Pharmacology

Question 1

what are four types of membrane-bound receptors?

Answer 1

1. ligand-gated ion channels
2. GPCR
3. receptor tyrosine kinase (kinase-linked receptors)
4. steroid hormone receptors

Question 2

what happens to ligand-gated ion channels when neurotransmitters bind?

Answer 2

causes a conformational change allowing influx/efflux of ions

Question 3

structure of a GPCR

Answer 3

7 transmembrane spans across membrane coupled with G-proteins

Question 4

role of G-proteins

Answer 4

stimulate or inhibit various effectors

Question 5

what does binding to the GPCR cause?

Answer 5

G-protein dissociation

Question 6

can GPCR do signal amplification?

Answer 6

yes

Question 7

what binds to receptor tyrosine kinases?

Answer 7

hormones

Question 8

what does binding of hormones do to receptor tyrosine kinases?

Answer 8

causes dimer formation and autophosphorylation of tyrosine residues and relay proteins activate divergent response

Question 9

what happens when there is binding to steroid hormone receptors?

Answer 9

pass through cell membrane and bind to response elements activating transcriptions

Question 10

three types of signalling

Answer 10

1. autocrine
2. paracrine
3. endocrine

Question 11

what does endocrine signalling need that the others do not?

Answer 11

a blood supply

Question 12

what are the three types of hormones?

Answer 12

protein/peptide
steroid
amines

Question 13

when are steroid hormones active?

Answer 13

when they are unbound

Question 14

what are the two types of amine hormones?

Answer 14

catecholamines

tyrosine amines

Question 15

what does hormone binding to carrier proteins facilitate?

Answer 15

transport

increased half-life

Question 16

specific hormone carriers

Answer 16

CBG
TBG
SSBG

Question 17

what are the actions of insulin?

Answer 17

glucose uptake by cells
glycogenesis
lipogenesis
protein formation

this collectively reduces blood glucose

Question 18

how is insulin secreted from the pancreatic beta cell?

Answer 18

• elevated blood glucose causes facilitated diffusion via GLUT2 into the beta cell
• glucose is phosphorylated by glucokinase and glycolysis yields ATP
• ATP-sensitive K+ channels are closed causing depolarisation and Ca2+ channels open triggering insulin release

Question 19

examples of sulfonylureas

Answer 19

tolbutamide
gliclazide
glipizide

Question 20

what do SUs require to work?

Answer 20

functional beta cells

Question 21

mechanism of action of SUs

Answer 21

displace ADP-Mg2+ from SUR1 closing KATP channels stimulating insulin release

Question 22

adverse of SUs

Answer 22

hypoglycaemia
weight gain (anabolic effect of insulin increases appetite)

Question 23

when are SUs first line?

Answer 23

for those intolerant to metformin

Question 24

what decreases the action of SUs?

Answer 24

thiazides

corticosteriods

Question 25

examples of glinides

Answer 25

repaglinide | nateglinide

Question 26

action of glinides

Answer 26

bind to SUR1 to close KATP channel and trigger insulin release

Question 27

when are glinides used?

Answer 27

in conjunction with metformin and TZDs

Question 28

what is the incretin effect?

Answer 28

insulin responds greater to oral glucose than IV

Question 29

what does the ingestion of oral glucose cause?

Answer 29

- stimulates GLP-1 and GIP to enter portal blood - enhance insulin release and delay gastric emptying - decrease glucagon all decrease blood glucose

Question 30

what breaks down the hormones GLP-1 and GIP?

Answer 30

DPP4 enzyme

Question 31

two pharmacological options that use the incretin effect?

Answer 31

1. DPP-4 inhibitors | 2. incretin analogues

Question 32

examples of DPP-4 inhibitors

Answer 32

sitagliptin | saxagliptin

Question 33

action of DPP-4 inhibitors

Answer 33

inhibit DPP4 actions causing insulin secretion to be preserved

Question 34

adverse of DPP-4 inhibitors

Answer 34

they are weak drugs so nothing really, can cause a bit of nausea

Question 35

examples of incretin analogues

Answer 35

extenatide | liraglutide

Question 36

what do incretin analogues do?

Answer 36

mimic action of GLP-1 but resist breakdown by DPP4 cause weight loss and reduce hepatic fat accumulation

Question 37

how are incretin analogues administered?

Answer 37

SC weekly

Question 38

adverse of incretin analogues?

Answer 38

nausea

Question 39

example of a biguanide

Answer 39

metformin

Question 40

mechanism of action of metformin

Answer 40

activate AMPK increasing glucose uptake, reducing absorption and increasing fatty acid oxidation prevents hyperglycaemia but doesn't cause hypoglycaemia

Question 41

when is metformin first line?

Answer 41

T2DM

Question 42

adverse of metformin

Answer 42

GI upset lactic acidosis causes weight loss but seen as a good thing

Question 43

example of thiazolidinediones (TZDS)

Answer 43

pioglitzone

Question 44

mechanism of action of TZDs

Answer 44

agonists of PPAR-gamma receptor and activated complexes act as transcription factors promoting encoding of proteins involved in insulin signalling and lipid metabolism shifts fat from visceral to liver

Question 45

adverse of TZDs

Answer 45

weight gain | fluid retention

Question 46

examples of sodium-glucose cotransporter-2 inhibitors (SGLT2i)

Answer 46

dapaliflozin | canagliglozin

Question 47

mechanism of action of SGLT2i

Answer 47

selectively block reabsorption of glucose by SGLT2 in proximal tubule causing glucosuria

Question 48

benefits of SGLT2i

Answer 48

weight loss | cardiovascular and renal disease benefits

Question 49

adverse of SGLT2i

Answer 49

increased risk of thrush | beware of euglycaemic DKA

Question 50

which drug class is infrequently used in the UK?

Answer 50

alpha-glucosidase inhibitors