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diabetic drugs Flashcards

1
Q

what 2 types of diabetic drugs have an insulin independent action

A

alpha-glucosidase inhibitors

SGLT2 inhibitors

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2
Q

sulfonylureas act by displacing the binding of ___ from the ___ subunit therefore closing the ____ channel which causes ____

A

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

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3
Q

what effect on the blood sugar do sulfonylureas have

A

decrease fasting and postprandial blood glucose

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4
Q

give an example of a short acting sulfonylurea

A

Tolbutamide

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5
Q

give 3 examples of a long acting sulfonylurea

which is ok for use in pregnancy in MODY

A

Glibenclamide

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6
Q

do sulfonylureas reduce micro or macrovascular complications

A

micro

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7
Q

are sulfonylureas orally active? are they well tolerated?

A

yes and yes

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8
Q

do sulfonylureas cause weight loss

A

no - undesirable weight gain

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9
Q

sulfonylureas will work in patients who no longer have a functioning mass of B-cells
true or false

A

false - require a functioning mass of beta cells

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10
Q

is there a risk of hypo with sulfonylureas?

A

yes

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11
Q

when should LA sulfonylureas be avoided?

A

CKD
elderly
pregnancy

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12
Q

when are sulfonylureas used first line

A

if metformin intolerant or if weight loss

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13
Q

what is the diabetic treatment ladder

A

metformin
+ sulfonylurea
+ TZD

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14
Q

when would a TZD be used 2nd line with metformin instead of a sulfonylurea

A

if hypo was a concern

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15
Q

when would a DPP4 inhibitor be used 2nd line with metformin instead of a sulfonylurea

A

if weight gain was a concern

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16
Q

when would a DPP4 inhibitor be used instead of a TZD 3rd line

A

if weight gain was a concern

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17
Q

when would a GLP-1 be used 3rd line instead of a TZD

A

if BMI > 30

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18
Q

when would insulin be used in diabetes? - last line

A

osmotic symptoms / rising HbA1c

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19
Q

what kind of drugs are repaglinide and nateglinide

A

glinides

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20
Q

how do glinides work?

A

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

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21
Q

are glinides orally active

A

yes

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22
Q

what is more likely to cause a hypo: glinide or sulfonylurea

A

sulfonylurea

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23
Q

are glinides safe to use in CKD

A

yes - mainly hepatic metabolism

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24
Q

what is the effect of glinides on blood glucose levels

A

reduce post prandial blood glucose - promote insulin secretion in response to meals

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25
what is the action of glinides like with regard to time
rapid onset (30-60 mins) and offset (4 hours) kinetics
26
are glinides safe to use in pregnancy
no
27
are glinides safe to use in breast feeding
no
28
are glinides safe to use in hepatic impairment
no
29
when can glinides be used
in conjunction with metformin and TZDs
30
what kind of drug is sitagliptin
DPP4 inhibitor / gliptin
31
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
32
are DPP4 inhibitors effective in a patient with no preservation of insulin secretion
no
33
when are DPP4 inhibitors used
in combination with sulfonylurea or metformin
34
can DDP4 inhibitors be used as a monotherapy
yes
35
is sitagliptin orally active
yes
36
does sitagliptin cause weight gain?
no - weight neutral
37
does sitagliptin cause hypo?
not when used as a monotherapy
38
what is a side effect of sitagliptin
nausea
39
what kind of drugs are extenatide and liraglutide
incretin analogues
40
what peptides do incretin analogues mimic the action of
GLP-1
41
what is more potent - DPP4 inhibitors or incretin analogues
incretin analogues
42
incretin analogues bind as (antagonists/agonists) to the GLP-1 GPCR
agonists
43
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
44
give 3 additional effects of incretin analogues
suppress glucagon secretion slow gastric emptying decrease appetite (hypothalamic cation)
45
are incretin analogues orally active
no - SC admin
46
do incretin analogues cause weight gain
no - modest weight loss
47
do incretin analogues cause hypo
no
48
what are some side effects of incretin analogues
nausea | rarely pancreatitis
49
what kind of drugs are miglitol, voglibose and acarbose
alpha-glucosidase inhibitors
50
what is alpha-glucosidase
brush border enzyme that breaks down dietary CHO (start and disaccharides) to absorbable glucose
51
when are alpha-glucosidase inhibitors taken
with meals
52
what is the effect of alpha-glucosidase inhibitors
delay absorption of glucose thus reduce post prandial increase in blood glucose
53
when are alpha-glucosidase inhibitors used
in T2DM poorly controlled by diet and other drugs (infrequently)
54
what are some side effects of alpha-glucosidase inhibitors
``` flatulence loose stools diarrhoea abdominal pain bloating ```
55
do alpha-glucosidase inhibitors cause hypo
no
56
what kind of drug is metformin
biguanide
57
biguandies increase (secretion of/sensitivity to) insulin
increase sensitivity to insulin
58
biguandies (increase/decrease) hepatic gluconeogenesis by stimulating _____
biguanides decrease hepatic gluconeogenesis by stimulating AMP-activated protein kinase
59
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
60
do biguandies have an effect on CHO absoprtion?
yes - reduce CHO absorption
61
biguandies increase/decrease fatty acid oxidation
biguandies increase fatty acid oxidation
62
when is metformin used
1st line in T2DM irrespective to obesity
63
do biguandies reduce microvascular complications
yes
64
how is metformin administered
orally
65
does metformin cause hypo
no
66
metformin is weight neutral | true/false
false - weight loss
67
metformin is used as a monotherapy only | true/flase
false | can be combined with other drugs
68
can metformin be used in pregnancy
yes
69
when is metformin contraindicated
severe renal/hepatic dysfunction
70
what are 2 side effects of metformin
``` GI upset (nausea, diarrhoea, anorexia, abdominal pain) lactic acidosis - excessive alcohol consumption, severe renal/cardiac/liver failure ```
71
at what GFR should metformin be stopped | and why?
GFR < 30 | tissue hypoxia
72
at what GFR should metformin be halfed
GFR 30-45
73
metformin starts at a certain dose and remains as that | true or false
false | start low and increase slowly
74
what kind of drug is pioglitazone
thiazolidinediones/glitazones
75
why are ciglitazone and troglitazone no longer used
serious hepatotoxicity - not with pioglitazone
76
when are TZDs used
in combination with either metformin or a sulfonylurea
77
how do TZDs affect the secretion of insulin
they dont | they decrease insulin resistance at target tissues
78
how do TZDs work?
they act as exogenous agonists of the nuclear receptor PPAR-Y which associates with RXR (retinoid receptor X)
79
where is PPAR-Y found
largely confined to adipocytes
80
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
81
what is the time of onset of action of TZDs
delayed
82
increasing gene transcription does what to the uptake of glucose and fatty acids
increases
83
do TZDs decrease microvascular complications
no | reduce MACROvascular comps
84
what is the effect of TZDs on heart problems
decrease risk of MI but worsen heart failure
85
do TZDs cause hypo
no
86
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
87
do TZDs cause weight loss
no - weight gain
88
why do TZDs cause fluid retention
promote Na+ reabsorption by the kidney
89
what increases in incidence in the use of TZDs
fractures
90
what kind of drugs are dapagliflozin, canagliflozin, ampagliflozin
SGLT2 inhibitors
91
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
92
what are 2 bad side effects of SGLT2 inhibitors and why do they happen
UTI and thrush | due to glucosuria
93
do SGLT2 inhibitors cause weight gain
no - weight loss
94
do SGLT2 inhibitors cause hypo
little risk

year 2 (19 decks)

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