Pharmacodynamics Question And Answers

Pharmacodynamics

Question 1. Write A Note On Synergism.
Or
Write A Short Note On Synergism.
Or
Write A Short Note On Drug Synergism.
Answer:

Drug Synergism

When the action of a drug is facilitated or increased by the other, they are said to be synergistic:

• In a synergistic pair both the drugs can have action in the same direction.
• Synergism can be:
  • Additive:  The effect of two drugs is in the same direction and simply adds up. For example, aspirin + paracetamol as analgesic/ antipyretic.
    Nitrous oxide + ethers as an anesthetic.

Read And Learn More: Pharmacology Question And Answers

• • Supra-additive: The effect of the combination is greater than the individual effect of the component. For example, levodopa + carbidopa causes inhibition of peripheral metabolism.
    Adrenalin + cocaine causes inhibition of uptake.

Question 2. Write A Note On Antagonism.
Or
Write A Short Note On Drug Antagonism.
Or
Write A Short Note On Antagonism
Answer:

Drug Antagonism

When one drug decreases or inhibits the action of another, they are said to be antagonistic.

Antagonism may be:

• Physical:  Based on the physical properties of the drug. For example, charcoal absorbs alkaloids and can prevent their absorption.
• Chemical: The two drugs react chemically and form inactive products. For example, KMnO4 oxidizes alkaloids used for gastric lavage* in poisoning.
• Physiological/Functional: The two drugs act on different receptors or by different mechanisms but have opposite effects on the same physiological function, for Example. glucagon and insulin on blood sugar levels.
• Receptor: The antagonist interferes with the binding of the agonist with its receptor or inhibits the generation of response consequent to such binding, for example, ACh and atropine, morphine, and naloxone.
  It can be competitive or non-competitive.

Competitive Antagonism

In this, both the agonist and the antagonist bind reversibly to the same site on the receptor, for Example. is the action of acetylcholine (agonist) and atropine (antagonist) on muscarinic receptors.

• The equilibrium type of competitive antagonism can be overcome by increasing the concentration of agonists.
  The log dose-response curve of the agonist shows a rightward parallel shift in the presence of a competitive antagonist.
• In non-equilibrium antagonism, the antagonist binds to the same site on the receptor as the agonist but binding is irreversible.
  Here antagonist forms a strong covalent bond with the receptor, for Example. phenoxybenzamine is an irreversible antagonist of adrenaline at alpha receptors.

Non­Competitive Antagonism

In this, an antagonist binds to different sites on the receptor and prevents the agonist from interacting with the receptor.

In non-competitive antagonism, the antagonistic effect cannot be overcome by increasing the concentration of agonists. The dose-response curve gets flattened.

Question 3. Write On Drug Interaction. One Example Of Synergism And One Example Of Potentiation.

Answer:

Drug Interaction

When two drugs are administrated together or one after the other or a new drug is added to therapy.

In a patient already taking a drug, the response to one drug may be modified, increased, or decreased. This is known as a drug interaction.

• Beneficial drug interaction is desirable and forms the basis of rational polypharmacy, for Example. use of naloxone to antagonize the effect of morphine in the treatment of morphine poisoning.
• Undesirable or harmful interactions may result in therapeutic failure or enhance the toxicity of interacting drugs.
  Example. use of oral contraceptives in patients already taking metabolic enzyme inducer can result in therapeutic failure.
  For example, the use of erythromycin + furosemide with an aminoglycoside antibiotic can result in increased toxicity.

Drug Interaction Clinical Importance 

Clinically important adverse drug interaction should be avoided in such cases:

• In the case of drugs having a narrow margin of safety, small changes in plasma concentration lead to marked enhancement of drug effect or toxicity.
  Example. drugs like digoxin, insulin, and anticoagulants.
• When drugs that are known inhibitors or inducers of metabolic enzymes are added to therapy or taken together.
• In patients with significantly impaired liver or hepatic function.
• When two or more drugs, each having a toxic effect on the same organ are combined together.
• Drugs used chronically and when need precise plasma concentration for sustained effect.
  Example. oral contraceptives, antiarrhythmics. A reduction in the plasma concentration of such a drug can result in therapeutic failure.

