A.2

Question 1

Qualitatively described reponse

Answer 1

Plots % of a population responding to a specific drug drug effect vs. drug dose.
It shows us variation in drug sensitivity in a given population, and permit estimation of median effective dose -> effective dose in 50% of a population.
- ED50 -> 50% of individuals responding.

Question 2

therapeutic index

Answer 2

Quantitive measurement of the relative safety of a drug.
- Safe drug: high toxic dose and much lower effective dose
- if ED and TD are close → administration of drug is dangerous (aminoglycosides, theophulline, warfarin, digoxin, lithium has a narrow Therapautic index

Question 3

How can TI be measured?

Answer 3

Therapautic index (TI)= Toxic dose in 50% of the individuals(TD50)/Effective dose in 50% in individuals (ED50).
- The higher therapautic index the better!

Question 4

What is therapautic window?

Answer 4

Therapautic window = TD-ED (Dosage range between the minimum effective therapautic dose and the minimum toxic dose

Question 5

Drug-receptor interactions:

Answer 5

1. Agonist
2. Partial agonist
3. Inverse agonist
4. Antagonist (competitive/noncompetitive)

Question 6

1. Agonist

Answer 6

Maximal effect is ahchieved when it is bound to the receptor. Intrinsic activity = 1 (e.g. morphine)

Question 7

2. partial agonist

Answer 7

Drug that binds to its receptor, but produces a smaller effect than a full agonist. In the presence of a full agonist, the partial agonist will act as an inhibitor (displaces the full agonist from the receptor). Has affinity, intrinsic activity <1 (e.g. buprenorphine)

Question 8

3. inverse agonist

Answer 8

Causes opposite effect of the full agonist. Drug binds to the non-active state of the receptor and decreases its constitutive activity. Intrinsic activity =-1 (e.g. Flumazenil)

Question 9

4. antagonist

Answer 9

Results in inhibition of receptor activation
Competitive antagonist: (e.g. Ticagrelor):
Drugs that bind to the agonist receptor site in a reversible way, without activating the effector system for that receptor. The antagonist can be overcome by increasing agonist concentration. The dose-response curve for an agonist is shifted to higher doses, but the same maximal effect may still be reached

Irreversible antagonist: non-competetive antagonist (e.g. Abciximab)
Effect cannot be overcome by adding more agonist. Causes a downward shift of the maximum effect. ED50 is not increased unless spare receptors are present

Question 10

the molecular targets of drugs

Answer 10

1. Receptors: GPCR, Ligand gated ion channels, tyrosine kinase, intracellular cytoplasmic etc.
2. Enzymes: COX, ACE, ACh-esterase, dihydrofolate reductase
3. Transporters: Serotonin, NE, dopamine reuptake inhibitors
4. Voltage gated ion channels: Na+ , K+, Ca2+ , Cl- channels
5. Non-receptorial drug targets: Nuclei acids, cholesterol, acids etc
   6: Other (novel targets): RNA, miRNA

Question 11

potency

Answer 11

EC50 or ED50
The concentration or dose of a drug producing 50% of maximum effect- It tells us the quantity of drug required to produce a given effect.
- If we have lower EC50 → higher potency!
Mainly determined by the affinity of receptor to the drug+ number of available receptors

Question 12

Efficacy - Emax

Answer 12

Maximal effect an agonist can produce by the highest tolerated dose level
- It´s a measure of effectiveness → how well a drug produces a response

Question 13

classical receptor theory

Answer 13

Ligands bind to receptors in a reversible fashion and reaches an equilibrium: R+L -> RL

Question 14

Kd

Answer 14

Dissociation constant Kd denotes the concentration of a drug required to bind 50% of the available receptor sites; measure of affinity of a drug molecule to its receptor. The smaller the Kd the greater the affinity of the drug for its receptor.
Kd=[L]*[R]/[LR]

Question 15

spare receptor theory

Answer 15

Receptors are said to be ´´spare´´ for a given pharmacologic response, if it is possible to elicit a maximal biological response at a concentration of agonist that DOESN´T bind all of the available receptors → No need to occupy all receptors to achieve maximal effect. Presence of spare receptors increases the sensitivity to the agonist, because the likelihood of a drug-receptor interaction increases in proportion to the number of receptors availabe.
Due to 2 mechanisms:
1.Duration of effector activation may be much greater than the duration of the drug-receptor interaction
2.Number of receptors may exceed the number of effector molecules available

Question 16

wo-state receptor theory

Answer 16

That ligand binding results in a change of receptor state from an inactive state to an active state, based on receptor conformation change

Question 17

the point of receptor theory

Answer 17

Application of receptor models to explain drug behavior

Question 18

Where does a orthosteric drug bind?

Answer 18

On the active site

Question 19

Where does an allosteric drug bind?

Answer 19

Elsewhere on the receptor than the active site, and changes the conformation of the protein binding sit