Diabetes Drugs Flashcards
(120 cards)
1
Q
What are the treatment goals for:
Fasting plasma glucose
2hr Peak postprandial glucose
HbA1C
A
Fasting plasma glucose: 90-130
2hr Peak postprandial glucose:
2
Q
What is the only current treatment for type I diabetes?
A
Insulin
3
Q
Insulin stimulates glucose uptake in liver, muscle, and adipose tissue via upregulation of ___ transporter
A
GLUT4 glucose transporter
4
Q
Rapid acting Insulin
A
Insulin aspart
Insulin lispro
Insulin glulisine
5
Q
Rapid acting insulin: (Insulin aspart, Insulin lispro, Insulin glulisine)
Onset
Peak
Duration
A
Onset: 5-15 mins
Peak : 45-75 mins
Duration: 2-4 hours
6
Q
Rapid acting insulin: (Insulin aspart, Insulin lispro, Insulin glulisine) Usage
A
For meals or acute hyperglycemia
Can be inject immediately before meals
7
Q
Regular insulin
Onset
Peak
Duration
A
Onset: 30-60 mins
Peak: 2-4 hours
Duration: 6-8 hours
8
Q
Regular insulin Usage
A
For meals or acute hyperglycemia, needs to be injected 30-45 mins prior to meal
9
Q
Intermediate acting insulin
A
NPH insulin (Isophane)
10
Q
Intermediate acting insulin Formulation
A
Conjugated with protamine peptide- delays absorption until proteolytically cleaved by tissue proteases
11
Q
Intermediate acting insulin
Onset
Peak
Duration
A
Onset: 1.5-2 hours
Peak: 6-10 hours
Duration: 16-24 hours
12
Q
Intermediate acting insulin Usage
A
Provides basal insulin and overnight coverage
13
Q
Long acting insulin
A
Insulin glargine
Insulin detmir
14
Q
Long acting insulin formulation:
Insulin glargine
Insulin detmir
A
Insulin glargine: amino acid substituted insulin
Insulin detmir : insulin with fatty acid side chain that associates w/ tissue bound albumin
SLOWS ABSORPTION
15
Q
Long acting insulin formulation: Insulin glargine Insulin detmir Onset Peak Duration
A
Onset: 2 hours Peak: no peak Duration: Insulin glargine: 20-24 hours Insulin detmir: 6-24 hours
16
Q
Long acting insulin formulation:
Insulin glargine
Insulin detmir
Usage
A
Provides basal insulin and overnight coverage
17
Q
Insulin administration
A
Give SQ
Syringe, pen, pump
18
Q
Sites of insulin administration
A
upper arms, thighs, buttocks, abdomen
19
Q
Sites of insulin admin should be rotated to avoid
A
lipodystrophy
20
Q
Conventional insulin therapy
A
2 daily injections of pre-mixed intermediated insulin (NPH) + regular insulin
21
Q
Risk of conventional insulin therapy
A
Hypoglycemia in afternoon or overnight (insulin> carb consumption)
Risk of hyperglycemia in the morning=Dawn phenomenon (cortisol raises glucose levels)
22
Q
Intensive insulin therapy
A
One/twice daily basal insulin (NPH or glargine)- lowers fasting glucose
Pre meal rapid acting insulin- postprandial glucose
23
Q
Dose of pre-meal bolus determined by
A
Blood glucose level
Size and composition of meal (amount of carbs)
Degree of anticipated physical activity
24
Q
Drawbacks of intensive therapy
A
patient commitment and effort
higher cost
increased risk of adverse effects
25
Major adverse effect of insulin therapy
Hypoglycemia
26
Hypoglycemia
blood glucose
27
Treatment of mild-moderate hypoglycemia
Oral dose of simple carbohydrate
28
Treatment of severe hypoglycemia
IV glucose or glucagon
29
Non-drug therapies for type II DM
Diet and exercise
decrease refined sugar
decrease fat
30
Bariatric surgery in treatment of type II DM
Roux-en-Y gastric bypass surgery can restore normoglycemia in obese
31
Insulin sensitizers
Biguanides (Metformin)
Thiazolidinediones (Pioglitazone, Rosiglitazone)
32
Insulin Secretagogue
Sulfonylureas (Chlorpropamide, Tolbutamide, Glimepiride, Glyburide, Glipizide)
Meglitinides (Repaglinide, Nateglinide)
33
Incretin Mimics and Modulators
GLP-1 homologs (Exenatide, Liraglutide)
DPP-IV inhibitors (Sitigliptin, Saxagliptin)
34
Inhibitors of carbohydrate digestion
a-glucosidase inhibitors (acarbose, miglitol)
35
SGLT2 inhibitors
Canagliflozin
| Dapagliflozin
36
Bile acid-binding resin
Colesevelam
37
Amylin Homolog
Pramlintide
38
What is the recommended initial drug of choice in the treatment of ALL types of DM 2 patients (unable to control with diet/exercise alone)?