Some Of The Clinically Important Drug Interactions

 

Drug Synergism

When the action of a drug is facilitated or increased by the other, they are said to be synergistic:

In a synergistic pair both the drugs can have action in the same direction.
Synergism can be:

• Additive:  The effect of two drugs is in the same direction and simply adds up. For example, aspirin + paracetamol as analgesic/ antipyretic.
  Nitrous oxide + ethers as an anesthetic.
• Supra-additive: The effect of the combination is greater than the individual effect of the component. For example, levodopa + carbidopa causes inhibition of peripheral metabolism.
  Adrenalin + cocaine causes inhibition of uptake.

Potentiation

It is also known as the supra-additive effect.

• Potentiation is defined as the enhancement of the action of one drug by another drug, which is inactive.
• Examples are a combination of acetylcholine + physostigmine, sulphamethoxazole + trimethoprim
• Here physostigmine and trimethoprim inhibit the breakdown of acetylcholine and sulphamethoxazole, thus enhancing their effects.

Question 4. Discuss Surmountable Antagonism.
Answer:

Surmountable Antagonism

When one drug decreases or inhibits the action of another this phenomenon is known as antagonism. It can take place through a variety of mechanisms.

When the antagonist interferes with the binding of the agonist with its receptor it is known as competitive antagonism.

Surmountable Antagonism:

In this, the agonist drug attaches to the receptor in a reversible fashion, i.e. it can be displaced from the receptor if the concentration of the agonist is increased.

It shifts the dose-response curve to the right, i.e. the maximal response can still be achieved by the agonist but at a higher dose.

Question 5. Describe the Receptor-Mediated Mechanism Of Drug Action.
Answer:

Receptor-Mediated Mechanism Of Drug Action

Receptors are macromolecules that lie on the cell surface or cytoplasm or in the nucleus by which the drug binds as well as interacts and leads to cellular changes.

Drug + Receptor ↔ Drug receptor complex → Tissue response

Two important terminologies which are related to receptors are affinity and intrinsic activity.

• Affinity: It is the ability of the drug to combine with the receptor. If the drug lacks affinity it will not bind to the receptor. All types of drugs act via receptors and possess some affinity for receptors.
• Intrinsic activity: The ability of the drug to produce pharmacological action after combining with a receptor is known as the intrinsic activity of the drug.

Based on the intrinsic activity drugs are divided into the following types:

• Agonist: It is a drug that produces pharmacological action after binding to a receptor and is known as an agonist. It has high affinity and high intrinsic activity.
• Antagonist: It is the drug that prevents the binding of agonists to its receptor or blocks its effects. It does not produce any effect through itself.
  The competitive antagonist has got high affinity without any intrinsic activity. It leads to blockage of receptors.
• Partial agonist: It is the drug that binds to the receptor and produces an effect that is less than the agonist. Partial agonist inhibits the effects of agonist. Partial agonist has a full affinity to receptor along with less intrinsic activity.
• Inverse agonist: This drug has a full affinity towards the receptor and produces an effect opposite to that of an agonist.

Question 6. Write A Short Note On Competitive Antagonism.
Or
Write A Short Note On The Competitive Antagonism Of Drug Action.
Or
Write A Note On Competitive Inhibition.
Answer:

Competitive Antagonism

• It is also known as reversible or surmountable or equilibrium-type antagonism.
• In competitive antagonism, the drug being structurally similar competes with the normal substrate for the catalytic binding site of the enzyme. So that the product is not formed or a nonfunctional product is formed and a new equilibrium is achieved in the presence of a drug.

 

 

This type of inhibition is commonly observed with antagonists that bind reversibly to the same receptor site as that of an agonist.

