Welcome to ePharmacology – The place to learn Pharmacology for free!
Before reading this article I suggest you go through my previous article which briefly introduces you to the wonderful world of pharmacology. It describes two important terms: Pharmacokinetic and Pharmacodynamic which are essential to learning pharmacology. So if you have missed that article, read it right now!
Alright let’s get on with this article. In this article I will discuss about
The pharmacological effects of drugs
What is prodrug including its definition and examples
Where you can find reliable information about any drugs
Pharmacological effect
Pharmacological effect may be defined as the physiological and/or biochemical changes in the body produced by a drug in therapeutic concentration. No drug has a single pharmacological effect. A drug usually produces several pharmacological effects.
Pharmacological effects may be classified as desired and undesired effects even when used in usual dose. For example, rifampicin is used for the treatment of tuberculosis. The desired effect of this drug is to kill the causative microorganism Mycobacterium tuberculosis so that the patient will be cured from tuberculosis. But The therapeutic concentration of rifampicin also causes some undesirable effects that are not avoidable.
Undesired effects may be harmless, harmful, or beneficial. For example, one undesired effect of rifampicin is that it alters the color of urine, feces, sweats, and tears to red-orange and this effect is harmless.
The harmful effect of rifampicin is the development of jaundice as a result of liver damage.
Promethazine is used for the treatment of allergy. The concentration at which it produces its desired effect, also produces sleep that is a beneficial effect. Treating hypertension with beta (β) adrenergic blocking drugs may also relief the patient ’s angina, a beneficial side effect. A depressed patient with irritable bowel syndrome may incidentally benefit from the anticholinergic side effect of tricyclic antidepressants.
So what determines whether a drug will have toxic or therapeutic effect?
An effective drug may be ineffective or toxic that depends on its concentration in plasma or at the site of action.
For example, theophylline, a drug used for the treatment of bronchial asthma, is ineffective when its plasma concentration is less than 10µg/ml. The therapeutic effect of theophylline is usually obtained at plasma concentration of 10 to 20µg/ml. Above this concentration it may cause toxic effect.
In case of digoxin, the therapeutic effect is unlikely if the plasma concentration is less than 1mmol/L. Beneficial effect with a low risk of toxicity is obtained when the plasma concentration of digoxin is in between 1 and 3.8mmol/L. However, the risk of toxicity is increased considerably when the concentration of digoxin is above 3.8mmol/L.
A barbiturate in low plasma concentration only produces sedation. But when the plasma concentration of that drug is increased, hypnosis develops. Coma or death may occur with further increase in concentration.
The concentration of drug in plasma or site of action is seriously taken into account when dealing with drugs having low therapeutic index (TI).
Therapeutic index is the ratio of median toxic dose (TD50) to median effective dose (ED50). If a drug having TD50 is 100 mg and ED50 is 5mg then its Therapeutic Index is 100/5 = 20.
Now the question is what do we mean by TD50 and ED50?
TD50 is the dose of the drug at which 50% of the drug-tested animal will show toxic effect.
ED50 is the dose of the drug at which 50% of the animal show therapeutic effectiveness.
Drugs like theophylline, digoxin have low TI. On the other hand, antibiotics have high TI. The drugs with high TI are considered to be relatively safer drugs.
So basically therapeutic index is a measure of the safety of a drug. The higher the therapeutic index, the higher the safety of that drug and vice versa.
What is Prodrug?
Definition of prodrug: Prodrugs are some chemical substances which do not produce pharmacological effects until they are chemically altered within the body. Such chemical substances are called prodrugs. So basically, prodrugs are inactive drugs which are converted to active drugs inside the body by chemical alterations.
The concept of prodrug was first coined when a red dye, protonsil, was found to be effective against microorganisms only in vivo, not in vitro. It was due to conversion of protonsil dye, in vivo, to sulfanilamide, the first sulfonamide. in vivo means with living body and in vitro means outside the living body.
So why do we have to use prodrugs?
The answer is simple. Because it has more advantages!
The advantages of using a prodrug:
Improves absorption from the site of administration.
Increases the duration of action of a drug that is rapidly eliminated
Reduce adverse effects of the drug
Promotes site-specific delivery of drug
Better patient compliance as some patient might not like the otherwise bad smelling or bad tasting active drug.
Improve bioavailability of the drug
Some detailed examples of prodrugs
Pivampicillin, talampicillin and bacampicillin are all prodrugs of ampicillin. These prodrugs are produced by esterification of the polar carboxylate group to form lipophilic, enzymatically labile esters.
Enalapril is the ethyl ester prodrug of the active diacid, enalaprilat. Enalaprilat is poorly absorbed from the gastrointestinal tract (less than 10%), but absorption of the prodrug enalapril is greatly improved (about 60%).
