Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHRM 844 Therapeutics > Exam 2 - Diabetes Hockerman > Flashcards

Exam 2 - Diabetes Hockerman Flashcards

1
Q

3 P’s of diabetes

A

polydipsia -> inc in thirst
polyuria -> inc urination
polyphagia -> inc appetite

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

criteria for the diagnosis of diabetes (4)

A

A1C greater than or equal to 6.5%
OR
fasting plasma glucose greater than or equal to 126
OR
2-h plasma glucose greater than or equal to 200 mg/dL during an OGTT
OR
a random plasma glucose greater than or equal to 200 mg/dL with symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

99% of type 1 diabetics have antibodies against which antigen?

A

IA-2 (islet antigen 2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

“non-obese” type 2 diabetes is due to ?

A

mutations in specific proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

“obese” type 2 diabetes is due to ?

A

insulin resistance/decreased BCM (beta cell mass)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

4 consequences of lack of insulin (slide 12)

A

-hyperglycemia
-glucosuria
-hyperlipidemia
-uninhibited glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

increase fatty acid oxidation leads to _____

A

ketoacidosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

current insulin therapy goals: keep average blood glucose levels below ___ mg/dL

A

150

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

an A1C of greater than ___ leads to more risk of retinopathy

A

6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

oxidation products of glucose react irrev. with proteins to form ?

A

advanced glycation end-products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what molecules are theorized to account for many long-term complications of diabetes?

A

advanced-glycation end-products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

glyoxal and methylglyoxal are advanced glycation end-products that turn into CML and CEL respectively, which bind to _____ and promote inflammation

A

RAGE (receptor for advanced glycation end-products)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

mechanism of cell damage initiated by hyperglycemia (4 pathways)

A

-polyol pathway
-hexosamine pathway
-protein kinase C pathway
-AGE pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

which pathway is the major cause of neuropathy for patients with hyperglycemia?

a. polyol pathway
b. hexosamine pathway
c. protein kinase C pathway
d. AGE pathway

A

a. polyol pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

insulin receptor role of alpha subunits

A

regulatory unit of the receptor

(represses the catalytic activity of beta subunit; repression is relieved by insulin binding)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

insulin receptor role of beta subunits

A

contains the tyr kinase catalytic domain (autophosphorylation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

insulin effects on liver: what processes does it inhibit? (3 things)

A

glycogenolysis
ketogenesis
gluconeogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

insulin effects on liver: what does it stimulate? (2 things)

A

glycogen synthesis
triglyceride synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

insulin effects on skeletal muscle: what does it stimulate? (2 things)

A

glucose transport
amino acid transport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

insulin effect on adipose tissue: what does it stimulate? (2 things)

A

triglyceride storage
glucose transport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

fasting state:
___% is non-insulin dependent: liver, GI, brain
___% insulin dependent in skeletal muscle

A

75%; 25%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

fed state:
80-85% is insulin-dependent in _____ _____
4-5% is insulin-dependent in _____ _____

A

skeletal muscle; adipose tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

insulin inhibits release of ___ ___ ___ from adipose tissue

A

free fatty acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

decreased serum free fatty acids effects (slide 25):

enhances insulin action on _____ _____
reduces _____ glucose production

A

skeletal muscle; hepatic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what is the Km of glut 2?

A

15-20 mM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

which glut is insulin-induced?

a. glut 1
b. glut 2
c. glut 3
d. glut 4

A

d. glut 4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

which glut is expressed in neurons?

a. glut 1
b. glut 2
c. glut 3
d. glut 4

A

c. glut 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

where is glut 4 expressed? (2 places)

A

skeletal muscle
adipocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

4 pancreatic polypeptide hormones to know

A

-glucagon
-somatostatin
-insulin
-amylin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

glucagon function (2; slide 28)

A

-stimulates glycogen breakdown
-increases blood glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

which polypeptide hormone stimulates glycogen breakdown and increases BG?

a. glucagon
b. somatostatin
c. insulin
d. amylin

A

a. glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

which polypeptide hormone is a general inhibitor of secretion?

a. glucagon
b. somatostatin
c. insulin
d. amylin

A

b. somatostatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

which polypeptide hormone stimulates uptake and utilization of glucose?

