PHARMACODYNAMICS-AN OUTLINE
It is very interesting to know about the drug which has been taken into our body how it acts against our body's physiology.
While pharmacokinetics is described in simple terms as the body vs the drug, pharmacodynamics on the contrary means simply the opposite term the drug vs. the body.
The concepts of pharmacodynamics include the theories of receptor reactions, mechanisms of therapeutic and toxic actions, and dose-response relationships.
RECEPTOR REACTIONS
Receptors are macro-molecules typically made out of proteins that interact with either an endogenous substance or an exogenous substance to mediate a pharmacological or physiological effect.
Receptors are functioning by ligand(an endogenous or exogenous substance) and activation of an effector messenger system
Effectors transduce a stimulus produced as a result of drug-receptor interactions into a physiologic effect. There are four types of effector mechanisms:-
1.Transmembrane
Some endogenous ligands such as insulin cannot enter inside the cell instead they interact with the outer component of its receptor present on the cell. This interaction produces a stimulus that is transduced into the inner component of the receptor present inside the cell that contains the enzyme tyrosine kinase to produce a physiologic effect that is the entry of glucose into the cell.
2.Ligand-Gated Ion Channels
When an active drug specialized for these kinds of receptors binds to them that makes a series of conductance of effects to open the ion gates situated by the sides of the receptors to produce powerful ion influxes and effluxes.
The best examples are benzodiazepines that make Cl- ion influx and acetylcholine that make Na+ ion influx.
3.Intracellular
In these types the ligands or substances react with the cellular receptors to form receptor complexes and enter inside the cell and interact directly on the DNA which causes changes in gene expressions. (e.g.)Thyroxine and steroid hormones.
4.Second Messenger Systems
Drugs bind to receptors that cause the activation of a second messenger system that involves G-proteins.
The second messengers the G-proteins such as Guanosine Tri Phosphates (GTP) and Guonosine Di Phosphates allow cell surface receptor signals to be converted and amplified into a physiologic cellular response.
There are three types of second messenger systems that follow below:-
1.Cyclic Guanosine Monophosphate(cGMP)
These are one of the major second messenger systems responsible for many physiologic cell responses such as ion channel conductance, glycogenolysis, and cellular apoptosis a process of older cell deaths by DNA defragmentation.
cGMP also causes vasodilation and increased blood flow. This action is well demonstrated by some erectile stimulating drugs like sildenafil(Viagra) which causes accumulation of cGMP to dilate the blood vessels of the penis to get more blood to flow into it for a perfect erection.
cGMP is produced by the enzyme guanylyl cyclase from GTP and is reconverted back into GTP by a cGMP specific Phospho Di Esterase(PDE).
2.cyclic Adenosine Mono Phosphate(cAMP)
the cAMP is a second messenger that is produced by adenylyl cyclase from ATP(adenosine triphosphate).cAMP involves many physiological effects such as glucose regulation.
3.Inositol Tri Phosphate (IP3)
This is produced by the enzyme Phospholipase-C. It is mostly used in signal transduction, and lipid signaling in biological cells.
Receptors are functioning by ligand(an endogenous or exogenous substance) and activation of an effector messenger system
Effectors transduce a stimulus produced as a result of drug-receptor interactions into a physiologic effect. There are four types of effector mechanisms:-
1.Transmembrane
Some endogenous ligands such as insulin cannot enter inside the cell instead they interact with the outer component of its receptor present on the cell. This interaction produces a stimulus that is transduced into the inner component of the receptor present inside the cell that contains the enzyme tyrosine kinase to produce a physiologic effect that is the entry of glucose into the cell.
2.Ligand-Gated Ion Channels
When an active drug specialized for these kinds of receptors binds to them that makes a series of conductance of effects to open the ion gates situated by the sides of the receptors to produce powerful ion influxes and effluxes.
The best examples are benzodiazepines that make Cl- ion influx and acetylcholine that make Na+ ion influx.
3.Intracellular
In these types the ligands or substances react with the cellular receptors to form receptor complexes and enter inside the cell and interact directly on the DNA which causes changes in gene expressions. (e.g.)Thyroxine and steroid hormones.
