Brainscape's Knowledge GenomeTM

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


See full index

Therapeutics II > Antidiabetic drugs for type II > Flashcards

Antidiabetic drugs for type II Flashcards

1
Q

Normal insulin release

A

-1st phase peak
-2nd phase peak

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

insulin release in Type II diabetics

A

-one short peak over longer period of time
-insulin resistance + reduced insulin secretion

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

Actions of antidiabetic drugs

A

-Insulin secretion
-Glucagon secretion
-Appetite control
-Neurotransmitter dysfunction
-Glucose reabsorption
-Glucose uptake and utilization
-lipotoxicity
-hepatic glucose output
-GI

-come back to slide 63

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

Agents that enhance insulin secretion

A

-Sulfonylureas
-Meglitinides (shorter duration)

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

Sulfonylurea drugs

A

-Tolbutamide
-Tolazaamide
-Chlorpropamide
-Glyburide
-Glipizide
-Glimepiride

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

Meglitinide drugs

A

-Nateglinide
-Repaglinide

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

Sulfonylurea MOA

A

-must have B cells
-inc release of insulin
-may restore first phace
-inc B-cell sensitivity to glucose and inc glucose stimulated insulin release

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

Sulfonylurea mech

A

-binds sulfonylurea receptors on B cells mimics atp (binds ATP binder on K channel)
-inactivates K channel
-dec cell polarization (depolarization)
-activate Ca channels
-inc Ca and activity of microfilaments =
-inc exocytosis of insulin containing granules

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

Sulfonylurea in high glucose setting

A

-GLUT 2 take glucose in B cell
-metabolized to ATP
-inc ATP activates sulfonylurea receptor = close K channels

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

Insulin release in low glucose setting

A

-dec glucose intake and metabolism
-more ADP keeps K channel open
-Ca stays closed
-insulin granules stay inside

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

1st gen sulfonylureas

A

-Tolbutamide* (lowest potency, shortest duration)(6-12h)
-Tolazamide (12-14h)
-Chlorpropamide* (higher potency and duration)(24-72h)

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

2nd gen sulfonyureas

A

-Glipizide (12-24)
-Glyburide
-Glimepiride

-way more potent and 24h
-used more than 1st gen
-lower doses than 1st gen

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

Structures of sulfonylureas vs meglitinides

A

-prob no sulfa

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

Repaglinide (prandin)

A

-meglitinide
-similar MOA to sulfonylurea agents
-quick onset, short duration
-tablet taken before each meal
-shorter t1/2 than sulfonylureas

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

Nateglinide

A

-meglitinide
-very specific for KATP blocking
-in pancreas vs CV tissue
-shorter t1/2 = lower risk of hypoglycemia
-synergistic w metformin

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

Adverse effects of sulfonylureas

A

-prolonged hypoglycemia (long half-life)
-Glyburide worse than glipizide, glimepiride
-misdiagnosed as stroke that leads to permanent neurological damage and death
-risk of CV events?
-GI probs
-weight gain and inc number of secondary failures

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

Drug interactions that may enhance sulfonylureas

A

-increase risk of hypoglycemia
-displace sulfonylureas from plasma protein binding
-may also dec the metabolism of sulfonylureas by liver
-salicylates
-phenylbutazone*
-sulfonamides*
-clofibrate*

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

Drugs with hypoglycemic effects

A

-alcohol excessive intake
-high dose salicylates

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

Drugs which cause hyperglycemia that will oppose therapy

A

-oral contraceptives
-epinephrine
-thiazide diuretics
-corticosteroids
-thyroid

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

Agents that enhance incretin effect

A

-GLP-1R agonists
-GLP1 and GIP dual agonist
-DPP-IV inhibitors
-Amylin analogs

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

GLP-1R agonist drugs

A

-Exenatide
-Liraglutide
-Lixenatide
-Dulaglutide
-Semaglutide

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

GLP1 and GIP dual agonist drug

A

-Tirzepatide

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

DDP-IV inhibitor drugs

A

-Saxagliptin
-Sitagliptin
-Linagliptin
-Alogliptin

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

Amylin Analog drug

A

-Pramlintide

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

Incretin effect

A

-oral glucose stimulates a larger insulin response than IV glucose
-something in the Gi tract must be increasing insulin response
-stimulating B-cell after meal
-cAMP pathway and ERK1/2 pathway
-GLP, GIP, DPP-IV

