tema 3

Question 1

DRUG

Answer 1

Chemical compound capable of producing an effect over a biological system.

specificity for the site of interaction with target

Question 2

DRUG TARGET

Answer 2

macromolecule in the body interacting with
the drug to produce a specific biological effect

ligand specificity

Question 3

Drug action (MoA)

Answer 3

molecular process modulated by the
drug (morphine action on opioid receptors and second messenger
activation)

Question 4

Drug effect

Answer 4

consequence of drug action.
Pharmacological effect (analgesic effect of morphine)

Question 5

Ideal drug characteristics

Answer 5

-specificity: drug selectivity of binding for a determined
drug target.
-affinity: determines the proportion of drug targets occupied
by the drug (drug-drug target complex).

Question 6

Proteins as drug targets

Answer 6

 Receptors
- ionotropic (LGIC)
- metabotropic (GPCR)
- with enzymatic activity
- intracellular
 Enzymes
 Ion channels
 Transporters

Question 7

Novel approaches for target inhibition

Answer 7

1) PROTEIN-PROTEIN interaction as a target
2) PROTAC approach

Question 8

Hypersensitization

Answer 8

-Increase in response Increase in number of receptors
-Increase in receptor signaling capability
-sometimes after prolonged withdrawal

Question 9

Quantitative aspects of drug-target interaction

Answer 9

• Binding curves
  – Study of the affinity
  The smaller the dissociation constant (Kd), the higher the
  affinity between the drug and the target.
  Ka=1/Kd»affinity constant

Question 10

Efficacy or intrinsic activity

Answer 10

property of each drug, once bound to
its binding site, to produce a biological action.

Question 11

Based on efficacy orthosteric drugs are:

Answer 11

Agonists: drugs that bind to the specific site and have an intrinsic activity.
Antagonists*: drugs that bind to the receptor but do not have intrinsic activity.
Partial agonists: drugs that bind to the site of action but have a lower intrinsic activity than an agonist.
Inverse agonists: drugs that bind their site of action and produce an effect opposite to that of agonist.

Question 12

Allosteric modulators:

Answer 12

-Positive (PAM)
-Negative (NAM) reduces the effects of the orthosteric ligand,
but is inactive in the absence of the orthosteric ligand

Question 13

Target occupancy model (premises):

Answer 13

a) Drug-target binding is reversible.
b) Drug effect is proportional to occupied targets.
c) Maximal drug effect occurs when all targets are occupied.

Question 14

Parameters in the dose-response curve

Answer 14

• Maximal effect:
  related to drug
  efficacy
• Potency: drug
  concentration
  needed for a
  certain effect
  (related to affinity)

Question 15

Types of antagonism

Answer 15

An antagonist drug will reduce the effect of an agonist drug.
- Functional antagonism
Drugs with opposite effects acting on different targets over the same variable.
- Chemical antagonism
Drugs that react among them, and result in the inactivation of
the active drug.
- Pharmacological antagonism
Drugs act on the same receptor
-Competitive
-Non competitive

Question 16

Partial agonism

Answer 16

Partial agonists have lower efficacies than full agonists.
Partial agonists combined with a full agonist may appear similar to a
competitive antagonist.

Question 17

Drug combination

Answer 17

Additivity and synergisms in Pharmacology
Representation of iso-efective doses for a given level of effect)
- Subadditive. 50% of response is only obtained
with higher doses of A and B combined
- Superadditive. 50% of response is obtained with
lower doses of A and B combined

Isobologram analysis, used to estimate the effect of combining compounds