Introduction to Pharmacology I – Characteristics of Drugs

Basics of Pharmacology I – Characteristics of Drugs


Pharmacology, oh pharmacology. Truly, quite a challenging field to master. Do I really have to know ALL these drug names?

But not to worry, mastering pharmacology comes with mastering the basics of this field.

For those of you who don’t know, pharmacology is a very broad term that refers to the study of substances that interact with living systems through chemical processes. These chemical processes can be triggered especially due to two major mechanisms:

  1. Activating or inhibiting normal body processes.
  2. Binding to regulatory molecules.

Furthermore, these substances that induce these chemical reactions can either have:

  1. Therapeutic Effects, by disrupting some negative process occuring in the patient.
  2. Toxic effects, as used by parasites on their host.

That’s right, pharmacology isn’t all the drugs we all assume it to be – it literally includes any substance that can act on the body, therapeutic or toxic.

Thus, it is important to specify what we mean exactly, by pharmacology.

The study of the therapeutic portion of pharmacology is referred to as medical pharmacology, which is the science of substances used to prevent, diagnose and treat a particular illness.

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In contrast, the study of the toxic or undesirable effects of substances on individual cells or entire ecosystems is toxicology.

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However, remember that although toxicology probably makes you think about poisons and parasites, any substance, even those intended to be therapeutic drugs, can be toxic in high amounts.

Just as an additional point of note, different drugs can actually have marginally (or majorly) different effects on the body based on each individual’s genetics. The study of the relationships of drugs in pharmacology to the genetic makeup of an individual is known as pharmacogenomics.

Now that we’ve covered some general terms, let’s talk about the real meat of pharmacology.

Nature of Drugs

We can define a drug as any chemical that brings about a change in biologic function through its chemical actions. Compare this to the definition of pharmacology! The “substances” referred to in the definition of pharmacology are in fact, drugs, be it therapeutic or toxic.

Any substance or drug can act either as an agonist or an antagonist. An agonist is a substance that acts as an activator, or promotes activity of a specific regulatory system or body process. An antagonist is a substance that acts as an inhibitor, having the opposite effect to the agonist.

But wait, what do these drugs act on? Drugs act on a regulator molecule, known as a receptor, which literally receives the agonist or antagonist molecule, and sends the signal to the body system it regulates, changing it to the liking of the agonist (activate) or antagonist (inhibit).

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A drug must have certain characteristics that make it appropriate for interacting with a receptor, and each receptor is very specific, only responding to a very specific drug. Furthermore, in pharmacology, a drug must also be easily delivered to a patient.

Thus, drugs that are artificially delivered to patients must have the following characteristics in order to be an effective pharmacological drug:

  1. The drug must have a very specific size, shape, atomic configuration and electrical charge to be able to interact with the receptor.
  2. A drug must have the necessary properties to travel to its site of action or receptor from its site of administration.
  3. It must be easily inactivated or excreted from the body once it has been used for its purpose.

These drugs can either be synthesized within the body, in which case they are called hormones, or chemically synthesized outside the body.

Of these drugs, poisons are drugs with harmful effects, HOWEVER, any drug or hormone in extremely high amounts can have harmful effects and thus, function as a poison. Of these poisons, toxins are poisons that are biologically synthesized.

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So if we think about a drug from here on out, we would have to think about two things:

  1. The effect of the drug on the body: This is known as pharmacodynamics.
  2. The effect of the body on the drug (eg. what does the body do with the drug? This includes factors like how the body breaks down the drug, and how the body transports and removes the drug). This is known as pharmacokinetics.
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(Diagram courtesy Basic and Clinical Pharmacology).

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Before we can talk about either of these though, we must consider the characteristics of a drug.

Characteristics of Drugs:

Physical and Chemical Nature of Drugs

Any drug given to the body can either be a solid (eg. aspirin), liquid (eg. ethanol) or gas (nitrous oxide).

What is the importance of this physical nature?

The physical nature of the drug determines how the drug is administered to the body.

