Mechanism of drug action- Receptor-Effector Linkage

 

The cellular effects may be
rapid  e.g. synaptic transmittion (in sec)
intermediate e.g. catecholamine (in min.)
very slow e.g. thyroid hormone (hours/  days)

effector

Three types of receptor-effector linkage  can be recognized:

a. Direct regulation of membrane permeability to ions.
*The fastest type of receptor- mediated response.
*When a neurotransmitter acts on the post synaptic membrane of a nerve or muscle cell, and transiently increase its permeability to a particular ions by control the opening or closing of the ions channels.
*Most excitatory neurotransmitters such as acetylcholine(Ach) at the neuromuscular junction, glutamate in the CNS—> cause increase of  the Na+ & K+ permeability–> a net incurrent carried mainly by Na+ ions which depolarizes the cell & increases the probability of generating an action potential, their action reaches a peak in fraction of a microsecond and usually decays within a few millisecond.

b. Mechanisms involving a second messenger

*The effect of an agonist on extracellular receptors is transmitted to the interior of the cell through the involvement of a second messenger: 

 i. Cyclic-adenosine-3‘ 5’-monophosphate (cAMP)  ii. Calcium ion

*They regulate many different kinds of cellular activity, including: muscle contraction, relaxation, secretion, change in membrane permeability to various ions, transport mechanism& cell division.
*In many cases, these cellular response are due to change in the state of phosphorylation of various intracellular protein by various specific protein kinases.

c. Regulation of DNA Transcription
* A characteristic of steroid hormones.
*Certain regions of DNA sequence show a high affinity for particular steroid-receptor complexes
*The binding of the complex to DNA switches on the process of gene transcription at a region of the DNA molecule several hundred base residues away from the region that binds the steroid-receptor complex.
*An increase in RNA polymerase activity and the production of specific mRNA occur within a few minutes of adding steroid.
*One steroid may result in the production of several different proteins, that leads to the great diversity of steroid actions.

http://www.drugnet.com.hk/edu/edu_phar_action.htm

 

Receptor Interactions- Agonists and Antagonists

agonistanta

 

 

The agonists
Agonists: “ activate” the receptors when they occupy it.

The ability of a drug molecule to activate the receptor is a continuously graded, rather than all-or-nothing.
i.e. The maximal response (the largest response that can be produced by the drug in high concentration) differs from one drug to another.

A full agonist is a drug that is capable, at a sufficiently high concentration, of producing a maximal cellular response.
A partial agonist is an agonist whose maximum effect is less than the maximal response of which the tissue is capable.
i.e. Even with the same affinity, the response at any given occupancy is much smaller, so that it cannot produce a maximal response even at 100% occupancy. A decrease in efficacy.
(When acting at receptors alone, partial agonists stimulate a physiological response, but antagonize the effects of a full agonist

The antagonist

anta

  • ( the antagonism by receptor block.)
    Antagonists: “ no activation” when they occupy the receptor.
  • Reversible competitive antagonism
    Reversible competitive antagonist :
    *A receptor antagonist also binds to the agonists receptor site and equilibrates sufficiently rapidly with the receptors that its occupancy is reduced when the agonist concentration is increased.
    *It causes the agonist log-conc. Parallel shifting the curve to the right without change in slope or maximum.
  • Irreversible competitive antagonism
    Irreversible competitive antagonist :
    *Bind to the agonist receptor site & forming strong bonding.
    *A receptor antagonist that dissociates from the receptor slowly or not at all.
    *The slope & maximum of the agonist log conc.-effect curve are likely to be reduced.
  • Non-competitive antagonism* Non-competitive antagonist: *Do not bind to the same receptor sites as the agonist *Blocks the chain of event at some point that reduce its effect in some other way.

So, the efficacy that varies between different agonists & expresses the ability of the agonist-receptor complex to elicit a physiological response. Efficacy is high for full agonist; low for partial agonist; zero for competitive antagonists. Also termed intrinsic activity.

http://www.drugnet.com.hk/edu/edu_phar_action.htm

Dose-Response Curve

dr curve

If the response is plotted against the drug concentration, a hyperbolic curve is often produced. If using the response against the logarithm of the agonist concentration, a sigma shaped log dose-response curve is plotted.

