Anti-diabetic Agents Flashcards
(151 cards)
1
Q
What type of insulin preparation is represented by the blue line?
A
Rapid acting (Lispro, Aspart, Glulisine, Inhaled)
2
Q
What type of insulin preparation is represented by the black line?
A
Short acting (Regular)
3
Q
What type of insulin preparation is represented by the red line?
A
Intermediate (NPH)
4
Q
What type of insulin preparation is represented by the pink and dark blue lines?
A
Long acting (Insulin detemir, Insulin glargine)
5
Q
What is the classic triad of symptoms associated with DM?
A
Polyuria, polyphagia, polydipsia
6
Q
Inability of the body to use glucose as an energy source leads to hyperlipidemia which causes what 2 associated conditions commonly seen with DM?
A
Atherosclerosis (of large and medium sized arteries) and HTN (with progressive renal involvement)
7
Q
Aside from the classic triad, and atherosclerosis and HTN, what are other common sxs seen with DM? (4)
A
Peripheral neuropathy, acanthosis nigricans, myoglobinuria (increased muscle breakdown), microangopathy (unknown cause)
8
Q
T1DM is characterized by virtually absent circulating insulin resulting in the need for exogenous insulin to be injected. What is the cause for this?
A
Pancreatic beta cells fail to respond to insulinogenic stimuli (glucose)
9
Q
What is typically the trigger of sustained beta cell stimulation leading to hyperinsulinism and receptor insensitivity in T2DM?
A
Chronic over feeding
10
Q
What may interrupt the disease cycle of T2DM?
A
Reduction of over feeding
11
Q
Why is T2DM considered a progressive disease?
A
Start losing pancreasβ ability to produce insuline (T2DM β T1DM)
12
Q
How does treatment progress as T2DM progresses?
A
Monotherapy β combo therapy β insulin
13
Q
What are the 4 diagnosis methods for DM?
A
- DM sxs and random blood glucose (β₯ 200mg/dL)
- Fasting blood glucose (β₯ 126 mg/dL)
- Oral glucose challenge (blood glucose β₯ 200 @ 2 hrs)
- HbA1C β₯ 6.5%
14
Q
Although an HbA1C level of β₯ 6.5% is diagnositc for DM, what is considered poorly controlled DM?
A
> 10%
15
Q
You typically want a DM pt to have an HbA1C of < 6 BUT under what condition?
A
If you can safely get them to that level without hypoglycemic events
16
Q
How is glycosylation affected as glucose levels increase?
A
Increases (A1C = glycosylated protein)
17
Q
Preproinsulin β insulin yields what?
A
Insulin + C-peptide
(C-peptide provides long term marker for measuring insulin)
18
Q
Release of insulin is activated by what?
A
Glucose, beta2 adrenergic agonist
19
Q
Insulin promotes entry of glucose into what tissues? (2)
A
Skeletal muscle and fat tissue
20
Q
Insulin is NOT required for glucose transport into what tissues? (2)
A
Brain and liver
21
Q
Insulin release is stimulated by beta2 adrenergic agonists but inhibited by what?
A
Alpha2 agonists
22
Q
How is insulin released from beta cells? (6 steps)
A
- Glucose transported via GLUT2
- Metabolism
- Increased ATP
- K+ channel closes and cell depolarizes
- Ca2+ channels open and Ca2+ enters cell
- Insulin released from cell via exocytosis
23
Q
The following actions of insulin are considered what?
Decreased gluconeogensis and increased glycogen synthesis in the liver, and glucose uptake in muscle and adipose tissue
A
Anabolic actions (because insulin inhibtits catabolic actions)
24
Q
Where do GLUT1 and GLUT3 act?
A
Brain
25
Where does GLUT2 act?
Beta cells of pancreas
26
Where does GLUT4 act?
Muscle and adipose
27
The affinity for glucose is greatest/ least in which GLUT transporters?
GLUT2 \< GLUT4 \< GLUT1/ GLUT3
28
How is uptake of glucose unique with respect to the GLUT4 transporter?
Insulin-mediated (aka insulin dependent)
29
Overproduction or underutilization of glucose can cause what imbalance?
Lactic acidosis
30
Which drugs are approved for treatment of T2DM in pts who also have ASCVD? (3)
Liraglutide, Canaglifozin, Empagliflozin
31
What is typically considered 1st line treatment for DM?
Lifestyle modification (important in treatment and CV health)
32
What contributes to \> 2/3 of all morbidity/ mortality/ costs of patients with DM?