For Example. is the action of acetylcholine (agonist) and atropine (antagonist) on muscarinic receptors.

• The equilibrium type of inhibition can be overcome by increasing the concentration of the agonist. The log dose-response curve of the agonist shows a rightward parallel shift in the presence of a competitive antagonist.
• In non-equilibrium antagonism, the antagonist binds to the same site on the receptor as the agonist but binding is irreversible. Here antagonist forms a strong covalent bond with the receptor, for Example. organophosphates react covalently with the esoteric site of the enzyme cholinesterase.
• The agonist in the presence of a competitive antagonist appears simply to be less potent.
• These characteristics reflect that the reversible antagonist dissociates faster from the receptor sites and hence the addition of a higher concentration of the agonist reduces.
  The rate of its association with the receptor sites by occupying the available spare receptors. Consequently, the overall antagonist occupancy falls and a new equilibrium is rapidly established.

Question 7. Write A Short Note On Functional Or Physiological Antagonism.
Answer:

Functional Or Physiological Antagonism

Functional or physiological antagonism is when two agonists, acting at different sites counterbalance each other by producing opposite effects on the same physiological system. Examples are:

• Histamine and adrenaline on bronchial muscles and BP.
• Hydrochlorothiazide and triamterene on urinary potassium excretion.
• Glucagon and insulin on blood sugar level.

Question 8. Write A Short Note On Receptors.
Answer:

Receptors

Receptors are defined as macromolecules or binding site located on the surface or inside the effector cell that serves to recognize the signal molecule/drug and initiate the response to it, but it itself has no other function.

Classification Of Receptors

Based On Transducer Mechanism

• G­protein coupled receptors: They are a large family of cell membrane receptors that are linked to the effector through one or more GTP-activated proteins for response effectuation.
• Receptors with intrinsic ion channel: These cell surface receptors are also known as ligand-gated ion channels which enclose ion-selective channels within their molecules.
• Enzyme-linked receptors: This class of receptors has a subunit with enzymatic properties or binds a JAK (Janus Kinase) enzyme on activation.
• Receptors regulating gene expression: Intracellular soluble proteins respond to lipid-soluble chemical messengers that penetrate the cell. Receptor protein is inherently capable of binding the specific genes.

Description Of Types Of Receptors

• Ligand-gated ion channels or ionotropic receptors
• Enzymatic receptors
• Receptors regulating gene expression or nuclear receptors.
• G protein-coupled receptors or metabotropic receptors

Ligand Gated Ion Channels Or Ionotropic Receptors

 

 

Enzymatic Receptors

 

 

Receptors Regulating Gene Expression Or Nuclear Receptors

They are slow acting and are present in cytoplasm or nucleus, for Example. receptors for thyroxine, vitamins A and D, etc.

 

Functions Of Receptors

• Recognition of specific legend molecule, i.e. whether it is agonist or antagonist, etc.
• Transduction of signals, i.e.
  • Propagation of signals from outside to inside of the effector cells
  • Amplification of the signals
• Integration of various regulatory signals, i.e. extracellular and intracellular.
• Maintenance of homeostasis by adopting the process of receptor regulation, i.e. regulation and down-regulation.

 

Regulation Of Receptors

• Down-regulation:  Continuous and prolonged exposure of the agonist to tissue leads to, a decrease in the number of receptors, this is called down-regulation.
  Example. tachyphylaxis (loss of efficacy with frequently repeated doses) as in asthmatics who uses salbutamol [α2 agonist] chronologically on a long-term basis.
• Up-regulation: When tissues are continuously or prolong exposed to an antagonist, leads to the formation of new receptors (increase in the number of receptors), this is called upregulation.
  For Example. precipitation of angina attack on sudden withdrawal of β-blockers (secondary prophylactic agents).