4.Second Messenger Systems
Drugs bind to receptors that cause the activation of a second messenger system that involves G-proteins.
The second messengers the G-proteins such as Guanosine Tri Phosphates (GTP) and Guonosine Di Phosphates allow cell surface receptor signals to be converted and amplified into a physiologic cellular response.
There are three types of second messenger systems that follow below:-
1.Cyclic Guanosine Monophosphate(cGMP)
These are one of the major second messenger systems responsible for many physiologic cell responses such as ion channel conductance, glycogenolysis, and cellular apoptosis a process of older cell deaths by DNA defragmentation.
cGMP also causes vasodilation and increased blood flow. This action is well demonstrated by some erectile stimulating drugs like sildenafil(Viagra) which causes accumulation of cGMP to dilate the blood vessels of the penis to get more blood to flow into it for a perfect erection.
cGMP is produced by the enzyme guanylyl cyclase from GTP and is reconverted back into GTP by a cGMP specific Phospho Di Esterase(PDE).
2.cyclic Adenosine Mono Phosphate(cAMP)
the cAMP is a second messenger that is produced by adenylyl cyclase from ATP(adenosine triphosphate).cAMP involves many physiological effects such as glucose regulation.
3.Inositol Tri Phosphate (IP3)
This is produced by the enzyme Phospholipase-C. It is mostly used in signal transduction, and lipid signaling in biological cells.
Mechanism Of Therapeutic and Toxic Action
These mechanisms involve a drug binding to a receptor in order to stimulate or inhibit it.
A drug that binds with a receptor in order to stimulate and produce a maximum 100% biological effect is known as a Full Agonist.
A drug that binds with a receptor in order to inhibit and block the biological effects is known as an Antagonist.
A drug that does not stimulate a receptor to a maximum extent and not to produce a 100% biological effect no matter whatever its concentration is known as Partial Agonist.
If an antagonist binds to the same receptor site of an agonist competitively and reversibly is known as Competitive Antagonist.
If an antagonist binds to the different receptor sites of an agonist non competitively and irreversibly is known as Noncompetitive Antagonist.
A competitive antagonist can be overcome by increasing the concentration of the agonist. The high concentration of the agonist can replace the reversibly bound antagonist from the receptor site.
A non-competitive antagonist cannot be overcome by increasing the concentration of the agonist.
A drug's maximum efficacy is reduced thus by the presence of a non-competitive antagonist.
A drug that does not stimulate a receptor to a maximum extent and not to produce a 100% biological effect no matter whatever its concentration is known as Partial Agonist.
If an antagonist binds to the same receptor site of an agonist competitively and reversibly is known as Competitive Antagonist.
If an antagonist binds to the different receptor sites of an agonist non competitively and irreversibly is known as Noncompetitive Antagonist.
A competitive antagonist can be overcome by increasing the concentration of the agonist. The high concentration of the agonist can replace the reversibly bound antagonist from the receptor site.
A non-competitive antagonist cannot be overcome by increasing the concentration of the agonist.
A drug's maximum efficacy is reduced thus by the presence of a non-competitive antagonist.
Dose-Responce Relations
Efficacy is defined as the ability of a drug to produce the expected biological response. A drug is said to be more efficacious if it produces the required biological response at a maximum level independent of the dosage quantity given.
On the contrary potency is defined as the minimum quantity of the drug to produce the required biological response. A drug is more potent if it produces the required biological response with a minimum quantity of dosage.
In simple terms, efficacy is a qualitative measurement whereas potency is a quantitative measurement
Examples can be described as follows:-
If two drugs A and be B both are claimed to reduce a person's heart rate by 35% and then we can say both are equally efficacious
If drug A requires 30mg to produce a heart rate effect of 35% while drug B requires 50mg to produce the same effect then drug A is said to be more potent than drug B.
The concentration of the drug required to occupy 50% of the receptor is known as the dissociation constant (Kd)
The concentration of the drug required to produce 50% of the maximum response is known as EC50.