Furthermore, drugs administered can all be carbohydrates, lipids or proteins, and this also affects their route of administration. The route of administration is a matter of pharmacokinetics, and will be discussed in detail in a later post, “Basics of Pharmacology III – Pharmacokinetics.”

One must also take note of the chemical nature of drugs. The addition of simple chemical groups have a large difference on the overall nature of the drug and its interactions with receptors and enzymes. As an example, a drug, acetylcholine, is usually hydrolyzed by acetylcholinesterase. When a methyl or a CH3 group is added however, the resultant methacholine is much more resistant to the effect of acetylcholineesterase. Furthermore, if an amine group is substituted for a methyl group, then the resultant carbachol is completely resistant to the effects of acetylcholineesterase.

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Drug Size

The molecular size of a drug varies from the very small, (eg. lithium ion, MW of 7) to very large (eg. alteplase, of MW 59,050).

Ideally however, a drug has a molecular weight between 100 and 1000.

Let us think about what sizes like this would mean for a drug.

Remember first of all, that a drug has to be sufficiently unique in order to have effects at receptors, which are very specific for size, charge, shape and atomic configuration. It is found that a drug must be of a certain size to have sufficiently unique characteristics that allow it to bind to a receptor. This size is approximately 100MW. Thus, the lower limit of drug size, 100MW, is determined by the need for the drug to be sufficiently unique and interact with the receptor.

This means the drug can be anything above 100MW right? Not particularly.

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Look at this dog trying to fit through the cat door – it just can’t fit!

If we think about the drug as the dog, and the cat door as the space allowed for transport of a drug, then we see the problem. All drugs must be able to carry out diffusion to move to the compartments in which they are needed. If the drug size is too large, then there is no way for the drug to diffuse into compartments, and the ability to diffuse decreases. Small drugs are able to fit through the small pores and into compartments where they can be used. Larger drugs just can’t fit.

It is found that the upper limit of drug size then, is determined by the need for the drug to be able to be transported or moved within the body. Thus, drugs larger than 1000MW do not diffuse readily, and thus most drugs are below 1000MW.

Note that however, drugs larger than 1000MW can still be used, but must be directly injected into the compartment where they act, so as to minimize the distance the drug must move, or be transported. As an example, alteplase, MW 59,050 is a clot dissolving drug that is injected directly to the vascular compartment by an intravenous or intra-arterial administration.

To summarize, the drug size must high enough to be unique to a receptor (this determines the lower limit of drug size, 100 MW – a drug ideally should not be lower than this), but must be low enough to still be able to move properly to the target cells (this determines the upper limit of drug size, 1000MW – a drug ideally should not be higher than this, as the transport of the drug will be negatively impacted.

Drug Reactivity and Drug Bonds

Drug-receptor bonds are of 3 major types:

  • Covalent
    • Covalent bonds, as you know, are very strong bonds, that are not readily broken. An example of a drug that uses a covalent mechanism of action is aspirin, which forms a covalent bond with its target enzyme, cyclooxygenase.
      • Aspirin works in two ways:
        • An anti-inflammatory drug for pain relief and anti-inflammation, by preventing production of the cyclooxygenase produced substance, prostaglandins.
        • An anti-clotting agent, or blood “thinner,” by preventing the production of thromboxane A2, another cyclooxygenase produced substance.
      • Wouldn’t you ideally want a blood thinning, pain relief drug to be long lasting? There lies the logic behind covalently bound drugs – their duration of action. The only way to reverse the effects of aspirin would be to synthesize new enzymes in new platelets, a process that would take several days to complete.
  • Electrostatic
    • This is a much more common type of bond in drug-receptor interactions, and is weaker than the covalent bonds.
    • They can either be:
      • Relatively strong ionic linkages between permanently charged molecules (eg. electrostatic interaction between Na+ and Cl-).
      • Weaker hydrogen bonds that occur in highly polar molecules.
      • Very weak induced dipole interactions such as Van Der Waals forces.
  • Hydrophobic
    • These bonds are quite weak.
    • Usually found in the interactions between highly lipid-soluble drugs and lipids in the cell membranes.