G Protein Coupled Receptors Or Metabotropic Receptors

 

 

• These get coupled to intracellular effectors via G proteins. G proteins are membrane proteins and consist of three subunits, i.e. α, β, γ with GDP binding to the α-subunit.
• These receptors control the functioning of cells via adenylyl cyclase, phospholipase C, etc.
• In this agonist which binds to the receptor is the first messenger and causes the generation of the molecule, i.e. second messenger which initiates the signaling mechanism of the cell.

Question 9. Write A Short Note On Partial Agonist.
Answer:

Partial Agonist

It is the drug that binds to the receptor and produces an effect that is less than the agonist.

• Partial agonist inhibits the effects of agonist.
• Partial agonist has a full affinity to receptor along with less intrinsic activity.
• An Example of a partial agonist is pentazocine a partial agonist at the μ receptor subtype of opioid receptor.
• Another example is Pindolol has partial agonistic activity at β₁ receptors.

Partial Agonist Of Mechanism

Partial agonists activate the receptor submaximally. So, in the absence of an agonist, it produces a submaximal action on the receptor.

On the other hand, because it has occupied the receptor, it prevents any other molecule (including an agonist) to attach with the receptor and producing action.

When the agonist is not able to bind to the receptor, it cannot produce its maximal action. Thus, in the presence of a partial agonist, the action of a full agonist is antagonized.

 

Question 10. Write A Short Note On Potentiation.
Answer:

Potentiation

It is also known as the supra-additive effect.

• Potentiation is defined as the enhancement of the action of one drug by another drug, which is inactive.
• Examples are a combination of acetylcholine + physostigmine, sulphamethoxazole + trimethoprim
• Here physostigmine and trimethoprim inhibit the breakdown of acetylcholine and sulphamethoxazole, thus enhancing their effects.

Question 11. Write A Short Note On Therapeutic Index.
Answer:

The therapeutic index is the measure of the safety of a drug. The therapeutic index is the ratio of a medial lethal dose of a drug to the median effective dose of a drug.

It is the statement of how selective the drug is in producing its desired effects versus its adverse effects.

\(\mathrm{TI}=\frac{\text { Median lethal dose }\left(\mathrm{LD}_{50}\right) \text { of the drug }}{\text { Median effective dose }\left(\mathrm{ED}_{50}\right) \text { of the drug }}\)

 

• Median lethal dose or LD₅₀: It is the dose of a drug that results in the death of 50% of animals who receive the drug. More is LD₅₀ safer is the drug.
  In preclinical studies of drugs, the median lethal dose is determined in experimental animals.
• Median effective dose or ED₅₀: It is the dose of a drug that will produce the desired effect in 50% of the population. More is ED₅₀, less is potency, and vice versa.
  So high is the value of the therapeutic index safe isv the drug, Example penicillin has a high therapeutic index while digitalis and phenytoin have a less therapeutic index.

Question 12. Write In Brief Formula For The Calculation Of The Therapeutic Index, In Humans.
Answer:

Formula For Calculation Of Therapeutic Index In Human

For obvious reasons, the lethal dose would not be administered in humans. So a modified parameter is used in clinical studies.

The dose or concentration (preferably) of a drug required to produce toxic effects is compared with the dose or concentration required for therapeutic effects in the population.

This parameter is called a clinical therapeutic index.

Therapeutic index in humans or clinical therapeutic index

\(=\frac{\text { Toxic Dose }\left(\mathrm{TD}_{50}\right) \text { of the drug }}{\text { Median effective dose }\left(\mathrm{ED}_{50}\right) \text { of the drug }}\)

 

Here, TD₅₀ is a dose of a drug required to produce toxic effects for 50%
of population. ED₅₀  is a dose of a drug that produces the desired effect in
50% of the population.

For many drugs, there are severe toxicities that occur at sublethal doses in humans, and these toxicities often limit the maximum dose of a drug.

A higher therapeutic index is preferable to a lower one—a patient would have to take a much higher dose of such a drug to reach the toxic threshold than the dose taken to elicit the therapeutic effect.