Metformin
39
Metformin Actions
Anti-hyperglycemia drug
Lowers fasting plasma glucose
Decreases hepatic gluconeogenesis
Increases insulin sensitivity/glucose uptake
40
What does Metformin require for its effects?
presence of insulin
41
How much does Metformin lower HbA1c?
1-5.2%
42
Advantages of metformin
NO hypoglycemia
NO weight gain
Improves lipid prodile
Decreases MI, DM death, mortality
43
Metformin MOA
Inhibits complex I of mitochondrial oxidative phosphorylation
Block ATP, Increase in AMP
Antagonizes Glucagon by inhibiting AC activity (x hep gluc)
Indues AMP-dependent kinase (Inc insulin sens)
44
Metformin adverse effects
Well tolerated
GI effects
Bad taste
Inhibits absorption of Vit B12 (megaloblastic anemia, neuropathy)
LACTIC ACIDOSIS
45
Rare but serious adverse effect of metformin?
```
Lactic acidosis
(Pts w/ renal/liver insuff, CHF, MI, hypoxia)
```
46
Symptoms of lactic acidosis
Deep and rapid breathing, vomiting, abdominal pain and severe weakening of muscles in the legs and arms
Increased lactic acid in the blood
47
Metformin contraindications
```
Pregnant/lactating
Impaired renal/liver function
Elderly >80
Iodinated contrast agent (contrast induced renal failure)
Alcohol abuse
CHF
MI
Shock/septicemia
Acute illness
Hypoxia
```
48
Thiazolidinediones
| "glitazones"
Pioglitazone
| Rosiglitazone
49
Thiazolidinediones
| "glitazones" description
Insulin sensitizers
| Increase sensitivity of adipose, muscle, and liver to insulin
50
Thiazolidinediones
| "glitazones" MOA
Agonists of peroxisome proliferator activated recepor-Y TF (PPAR-y)
Increases insulin sensitivity
Decreased plasma glucose levels
51
Thiazolidinediones
| "glitazones" Indications
Monotherapy or combo w/ metformin, sulfonylureas or insulin for DM T2
Decreases fasting blood glucose, moderate effects on postprandial glucose
52
How much do Thiazolidinediones
| "glitazones" decrease HbA1C?
0.5-1.4%
53
How long does it take Thiazolidinediones
| "glitazones" to have a max effect?
6-14 weeks
54
Thiazolidinediones
| "glitazones" adverse effects
```
Weight gain (subQ)
Fluid retention > edema
Risk of heart failure
Bone fracture risk
Bladder cancer risk
Hepatotoxicity
```
55
Thiazolidinediones
| "glitazones" Contraindications
Liver disease
Heart failure (BLACK BOX)
Pregnancy
56
Thiazolidinediones
| "glitazones" BLACK BOX WARNING
Increased risk of heart failure (fluid retention)
57
Sulfonylureas vs. Meglitinides onset and half life
Sulfonylureas: slow onset, long half life > fasting glucose
Meglitinides: Rapid onset, short half life > postprandial glucose
58
Sulfonylureas
First generation (rarely used)
Chlorpropamide
Tolbutamide
Second generation
Glimepiride
Glyburide
Glipizide
59
Sulfonylureas Description
Oral drugs that lower blood glucose levels by stimulating beta cells to secrete insulin
60
Sulfonylureas MOA
Directly bind to the regulatory subunit of the K channel (Sur1)
Mimic the effects of ATP, block channel
> K induced membrane depol
release of insulin
61
Sulfonylureas Uses
Long duration of glucose lowering effect (16-24 h)
Stimulate insulin production in absence of glucose
REDUCE FASTING PLASMA GLUCOSE
62
How much do Sulfonylureas reduce HbA1c?
