Diabetes Oral Meds Flashcards
(130 cards)
1
Q
Glucagon
A
Made by 𝛼 cells
Stimulates breakdown of stored liver glycogen
Promotes hepatic gluconeogenosis and ketogenesis
2
Q
Insulin
A
Made by β cells
Affects glucose metabolism and storage of ingested nutrients
Promotes glucose uptake by cells
Suppresses postprandial glucagon secret ion
Promotes protein and fat synthesis
Promotes use of glucose as an energy source
3
Q
Amylin
A
Made by β cells
Suppresses post prandial glucagon secretion
Slows gastric emptying
Reduces food intake and body weight
4
Q
GLP-1
A
Enhances glucose dependent insulin secretion
Suppresses postprandial glucagon secretion
Slows gastric emptying
Reduces food intake and body weight
Promotes Β cell health
5
Q
Which works when BG is high, insulin or glucagon?
A
Insulin
6
Q
______ signals muscles cells to convert glycogen back to glucose
A
Glucagon
7
Q
_________ signals liver to release glucose from glycogen
A
Glucagon
8
Q
_________ signals the liver to store glucose as glycogen
A
Insulin
9
Q
__________ moves BG into muscle cells for energy or to be stored as glycogen
A
Insulin
10
Q
___________ signals fat cells to make ketones as an alternate energy source
A
Glucagon
11
Q
__________ signals fat cells to store excess glucose as fat
A
Insulin
12
Q
What should happen in a normal person without diabetes?
A
Insulin should be released from the pancreas—> insulin binds to receptors—> glucose can enter the cell
13
Q
What happens in Type 1 DM?
A
No insulin is produced by the patient—> nothing binds to the insulin receptor—> glucose stays in blood stream and does NOT enter the cell
14
Q
What happens in Type 2 DM?
A
Insulin is secreted in an amount which may or may not be sufficient + resistance to the insulin binding to the receptor—> glucose cant get into cell
15
Q
Most common type of DM for someone to have
A
Type 2
16
Q
TYPE 1 DM
A
Absolute lack of insulin
Due to cellular-mediated AI destruction of pancreatic β cells
Possible triggers: Genetic, viral, environmental
17
Q
Idiopathic Type 1 DM
A
No known etiology
no β cell AI
STRONG HEREDITARY COMPONENT
18
Q
TYPE 2 DM
A
Relative insulin deficiency
Also have peripheral insulin resistance
NO AI DESTRUCTION
Typically overweight or obese
19
Q
TYPE 2 DM risk factors
A
> 45
Fam hx
Obesity
Physical inactivity
Prior gestational DM
HTN
Dysplipidemia
PCOS
Ethnicity (AA, Latino, Asian American)
20
Q
S&S of diabetes (hyperglycemia)
A
Fagtigue
Polydipsia
Polyphasic
Polyuria
Tingling, numbness in extremities
Poor healing
Blurred vision
21
Q
3 P’s of diabetes
A
Polydipsia
Polyphasic
Polyuria
22
Q
Criteria for diabetes dx
A
FPG > 126mg/dL (no caloric intake for at least 8 hr)
2- hg PG ≥ 200mg/dL during OGTT
A1C ≥ 6.5%
Classic sx of hyperglycemia or hyperglycemic crisis + PG ≥ 200mg/dl
23
Q
Macrovascular chronic complications of diabetes
A
CAD
CVD
PVD (increased risk infection or amputation)
24
Q
Microvascular complications of chornic diabetics
A
Retinopathy
Nephropathy—> leading cause of ESRD
25
Risks of Microvascular complications including retinopathy, neuropathy, and nephropathy can be controlled with _________
Adequate glycemic control
26
Non- Pharmacologic therapies to improve glycemic control include:
Weight reduction ( <3500kcal/wk)
Increased activity
Reduced alc intake
Smoking cessation
27
Classes of Pharmacotherapy for diabetes
Biguanides
Sulfonylureas
Meglitinides
Thiazolidinediones
𝛼 Glucosidase inhibitors
SGLT2 inhibitors
Others
28
7 class targets for treatment of T2DM
Increased insulin availability
Improving sensitivity to insulin
Decrease hepatic glucose ouput
Decrease glucagon
Delay delivery and absorption of CHO
Slow gastric emptying
Increase urinary glucose excretion
29
How is insulin sensitivity measured?
As the amount of glucose cleared from the blood in response to a fixed dose of insulin
30
What is insulin resistance
Failure of normal amounts of insulin to elicit the expected response
31
What factors are insulin sensitivity affected by?
