1. Introducing Pharmacology
2. Importance of Pharmacology in Medical Sciences
4. Therapeutic activity Vs Side-effects
1A. What is pharmacology?
The definition of pharmacology arises from its literal meaning. Most words in medical sciences have roots in ancient Greek language, and pharmacology is no exception:
In modern context, pharmacology is defined as the study of drugs; mainly in terms of their mechanism of action and their therapeutic or adverse effects, rather than their chemical structure (medicinal chemistry), dispensing (pharmacy) or prescribing suitability with regards to a particular diagnosis (medicine). A pharmacologist is the scientist that studies what a drug does in a particular system, model or molecular pathway, how the body reacts to it and determines its functional or physicochemical properties.
1B. A Brief history of development
Pharmacology as a discipline is relatively new (about 150 years old), since the science of pharmacology has sprung from the research of 19th-century chemists, biologists and medics. Due to its vital role in the development of drugs and the successful treatment of diseases, it was soon characterized as a separate scientific discipline.
Ancient civilizations like the Greeks, Egyptians, Chinese, Persians and Romans had extensive knowledge about the use of different medicines and where they could be found in nature. However, since the efficient study of drugs is vastly dependent on sufficient knowledge in other fields (i.e. successful extraction or synthesis, efficient purification methods, knowledge of its chemical structure, knowledge on the physiology of a particular disease state), pharmacology has developed only after advances in these fields (or simultaneously at best).
Since the early 18th century, the development of pharmacology mostly follows a specific pattern:
The general goal of pharmacology is to understand the underlying molecular mechanisms responsible for the biological activity of drugs in order to enable their rational use and enhance their improvement. Recently, swift advances in a variety of scientific fields (molecular biology, genetics, chemical modeling, electrophysiology, physics, computing) have provided a platform for future pharmacological innovations. During the last decade, these scientific fields have developed sophisticated tools that are being used in modern pharmacology for greater advances in the prognosis, diagnosis and treatment of medical disorders.
2A. Pharmacology & related sciences
In the biomedical world, there are a number of different disciplines that can overlap or even combine with others to structure their identity. There are six major disciplines that can be regarded as discrete sciences and combine together to produce more general sciences/professions, like pharmacy (preparation, storage and dispensing of drugs), medicine (diagnosis, treatment and prevention of diseases) and pharmaceutics (formulation and physical properties of pharmaceutical products).
The Major-Six disciplines are:
Of course, in modern biomedicine the rational study of any of the Major-Six premises substantial knowledge in all of them in order to make the most of its capabilities and applications (e.g. study of pharmacology presupposes some knowledge of biochemistry, molecular biology and genetics).
2B. Subdivisions of Pharmacology
Another consequence of the rapid advance in most of the Major-Six is the development of subdivisions in order to focus their training and research in discrete topics. For example, in pharmacology, some of the subdivisions that can be often found as discrete degrees or research areas are:
For obvious reasons, the boundaries between these rapidly-developed areas of research are not evident and refined. Their scope of study and research objectives should be viewed as a continuous and overlapping research across the spectrum of pharmacology, such as the colours overlap across the light spectrum. Also, their major differences are not based on the diseases they implicate, but rather on the angle of research they use to approach a specific disease (e.g. molecular, pathological, psychological, behavioural, genetic).
2C. Pharmacokinetics & pharmacodynamics: the heart and soul of pharmacology!
From the time that a drug enters the body to the point of its excretion, pharmacology looks at every aspect of the relationship ‘drug-body’:
Pharmacokinetics involve the administration of the drug in the body (and the various barriers of the latter to its diffusion – i.e. the blood brain barrier), absorption of the drug from the tissues, metabolism of drug by the body (as a defense mechanism for an external unknown substance), distribution of the drug to the tissues (and its site of action) and excretion of the drug (removal from the body – i.e. sweat, urine, feces). You can see that all the aspects of pharmacokinetics involve actions of the body to the drug.
Pharmacodynamics involve the ‘soul’ of pharmacology, what the drug does to the body once it reaches its target, what biological effects does the drug produce and how these effects change the body from a diseased state to a healthy one. Using a useful metaphor for pharmacokinetics and pharmacodynamics, it can be seen as the missions to the moon: the launch of the rocket, the travel in space, the landing to the moon, the later departure from the moon and the landing on earth they all represent ‘pharmacokinetics’. What the landing spacecraft does in the moon once it arrives there represents ‘pharmacodynamics’.
On Fastbleep you can find analytical texts that explain in detail these two main parts of pharmacology.
2D. Why should a Medic master pharmacology?
All the aspects of medicinal science have their own importance to the therapeutic outcome: accurate diagnosis, correct prescribing, effective treatment and a thorough follow-up are all part of the job of a good doctor. However, deep knowledge of pharmacology marks the difference between a good doctor and an excellent doctor.
Mastering pharmacology means that you know the major differences in various similar drugs, you are aware of the contraindications which are vital for tailoring a prescription to each patient’s own needs, you acknowledge all the drug-drug interactions between a patients’ simultaneous treatments, you are able to identify a drug’s side-effect and choose a different drug therapy for the same disease, etc.