a. glucagon
b. somatostatin
c. insulin
d. amylin

A

c. insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

which polypeptide hormone is co-secreted with insulin, slows gastric emptying, decreases food intake, and inhbits glucagon secretion?

a. glucagon
b. somatostatin
c. insulin
d. amylin

A

d. amylin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

in secretory granules, proinsulin is cleaved to A and B chains, and C (connecting) peptide by __________

A

proconvertases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

human insulin cDNA in plasma expressed in E. Coli

a. Humulin
b. Novolin
c. Glargine
d. Degludec

A

a. Humulin

(recombinant)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

human insulin cDNA in plasmid expressed in transformed yeast

a. Humulin
b. Novolin
c. Glargine
d. Degludec

A

b. Novolin

(recombinant)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

ultra rapid onset/very short action insulin (3 of them)

A

lispro (Humalog)
aspart (Novolog)
glulisine (Apidra)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

rapid onset/short action insulin (1)

A

regular (R)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

intermediate onset/action insulin (1)

A

NPH (N)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

slow onset/long action insulin (3 of them)

A

glargine (Lantus)
detemir (Levemir)
degludec (Tresiba)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

the “lente” insulins include which element?

A

zinc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

why does NPH insulin have a slow absorption and long duration of action?

A

it is bound to protamine and needs to be broken down by tissue proteases to yield free insulin, which is then released into the bloodstream

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

which insulin is made by reversing positions of P28 and K29 on insulin B chain?

A

Lispro insulin (Humalog)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

when are Humalog, Novolog, and Apidra injected, before or after meals?

A

immediately before meals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

what modification is made to the beta chain for insulin aspart (Novolog)?

A

proline 28 switched to aspartate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

what modification is made to the beta chain for insulin glulisine (Apidra)?

A

asparagine 3 (Asn 3) and Lys 29 are switched to Lys and Glu

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

what modifications are made to insulin to make insulin glargine (Lantus)? (2 of them)

A

-Asn 21 of a-chain is changed to Gly
-2 Arg residues added to end of b-chain (30 & 31)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

insulin glargine is a clear solution at what pH?

A

pH 4 (precipitates when neutralized; post injection)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

what modifications are made to the b-chain for insulin detemir (Levemir)? (2 of them)

A

Thr 30 is deleted
Lys 29 is myristylated (fatty acid modification)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

what modifications are made to the b-chain in insulin degludec (Tresiba)?

A

Thr 30 is replaced by gamma-Glu/C16 fatty acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

which 3 insulins are extensively bound to serum albumin?

A

-insulin detemir (Levemir)
-insulin degludec (Tresiba)
-semaglutide (Ozempic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

for multi-dose insulin regimens, when are fast onset, short acting insulins taken?

A

before meals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

for multi-dose insulin regimens, when are long, or intermediate acting insulins taken? (2 options)

A

at bedtime
OR
at bedtime and after breakfast

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

what are the 2 components of a Humulin mixture?

A

NPH (neutral protamine hagedorn) + regular

(Humulin 70/30 or 50/50)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

what are the 2 components of a Humalog mixture?

A

NPL (neutral protamine lispro) + Lispro

(Humalog 75/25 or 50/50)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

what are the 2 components of Ryzodeg?

A

70% degludec + 30% aspart

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

inhaled insulin example

A

Afrezza

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Afrezza has _____ onset, _____ duration of action than subQ injection

a. rapid; longer
b rapid; shorter
c. slow; longer
d. slow; shorter

A

b. rapid; shorter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Afrezza contraindications

A

pts with asthma and COPD (may reduce lung function; decreased FEV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

what kind of particle does Afrezza use?

A

technosphere particle (FDKP + polysorbate 80)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

3 modes of action of insulin in diabetics

A
  1. dec liver glucose output
  2. inc fat storage
  3. inc glucose uptake
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

hypoglycemia is BG < ?