Age
Body weight
Physical activity levels
Illness
Meds
32
What type of diabetes has a reduced response to isulin?
Type 2
33
Major insulin-responsive tissues
Skeletal muscle
Adipose tissue
Liver
34
Metformin MOA
Reduces hepatic glucose p roduction
Increases skeletal muscle glucose uptake (increases sensitivity)
Decreases intestinal absorption of glucose
35
First line Oral diabetes agent
Metformin
36
Metformin advantages
Rarely Causes hypoglycemia
Effective A1C reduction (1-2%)
37
Impact of Metformin on Cardiovascular system
May reduce CV mortality
38
Weight impact of Metformin
Weight neutral
39
Side effects of metformin
GI: diarrhea, abdominal, cramping, nausea
Lactic acid (rare)
Vit B-12 deficiency with long term use (monitor for peripheral nephropathy)
40
Metformin Precautions
GFR:
- contraindicated <30ml/min
- nor recommended 30-45ml/min
Increase risk lactic acidosis:
Acute CHF, dehydration, excessive alc intake, hepatic and renal impairment, sepsis
Iodinated Contrast media
- can lead to renal failure and increase risk of lactic acidosis
- withhold Metformin before procedures and for at least 48hrs after until GFR normalized
41
What can you do to alleviate abdominal sx on metformin?
Decrease dosage
42
Sulfonylureas MOA
Increases insulin release
Stimulates insulin release by binding to a specific site on the β cell Katp channel complex and inhibiting its activity—> binding inhibits efflux of K+ ions—> depolarization—> influx of Ca+ ions—> release of preformed insulin
43
Advantages of Sulfonylureas
Effective A1C reduction (1.5-2%)
44
What is the CV impact of first generation Sulfonylureas?
Tolbutamide—> associated with worse CV outcomes
Others unknown
45
What are the CV impacts of second generation Sulfonylureas?
Unknown/ not clearly establishes
46
Weight impact of Sulfonylureas
Weight gain
47
Sulfonylurea Precautions
Cross-allergenicity with sulfa allergy & sulfonamides
48
Side effects of Sulfonylureas
Hypoglycemia
Primary or secondary failure
49
What is primary failure of Sulfonylureas?
They never worked in the first place
50
What is secondary failure of Sulfonylureas?
More prevalent failure
Works then stops working
51
Causes of secondary failure of Sulfonylureas?
Progression of disease with pancreatic failure
Poor diatary compliance
Exogenous diabetogenic factors (obesity, illness, drugs, thiazides, corticosteroids)
Tachyphylaxis
52
First gen Sulfonylureas
Chlorpropamide
Tolbutamide
Tolazamide
53
Second Gen Sulfonylureas
Glyburide
Glipizide
Gilmepiride
54
Glyburide
Longer DOA than Glipizide
Associated with severe, prolonged hypoglycemia
55
Who should we be careful with using Glyburide in?
Caution in frail, elderly, or patients predisposed to hypoglycemia
56
What Sulfonylurea is a better choice for elders, those with renal impairment, or those at risk for hypoglycemia?
Glipizide
57
Why is Glipizide best for the elders, renal impaired, and those at risk for hypoglycemia?
Short half life
Broken down to inactive metabolites
58
Indications of use for Sulfonylureas:
Initial therapy when contraindication to metformin
Can be used in combo with other orals in patients who fail initial therapy with metformin
59
Can Sulfonylureas be added to metformin? If so, when?
Sulfonylureas can be added to metformin if the desired A1C is not being attained with just metformin alone
60
MOA of Meglitinides
Close K-ATP channels on β cell membranes—> increased insulin secretion
Quick onset (15-60min) and short DOA— concentrates effect around the meal time glucose load
61
What is the difference between Meglitinides and Sulfonylureas?
Meglitinides are fast acting so you use them around meal time and if you dont eat, you skip the dose
62
Advantages of Meglitinides
A1C reduction .5-1.5%
Reduces postprandial glucose
1-30 min before meals
FLEXIBLE DOSING- skip meal—> skip dose
63
Why would Sulfonylureas not be a good choice for diabetes treatment in patients who skip meals?