What is important is not the actual nature of the chemical bond, but the strength of the bond, and it’s significance to the drug-receptor interaction.

Suppose we want a drug that is highly specific, and only interacts with very few and very specific target cells, then would it make sense to use an extremely reactive drug, that would easily react with a number of substances along its way to the target cell, or would not be able to differentiate between two resembling, but different receptors?

The answer is no. Therefore, the strength of the drug-receptor bond determines the specificity of the drug. Drugs that bond via weak interactions usually are more specific, simply because only one particular type of receptor can be able to bind it and thus induce its effect. Another side effect of using a weakly reactive drug is that the drug cannot remain bound for very long, and thus has only short acting effects.

Thus ,to summarize, if we wish to have a specific, short-acting effect, a drug with low reactivity is ideal. If we wish to have a broad acting, powerful and long-lasting effect (think aspirin, as discussed above), we use drugs with higher reactivity.

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Drug Shape

Look at the picture below:

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Conceptually, think of a receptor as a lock, and the enzyme as the key that “activates” the lock. For this to happen, the drug has to be a perfect shape to “fit” into the receptor.

Chemically, a drug has to have a certain configuration that allows it to be chemically active and thus, react with a drug.

Hence, the drug must be of a specific shape that allows it to interact with the receptor.

Now look at this image below:

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It’s easy to see why a right hand would fit into a right sided glove, than the left hand right? Similarly, remember that many molecules demonstrate chirality, and form enantiomers. To elaborate, I mean that some molecules and drugs have the same chemical and structural formulae, but they are arranged differently in space. As an example:

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Both of these molecules are exactly the same in all ways except that one is like a mirror reflection of the other. This is just like looking at our hands isn’t it? Our hands are basically a reflection of each other, but have very similar anatomies.

Now imagine the receptor being specifically, a left sided glove. It is easy now to see why chirality is important. Only the one that is correctly placed in space or oriented, will fit into the receptor, and this is why both drug chemical makeup and chirality are important for the drug-receptor interaction.

However, remember that the more active enantiomer at one receptor does not necessarily have to be the more active enantiomer at another receptor. For example, in a drug called carvedilol, one enantiomer, the (S)(-) enantiomer, is a potent Beta-receptor blocker, while the (R)(+) enantiomer is 100 times weaker. However, both enantiomers are equally effective with Alpha receptors. When a drug is given that contains both chiral forms of the drug, it is referred to as a racemic mixture.

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Similarly, one should remember that enzymes and drug transporters are also sensitive to different enantiomers, and thus act more strongly against one enantiomer to another, affecting ease of transport and length of action of the drug. This is another way in which chirality affects the action of a drug.


That’s all for the introduction guys! These are all the characteristics of a drug we need to take note of. I’ll be discussing Pharmacodynamics and Pharmacokinetics next time I visit Pharmacology! Hope you guys enjoyed this!

VIDEOS:

Desired Characteristics of a Drug – Interview with Dr. Dennis Liotta

Desirable Properties in a Drug – Interview with Dr. David Fry

EXTRA RESOURCES

http://epharmacology.hubpages.com/hub/Characteristics-of-Drug

QUESTIONS:

1. Which of the following is not true?

A. The upper limit for drug size is 1000MW.

B. Drugs with high MW need to be administred directly into the compartment where they will be used.

C. Pharmacokinetics is the study of the effects of the drugs on the body.

D. The strongest type of drug-receptor interaction is the covalent bond.

2. Which of the following is true?

A. Smaller drugs with lower MWs are worse able to diffuse across to areas where they are used.

B. Ionic bonds are weaker than hydrophobic bonds.

C. A short acting, specific drug would be a drug with hydrophobic bonds.

D. Aspirin has broadly affecting, long lasting effects that are anti-inflammatory only.

ANSWERS: C, C

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