1.5-2%
63
Activity of Sulfonylureas is dependent on
Functional beta cells
| Most effective in pts w/ DM
64
Sulfonylureas adverse effects
```
Hypoglycemia (renal/hepatic impairment, eldly)
Weight gain (subQ)
```
65
Sulfonylureas metabolism
Met in liver
Excreted in kidney
Glyburide and Glimepiride increase conc in R/H insuff
Glipizide is safer for patients with renal insufficiency
66
Which Sulfonylurea is safer in pts with renal insufficiency and elderly?
Glipizide
67
Sulfonylureas Contraindications
```
Elderly (give Glipizide)
Impaired R/H function (give Glipizide or Repaglinide for R)
Type 1 diabetes
Pregnant (teratogenic)
Sulfa allergies
```
68
Sulfonylureas Drug Interactions
Highly protein bound
| Displacement > high risk of hypoglycemia
69
Meglitinides (Insulin Secretagogues)
Repaglinide
| Nateglinide
70
Meglitinides Description
Short acting glucose-lowering oral drugs
| Stimulate pancreatic beta cells to secrete insulin
71
Meglitinides MOA
Trigger insulin secretion similarly to sulfonylureas but bind a different region of the SUR1 K/ATP channel
72
Important difference between Meglitinides and Sulfonylureas
Rapid, shorter duration
Glucose dependent
**Decreased risk of hypoglycemia
73
How much do Meglitinides reduce HbA1c?
1-1.5%
74
Meglitinides Indications
Post prandial glucose elevations
| Often used in combo w/ drugs that affect fasting plasma glucose (metformin, thiazolidinediones)
75
What is the difference between Nateglinide and Repaglinide?
Nateglinide affects POSTPRANDIAL glucose, and is rapidly reversed
Repaglinide affects postprandial and fasting glucose and effect is more prolonged
76
Meglitinides metabolism
Repaglinide:
100% met in liver
90% fecal elimin
*good alternative to sulfonyl in renal insufficiency
Nateglinide:
80% met in liver
80% elim in urine
*Does not require dosage adjustment in renal insufficiency
77
Meglitinides adverse effects
Hypoglycemia (less than sulfonyl)
| Weight gain
78
Meglitinides Contraindications
Liver disease
| Pregnancy
79
GLP-1 homologs
Exenatide
| Liraglutide
80
DPP-IV inhibitors
Sitagliptin
| Saxagliptin
81
GLP-1 homolog description
Analogs of GLP-1
| GLP-1 is made in L cells of SI, mediates the incretin effect on plasma insulin
82
GLP-1 MOA
Binds GLP-1 receptor on beta cells and potentiates glucose-induced insulin secretion
Suppresses hepatic glucose production (inhibits production of glucagon)
Promotes beta cells survival
Slows gastric emptying
Increases satiety
83
GLP-1 homolog indications
Alterative to starting insulin in DM T2
| Reduces both Fasting and postprandial glucose
84
GLP-1 homolog duration of action
Exenatide: 6-8 hours
Liraglutide: 11-15 hours
85
How much do GLP-1 homologs reduce HbA1c?
0.5-0.7%
86
GLP-1 homolog advantages
Little risk of hypoglycemia (glucose dependent)
| Promotes weight loss
87
GLP-1 homolog adverse effects
Frequent; nausea vomiting diarrhea
88
DPP-IV inhibitors
Sitagliptin
| Saxagliptin
89
DPP-IV inhibitors
Decrease fasting and postprandial glucose
90
How much do DPP-IV inhibitors reduce HbA1c?