However, the response = the occupancy?????????
Rarely valid, the response is a complex, non-linear function of the occupancy.
Thus , in addition to having affinity for the receptor, an agonist has another chemical property called intrinsic efficacy which is its ability to elicit a response when binds to a receptors.

http://www.drugnet.com.hk/edu/edu_phar_action.htm

How do the drugs act and effect treatment?

 

The fact that drugs differ in their actions means that they must be selective in  the biological structures with which they interact.

The selective action (specificity) of a drug depends on forming a combination(binding) with certain tissue components (receptors).

drug receptor

* Agonist is the drug, hormone or transmitter substance that elicit a cellular response when it combines with receptors.

* Antagonist combines with the receptor, but do not activate them. Antagonist s reduce the probability of the transmitter substance ( or another agonist) combining with the receptors and so reduce or block its action.

Drug – Receptors Interactions

*Receptors are protein molecules which are normally located in the cell membrane .
*They are normally activated by transmitters or hormone.
*The interaction between a drug and the binding site of the receptor depends on the complementarity of ‘fit’ the two molecule ( Lock and Key Hypothesis)
*The closer the fit, the greater the number of bonds (usually non-covalent), the stronger will be the attractive forces between them, and the higher the affinity of the drug for the receptor.
*The ability of a drug to combine with one particular type of receptor is called specificity . However , no drug is truly specific, if the drugs can also act on other receptors or systems, side effects are produced.
http://www.drugnet.com.hk/edu/edu_phar_action.htm

 

Mechanism of Drug Action- Understanding basic Pharmacology

 

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What are the major drug mechanisms:

1. Act by their physicochemical properties e.g. general anaesthetics, osmotic diuretics. (With non-specific actions)

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2. Some act as false substrates or inhibitors for certain transport systems or enzyme. e.g. angiotensin converting enzyme (ACE) inhibitors, proton pump inhibitors (e.g. Losec)

3. Most drugs produce their effects by acting on specific protein molecules (receptors), usually located in the cell membrane.

 

For example, acetylcholine is a transmitter substance released from motor nerve endings and it activates receptors in skeletal muscle initiating a sequence of events that results in contraction of muscle

http://www.drugnet.com.hk/edu/edu_phar_action.htm

Conventional Medicine/ Western Medicine/ Allopathy – Intro

 

 

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Definition

Medicine as practiced by holders of M.D. (medical doctor) or D.O. (doctor of osteopathy) degrees and by their allied health professionals, such as physical therapists, psychologists, and registered nurses. Other terms for conventional medicine include allopathy and allopathic medicine; Western medicine, mainstream medicine, orthodox medicine, and regular medicine; and biomedicine

http://www.medicinenet.com/script/main/art.asp?articlekey=33527

According to MedTerms Dictionary, allopathic medicine is defined as “The system of

medical practice which treats disease by the use of remedies which produce effects

different from those produced by the disease under treatment. M.D.s practice allopathic

medicine.  The term “allopathy” was coined in 1842 by C.F.S. Hahnemann to designate the

usual practice of medicine. http://web.jhu.edu/prepro/health/allopathic.html

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Treatment, cure, Remedy, Relief

  1. Medications (Drugs, medicines)

Drugs are chemical substance which, by interacting with biological systems, are able to change them in some way.
*Contraction of muscles
*Secretion by glands
*The release of hormones
*Alterations in nervous activity
*killing cells , and many more

2.  Surgery

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http://www.drugnet.com.hk/edu/edu_phar_action.htm

About

The purpose of this blog is to share about the various kinds of treatments available for common diseases from a Pharmacist point of view.

I am a Pharmacist and an avid blogger. After doing my post graduation in pharmacy from Mumbai University, India; I have worked in R&D of various companies both in India and in Singapore. The thought of compiling the conventional and alternative therapies for various diseases prompted me to start this blog.

Rx is to indicate the conventional, modern or western system of medicine and CAM indicates complementary and alternative medicines.

alternative-medicine-25541159

In this blog I intend to give a brief about the disease, how it is caused from a physiological point of view and how a conventional drug acts on it, the side effects involved , other alternative therapies and their functioning, current medications & treatments available , patients’ forum, the kind of population affected including gender, genetic and other factors which cause these.

The research shared is not my work; it is only the information available from reliable websites which I have compiled for ease of use. Due credits and acknowledgement will be given to the sites from which the information is being taken.

The contents here does not claim any cure, treatment which can substitute a doctor or physician. Never self-medicate. Always consult your doctor or physician before starting any kind of medication and treatment.

Nandini