A

60 mg/dL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

_____ is the preferred fuel for the nervous system

A

glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

4 adverse reactions to insulin (slide 55)

A

-lipodystrophy
-lipoatrophy
-lipohypertrophy
-antibodies against insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

which insulin preparation is not genetically modified?

a. lispro
b. glulisine
c. NPH
d. aspart

A

c. NPH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

which insulin preparation has the longest duration of action?

a. lispro
b. aspart
c. glulisine
d. glargine

A

d. glargine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

what is lipodystrophy?

a. loss of fat in subq tissue
b. accumulation of fat in subq tissue
c. changes in fat at over used injection site

A

c. changes in fat at over used injection site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

what is lipoatrophy?

a. loss of fat in subq tissue
b. accumulation of fat in subq tissue
c. changes in fat at over used injection site

A

a. loss of fat in subq tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

what is lipohypertrophy?

a. loss of fat in subq tissue
b. accumulation of fat in subq tissue
c. changes in fat at over used injection site

A

b. accumulation of fat in subq tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

ethanol inhibits gluconeogenesis, and may __________ the risk of insulin hypoglycemia

a. increase
b. decrease

A

a. increase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

two classes of drugs that enhance insulin secretion

A

sulfonylureas, meglitinides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

for sulfonylureas, the pt must have functioning _____ cells

A

beta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

effects of sulfonylureas on beta cell insulin release (6 steps; slide 62)

A
  1. binds to sulfonylurea receptors
  2. inactivates K+ channel
  3. decreased cell polarization
  4. activates voltage sensitive Ca+ channels
  5. inc Cai2+ and activity of microfilaments
  6. inc exocytosis of insulin containing granules
75
Q

nateglinide and repaglinide are part of what drug class?

A

meglitinides

76
Q

1st gen sulfonylureas (3 of them)

A

-tolbutamide
-tolazamide
-chlorpropamide

77
Q

2nd gen sulfonylureas (3 of them)

A

-glipizide
-glyburide
-glimepiride

78
Q

which are more potent?

a. 1st gen sulfonylureas
b. 2nd gen sulfonylureas

A

b. 2nd gen sulfonylureas

79
Q

which is false about Repaglinide (Prandin)?

a. it is a non-sulfonylurea hypoglycemic agent
b. its MOA is same as sulfonylureas
c. it has a slow onset and long duration of action
d. taken before each meal

A

c. it has a slow onset and long duration of action

(quick onset, short duration of action t1/2 ~ 1 hour)

80
Q

which sulfonylurea has the lowest potency?

a. tolazamide
b. chlorpropamide
c. glyburide
d. glimepiride
e. tolbutamide
f. glipizide

A

e. tolbutamide

81
Q

which drugs are non-sulfonylurea Katp channel blockers?

A

meglitinides

82
Q

nateglinide is very specific for Katp channels in _____ vs _____ tissue

A

pancreas; CV

83
Q

nateglinide has a shorter half-life than prandin i.e. less risk of __________

A

hypoglycemia

84
Q

of these 3, which has the longest half life, and thus the highest risk of prolonged hypoglycemia?

a. glipizide
b. glimepiride
c. glyburide

A

c. glyburide

85
Q

one adverse effect of sulfonylureas includes weight gain and increased number of _____ _____

A

secondary failures

86
Q

2 drugs that have their own hypoglycemic effects which may be additive to the sulfonylureas (bolded on slide 73)

A

-alcohol
-high dose salicylates

87
Q

what is the incretin effect?

A

oral glucose stimulates a larger insulin response than IV glucose in humans

88
Q

GLP-1: stimulated insulin secretion is

a. glucose-independent
b. glucose-dependent

A

b. glucose-dependent

89
Q

GLP-1 is secreted from which cells in the intestine?

A

ileal L cells

90
Q

2 potential outcomes of GLP-1 receptor signaling (slide 78)

A

-glucose-stimulated insulin secretion (GSIS)
-gene transcription and beta-cell proliferation

91
Q

the incretin effect is diminished in which diabetics?

A

type 2

92
Q

insulin is _____ and causes weight _____

a. anabolic; loss
b. anabolic; gain
c. catabolic; loss
d. catabolic; gain

A

b. anabolic; gain

93
Q

GLP-1R agonists (5 drugs)

A

-exenatide (Exendin 4; Byetta)
-lixisenatide (Adlyxin)
-liraglutide (Victoza)
-dulaglutide (Trulicity)
-semaglutide (Ozempic; Rybelsus)

94
Q

which GLP-1R agonist is derived from Gila Monster saliva?

