Introduction to pharmacology

Question 1

What is pharmacology?

Answer 1

• Greek word
• pharmacon + logos
• 19th century
• study all aspects of drug

Question 2

History of pharmacology?

Answer 2

• the idea: Galen
• the impetus: Paracelsus
• the early beginning: Johan Jakob Wepfer

Question 3

Fathers of modern pharmacology?

Answer 3

• the foundation of the First Institute for Pharmacology (Rudolf Buchheim)
• established high reputation (Schmiedeberg)
• mentioned concept of receptors (Langley)

Question 4

Impact of biotechnology on pharmacology?

Answer 4

It has improved pharmacology in the way of discovering a new therapeutic agent, such as antibodies, regulatory proteins, and enzymes, by using genetic engineering. Bust overall the core of pharmacology remained the same. Biological drugs made from living organisms have a greater impact on treating serious conditions, such as cancer, diabetes, etc. Biosimilars are drugs similar to biological drugs in quality, biological activity, safety, and effectivness.

Question 5

General principles? What is meant by the nature of drugs and drug-body interaction?

Answer 5

1. The nature of the drug, includes:
   a. physical properties and chemical structure
   b. size and shape
   c. reactivity and drug-receptor interaction
2. drug-body interaction, includes:
   a. pharmacodynamics - what drug does to the body
   b. pharmacokinetics - what body does to the drug

Question 6

How drug produces an effect?

Answer 6

Paul Ehrlich said: ˝Copora non agunt nisi fixata˝ or ˝A drug will not work unless it is bounded˝. A drug must be bound to a constituent of a cell or tissue in order to produce an effect.

Question 7

Who is the father of modern receptor theory?

Answer 7

Rang

Question 8

What are drugs and receptor?

Answer 8

The drug is a chemical substance of known structure, other than nutrients and dietary ingredients, which when administered to living organisms produces biological effects. Component of a cell that interacts with drug and produces chains of events leading to drug observed effect.

Question 9

The most important fact about receptors?

Answer 9

1. macromolecules
2. proteins
3. regulatory function
4. present on the surface of the cell membrane and cytoplasm
5. would be activated in order to produce a chain of events
6. tend to be inactive
7. used for drug development and for making therapeutic decisions in clinical practice
8. used for investigation of drug effects and their mechanism of action

Question 10

What is a ligand?

Answer 10

The ligand is a component that binds to receptors, it can be drugs, hormones, neurotransmitters, and autocoids (substances produced by the body and characterized by local effects).

Question 11

What are drug receptors and what are other types?

Answer 11

Drug receptors are regulatory proteins that differ in the intracellular processes they produce when they are activated. Receptors are mainly ion-gated channels. Enzymes have the same functions in cytoplasm to transform one form of molecule into another. Transporters transport molecules from one side of the cell membrane to another. They can bind extracellular molecules and perform intracellular process

Question 12

Which types of receptor fo drugs we have?

Answer 12

1. ligand-gated ion channels
2. G-protein coupled receptors
3. intracellular receptors
4. enzyme-linked receptors

Question 13

Which receptors are not for drugs?

Answer 13

In pharmacology receptor is a protein that recognize and respond to endogenous chemical substance. Other molecules that recognize drugs and produce effect are known as drug targets. LDL receptors for lipid metabolism, and transferrin for iron absorption. Some drugs react with other drugs whereas some drugs react with H2O.

Question 14

Terms important for drug-receptor interaction?

Answer 14

1. Affinity, ability of molecule/drug to bind to receptor or drug tendency to bind to receptor.
2. Activation, affection of bound molecule to alter cell and elicit tissue response.
3. Specificity, binding of molecules of a certain precise type due to a high degree of selectivity.
4. Efficacy, intrinsic activity, how well the drug produces a response, the ability of drug once it is bound to cause activation.
5. Potency, is the ability of the drug to occupy a significant proportion of receptor even at low concentration, power, or strength of a drug.

Question 15

How drug acts on receptors?

Answer 15

It behaves as an agonist meaning that the drug binds to the receptor, activates it, and produces effect. On the other hand we have antagonist, drug binds to receptor, but does not activate it, there is no efficacy.

Question 16

How we can explain the binding of the drug to the receptor?

Answer 16

It can be described by the law of mass action that says:˝Changes in conc. of any component of reaction leaders to change in rate of reaction.˝ KD refers to the amount of drug that occupies 50% of the receptor. Low KD means high affinity and high KD means low affinity.

Question 17

Reversibility?

Answer 17

The binding of drugs to receptors is a dynamic process. Reversibility is a major interaction between a drug and a receptor. When the drug dissociates receptor continuous its effect.

Question 18

Drug-response curve?

Answer 18

A tool that represents the connection between a drug and its efficacy. Emax is the maximal effect prudent by the drug. Ec50 is the concentration of drug required to occupy 50% of the receptor. Lower EC50 higher potency and higher EC50 lower potency.

Question 19

Types of agonist?

Answer 19

a. full agonist - reaches maximum efficacy
b. partial agonist - reaches intermediate efficacy
c. inverse agonist - when ligand binds to receptor it doesn’t undergo fraction so there is no active conformation of a receptor (competitive antagonist)

Question 20

Explain competetive and non-competetive antagonism?

Answer 20

Competitive antagonism, agonist, and antagonist compete to occupy the same binding site on the receptor. By increasing the concentration of an agonist it outcompete the antagonist and reaches its maximum effect, it is known as reversible antagonism, where growing concentration for one drug reduces the effect of another due to the presence of weak bonds.
Histamine/fexofenadinene. Non-competitive antagonism, when agonist and antagonist occupy different binding sites on receptor at the same time, is known as irreversible antagonism because by increasing conc. of the antagonist, it will reduce the efficacy of the agonist due to the presence of strong bonds.

Question 21

Other types of antagonists?

Answer 21

Physical antagonists are substances that react in opposite directions from one another and none of them occupy the same receptor population. Chemical antagonists are when two substances are combined in a solution, and as a result active drug is lost. Pharmacokinetic antagonists, antagonist reduce the conc. of active drugs at the same site of action.

Question 22

What are spare receptors?

Answer 22

Spare receptors are additional receptors that do not elicit maximum response.

Question 23

Define desensitization and tolerance, what causes it?

Answer 23

The destination is when the drug gradually diminishes because it is repeatedly used. Tolerance is gradual responsiveness to the drug. They are caused by:
a. change of receptor.
b. transformation of the receptor,
c. exhaustion of mediators.
d. increase metabolic degradation of drug
e. physical adaptation

Question 24

Define refractoriness and drug resistance?

Answer 24

Refractoriness is the loss of drug effectiveness, and drug resistance is the loss of the effectiveness of antimicrobial and antitumor drugs.