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

GIP

A

-glucose-dependent insulinotropic peptide
-duodenal cells

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

GLP-1

A

-glucagon like peptide 1
-glucose dependent

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

GLP-1 MOA

A

-secreted from L cells in intestine after food eaten
-stimulates insulin secretion
-dec glucagon secretion
-slow gas emptying
-reduce food intake
-inc B cell mass and maintain function
-improve insulin sensitivity
-enhance glucose disposal
-STIMULATED INSULIN SECRETION IS GLUCOSE DEPENDENT

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

GLP-1 receptor signaling

A

-Gs to cAMP or Gq to Ca = glucose stimulates insulin secretion

-GBy to P13K and Ca and cAMP = glucose stimulated ERK1/2 phosphorylation = gene transcription and B cell proliferation

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

Incretin effect in type II diabetics

A

-diminished
-insulin doesn’t respond as well to nutrient

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

GLP-1 tx of type 2

A

-provide long lasting GLP-1 analog OR
-prevent degradation of endogenous GLP-1 OR
-positive modulators for GLP-1 receptor

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

Benefits of GLP-1s

A

-reduce HYPERglycemia w low risk of HYPOglycemia
-weight loss
-inc beta cell mass (maybe)

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

Exenatide (Byetta)

A

-GLP-1 for type 2
-39aa peptide from Gila monster saliva
-activates GLP1 receptor
-enhance 1st phase secretion
-longer t1/2 than GLP-1

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

Exenatide counseling

A

-longer t1/2 = twice daily or once a week injections
-co admin w metformin, TzDs, or sulfonylureas

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

Exenatide side effects

A

-N/V, pancreatitis
-risk thyroid C-cell tumors
-DO NOT USE in pt w family hx of thyroid cancer

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

Liraglutide

A

-Victoza
-hGLP-1 aa7-37
-DPP can recognize and inactivate it still
-fatty acid chain added
-13 hour t1/2
-subQ daily
-can co admin w metformin, TzDs, sulfonylureas

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

Liraglutide side effects

A

-N/V
-pancreatitis
-risk of thyroid tumors (monitor calcitonin levels)

37
Q

Dulaglutide

A

-Trulicity
-inj SQ once/week
-more resistant to DPP-4
-IgG is carrier that keeps it together for long time and slowly released by breaking disulfide bonds
-GLP-1 peptides slowly released from IgG Fc domain by reduction of disulfide bonds in linker region

38
Q

Dulaglutide side effects

A

-N/V
-pancreatitis
-risk of thyroid C-cell tumors
-do NOT use if fam hx of thyroid cancer

39
Q

Lixisenatide

A

-Adlyxin
-44 aa peptide
-exanatide w polylysine tail
-GLP-1 agonist
-inj SQ daily before breakfast
-Soliqua (100 U glargine + 33 ug lixisenatide/mL) inj once daily

40
Q

Lixisenatide side effects

A

-N/V
-pancreatitis
-risk of thyroid tumors
-AVOID if fam hx of thyroid cancer

41
Q

Semaglutide

A

-Ozempic
-31aa peptide
-more resistant to DPP
-big fatty acid chain
-GLP-1 agonist
-inj SQ once weekly
-extensively bound to serum albumin
-t1/2 about a week

42
Q

Semaglutide side effects

A

-N/V
-pancreatitis
-Thyroid tumor
-AVOID if fam hx of thyroid cancer

43
Q

semaglutide oral

A

-Rybelsus
-little bit of oral bioavailability
-absorbed from stomach
-once daily 3, 7, 14 mg
-dimethylalanine, C-18 FA, hydrophillic spacer (Huge)
-Salcaprozate

44
Q

insulin + GLP-1 combos

A

-Soliqua (glargine + lixisenatide) max 60/20
-Xultophy (degludec + liraglutide) max 50/1.8

45
Q

Tirzepatide

A

-MOUNJARO
-full GIP agonist
-biased GLP-1 (prefer cAMP over B-arrestin)
-reduces internalization (desensitization) of GLP-1 receptor to maintain effect
-weekly Sq
-allegedly reduces A1c and body weight more effectively than just GLP-1 agonists

