diabetic drugs Flashcards
what 2 types of diabetic drugs have an insulin independent action
alpha-glucosidase inhibitors
SGLT2 inhibitors
sulfonylureas act by displacing the binding of ___ from the ___ subunit therefore closing the ____ channel which causes ____
sulfonylureas work by displacing the binding of ADP-Mg2+ from the SUR1 subunit therefore closing the K-ATP channel which causes the release of insulin
what effect on the blood sugar do sulfonylureas have
decrease fasting and postprandial blood glucose
give an example of a short acting sulfonylurea
Tolbutamide
give 3 examples of a long acting sulfonylurea
which is ok for use in pregnancy in MODY
Glibenclamide
do sulfonylureas reduce micro or macrovascular complications
micro
are sulfonylureas orally active? are they well tolerated?
yes and yes
do sulfonylureas cause weight loss
no - undesirable weight gain
sulfonylureas will work in patients who no longer have a functioning mass of B-cells
true or false
false - require a functioning mass of beta cells
is there a risk of hypo with sulfonylureas?
yes
when should LA sulfonylureas be avoided?
CKD
elderly
pregnancy
when are sulfonylureas used first line
if metformin intolerant or if weight loss
what is the diabetic treatment ladder
metformin
+ sulfonylurea
+ TZD
when would a TZD be used 2nd line with metformin instead of a sulfonylurea
if hypo was a concern
when would a DPP4 inhibitor be used 2nd line with metformin instead of a sulfonylurea
if weight gain was a concern
when would a DPP4 inhibitor be used instead of a TZD 3rd line
if weight gain was a concern
when would a GLP-1 be used 3rd line instead of a TZD
if BMI > 30
when would insulin be used in diabetes? - last line
osmotic symptoms / rising HbA1c
what kind of drugs are repaglinide and nateglinide
glinides
how do glinides work?
they act similarly to sulfonylureas although their action is augmented by glycaemia - they lack the sulfonylurea moiety - bind at a distinct benzoamido site to close the Katp channel causing insulin to be released
are glinides orally active
yes
what is more likely to cause a hypo: glinide or sulfonylurea
sulfonylurea
are glinides safe to use in CKD
yes - mainly hepatic metabolism
what is the effect of glinides on blood glucose levels
reduce post prandial blood glucose - promote insulin secretion in response to meals
what is the action of glinides like with regard to time
rapid onset (30-60 mins) and offset (4 hours) kinetics
are glinides safe to use in pregnancy
no
are glinides safe to use in breast feeding
no
are glinides safe to use in hepatic impairment
no
when can glinides be used
in conjunction with metformin and TZDs
what kind of drug is sitagliptin
DPP4 inhibitor / gliptin
DDP4 inhibitors (competitively/non-competitively) inhibit the action of DPP4 and so (shorten/prolong) the action of __ and __
competitively inhibit
prolong action of GLP-1 and GIP
are DPP4 inhibitors effective in a patient with no preservation of insulin secretion
no
when are DPP4 inhibitors used
in combination with sulfonylurea or metformin
can DDP4 inhibitors be used as a monotherapy
yes
is sitagliptin orally active
yes
does sitagliptin cause weight gain?
no - weight neutral
does sitagliptin cause hypo?