In order for a doctor to be capable and skillful for completing the above, he/she has to master the knowledge of where it acts, how it acts and what are its disadvantages and advantages compared to another similar drug.
3A. Definition of drugs & classification
Drug can be defined as ANY substance that causes a biological effect, either therapeutic or toxic. The classification of drugs exists in different forms.
Major classifications include two:
"Indications" are a minor classification of drugs (e.g. for epilepsy there are barbiturates and benzodiazepines, for asthma there are bronchodilators, corticosteroids, cromolyns and leukotriene-receptor antagonists).
3B. Routes of administration & drug preparations
It has been mentioned above that drug administration is part of pharmacokinetics. There are a number of different routes of administration that a drug can enter the body.
To classify the different routes we divide into two main sections: topical (the drug acts at the site of application and might enter the systemic circulation) and systemic (the drug is delivered on purpose into the general blood circulation).
Also, there can be a number of different preparations for the same drug so that, either to make use of different physicochemical advantages (i.e. for the oral route; tablets, capsules and syrups, have different physicochemical characteristics) or to make use of a different route of administration (i.e. morphine exists in tablets, capsules, solutions, suppositories, injections and transdermal patches) - See table below.
Choosing a particular preparation of a drug is based on the acknowledgment of the advantages & disadvantages of each one related to the disease to be treated and the particular needs of the patient.
It is known that the body has a number of defense mechanisms in order to protect itself from harmful substances. These mainly are the metabolism of drugs by the liver (the ‘first-pass effect’) - where the blood is ‘screened’ by the liver for unknown substances - and the ‘blood brain barrier’ (BBB) which protects the brain from active substances reaching the brain. Depending on factors such as the physicochemical properties of the drug (molecular weight, lipophilicity, ionization constant, molecular stability etc) and its pharmacological properties, the doctor decides which particular preparation of a drug is appropriate.
When a tablet is given, the drug must overcome a number of ‘barriers’ before reaching its target:
In some cases, a drug is given in an inactive or less active form (called a “pro-drug”) and it is metabolized by the liver into an active form, thus using the first pass effect to our advantage. Examples: Valaciclovir is an antiviral pro-drug that converts into the active acyclovir. Heroin is an opiate pro-drug that is converted to morphine by the liver. Prednisone is a cortico-steroid that is activated by the liver to prednisolone.
If you think about it, for a drug to be effective it must in one way or another be delivered unchanged or in a form and concentration that is effective to a target. The target might be a metabolic system, a cell, an enzyme or a specific tissue, or a bacterium. How the drug is delivered to its target depends on the chemical characteristics of the drug and the available product formulations (as discussed earlier in the article). Where a drug can be formulated for a range of routes of administration, it is up to the doctor to decide which form will be most effective and convenient for the patient (e.g. some elderly patients find it difficult to swallow and therefore large tablets should be excluded if possible when prescribing).
4A. Selectivity and Specificity of drugs: an out-of-date outopia
When a drug has a therapeutic effect through its activity on a particular tissue or molecular target, it is only logical that any other "secondary" activity of the drug will produce a biological effect that is not intented. This effect is called a side-effect (or adverse reaction).
A general notion among pharmacologists was that side-effects were produced solely because of the non-specificity of a drug's action and so the main aim of the pharmaceutical industry and the pharmacological science should be to produce and develop drugs that are more selective on the desired target or tissue.
Nevertheless, new ideas have promoted "multi-functionality" in drug development, a strategy that takes advantage of the variability of the targets and their expression in different tissues and keeps away from selectivity and specificity. "Multiple Receptor Selectivity" is a new term that has been introduced to distinguish the intentional design of drugs to be multi-selectivity, with the unintentional non-selective drugs existed.
Important: The concept of selectivity should not be regarded as outdated or without scientific essence in terms of pursuing it in research. The development of side-effects due to the activity of drugs in "secondary" targets is quite real indeed. Equally, it has to be acknowledged that the complexity of biological systems and the relationship between 'therapy-target-drug' is constantly changing in a dynamic manner. Appreciating this concept of constant change brings forward new strategies that seek to explore and take advantage of this variability in drug targets and drug structures so that a therapeutic effect and a reduction in side-effects is achieved by creating multifunctional drugs.
4B. Therapeutic window & side-effects
To understand the meaning of the "therapeutic window", one has to realise that ALL substances in the universe may cause side-effects (or toxic effects) if their DOSE is adjusted accordingly. Additionally, if the DOSE of any drug is too low, there will be no therapeutic effect. This dose-effect relationship of drugs is the main study of Pharmacodynamics.
The logarithmic sigmoidal relationship of a drug's action (see picture below) shows that there is only a particular "dosing window" that can produce a therapeutic effect when gradually increasing the dose of a drug (below that window there is no effect, above that window there are toxic effects).
Side-effects are not only part of a standard practical & theoretical approach. Apart from variations in the dose of drug and its non-selective "unwanted" effects, there are other issues that may produce a side-effect which is not expected. These issues are similar to those responsible for drug variability among a population:
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