Pharmacology Flashcards
what are four types of membrane-bound receptors?
- ligand-gated ion channels
- GPCR
- receptor tyrosine kinase (kinase-linked receptors)
- steroid hormone receptors
what happens to ligand-gated ion channels when neurotransmitters bind?
causes a conformational change allowing influx/efflux of ions
structure of a GPCR
7 transmembrane spans across membrane coupled with G-proteins
role of G-proteins
stimulate or inhibit various effectors
what does binding to the GPCR cause?
G-protein dissociation
can GPCR do signal amplification?
yes
what binds to receptor tyrosine kinases?
hormones
what does binding of hormones do to receptor tyrosine kinases?
causes dimer formation and autophosphorylation of tyrosine residues and relay proteins activate divergent response
what happens when there is binding to steroid hormone receptors?
pass through cell membrane and bind to response elements activating transcriptions
three types of signalling
- autocrine
- paracrine
- endocrine
what does endocrine signalling need that the others do not?
a blood supply
what are the three types of hormones?
protein/peptide
steroid
amines
when are steroid hormones active?
when they are unbound
what are the two types of amine hormones?
catecholamines
tyrosine amines
what does hormone binding to carrier proteins facilitate?
transport
increased half-life
specific hormone carriers
CBG
TBG
SSBG
what are the actions of insulin?
glucose uptake by cells
glycogenesis
lipogenesis
protein formation
this collectively reduces blood glucose
how is insulin secreted from the pancreatic beta cell?
- 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
examples of sulfonylureas
tolbutamide
gliclazide
glipizide
what do SUs require to work?
functional beta cells
mechanism of action of SUs
displace ADP-Mg2+ from SUR1 closing KATP channels stimulating insulin release
adverse of SUs
hypoglycaemia weight gain (anabolic effect of insulin increases appetite)
when are SUs first line?
for those intolerant to metformin
what decreases the action of SUs?
thiazides
corticosteriods
examples of glinides
repaglinide
nateglinide
action of glinides
bind to SUR1 to close KATP channel and trigger insulin release
when are glinides used?
in conjunction with metformin and TZDs
what is the incretin effect?
insulin responds greater to oral glucose than IV
what does the ingestion of oral glucose cause?
- stimulates GLP-1 and GIP to enter portal blood
- enhance insulin release and delay gastric emptying
- decrease glucagon
all decrease blood glucose
what breaks down the hormones GLP-1 and GIP?
DPP4 enzyme
two pharmacological options that use the incretin effect?
- DPP-4 inhibitors
2. incretin analogues
examples of DPP-4 inhibitors
sitagliptin
saxagliptin
action of DPP-4 inhibitors
inhibit DPP4 actions causing insulin secretion to be preserved
adverse of DPP-4 inhibitors
they are weak drugs so nothing really, can cause a bit of nausea
examples of incretin analogues
extenatide
liraglutide
what do incretin analogues do?
mimic action of GLP-1 but resist breakdown by DPP4
cause weight loss and reduce hepatic fat accumulation
how are incretin analogues administered?
SC weekly
adverse of incretin analogues?
nausea
example of a biguanide
metformin
mechanism of action of metformin
activate AMPK increasing glucose uptake, reducing absorption and increasing fatty acid oxidation
prevents hyperglycaemia but doesn’t cause hypoglycaemia
when is metformin first line?
T2DM
adverse of metformin
GI upset
lactic acidosis
causes weight loss but seen as a good thing
example of thiazolidinediones (TZDS)
pioglitzone
mechanism of action of TZDs
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
adverse of TZDs
weight gain
fluid retention
examples of sodium-glucose cotransporter-2 inhibitors (SGLT2i)
dapaliflozin
canagliglozin
mechanism of action of SGLT2i
selectively block reabsorption of glucose by SGLT2 in proximal tubule causing glucosuria
benefits of SGLT2i
weight loss
cardiovascular and renal disease benefits
adverse of SGLT2i
increased risk of thrush
beware of euglycaemic DKA
which drug class is infrequently used in the UK?
alpha-glucosidase inhibitors