0.48-0.61%
91
DPP-IV inhibitors MOA
Inhibitors of DPP-IV, promotes actions of GLP-1
92
DPP-IV inhibitors adverse effects
metabolism of other hormones?
93
Alpha-glucosidase inhibitors
Acarbose
| Miglitol
94
Alpha-glucosidase inhibitors Description
Reduce postprandial glucose
| Inhibit digestion of polysaccharides in small intestine
95
Alpha-glucosidase inhibitors MOA
Inhibit alpha-glucosidase (enzyme in brush border of SI - hydrolysis of dietary carbs)
96
Alpha-glucosidase inhibitors Indications
Control of postprandial glucose (needs to be taken with meal)
Not considered first line anti-diabetic drug
Less potent than sulfmet
NO hypoglycemia
97
How much do Alpha-glucosidase inhibitors lower HbA1c?
0.5-0.8%
98
Alpha-glucosidase inhibitors Adverse effects
GI (abd pain, flatulence)
99
Alpha-glucosidase inhibitors Contraindications
Chronic intestinal disease
Inflammatory bowel disease
Colonic ulceration/ intestinal obstruction
100
SGLT2 Inhibitors
Canagliflozin
| Dapagliflozin
101
SGLT2 Inhibitors Description
Drugs that reduce hyperglycemia by promoting glucose excretion in the urine
102
SGLT2 Inhibitors MOA
Inhibit sodium-glucose linked transporter 2 protein (SGLT2)
| prevents glucose reabsorption in proximal renal tubules
103
SGLT2 Inhibitors Indications
Mono/ combo
Low risk of hypoglycemia when used mono
Decreases body weight
decreases BP
104
How much do SGLT2 Inhibitors decrease HbA1c?
0.5-0.9%
105
SGLT2 Inhibitors Adverse Effects
```
UTI
Thirst/Dehydration
Hypotension
Increased LDL cholesterol
Hyperkalemia
```
106
SGLT2 Inhibitors Contraindications
Renal impairment
107
Bromocriptine description
Sympatholytic dopamine D2 receptor agonist
Normalize decreased AM dopamine levels in DMT2
Take within 2 hours of waking
108
How much does Bromocriptine lower HbA1c?
0.5%
109
Colesevelam Description
Bile acid binding resin
LDL-lowering drug
Used as adjunct
Indirectly increases GLP-1
110
Colesevelam MOA
```
Bind bile acids in SI
Form insoluble complexes
Excreted in feces
Prevents bile acid reabsorption
Bile acid bind to TGR5 in colon >stimulation GLP-1 secretion
```
111
Colesevelam Indications
+ metformin, sulf, insulin
NOT 1st line
Helpful in pts w/ high LDL
112
How much does Colesevelam lower HbA1c?
0.5%
113
Which medication should be considered as initial therapy for patients presenting with HbA1c >1%
Insulin
114
Who requires more insulin - DM Type 1 or 2?
Due to insulin resistance, type-2 diabetics require considerably more Insulin compared to the doses used in the treatment of type-1 diabetes
115
Amylin homolog
Pramlintide
116
Amylin homolog Description
Synthetic analog of amylin (co-secreted with insulin, helps with postprandial glucose control)
Amylin is absent in diabetics
Used w/ insulin in DM T1&2
117
Pramlintide actions
Decreases hepatic gluconeogeneiss
Decreases postprandial glucagon
Slows gastric emptying
Increases satiety
118
Amylin homolog (pramlintide) indications
Adjunct + insulin
Post prandial glucose control
Effects are ADDITIVE to sinulin (reduce insulin by 50%)
Weight loss
119
How much does amylin homolog lower HbA1c?
0.5-0.7%
120
Amylin homolog adverse effects
Nasuea, vomiting, anorexia, headache
| Increases risk of severe hypoglycemia (w/ insulin)