Increased risk of hypoglycemia
64
CV impacts and weight impacts of Meglitinides
CV- unknown
Weight impact—> weight gain
65
Side effects of Meglitinides
Hypoglycemia
66
Meglitinides indications
Alone or in combo with metformin or other oral diabetes meds
NO WITH SULFONYLUREAS (SU)
Consider them over Sulfonylureas (less risk hypoglycemia and better postpranidal glucose control)
67
Names of Meglitinides
Nateglinide
Repaglinide
68
MOA of Thiazolidineodiones (TZDs)
Increase tissue sensitivity of insulin by activiating Peroxisome Proliferator-activated receptor γ (PPAR-γ ) nuclear receptors
Causes increased glucose uptake in muscles and adipose tissues, inhibits hepatic gluconeogenesis
Circulating insulin levels decrease—> reduction in insulin resistance
69
Why did the FDA restrict prescription of Rosiglitazone prior to 2013?
Increased risk of acute MI and CV deaths
70
Advantages of Thiazolidineodiones
A1C reduction of .5-1.4%
Hypoglycemia (rare)
71
CV impact of thiazolidinediones
Pioglitizone and Rosiglitazone—> risk of HF
72
TZD weight impact
Weight gain
73
Side effects of TZDs
Fluid retention
Peripheral edema
Increased risk of bone fractures
Hepatotoxicity (mon LFTs)
Possible increased risk of bladder CA—> pioglitiazone
74
How does Pioglitazone affect patient lipid levels?
Reduces triglycerides
75
How does Rosiglitazone affect lipid profiles
Increases LDL
76
Contraindications of TZDs
Symptomatic HF
NYHA class III or IV HF
Active or hx of bladder CA
Hx of fx or high risk of bone fx
Active liver disease
77
Indications of use for TZDs
Patients with contraindications to metformin or Sulfonylureas—> Pioglitazone
For combo, try other agents bc side effect profile is high with TZDs
78
Names of TZDs
Pioglitazone
Rosiglitazone
79
𝛼 glucosidase inhibitor MOAs
Inhibit the upper GI enzymes (𝛼-glucosidase) that convert complex polysaccharide CHOs into monosaccharides
SLOWS ABSOPRTION of glucose and reduces prostprandial glucose concentrations
80
What to 𝛼 glucosidase inhibitors target?
Target post-prandial glucose excursions and are taken with first bite of meal
81
When should you take AGIs?
With the first bite of a meal because drug needs to be onboard to prevent absorption of CHOs
82
Advantages of 𝛼 glucosidase inhibitors
Rarely causes hypoglycemia
Will get an A1C reduction of .3-1%
83
CV impact of AGIs
Miglitol- unknown
Acarbase- neutral
84
Weight impact of AGIs
Neutral
85
Side effects of AGIs
Flatulence and diarrhea
86
Contraindications of AGIs
Cirrhosis- increase liver enzymes
SrCr >2mg/dL
Major intestinal issues (IBD or CID)— worsened by increased gas formation such as colonic ulceration or partial intestinal obstruction
87
How to treat hypoglycemia caused by miglitol or acarbose?
glucose tablets of glucose gels
88
Why are CHOs not effective in treating Hypoglycemia caused by AGIs?
Will not be absorbed
89
Are AGIs considered 1st line therapy? If not why?
No they are not
Reduced efficacy and poor tolerance
90
What are the 2 𝛼 glucosidase inhibitors used?
Acarbose
Miglitol
91
DPP-4 inhibitor MOA
Increases GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like-protein) , which are incretin hormones, via DPP-IV inhibition—> increased insulin secretion and decreased glucagon section—> decreased hepatic glucose production
92
What hormones do DPP-IV inhibitors enahnce? Decrease?
Decrease: glucagon,, insulin, amylin
Enhance- GLP-1 (suppresses postprandial glucagon section and slows gastric emptying)
93
Advantages of DPP-IV inhibitors
Rarely cause hypoglycemia
A1C reduction .5-.8%
94
CV impact of DPP-IV inhibitors
Neutral in regard to morbidity and mortality
Increased risk of HF related admissions with alogliptin and saxagliptin
95
Weight impact of DPP-IV inhibitors
Neutral
96
Side effects of DPP-IV inhibitors
Angioedema
Urticaria and other immune-mediated derm effects
Acute pancreatitis
Arthralgias
Headache
Nasopharyngitis
97
Who should we caution use pf DPP=IV inhibitors in?
HF patients (increased HF hospitalizations)
98
Indications of use of DPP-IV inhibitors
Add on therpay for those not well controlled on metformin, TZDs, or Sulfonylureas
Monotherapy IF intolerant of or have contraindications to metformin, Sulfonylureas, or TZDs
FOR PATIENTS WITH CKD—> Linagliptin (bold)
99
What hormones do DPP-IV inhibitors enahnce? Decrease?