A

exenatide

95
Q

basal insulin is _____-acting

a. fast
b. slow

A

b. slow

(it is taken between meals and before bedtime to control blood sugar outside of eating)

96
Q

exenatide activates _____ receptor and enhances _____ phase secretion

A

GLP-1; 1st

97
Q

contraindication for exenatide, liraglutide, dulaglutide, lixisenatide, semaglutide (Ozempic)

A

family history of medullary thyroid cancer

(risk of thyroid C-cell tumors)

98
Q

GLP-1 analogs common side effects (2 of them)

A

-N/V
-pancreatitis

99
Q

true or false: exenatide is only available as a once weekly injection

A

false

(twice daily or once weekly injections)

100
Q

we should monitor _____ levels when taking liraglutide (Victoza)

A

calcitonin

101
Q

what modifications are made to create liraglutide? (2 of them)

A

-glu and arg added
-fatty acid added to glu linker

102
Q

what amino acid is inserted to make dulaglutide?

A

valine

(increases susceptibility to proteolysis)

103
Q

GLP-1 agonist peptides are _____ released from IgG Fc domain by reduction of _____ bonds in linker region

A

slowly; disulfide

104
Q

how often is dulaglutide (Trulicity) injected?

A

once weekly

105
Q

when is lixisenatide (Adlyxin) injected?

A

once daily, before breakfast

106
Q

difference between structure of lixisenatide and exenatide

A

lixisenatide is exenatide with a polylysine tail

107
Q

soliqua is a combo of what two insulins?

A

glargine and lixisenatide

108
Q

which insulin has these modifications?

2-aminoisobutyrate inserted
Hydrophilic spacer and fatty acid added to lysine

a. exenatide
b. dulaglutide
c. liraglutide
d. semaglutide
e. lixisenatide

A

d. semaglutide

(Ozempic)

109
Q

half life for semaglutide (Ozempic)

A

1 week

(it is extensively bound to serum albumin)

110
Q

only orally available GLP-1R agonist

A

semaglutide oral (Rybelsus)

111
Q

3 important structural things to know about Rybelsus

A

-dimethylalanine added
-hydrophilic spacer and C-18 fatty acid added to lysine
-salcaprozate is in complex (makes molecule more absorbable in GI tract)

112
Q

Rybelsus is absorbed from what organ?

A

stomach

113
Q

Rybelsus has a low oral bioavailability, so the strength of medication is _____ than injections

A

higher

114
Q

basal insulin/GLP-1R agonist combination drugs (2 of them)

A

-Soliqua -> glargine + lixisenatide
-Xultophy -> degludec + liraglutide

115
Q

which drug is a GLP-1 & GIP dual agonist?

A

tirzepatide (Mounjaro)

116
Q

Mounjaro:
full _____ receptor agonist
biased _____ receptor -> preferential coupling to cAMP over _____

A

-GIP
-GLP-1
-beta-arrestin

117
Q

how does Mounjaro maintain GLP-1 effect?

A

reduces internalization (desensitization) of GLP-1 receptor to maintain GLP-1 effect

118
Q

how often is Mounjaro injected?

A

once weekly

119
Q

what enzyme degrades GLP-1?

A

dipeptidyl peptidase 4 (DPP-4)

120
Q

4 drugs that are DPP-4 inhibitors (GLP-1 modulators)

A

-sitagliptin (Januvia)
-linagliptin (Tradjenta)
-saxagliptin (Onglyza)
-alogliptin (Nesina)

121
Q

how often are Januvia, Onglyza, Tradjenta, and Nesina taken?

a. once weekly
b. once daily
c. twice daily
d. every other day

A

b. once daily

(these are all oral drugs)

122
Q

which drug is extensively metabolized?

a. Januvia
b. Nesina
c. Tradjenta
d. Onglyza

A

d. Onglyza

(the other 3 are not)

123
Q

which is not excreted in urine (kidney)?

a. Januvia
b. Onglyza
c. Tradjenta
d. Nesina

A

c. Tradjenta

(excreted in feces (liver))

124
Q

Onglyza is a substrate of which cyp?

