1. Definition of drug. Pharmacodynamics: Structure-dependent and independent drug actions

Question 1

Give the definition of ‘pharmacology’

Answer 1

Investigating the function-altering effect of several (exogenic and endogenic) substances in living entities.

Question 2

Define pharmaceutical substances

Answer 2

If a substance can be used for treatment

Question 3

Give the etymology of “Drug”

Answer 3

“Drug” (“droog” → “dry”)

Question 4

What are pharmacodynamics?

Answer 4

The process of the drug entering the body

Question 5

What are pharmacokinetics?

Answer 5

The interaction of the body on the drug

Question 6

Which mnemonic is used to represent the pathway of the drug (pharmacodynamics)

Answer 6

ADME

Question 7

“Corpora non agunt nisi fixata”

Answer 7

“A drug will not work unless it is bound”

Question 8

Most drugs achieve their therapeutic effects by…

Answer 8

Interacting selectively with target molecules

• These play roles in physiologic or pathologic functioning

Question 9

The selectivity of the drug binding may determine…

Answer 9

Adverse effects of a drug

Question 10

Drug receptors are…

Answer 10

Macromolecules that, upon binding to a drug, mediate those biochemical and physiologic changes

Question 11

Drugs binding to intracellular receptors

Answer 11

Highly lipophilic drugs that can easily pass through plasma membrane & also special barriers

Question 12

Extracellular receptors

Answer 12

Surface protein receptors with extracellular domains linked to intracellular effector molecules

Question 13

Which receptor types do drugs interact with?

Answer 13

1. Ligand-gated ion channels
2. G-protein coupled receptors
3. Receptor-activated tyrosine kinases
4. Intracellular nuclear receptors

Question 14

Ligand-gated ion channels

Answer 14

Nicotinic ACh (nACh) receptors composed of 5 subunits

Question 15

Give the area of the physiological function of nACh channels

Answer 15

• Neuromuscular junction
• Autonomic ganglia
• CNS

Question 16

Give the function of the nACh receptor

Answer 16

1. ACh binds to both α-subunits
2. Channels open
3. Na⁺ passes down its conc. gradient into cell

Question 17

Give the types of nACh receptors (ligand-gated ion channels) involved in pharmacology

Answer 17

• N_m
• N_{<span>G</span>}

Question 18

N_m receptor - Area of function

Answer 18

Motor endplate of neuromuscular junctions of somatic nerves & skeletal muscles

Question 19

N_{<span>G</span>} Receptor - Area of function

Answer 19

Autonomic ganglia in adrenal medulla & certail areas in the brain

Question 20

GABA_A receptor-gated chloride ion channel

Answer 20

• Orthosteric ⇔ Allosteric effect (propofol acts as both)
• PAM = Positive allosteric modulator = Allosteric agonist

Question 21

G-protein coupled receptors

Answer 21

7-transmembrane receptors

Question 22

Give the types of G-protein coupled receptors

Answer 22

• Gαs (Stimulatory)
• Gα_{I (Inhibitory)}
• G_q

Question 23

Gα_s receptors - Action of function

Answer 23

1. GTP → GDP
2. Interaction with adenylate cyclase
3. Catalyses: ATP → cAMP
4. cAMP activated PKA
5. Phosphorylation & activation of effector proteins
6. Drug effect is carried out

Question 24

List some Gα_s receptors

Answer 24

• H₂
• β₁ Adrenoceptors
• β₂ Adrenoceptors

Question 25

H₂ (Histamine) receptor function

Answer 25

* ↑ gastric production * Vasodilation * Relaxes SM

Question 26

β₁ adrenoceptors

Answer 26

(Excitatory) * ↑ Heart rate & contractility * ↑ Fat cell lipolysis

Question 27

β₂ adrenoceptors

Answer 27

(Inhibitory) * Vasodilation * Intestinal SM relaxation * Bronchial SM relaxation * Uterine SM relaxation

Question 28

Gα_i receptors

Answer 28

1. GDP→GTP 2. Inhibition of Adenylate Cyclase 3. ↓cAMP production

Question 29

Give an example of a Gα_i receptor

Answer 29

α₂ adrenoreceptors

Question 30

α₂ ​adrenoreceptors - Function

Answer 30

Prejunctional inhibition of norepinephrine & other neurotransmitter release

Question 31

G_q receptors - Function

Answer 31

1. ↑ Phospholipase activity 2. Cleaves: Membrane phospholipid → DAG + IP 3. DAG activated Protein Kinase C 4. Phosphorylation & activation of cellular proteins 5. IP releases Ca²⁺ from ER → cytoplasm 6. Cellular processes activated

Question 32

List some G_q coupled receptors

Answer 32

* α₁ adrenoreceptors * H₁ receptors * Serotonin receptors

Question 33

H₁ receptor - function

Answer 33

* ↑ Awakeness * ↑ Vasodilation * ↑ Permiability

Question 34

α₁ adrenoreceptors - Function

Answer 34

* Vasoconstriction * GI relaxation * Mydriasis

Question 35

Receptor-activated tyrosine kinases

Answer 35

* Many growth-related signals * Liganded receptors autophosphorylate tyrosine

Question 36

Give an example of a receptor-activated tyrosine kinases

Answer 36

Insulin receptor substrate (IRS) → Insulin receptor

Question 37

JAK inhibitors - function

Answer 37

"Janus kinase inhibitors" * Inhibits JAK-1 * Interleukins-4 /-13 /-31 (Allergy, inflammation, pruritus) * Used in atopic dermatitis

Question 38

Intracellular nuclear receptors (NR) - Function

Answer 38

* Lipophylic ligands 1. Binding ligand → structural changes in receptor 2. Dissociation of chaperones → Receptor enters the nucleus 3. Hetero-/homodimerisation of receptors & interaction with DNA

Question 39

Give examples of intracellular nuclear receptors

Answer 39

* Ligand (pl. cortisol) * HSP90 (Heat shock protein) * CoA (Coactivator) * Pol II (RNA polymerase II)

Question 40

Identify receptor 1

Answer 40

Ligand-gated ion channel

Question 41

Identify receptor 2

Question 42

Identify receptor 3

Answer 42

Receptor-activated tyrosine kinases

Question 43

Identify receptor 4

Answer 43

Intracellular nuclear receptors

Question 44

Answer 44

Activation of conductance

Question 45

Answer 45

1. G-protein activation 2. Generation of second messenger 3. Activation of cell signaling

Question 46

Answer 46

1. Phosphorylation of tyrosines on key signalling molecules 2. Activation of cell signalling

Question 47

Answer 47

1. Transport to the nucleus 2. Activation of transcription and translation