not when used as a monotherapy
what is a side effect of sitagliptin
nausea
what kind of drugs are extenatide and liraglutide
incretin analogues
what peptides do incretin analogues mimic the action of
GLP-1
what is more potent - DPP4 inhibitors or incretin analogues
incretin analogues
incretin analogues bind as (antagonists/agonists) to the GLP-1 GPCR
agonists
what does the binding of the incretin analogue to the GLP-1 GPCR cause
increase in intracellular cAMP concentration in pancreatic beta cells to stimulate insulin secretion/expression
give 3 additional effects of incretin analogues
suppress glucagon secretion
slow gastric emptying
decrease appetite (hypothalamic cation)
are incretin analogues orally active
no - SC admin
do incretin analogues cause weight gain
no - modest weight loss
do incretin analogues cause hypo
no
what are some side effects of incretin analogues
nausea
rarely pancreatitis
what kind of drugs are miglitol, voglibose and acarbose
alpha-glucosidase inhibitors
what is alpha-glucosidase
brush border enzyme that breaks down dietary CHO (start and disaccharides) to absorbable glucose
when are alpha-glucosidase inhibitors taken
with meals
what is the effect of alpha-glucosidase inhibitors
delay absorption of glucose thus reduce post prandial increase in blood glucose
when are alpha-glucosidase inhibitors used
in T2DM poorly controlled by diet and other drugs (infrequently)
what are some side effects of alpha-glucosidase inhibitors
flatulence loose stools diarrhoea abdominal pain bloating
do alpha-glucosidase inhibitors cause hypo
no
what kind of drug is metformin
biguanide
biguandies increase (secretion of/sensitivity to) insulin
increase sensitivity to insulin
biguandies (increase/decrease) hepatic gluconeogenesis by stimulating _____
biguanides decrease hepatic gluconeogenesis by stimulating AMP-activated protein kinase
biguandies (increase/decrease) glucose and fatty acid uptake and utilisation by skeletal muscle by increasing insulin secretion
biguandies increase glucose and fatty acid uptake and utilisation by skeletal muscle by increasing insulin secretion
do biguandies have an effect on CHO absoprtion?
yes - reduce CHO absorption
biguandies increase/decrease fatty acid oxidation
biguandies increase fatty acid oxidation
when is metformin used
1st line in T2DM irrespective to obesity
do biguandies reduce microvascular complications
yes
how is metformin administered
orally
does metformin cause hypo
no
metformin is weight neutral
true/false
false - weight loss
metformin is used as a monotherapy only
true/flase
false
can be combined with other drugs
can metformin be used in pregnancy
yes
when is metformin contraindicated
severe renal/hepatic dysfunction
what are 2 side effects of metformin
GI upset (nausea, diarrhoea, anorexia, abdominal pain) lactic acidosis - excessive alcohol consumption, severe renal/cardiac/liver failure
at what GFR should metformin be stopped
and why?
GFR < 30
tissue hypoxia
at what GFR should metformin be halfed
GFR 30-45
metformin starts at a certain dose and remains as that
true or false
false
start low and increase slowly
what kind of drug is pioglitazone
thiazolidinediones/glitazones
why are ciglitazone and troglitazone no longer used
serious hepatotoxicity - not with pioglitazone
when are TZDs used
in combination with either metformin or a sulfonylurea
how do TZDs affect the secretion of insulin
they dont
they decrease insulin resistance at target tissues
how do TZDs work?
they act as exogenous agonists of the nuclear receptor PPAR-Y which associates with RXR (retinoid receptor X)
where is PPAR-Y found
largely confined to adipocytes
what does the activated PPARY-RXR complex do
acts as a transcription factor that binds to DNA to promote the expression of genes encoding several proteins involved in insulin signalling and lipid metabolism
what is the time of onset of action of TZDs
delayed
increasing gene transcription does what to the uptake of glucose and fatty acids
increases
do TZDs decrease microvascular complications
no
reduce MACROvascular comps
what is the effect of TZDs on heart problems
decrease risk of MI but worsen heart failure
do TZDs cause hypo
no
give 4 other benefits of using TZDs
- promote fatty acid uptake and storage in adipocytes rather than in skeletal muscle and liver
- reduce hepatic glucose output
- enhances peripheral glucose uptake
- improves microalbuminuria
do TZDs cause weight loss
no - weight gain
why do TZDs cause fluid retention
promote Na+ reabsorption by the kidney
what increases in incidence in the use of TZDs
fractures
what kind of drugs are dapagliflozin, canagliflozin, ampagliflozin
SGLT2 inhibitors
how do SGLT2 inhibitors work
they selectively block the reabsorption of glucose by SGLT2 in the proximal tubule of the kidney - enhance renal secretion of glucose
what are 2 bad side effects of SGLT2 inhibitors and why do they happen
UTI and thrush
due to glucosuria
do SGLT2 inhibitors cause weight gain
no - weight loss
do SGLT2 inhibitors cause hypo
little risk