A

CYP3A4/5

(major metabolite is active)

125
Q

side effects of DPP-4 inhibitors (3 of them; highlighted in red on slide 96)

A

-pancreatitis
-joint pain
-heart failure

126
Q

DPP-4 is present on immune cells, which can lead to _____ WBC counts, which leads to increased _____ and potential increased risk of cancers

A

reduced; infections

127
Q

which drug is an amylin analog?

A

pramlintide (Symlin)

128
Q

which drug blunts postprandial rise in blood glucose, and is used in conjunction with insulin?

A

pramlintide (Symlin)

129
Q

pramlintide (Symlin) is useful for which patients?

a. type 1 diabetes
b. type 2 diabetes
c. both

A

c. both

130
Q

tolbutamide MOA

a. activation of Katp channels
b. prolonged block of Katp channels
c. activation of GLP-1 receptors
d. short duration block of Katp channels

A

b. prolonged block of Katp channels

131
Q

the acute increase in insulin secretion observed with GLP-1 is

a. result of direct and persistent activation of the Katp channel
b. result of activation of the ERK1/2 pathway
c. glucose independent
d. glucose dependent

A

d. glucose dependent

132
Q

two alpha-glucosidase inhibitors drugs to know

A

Acarbose (Precose)
Miglitol (Glyset)

133
Q

alpha-glucosidase inhibitors MOA

A

dec absorption of carbohydrate from the intestine via inhibition of gut alpha glucosidases

134
Q

3 gut alpha glucosidases to know

A

sucrase, maltase, glucoamylase

135
Q

alpha-glucosidase inhibitors are taken _____ meals

a. with
b. without

A

a. with

136
Q

which is completely absorbed?

a. Acarbose
b. Miglitol

A

b. Miglitol

(Acarbose is only minimally absorbed)

137
Q

adverse effect of Acarbose and Miglitol

A

GI- diarrhea, nausea, flatulence

138
Q

Acarbose has risk of _____ damage at doses > 100 mg tid

A

liver

139
Q

SGLT2 inhibitors MOA

A

they inhibit SGLT2 in the PCT, to prevent reabsorption of glucose (in kidney) and facilitate its excretion in urine

140
Q

SGLT2 inhibitors are derived from what natural product? What functional group of this molecule is responsible for why it doesn’t last very long?

A

phlorizin; ether group

141
Q

SGLT2 inhibitors drugs to know (5 of them)

A

-empagliflozin (Jardiance)
-canagliflozin (Invokana)
-dapagliflozin (Farxiga)
-ertugliflozin (Steglatro)
-bexagliflozin (Benzavvy)

142
Q

SGLT2 inhibitors cause an increase in what 3 things?

A

-inc risk of genital/UT infections
-inc urine flow/volume depletion/hypotension
-inc risk of DKA

143
Q

SGLT2 inhibitors contraindications

A

pts with renal impairment

144
Q

SGLT2 inhibitors have an increased risk of ____ ____ ____

A

lower limb amputation

145
Q

what class of drug is metformin in?

A

biguanides

146
Q

most common cause of insulin resistance

A

obesity

(especially accum of fat in the abdominal cavity)

147
Q

raising _____ levels causes insulin resistance

A

FFA

148
Q

2 drugs that are thiazoladinediones

A

-pioglitazone (Actos)
-rosiglitazone (Avandia)

149
Q

Insulin resistance can be due to polymorphisms in insulin receptor. What modification did we talk about in class?

A

ser (instead of tyr) phosphorylation of insulin receptor and insulin receptor substrate proteins

(inhibits signaling; promoted by FA uptake, lipid by-products, inflammatory mediators)

150
Q

metformin is classified as an __________ agent

A

antihyperglycemic

151
Q

metformin has a lower risk for _____ _____ than the older biguanides

A

lactic acidosis

152
Q

metformin MOA

A

activator of AMP-activated kinase (AMPK)

(inc efficiency or sensitivity to insulin in liver, fat, and muscle cells)

153
Q

what is metformin’s effect in the liver?

A

dec gluconeogenesis

154
Q

what is metformin’s effect in muscle and fat cells?

