Have you ever heard your Pharmacology teacher or Physician saying that a drug, for example, lithium has a “narrow therapeutic window” or “Low therapeutic Index”…..

well, what is the meaning of this……

Lets Explore…..

In simple words Therapeutic Index is a measure of “safety of drug” .

Means if a drug has High Therapeutic index it is more safe ……..

So, we always want to give a drug with higher Therapeutic index because they are more safe.

and how do we calculate the “Therapeutic index” ….. well, it is calculated in Experimental animals (I know , animal cruelty )

First, we start with a low dose of drug in animals and start increasing the dose gradually, and then there comes a dose which produces the desired effect in 50% of the population of the animal (Termed as Median Effective Dose “ED50” ) and we kept increasing the dose and there comes a dose on which 50 % animals dies (Termed as Median Lethal dose “LD 50”)

And after this killing, we are now ready to calculate the Therapeutic index which is …..

Therapeutic index = LD50/ED50

and i always get confused in the formula (Yep, i am too forgetful)…….. so i remember it by TILE (TI=L/E)

So, now you have learned so much …. then imagine how do we calculate it in humans..(I hope, you are not thinking about killing your 50% of the patients by drug toxicity)

And the good news is, in humans we prefer Therapeutic range or Therapeutic window……

Therapeutic range / Therapeutic window

Therapeutic range or Therapeutic window is calculated in humans and by definition “it is the range of drug, which is bounded by the dose which produce minimum therapeutic effect and the dose which produces maximum acceptable adverse effect”.

If you are not understanding the above definition, then Don’t loose hope, keep reading, lets take an example…..

For example- Therapeutic window of Lithium is 0.5-1.3 mEq/L. (it means below 0.5 mEq/L lithium will not produce therapeutic effect and above 1.3 (nearly on 1.5 mEq/L) toxicity symptoms occur frequently.

So, a drug with a small therapeutic window must be given carefully, and sometimes measuring response or blood concentration of the drugs, is needed to avoid the serious Adverse effects.

Now, lets talk about the drugs which have low Therapeutic Index, now i think that you understand that low Therapeutic Index, means naturally small Therapeutic window.

Example- Lithium (it is used in Bipolar disorders), Carbamazepine, phenytoin (Antiepileptic drugs) theophylline (used in asthma) and warfarin (Anticoagulant) etc.

Hope this post will clear your concepts…….

Happy learning…..

Lets Explore this amazing concept of Plateau Principal of Drug Accumulation ………..

If the dose of a drug is repeated at short intervals before its complete elimination, the drug start accumulating in the body. ( Its normal, because we are giving the drug before its complete removal)

And nearly after five half lives, the drug in the body attains a state, where the rate of drug elimination equals to the rate of drug administration and this state is termed as Steady state .

Steady State Concentration where…

Rate of Drug Elimination = Rate of Drug Administration

or we can say that Plasma Concentration is at Plateau , and don’t confuse the plateau state with a constant plasma concentration, the plasma concentration is fluctuating , it is high when we administer drug and decreased gradually due to elimination, has a spike after delivering the drug again , but after the 5 plasma half life’s it will achieve a condition where it fluctuates about an average steady state level (Plateau)

And this is termed as Plateau Principal of Drug Accumulation.

So…………

Time required to achieve a steady state is ENTIERLY DEPENDS OF PLASMA HALF LIFE.

Now if you are with me…..Great, but most of the time, its the point where the students seem confused,

Let me clear this fog with an example…….

If we double the dose of drug (If previously we are giving 100 mg, we start giving 200 mg) then again after nearly five half lives the NEW STEADY STATE will achieved…..and obviously this time the plasma concentration Plateau will be higher…….(We are assuming here that drug follows first order kinetics)

And we are still experimentig……….so again after some time, we reduce plasma concentration to one fourth of previously (200/4=50 mg) , then we will see that again after Five half life the NEW STEADY STATE is achieved…..and obviously this time the plasma concentration Plateau will be much lower…….

So we are trying to make a point here, that after nearly five half lives there comes a condition where our body is adjusted to a condition where rate of drug elimination is equals to the rate of dug administration.

And what will happen if we reduce the intervals of administering the drug ?