CV disease
33
What has shown to be more important in treatment of patients with CV disease + DM?
Control of BP/ cholesterol levels \> tightly controlled blood glucose levels
34
What 3 things must be treated simultaneously in patients with DM and CV disease?
A1C, BP, cholesterol
(bottom line = start intensive therapy immediately for best effect on CV health, but individuaize treatment and avoid hypoglycemia)
35
If a pt has a history of poor glycemic control, what might this indicate about intensive glycemic control?
No CV benefit
36
What is the MOA of insulin?
Stimulates GLUT4 (insulin mediated) uptake of glucose into muscle and adipose tissues
37
The goal of what DM treatment is to mimic what the body does (both meal-stimulated insulin and basal insulin)
Injections
(create insulin profile and eat to fill it)
38
Regular + intermediate insulin mix injection is given when?
1 hour before breakfast and dinner
39
Rapid-acting + long-acting insulin injections are given when?
Rpaid acting injected 1 hour before meals, long acting injected before bedtime
40
What DM treatment involves basal levels of rapid acting insulin maintained throughout the day but increased right before meal based on meal components (pt stimulated bolus)
Insulin pumps
41
What are the most common sxs of hypoglycemia? (4)
Tachycardia, confusion, vertigo, sweating
(dangerous b/c SEs will disappear w repeated events)
42
Besides hypoglycemia, what is a common side effect of insulin treatment for DM?
Weight gain (increased lipolysis)
43
What is the treatment for hypoglycemia? (2)
Give 50-100mL of 50% glucose solution IV, 0.5- 1mg glucagon injection
44
Which 2 types of insulin are given IV?
Rapid-acting and short-acting
45
Which 2 types of insulin are NOT given IV?
Intermediate-acting and long-acting (basal)
46
Why is rapid-acting insulin preferred over regular insulin (short-acting)?
Less hypoglycemia
47
What type of insulin is Insulin lispro (Humalog)?
Rapid-acting
48
What type of insulin is Insulin aspart (NovoLog)?
Rapid-acting
49
What type of insulin is Insulin glulisine (Apidra)?
Rapid-acting
50
What type of insulin is Insulin, inhaled (Afrezza) and what is a SE of it?
Rapid-acting, SE: cough
51
What are the short-acting insulins?
Regular insulin (Novolin R, Humulin R)
52
What are the intermediate acting insulins?
NPH insulin (Humulin N, Novolin N)
53
What type of insulin is Insulin glargine (Lantus)?
Long-acting (basal)
54
What type of insulin is Insulin detemir (Levemir)?
Long-acting (basal)
55
What type of insulin is Insulin degludec (Tresiba)?
Long-acting (basal)
56
What is 1st line treatment for T2DM when A1C is \> 10%?
Long-acting (basal)
(Insulin glargine (Lantus), Insulin detemir (Levemir), Insulin degludec (Tresiba))
57
What hormone antagonizes insulin?
Glucagon
58
What are the 3 routes of administration for glucagon?
SC, IM, IV (but gradual onset)
59
What is the MOA for glucagon?
Increase blood glucose levels by mobilizing hepatic glycogen (when glycogen stores available)
60
What are the indications for use of glucagon? (2)
Beta blocker overdose, radiology
(potent inotropic and chronotropic effects on heart via 2nd messenger, relaxation of intestine)
61
Glucagon drug class?
Hyperglycemic agents
62
Diazoxide drug class?
Hyperglycemic agents
63
How is Diazoxide administered?
Oral (long t1/2)
64
What is the MOA for Diazoxide?
Directly inhibits insulin secretion
(decreases peripheral glucose utilization OR stimulates hepatic glucose production)
65
Which hyperglycemic agent is a non-diuretic thiazide?
Diazoxide
66
What is the indicated use of Diazoxide?
Insulinoma (insulin secreting tumor that leads to hypoglycemia)
67
What are the only 2 anti-DM agents indicated for treatment of both T1 and T2?
Alpha-glucosidase inhibitors and Pramlintide
(Pramlintide used only as insulin adjunct)
68
What is the administration method of most anti-DM agents?
Oral
69
What are the the 4 compelling indications of anti-DM agents?
1. Effect on ASCVD (#1 killer of DM pts)
2. Effect on CKD
3. Impact on weight (helps w weight loss = benefit)
4. Hypoglycemia risk
70
Metformin drug class?