Decrease: glucagon,, insulin, amylin
Enhance- GLP-1 (suppresses postprandial glucagon section and slows gastric emptying)
100
Advantages of DPP-IV inhibitors
Rarely cause hypoglycemia
A1C reduction .5-.8%
101
CV impact of DPP-IV inhibitors
Neutral in regard to morbidity and mortality
Increased risk of HF related admissions with alogliptin and saxagliptin
102
Weight impact of DPP-IV inhibitors
Neutral
103
Side effects of DPP-IV inhibitors
Angioedema
Urticaria and other immune-mediated derm effects
Acute pancreatitis
Arthralgias
Headache
Nasopharyngitis
104
Who should we caution use pf DPP=IV inhibitors in?
HF patients (increased HF hospitalizations)
105
Indications of use of DPP-IV inhibitors
Add on therpay for those not well controlled on metformin, TZDs, or Sulfonylureas
Monotherapy IF intolerant of or have contraindications to metformin, Sulfonylureas, or TZDs
FOR PATIENTS WITH CKD—> Linagliptin
106
are the 4 DPP-IV inhibitors used in treatment of diabetes?
Sitagliptin
Saxaliptin
Alogliptin
Lingaliptin
107
What DPP-IV inhibitor DOES NOT require renal dosing?
Lingalipitin
108
SGLT2 inhibitor MOA
Inhibit SGLT2 receptors in the proximal nephron—> blocks glucose reabsorption by the kidney—> increased urinary excretion of glucose—> decreased plasma glucose
109
Advantages of SGLT2 inhibitors
Reduce A1C by .7-1%
Rare hypoglycemia
Reduces blood pressure (bc cuases slight osmotic diuretic effect)
110
Weight impact of SGLT2 inhibitors
Weight LOSS
111
CV impacts of SGLT2 inhibitors
Ertugliflozin- neutral
Canagliflozin, Dapagliflozin, Empagliflozin—> improves outcomes
112
Renal impact of SGLT2 inhibitors
Can prevent kidney endpoints by reducing the progression of kidney disease
Empagliflozin, Dapagliflozin, & Canagliflozin= improve renal outcomes
113
Side effects of SGLT2 inhibitors
GU fungal infections
UTIs—> urosepsis
Diuresis
Volume depletion—> dehydration
Hypotension
Ketoacidosis
Necrotizing Fasciiitis of the perineum (Fournier gangrene)
114
Canagliflozin specific SE
Increased risk of bone fractures
Increased risk of LE amputation
115
Specific Side effect with Dapagliflozin
Increased risk bladder cancer
116
What population is likely to develop Ketoacidosis with SGLT2 inhibitor use and should avoid them?
Diabetic patients which have fx predisposing to DKA
Pancreatic insufficiency
IVDU or alcohol use disorder
117
Biggest thing to keep in mind about SLGT2 inhibitors
They is no long term safety data with regards to its effect of chronic glucosuria
118
If you do lab work on a patient taking an SGLT2 inhibitor, what will you expect to find?
Glucose in urine
119
Contraindications/ Precaustions of SLGT2 inhibitors
Older patients or those taking diuretics, ACEi, or ARBs—> can cause symptomatic HTN
Caution in conjunction with other meds that predispose people to acute renal injury (ACE, ARB, NSAIDs)
120
What are the 4 SGLT2 inhibitors
CEED
Canagliflozin
Empagliflozin
Ertugliflozin
Dapagliflozin
121
How are SGLT2 inhibitors dosed?
Renally (dose reductions dependent on the SGLT2 and whether or not they are being used for glycemic control)
122
Indications of use for SGLT2 inhibitors
Not considered initial therapy for T2DM
Cardiorenal comorbidities- consider SGLT2 inhibitors for their benefit in this pop
123
Bile Acid Sequestrants MOA in diabetes
Uncertain
Proposed:
act in GI tract to reduce glucose absorption
Reduce hepatic glucose production and increase incretin levels
124
Advantages of Colesevelam (BAS)
A1C reduction .5%
Rarely cause hypoglycemia
125
Effect of Colesevelam on lipids
Decreased LDL
Increase triglycerides
126
Colesevelam side effects
Constipation
127
MOA of dopamine 2 agonists in DM
Believed to affect circadian rhythms
May reset hypothalamic circadian activities (altered by obesity)—> reversal of insulin resistance and decreased hepatic glucose production
128
A1C reduction caused by dopamine 2 agonists
.4-.5%
129
Side effects of Dopamine 2 agonists
Dizziness
Syncope
Nausea
Fatigue
130
What is the name of the Dopamine 2 agonist used in diabetes treatment?
Bromocriptine