Lets again take an Example…………Assuming the half life of a drug is four hour and we were repeating it at interval of four hours, after some time, we reduce the duration to one hour …… then now the amplitude of the fluctuation of plasma concentration will decrease (the ups and downs of the drug plasma levels or in pharmacology … Peaks and Troughs), because we are giving the drug more frequently.

In nutshell…..

If we increase the frequency of giving the drug or the dose is increased then Steady state concentration will be higher ………..BUT the TIME TO ATTAIN the steady state shall remain the same in both (Because it depends in plasma half life)

And what is the clinical importance of this…….did you remember lithium (Yes , the same drug we are using in the Bipolar disorders and having a narrow therapeutic index i.e. 0.5-1.3 mEq/L)

we know that we have to select the dose appropriately, so that the Steady state concentration will be the desired plasma concentration (i.e. 0.5 – 1.3 mEq/L).

and we have to decide the dosing interval properly because if the dosing interval will be more then ups and downs will be more, and during the ups it will produce toxicity and become ineffective during downs, so we can use this knowledge to decide the dose and dosing intervals so we can attain a desired range of plasma concentration.

Hope you will understand the concept………..

Happy learning…

These are the adhesive patches which contains the drug and when applied to the skin surface, they deliver the drug at constant rate, into the systemic circulation

Glyceryl trinitrate, Fentanyl, Nicotine, Oestradiol, Isosorbide dinitrate , Hyoscine are example of drugs which can be administered through Transdermal patches

Diclofenac transdermal patch are also now available.

The Transdermal therapeutic system contains the drug in reservoir (a place where drug is stored) and the release of drug is controlled by another layer having micropores.

when the adhesive layer is applied on skin, the drug from the reservoir part is delivered to the skin in a controlled manner (yes, due to rate controlling micropore membrane)

Advantages of the TTS (Transdermal therapeutic system)

• Prolonged and sustained effect of drug is maintained (Duration of action is increased and at constant plasma level)
• Patient compliance is good (what an easy and convenient way to administer a drug…..)
• Little first pass metabolism

Disadvantages of the TTS

• Can cause local irritation, erythma. (usually mild, can be minimized by applying it to different site every time).
• Comparatively more expensive
• Large doses of drug cannot be given

lets have some example of the patches and their uses…….

1.Glyceryl trinitrate transdermal patch — used in angina pectoris — applied at chest

2.Nicotine transdermal patch –used to quit smoking—applied at arm

3.Testosterone transdermal patch— used in testosterone deficiency—applied at scrotum

4.Fentanyl transdermal patch— used to produce analgesia (eg. in cancer pain)— applied at arm/back

Hope you enjoyed the concept ……. have a great time ……

Starting with definition……..

Drugs which can be legally procured without the prescription of a registered medical practitioner.

So, in brief these drugs does not requires prescription or these drugs can be taken as self medication.

This concept is more popular in the USA where their drug regulatory authority US Food and Drug Administration (USFDA) classifies their drugs into –

• Drugs which are restricted to sale by prescription
• And nonprescription or over-the-counter medications

The USFDA reviews the OTC ingredients for both safety and efficacy and they can also switch the drugs from prescription drugs to non prescription category after proper reviews, when they think that these drugs are safe for use without medical supervision.

In USA directions for safe use of OTC agents are mentioned on leaflets in form of “Drug Facts” label which includes indications, contraindications (when to use and when not), status in pregnancy etc. They also provide their information regarding OTC drugs online.

you can visit the site of USFDA by clicking on the following link and see the switch list of drugs…..

https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/prescription-over-counter-otc-switch-list

While in India we don’t have any Separate category of “OTC drugs” in Drugs and Cosmetic rules 1945 (D&C rules 1945).

“Oh”, then how we decide that which drug is OTC in India ?

As we don’t have any legal definition of OTC drugs in D&C rules 1945, we have list of prescription only drugs (Drugs which need prescription to procure, eg. drugs in schedule G,H,H1 and X), and drugs which are not mentioned in these lists are considered as OTC drugs in India.

Ayurvedic Medicines / Herbal ingredients does not need sale license and can be sold even by non chemist also.

So, hopefully this information will make you understant this topic more clearly……

Have a great time…….........

