CEP WK2 - PHARMACOLOGY

Question 1

CHARACTERISTICS OF DRUGS

Answer 1

• high potency (occur at low conc)
• chemical specifity
• biological specifity (receptor it binds to)

Question 2

ORGANOID

Answer 2

• small & simplified version of organ used for drug testing & monitoring disease development
• formed by taking stem cell & culturing & petri dish

Question 3

DRUG CONC & RESPONSE RELATIONSHIP

Answer 3

• as agonist conc rises, response rises until level off but has a threshold to start which you can’t see unless log curve
• Kd never changes but stronger agonists just open channels more frequently

Question 4

P = ([A]) / ([A] + Kd)

Answer 4

• p = response
• Kd is a constant which we can be given and then we use agonist conc (coupled with given Kd) to find out response (p) & plot curve

Question 5

NUCLEAR RECEPTORS (steroid) (structure - 2 domains)

Answer 5

have ligand binding domain (when ligand binds, whole protein is folded to 3d) & DNA binding domain (mediates binding of these nuclear receptors to thousands of sites in genome)

Question 6

CYTOKINE RECEPTORS

Answer 6

• no catalytic activity & no naturally bound kinases (as bigger extracellular domain)
• JAK2 protein kinase is near receptor & has high affinity
• when EPO dimerises the receptor, the tiny intracellular bits come closer (nearer to JAK2) so JAK2 can phosphorylate receptor to cause response

Question 7

DIRTY DRUGS (1 DRUG MANY TARGETS)

Answer 7

forms ‘wanted’ side effects e.g. drug may bind to 1 wanted & 1 unwanted receptor but trying to fix it causes issues as tips balance

Question 8

WAYS A DRUG CAN REGULATE CELL FUNCTION (3)

Answer 8

• alter membrane potential
• alter enzyme activity
• alter gene expression

Question 9

INTEGRAL ION CHANNELS

Answer 9

• transport ions
• inhibited by nicotinic substances
• regulated by AcH

Question 10

INTEGRAL TYROSINE KINASES

Answer 10

ligand binds & then the receptors phosphorylate each other

Question 11

PATCH-CLAMP METHOD (to check when receptors in membrane open or closed)

Answer 11

• small pipette put on membrane (seals gap between membrane & pipette so no ions flow unless through receptor) & then electrode measures when ion channel open or shut
• shows that agonists open channels & receptors are binary (open or shut)

Question 12

ALTERNATIVE TO PATCH-CLAMP

Answer 12

• add GFP (fluoresce) into unstable gene & add control values into 96 well plate
• increased fluorescent expression of stabilised gene shows result

Question 13

GLUTAMATE-GATED CHLORIDE RECEPTORS

Answer 13

• target for anti-parasitic drugs, found in NS, pentamer

Question 14

SUPER AGONIST

Answer 14

produce maximal response from cell without even needing to bind to all available receptors (only binding to some is enough)

Question 15

PARTIAL AGONIST

Answer 15

low efficacy & can’t produce maximal response even when bound to all available receptors

Question 16

COMPETITIVE ANTAGONIST

Answer 16

bind (reversibly) at same site as agonist but doesn’t activate protein (just blocks agonist action)

Question 17

IRREVERSIBLE ANTAGONIST

Answer 17

• bind (irreversibly) at same site as agonist to form covalent bond & destroy receptor (later destroyed by lysosomes)
• proves concept of spare receptors as if we destroy some receptors, the super agonists still provide max efficacy

Question 18

ALLOSTERIC ANTAGONIST

Answer 18

bind (reversibly) at different site to agonist & decrease agonist affinity (less likely to bind)

Question 19

PHYSIOLOGICAL ANTAGONIST

Answer 19

binds to completely different receptor but blocks agonist action

Question 20

DESENSITIZATION

Answer 20

prolonged exposure to agonist reduces response to that drug (high tolerance)