46
Q

Dipeptidyl Peptidase (DDP) 4

A

-inhibiting incretin proteolysis
-enzyme degrades GLP-1
-serine and histidine?
-hangs out in capillaries

47
Q

DDP inhibitors

A

-enhance actions of endogenous GLP-1

48
Q

DDP inhibiting drugs (GLP-1 monitors)

A

-oral

-Sitagliptin (Januvia)
-Saxagliptin (Onglyza)
-Linagliptin (tradjenta)
-Alogliptin (Nesina)

49
Q

Saxagliptin binding

A

-binds in active site of DDP-4

50
Q

GLP-1 moderators (DDP inhibitors)

A

-admin PO qd
-reduce HYPERglycemia and A1c
-low risk of hypoglycemia
-weight neutral
-can coadmin w metformin, TzDs

51
Q

Januvia and Nesina metabolism and excretion

A

-not extensively metabolized
-excreted in urine (kidney)

52
Q

Tradjenta metabolism and excretion

A

-not extensively metabolized
-excreted in feces (liver)

53
Q

Onglyza metabolism and excretion

A

-CYP3A4/5 substrate
-metabolite active
-excreted in urine (kidney)

54
Q

side effects of DDPIV inhibitors (GLP-1 mods)

A

-N/V, constipation
-HA, skin reactions
-pancreatitis*
-joint pain*
-HF*

-immunosuppression
-maybe cancer

55
Q

DDP-4 on immune cells

A

-inhibitors reduce WBC counts = infections
-potential inc risk of cancer

56
Q

Pramlintide (Symlin)

A

-amylin analog
-peptide hormone tx
-37aa co secreted w insulin
-slows gastric emptying, decreases food intake, inhibits glucagon secretion
-blunts postprandial rise in BG
-use w insulin subQ
-type 1 and type 2 tx

57
Q

Agents that reduce glucose absorption or increase glucose excretion

A

-a-glucosidase inhibitors
-SGLT2 inhibitors

58
Q

a-glucosidase inhibitors

A

-Acarbose
-Miglitol

59
Q

a-glucosidase inhibitor moa

A

-dec absorption of carbs from intestine via inhibition of gut a-glucosidases (sucrase, maltase, glucoamylase)
-acarbose minimally absorbed
-migitol completely absorbed

60
Q

a-glucosidase inhibitor counseling (acarbose, miglitol)

A

-take orally w meals
-diarrhea, nausea, flatulence (glucose in colon getting fermented by bacteria)
-acarbose risk of liver damage at doses > 100 mg tid

61
Q

Sodium Glucose coTransporter 2 inhibitors (SGLT2) MOA

A

-decrease threshold for glucose excretion in urine = more excretion
-reduce blood glucose levels
-dec A1C (monotherapy or with metformin or sulfonylureas)

62
Q

SGLT2 inhibitor drugs

A

-empagliflozin (jardiance)
-canagliflozin (Invokana)
-dapagliflozin (Farxiga)
-Ertugliflozin (Steglatro)
-Bexagliflozin (Benzavvy)

-structures have glucose like molecule that gets them recognized (aromatic groups for high affinity)(irreversible?)

63
Q

SLGT2 inhibitor counseling

A

-type 2
-DO NOT use in type 1 (ketoacidosis)
-dec A1c +/- metformin/sufonylureas
-weight loss
-inc UTI risk (glucose in urine)
-inc urine flow/hypotension
-inc risk of diabetic ketoacidosis
-DO NOT USE in pt w renal impairment (risk of lower limb amputation)

64
Q

Agents that reduce insulin resistance/lipotoxicity

A

-Biguanides (Metformin)
-Thiazoladinediones (Pioglitazone, Rosiglitazone)

65
Q

Insulin resistance

A

-decreased response to insulin
-OGTT w prolonged elevation of BG with normal or elevated insulin levels

66
Q

Insulin resistance causes

A

-polymorphisms in insulin signaling pathway proteins (rare)
-Obesity (esp fat in abdominal cavity)
-inactivity

67
Q

Insulin resistance effects

A

-muscle: impaired uptake
-Adipose: impaired uptake, impaired inhibition of lipolysis mobilization of FAs to other tissues
-liver: impaired inhibition of glucose output (gluconeogenesis or glycogenolysis)