Pharmacology

It is the science of drugs.

Clinical Pharmacology

Scientific study of drugs in humans is termed as clinical pharmacology.

Drug

As per WHO drug is “Any substance or product that is used or intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient”.

Receptor

A receptor is a macromolecule, which recognize the drug (or signal molecule or agonist) and initiate a response.

Affinity is the capacity of a drug to bind a receptor.

when a drug is combined with receptor, the ability of drug to activate the receptor is termed as Intrinsic activity. (Intrinsic activity can vary from +1 to 0 to -1, where +1 indicates the maximum intrinsic activity, shown by agonist and 0 means no intrinsic activity and this is seen in antagonist)

Agonist-

Agonist is a substance, which binds to the receptor and produce response.

It has affinity (yes, it needs to bind from receptor to produce a response)

It has maximum intrinsic activity (i.e +1, means it has ability to activate receptor at its maximum capacity)

Antagonist-

Antagonist is a substance which binds to receptor (yes, it has affinity), But it produces no response….i repeat, it produces no response means its intrinsic activity is Zero.

In other words we can say that it prevent the agonist from acting on receptor (because antagonist attached from receptor), but itself antagonist produce nil response (How innocent….)

Pharmacokinetis

“What the body does to the drug”.

In pharmacokinetics we study how the drug is going into, through and out of the body and how does the body is affecting the drug during whole process. we divide pharmacokinetics into absorption, distribution, metabolism (biotransformation) and execration (ADME).

Pharmacodynamics

Is “What the drug does to the body”

It is the study of actions of drug on the body and their mechanism of action, so, we can say that in this branch of pharmacology, we study how the drug works in our body and we study about Mechanism of drug action, receptors, effect of the dose and how they interact with physiological systems.

Essential medicines

As per WHO ” Essential drugs are those drugs that satisfy the priority healthcare needs of the population.”

we select these drugs with the relevance of the population, they must be effective and safe, cost effective, and available all the time in adequate amount and appropriate dosage forms in healthcare facility.

Pharmacovigilance-

As defined by WHO ” science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug related problems”

Pharmacogenetics

This branch deals with variability in drug response due to genetic basis.

Pharmacogenomics

Now this branch use the knowledge of genetics to guide the proper drug and its dose on an individual basis.

“Confused” …………..let me help you, when you just study a drug that how does it differ from person to person due to their genetic difference it is termed as Pharmacogenetics.

But when you study the genetic information and decide which drug and in what dose is best suited as per the individual genetic makeup then it is Pharmacogenomics.

Oswald Schmiedeberg- Father of Pharmacology

Hope this post will help you to remember these definitions……….Happy learning…

Today we are going to discuss about prodrug.

Q. What is Prodrug?

The prodrug is a drug which is inactive initially and convert into active form by process of metabolism (one or more active metabolites are produced after metabolism in body ).

Q. But why this concept of prodrug is important?

The answer lies in process of metabolism. usually, when we take a drug our body deal with it by metabolism followed by execration, and three types of fates of this drug can be possible due to metabolism

1.Most of the drugs we consume are in active form and our body soon convert them into inactive form.

2. Many drugs we take are in active form and after consuming they are converted into another active form (one or more active metabolites).

for example Diazepam, it is an active drug used in the seizures, which is converted into oxazepam in body, which is also an active metabolite.

3.For few drugs there is Activation of inactive drug, as these drugs which are inactive initially, will convert into one or more active metabolites and these drugs are termed as Prodrugs.

Example of Prodrug-

Levodopa (Prodrug) – Dopamine (Active form)
Enalapril (Prodrug) – Enalaprilat (Active form)

Lets discuss about prodrug “Levodopa”

• Prodrug levodopa is used in Parkinsonism
• when taken orally, it crosses the blood brain barrier and converted into Dopamine (active form) by metabolism at site of action i.e. CNS.
• so, the active form of drug (Dopamine) is reached at the target organ (CNS) easily as dopamine itself can not cross the blood brain barrier.

Prodrugs can be used to

• Prolong duration of action

• Improve taste

• Increase availability at site of action (like levodopa) etc.

Hope you enjoyed the article…..