Dopamine cannot be distributed into the central nervous system (CNS) as it cannot cross the blood-brain barrier. But dopamine is essential for the treatment of Parkinson ’s disease. Thus its prodrug levodopa is used for the treatment of Parkinson ’s disease. Levodopa can easily cross the blood-brain barrier via an amino acid carrier and is then converted (decarboxylated) into dopamine by dopa decarboxylase with the CNS.
Drug Information:
If you want to find reliable information about a drug then there are several places you can search:
Pharmacopeia (also pharmacopoeia)
Formulary
Textbooks
Medical Journals
Representatives from the pharmaceutical companies
Other sources like internet.
Some sources are commercial and independent, others are non-commercial. Information may be available in written form, verbally, tape, video, CD-ROM, or online.
What is Pharmacopeia/Formulary?
Definition of Pharmacopeia: Pharmacopeia is a book containing a list of drugs with descriptions, tests, formulas for preparing the same drug.
The word pharmacopeia comes from the Greek word pharmakon and poiein. Poiein means make.
The term pharmacopeia was first used in Italy in 1580.
In England, the London Pharmacopeia, the Edinburgh Pharmacopeia, and the Dublin Pharmacopeia were used throughout the United Kingdom until 1864, when they were replaced by theBritish Pharmacopeia (BP).
The United States Pharmacopeia (USP) was first published on December 15th, 1820. The authorized body to prepare the pharmacopeia is usually formed by the pharmacologists, pharmacists, physicians, chemists, biologists and other scientific and allied personnel. It is in most cases supported by the Government.
In the United States Pharmacopeia the drugs are defined according to the source, physical and chemical properties, and standard for identity, quality, strength and purity, methods of storage, dosage range for therapeutic use. USP is revised every five years by outstanding pharmacologists, physicians, and pharmacists.
The criteria for selection of drug in the USP are on the basis of their proved therapeutic value and low toxicity. Drugs may be supplemented by newer or better drugs or where there is high incidence of toxic reactions after extensive use.
The name of other well-known pharmacopeias and formularies are European Pharmacopeia, Codex Francais, Japanese Pharmacopeia, Chinese Pharmacopeia, Indian Pharmacopeia, British National Formulary (BNF), British Pharmaceutical Codex (BPV) etc.
To serve as a reference for the establishment international standard, WHO started to publish The International Pharmacopeia in 1951. The book is published in English, Spanish and French and is revised every 5 years.
Textbooks
In the textbooks, the emphasis is given on established drugs and their application to therapeutics. However, only a relatively small section is devoted to describe the basic principles of pharmacology. There is a trend to write most of the pharmacological books by a number of authors. The selection criteria depend on the frequency of new editions. Only publications that are revised every two to five years can provide up-to-date knowledge.
I have added few of the most popular text books on pharmacology to the right. These books are written by the best authors on pharmacology and they are really worth buying!
List of Med JournalsAnn Rev Pharmacol Toxicol
Biochem Pharmacol
Bri J Pharmacol
BMJ
Can J Physio Pharmacol
Cli Pharmacol Thera
Drugs
Eur J Cli Pharmacol
Eur J Pharmacol
Ind J Pharmacol
Jap J Pharmacol
JAMA
J Pharmacol Exp Thera
J Pharma Pharmacol
Lancet
Mol Pharmacol
New Engl J Med
Pharmacol Rev
Trends Pharmacol Sci
Medical journals
Medical journals will provide excellent information about drugs. The articles may be reviewed or original. Some of the journals which usually provide current information about drugs are mentioned in the box. Journals like the Lancet, New England Journal of Medicine, or British Medical Journal are general. Other are more specialized.
Pharmaceutical company
The pharmaceutical companies provide information which are invariably attractive and easy to digest. They have medical representatives, stands at professional meetings, advertising in journals and direct mailing. But the problem with them is that the information they provide may sometimes be biased.
Computer-based information
The single most comprehensive source of drug information is computer based.
Data-based software for pharmacokinetic designing drug-dose regimen includes PCONLINE, PHARMKIN and MINSQ. Other programs like AskRx, S-O-A-P Rx, and Rx Triage also provide ready access to monographs on each drug. Rx Triage limits its interaction to those that are well-established or of serious impact.
You can get online authentic information about drug from the Food and Drug Administration (FDA) using their website http://www.fda.gov.
The information about drugs can also be obtained from AMA Drug Evaluation, Merck Index, Physicians ’ Desk Reference, Ramington ’s Pharmaceutical Sciences, Marindale ’s Extra Pharmacopeia, The United States Pharmacopeia Dispensing Information, American Drug Index, WHO drug information, Drug and Therapeutic Bulletin, and The Medical Letter. These provide unbiased information about drugs.
in case you missed my first article, here is the link to it:
Learn Pharmacology Online for FREE! Introduction to Pharmacology
That’s it for now. Keep coming back because I’ll be adding more articles soon!
And as usual make sure you take the self-assessment quiz to test your new knowledge!
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