Biguanide
71
What is the MOA for Metformin? (2)
Decrease glucose levels in an **insulin-independent manner**, increase glucose removal from blood with **AMPK**
72
What is the DOC for T2DM if A1C is \< 10%?
Metformin
73
What is the DOC for diabetes prevention (prophylaxis for pre-diabetic pts)?
Metformin
74
Besides A1C and prophylaxis, what are the other uses of Metformin? (2)
PCOS (euglycemic state), decrease macrovascular events (but not direct CV drug)
75
How is Metformin excreted?
Renally
76
What are the SEs of Metformin? (4)
Hypoglycemia (rare), **diarrhea** (most common), **lactic acidosis** (most dangerous, dose dependent), reversible vit B12 deficiency (check levels anually)
77
What are the contraindications to Metformin?
Kidney disease (GFR \< 30), HbA1C \> 10% (give basal insulin instead)
(kidney disease causes lactic acidosis which is a SE)
78
How does Metformin impact weight and mortality events?
Weight neutral and decreases all cause mortality events
79
Exenatide drug class?
GLP-1 agonist
80
Liraglutide drug class?
GLP-1 agonist
81
Semaglutide drug class?
GLP-1 agonist
82
Which GLP-1 agonists are given as SC injections?
Exenatide and Liraglutide
83
Which GLP-1 agonist is given orally?
Semaglutide
84
What is the MOA of all GLP-1 agonists?
GLP-1 agonists that are resistant to DPP-4 degredation (inhibits glucagon release and increases insulin released from pancreas)
85
What are the uses of GLP-1 agonists besides T2DM? (2)
Slows gastric emptying = weight loss, potential increase in beta cell # and function
86
Which GLP-1 agonist decreases macrovascular events in T2DM and is independently approved for weight loss?
Liraglutide
87
What are the SEs of GLP-1 agonists? (2)
Hypoglycemia (low risk), acute pancreatitis
88
What are the precautions of GLP-1 agonists? (2)
GI disease, on meds that can't be exposed to stomach acid too long (b/c GLP-1 agonists slow gastric emptying)
89
What are the contraindications of GLP-1 agonists? (2)
Hx of/ current acute pancreatitis, personal/ family hx of thyroid CA (black box warning)
90
Sitagliptin drug class?
DPP-4 inhibitor
91
Linagliptin drug class?
DPP-4 inhibitor
92
How are the DPP-4 inhibitors administered?
Orally
93
What is the MOA of DPP-4 inhibitors?
DPP-4 inhibitors, potentiates effects of endogenous incretin hormones (inhibits breakdown by DPP-4)
94
How is Sitagliptin eliminated?
Renally
95
How is Linagliptin eliminated?
Liver/ GI elimination
96
What are the SEs for the DPP-4 inhibitors? (2)
Hypoglycemia (low risk), acute pancreatitis
97
What is the precaution for Sitagliptin?
Renal impairment
98
What are the contraindications to DPP-4 inhibitors?
Hx of/ current acute pancreatitis
99
Canagliflozin drug class?
SGLT-2 inhibitor
100
Dapagliflozin drug class?
SGLT-2 inhibitor
101
Empagliflozin drug class?
SGLT-2 inhibitor
102
What is the MOA for SGLT-2 inhibitors?
SGLT-2 inhibitors, inhibits sodium-glucose co-transporter 2 in kidney = glucose not reabsorbed and then excreted in the urine
103
What are the uses for SGLT-2 inhibitors aside from T2DM? (2)
Decreased BP, weight loss
104
Which SGLT-2 inhibitors are used to decrease CV events?
Canagliflozin and Empagiflozin
105
Which SGLT-2 inhibitors are used to decrease CKD progression?
Canagliflozin
106
Which SGLT-2 inhibitors are used to decrease HF hospitalizations?
Canagliflozin and Dapagliflozin
107
What are the most common SEs of the SGLT-2 inhibitors? (3)
Genital candida infection, UTI, increased urinary frequency
108
What are the less common SEs of SGLT-2 inhibitors? (3)
Hypoglycemia (rare), osmotic diuresis, renal impairment/ AKI
109
What are the contraindications to SGLT-2 inhibitors? (3)
Females with recurrent UTIs, ESRD, dialysis
110
Pioglitazone drug class?
Thiazolidinedione
111
Rosiglitazone drug class?
Thiazolidinedione
112
The following is the MOA for which drug class?