A

inc glycolysis, glucose uptake

155
Q

metformin action in skeletal muscle (3 steps)

A

-AMP accumulates during exercise and activates AMPK
-AMPK phosphorylates TBC1D1/4 which promotes GTPase activity of Rab
-Rab dissociates from GLUT4 allowing translocation

156
Q

metformin decreases which vitamin’s absorption?

A

B12

157
Q

metformin effects on blood lipid profile: decreases serum _____ and _____

A

triglycerides; LDL

(reduces risk of adverse CV events)

158
Q

what transcription factor do thiazolidinediones activate?

A

PPAR gamma (peroxisome proliferator-activated receptor gamma)

159
Q

main target of thiazolidinediones

a. liver
b. skeletal muscle
c. adipocytes

A

c. adipocytes

160
Q

why do thiazolidinediones have restricted prescribing?

A

due to CV toxicities

(CI in NYHA class III or IV heart failure)

161
Q

true or false: thiazolidinediones can cause hypoglycemia

A

false

162
Q

which is decreased in type 2 diabetics?

a. resistin
b. adiponectin
c. TNF alpha

A

b. adiponectin

163
Q

which factor, when injected into mice, stimulates glucose export by the liver & insulin resistance?

a. resistin
b. TNF alpha
b. adiponectin

A

a. resistin

164
Q

which factor reduces blood glucose and insulin resistance in diabetic mice?

a. TNF alpha
b. adiponectin
c. resistin

A

b. adiponectin

165
Q

which factor stimulates lipolysis in white adipose tissue, & insulin resistance in skeletal muscle?

a. adiponectin
b. resistin
c. TNF alpha

A

c. TNF alpha

166
Q

3 factors regulated by activation of PPAR gamma

A

resistin, adiponectin, TNF alpha

167
Q

__________ decrease differentiation of mesenchymal stem cells into osteoblasts

A

thiazolidinediones (TdZ’s)

168
Q

Why is there an increased insulin response in early pregnancy? (2 of them; slide 124)

A

growth of placenta, increase maternal fat storage

169
Q

During late pregnancy, why is there reduced insulin sensitivity?

A

growth of fetus

170
Q

gestational diabetes definition

A

hyperglycemia during pregnancy in non-diabetic women

171
Q

how is gestational diabetes diagnosed?

A

24-28 week OGTT

172
Q

when does gestational diabetes usually appear?

A

around week 24 of gestation, in the rapid growth stage of gestation, after fetus has formed

173
Q

how does gestational diabetes affect the growth of the fetus?

A

can lead to macrosomia (“Fat Baby”), because fetus has access to excessive glucose, it produces high levels of insulin and stores excess glucose as fat

174
Q

true or false: insulin crosses the placenta, but glucose does not

A

false

(insulin does not cross placenta, glucose does)

175
Q

which hormone is one of the main contributors to insulin resistance?

a. CRH- cortisol
b. placental GH (GH-V)
c. progesterone
d. placental lactogens (PL)

A

d. placental lactogens (PL)

176
Q

which does not increase as pregnancy progresses like the others?

a. CRH- cortisol
b. progesterone
c. placental GH (GH-V)
d. placental lactogens (PL)

A

c. placental GH (GH-V)

(this is only released during last half of gestation, the others all increase as pregnancy progresses)

177
Q

glucocorticoids _____ insulin action

A

oppose

178
Q

how does prolactin inc beta-cell mass during pregnancy?

A

stimulates beta cell proliferation

179
Q

mutations in which receptor are associated with gestational diabetes?

A

PRL (prolactin) receptor

180
Q

placental lactogen activates PRL with _____ affinity and GH receptors with _____ affinity

A

high; low

181
Q

gold standard drug for gestational diabetes

A

insulin (does not cross placenta)

182
Q

glyburide vs metformin for gestational diabetes

A

glyburide works but may harm fetus (crosses placenta), while metformin crosses placenta but doesn’t harm fetus

183
Q

true or false: thiazoladinediones are not used for gestational diabetes

A

true

184
Q

GIP (gastric inhibitory peptide) is secreted by which cells in the intestine?

A

duodenal K cells

PHRM 844 Therapeutics (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions