral center is designated as R or S to unambiguously describe the 3-dimensional structure of the molecule. R is from the Latin rectus and means to the right or clockwise, and S is from the Latin sinister for to the left or counterclockwise."

Potency vs. Efficacy, Affinity & Specificity

 * Potency** is recognized as "the relationship between the dose of a drug and its therapeutic effect" and often refers to a drug's strength, which is brought about by many factors, one of which is polarity. Thus, a drug is considered potent when a small concentration of it achieves the intended effect. It is important to note that many highly potent drugs often, but not always, bring about more side effects.


 * Specificity** refers to the behavioral pattern for a certain drug to bind to a hand-picked receptor.


 * Affinity** is the ability of the drug to bind to a receptor and is affected by factors such as the conformation, bonding, and size of the drug and receptor.


 * Efficacy** therefore, is the relationship between receptor occupancy and the ability to initiate a response at the molecular, cellular, tissue or system level, regardless of the drug's potency. In other words, it is the ability for a drug to achieve a given effect.

As shown in Figure 1, although the first drug (shown in blue) achieves the desired effect while reacting a lesser concentration, both are effective as they both, at one point or another, achieved the desired effect. For this case to be true, both drugs would have to have a similar molecular shape, since their affinities are equal.

Cisplatin vs. Transplatin
A common of example of a way in which different enantiomers have different effects in an organism is the recurrent chemotherapy drug cisplatin (//cis-diamminedichloroplatinum(II), H 6Cl2N2Pt // ) which is used to treat various types of cancers, including testicular and ovarian cancer. It works because this cis- stereoisomer has an affinity that allows it cross link DNA thus triggering apoptosis (programmed cell death), in this case, the cancerous cells.

The trans stereoisomer, on the other hand seems to have little or no effect on living organisms. This is because its molecular structure doesn't have the correct stereochemistry to bond to two guanine bases on the DNA, unlike its cis- counterpart.



Polarity
"Heroin is much more potent and produces a much greater feeling of euphoria the morphine. This can be explained by the difference in the polarity of the two substances. Morphine molecules contain two polar -OH groups. When morphine is converted into heroin these are replaced by much less polar ethanoate groups. This makes heroin much more soluble in lipids which are non-polar. Heroin is then able to rapidly penetrate the lipid-based blood-brain barrier and reach the brain in higher concentrations than morphine." Suffice to say, heroin's side-effects are much more dangerous than those of morphine's due to its greater potency.

Ring Strain
Coming up as soon as I figure out what on earth it means...

IB Practice Questions
I have to learn how to make a decent graph first (using autograph)... hang in there.