Binds to nuclear PPARπ receptor β post-receptor insulin mimetic action (induces insulin response w/o insulin present) β β insulin sensitivity, β GLUT 4 and β hepatic glucose production
Thiazolidinediones (insulin sensitizers)
113
What is 2nd line treatment for diabetic prophylaxis?
Thiazolidinediones
(1st line = Metformin)
114
What are the SEs for Thiazolidinediones? (4)
Hypoglycemia (low risk), weight gain, edema, increased bone fracture risk
115
What are the contraindications to Thiazolidinediones? (2)
HF and hepatic disease
116
Acarbose drug class?
π°-glucosidase inhibitor
117
Miglitol drug class?
π°-glucosidase inhibitor
118
What is the MOA for π°-glucosidase inhibitors?
π°-glucosidase inhibitors, taken right before a meal = delayed carb digestion/ absorption
119
π°-glucosidase inhibitors can be used to treat what?
T1 AND T2DM
120
What are the SEs to π°-glucosidase inhibitors? (3)
GI effects/ **flatulence**, increased hepatic enzymes, jaundice
(flatulence b/c bacteria thrive on excess carbs)
121
What is a precaution to treatment with π°-glucosidase inhibitors?
Hepatic and renal disease
122
What is the contraindication to π°-glucosidase inhibitors?
GI condition/ obstruction
123
Glyburide drug class?
Sulfonylureas
124
Glipizide drug class?
Sulfonylureas
125
Glimepride drug class?
Sulfonylureas
126
The following is the MOA for which drug class?
Bind and block/ close K channel β membrane depolarization β β Ca into cell β β insulin release
Sulfonylureas
127
The long half life of Sulfonylureas allows for what?
Insulin secreted all day
128
What are the SEs for Sulfonylureas? (4)
**Hypoglycemia** (highest risk), weight gain, GI SEs, progressive disease process of DM
129
Which drug class has the highest risk for hypoglycemia?
Sulfonylureas
130
Of the Sulfonylureas (Glyburide, Glipizide, Glimepride) how does the risk for hypoglycemia compare?
Glyburide = **worst** hypoglycemia (24 hr effect)
Glipizide = **least** hypoglycemia (2-4 hr tΒ½)
Glimepiride = **no** hypoglycemic effect (once a day dosing)
131
What are the precautions of the Sulfonylureas? (2)
Severe renal disease and hepatic dysfunction
132
What is a contraindication to the Sulfonylureas?
Sulfa allergy
133
Repaglinide drug class?
Meglitinides
134
Meglitinides have the same MOA as Sulfonylureas (bind and block/ close K channel β membrane depolarization β β Ca into cell β β insulin release) with the exception of what?
They are not sulfonamides so they are **safe in pts with sulfa allergies**
135
What is important about the pharmacokinetics of Repaglinide?
Short t1/2 = rapid acting (better at mimicking insulin), postprandial
136
What is a SE of Repaglinide?
Hypoglycemia (moderate risk, less than all Sulfonylureas)
137
What is a precaution to treatment with Repaglinide?
Liver impairment
138
What is a contraindication to treatment with Repaglinide?
Do not use with Sulfonylureas
139
Colesevelam drug class/ MOA?
Bile acid binding resin
(but MOA unknown for glycemic effect)
140
How is Colesevelam used?
Used in **combo** to decrease basal plasma glucose, also decreases LDL (CV effects)
141
What are the SEs to Colesevelam? (2)
Constipation and bloating
142
Bromocriptine drug class?
Dopamine agonist
143
What is the MOA of Bromocriptine?
Dopamine agonist (quick release), enhanced suppression of hepatic glucose production
144
What is the use of Bromocriptine?
Post-prandial glucose
145
What is the precautions with Bromocriptine?
Caution w/ CYP3A4 inhibitors/ inducers/ substrates
146
Pramlintide drug class?
Amylyn-like peptide
147
What is the MOA for Pramlintide?
Amylyn-like peptide, **synthetic analog of amylin**, regulates post-prandial glucose by **β gastric emptying**
(amylin = hormone co-secreted with insulin)
148
How is Pramlintide used/ what are its uses?
IN **COMBO** w/ insulin for glycemic control in **T1 and T2DM**, weight loss
149
How is Pramlintide administered?
SC injection, 3x per day (in additional to insulin injections)
150
What is a SE of Pramlintide if used with insulin?
Hypoglycemia
151
What is the contraindication to Pramlintide?
Gastroparesis (slow stomach emptying)