68
Q

Obesity and insulin resistance

A

-high FFA levels
-rising levels cause insulin resistance
-lowering of plasma FFA levels reduces chronic insulin resistance
-predominant effect is on insulin-stimulated glucose transport

69
Q

Poymorphisms in insulin receptor lead to resistance

A

-Ser instead of Tyr phos of IR and IRS proteins (tyrosine kinase)
=inhibit signaling
-promoted by FA uptake, lipid by-products, inflammatory mediators

70
Q

Insulin resistance mechanisms

A

-FFA activates mTOR and that phosphorylates IRS proteins by serines instead of tyrosines = degradation
-inc cytokines in obesity (TNFa) activate kinases = phosphirylate IRS proteins on serines (interferes function)
-phosphorylation happens on serines

  1. Too much P13K reduces PIP3 (less?) inhibits PI3K that reduces glucose transport
71
Q

Obesity induced inflammation and insulin resistance

A

-hypertrophied adipocytes in obesity
-secrete MCP-1 to acttract macrophages
-infiltrated macrophages that differentiate to M1 = insulin resistance

72
Q

Metformin (Glucophage)

A

-antihyperglycemic agent
-biguanide w lowest risk of lactic acidosis
-first choice in type 2 usually
-dec BG in type 2 w/o risk of hypoglycemia

73
Q

Metformin (biguanide) advantage over sulfonylureas

A

-rarely cause hypoglycemia
-rarely cause weight gain

74
Q

Metformin (glucophage) MOA

A

-biguanide
-activate AMPK
-inc efficiency/sensitivity to insulin in liver, fat, and muscle
-dec gluconeogenesis in liver
-inc glycolysis and glucose uptake in muscle/fat cells
-500-850 BID/TID AC to eliminate diarrhea

75
Q

Metformin action in liver

A

-elevate AMPK at cost of ATP

-metformin inhibit production of ATP
-elevates AMP
-activates AMPK
-dec glucose production and lipid/cholesterol synthesis in liver

76
Q

Metformin action in skeletal muscle

A

-AMP accumulates during exercise
=activation of AMPK
-AMPK phosphrylates TBC1D1/4 which promotes GTPase activity of Rab
-Rab dissociates from GLUT4 allowing translocation

77
Q

Metformin counseling

A

-DO NOT USE in disorders w higher risk of lactic acidosis
-dec B-12 absorption
-N/V/D
-can use in combo with sulfonylureas

78
Q

Metformin effects on blood lipid profile

A

-dec serum triglycerides
-dec serum LDL
-reduces risk of adverse CV events

79
Q

Thiazolidinediones MOA

A

-dec insulin resistance or improve target cell response to insulin
-activators of peroxisome proliferator-activated receptor gamma (PPARy) (transcription factor)
-target adipocytes, liver, muscle

80
Q

Main target of thiazolidines

A

-adipocytes

-enhance differentiation
-enhance FFA uptake into subQ fat
-reduce serum FFA
-shifts lipids into fat cells from non-fat cells

81
Q

Thiazolidinedione effect on liver and muscle

A

-enhance glucose uptake in both
-reduces hepatic glucose production

82
Q

Thiazolidinedione drugs

A

-Rosiglitazone (Avandia)
-Pioglitazone (Actos)

83
Q

Thiazolidinedione counseling

A

-RESTRICTED PRESCRIBING bc CV toxicities
-associated w inc risk of bladder cancer
-some hepatotoxicity (check liver function)
-do not cause hypoglycemia
-FDA warning: do NOT USE in NYHA class 3-4 Heart failure

84
Q

PPARy structure and function

A

slide 117

85
Q

TZD modulation of blood glucose via adipokines

A

slide 118

86
Q

Factors regulated by PPARy activation

A

-Resistin (high in type 2)
-Adiponectin (low in type 2)
-TNFa (high in type 2)

87
Q

Resistin

A

-stimulate glucose export by liver and insulin resistance
-protein from white adipose tissue (WAT)
-mRNA levels dec in response to TZD

88
Q

Adiponectin

A

-reduces blood glucose and insulin resistance
-protein from WAT
-mRNA levels inc w TZD

89
Q

TNFa

A

-stimulates lipolysis in WAT
-insulin resistance in skeletal muscle
-from WAT
-mRNA levels decrease w TZDs

90
Q

Drug summary

A

slide120-121

Therapeutics II (55 decks)

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