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Insulin an other anti diabetic agents Flashcards

1
Q

Treatment for hypoglycemia

A
  • Give 50-100 ml of 50% glucose solution IV

- 0.5-1 mg glucagon injection

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2
Q

Glucagon MOA

A
  • Regulates glucose, amino acids, and possibly free fatty acid homeostasis
  • Increases blood glucose levels by mobilizing hepatic glycogen when available
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3
Q

Glucagon therapeutic effects

A
  • Juveniles respond less favorably than adults w/stable diabetes
  • Not very effective in patients w/reduced glycogen stores
  • Potent inotropic and chronotropic effects on the heart (used in beta blocker overdose)
  • Produces profound relaxation of the intestine (used in radiology)
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4
Q

Glucagon pharmacokinetics

A
  • Administered parenterally (S.C., I.M., I.V)

- Onset of action is gradual

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5
Q

Diazoxide (Proglycem)

A

-Non-diuretic thiazide, vasodilator, and hyperglycemic

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6
Q

Diazoxide MOA

A

-Hyperglycemia by: directly inhibiting insulin secretion or decreasing peripheral glucose utilization, or stimulating hepatic glucose production

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7
Q

DIazoxide Therapeutic effects

A

-Used in patients w/insulinoma*

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8
Q

Diazoxide pharmacokinetics

A
  • oral administration

- Fairly long duration of action (half life=24-36 hrs)

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9
Q

Other anti diabetic patients (6)

A
  • Insulin secretagogues
  • Biguanides
  • Thiazolidinediones
  • Alpha-glucosidase inhibitors
  • Incretin-affecting agents
  • Centrally-affecting agents
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10
Q

Other anti diabetic agents uses

A
  • Type 2 diabetic mostly

- Mostly oral administration

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11
Q

Other anti diabetic agents MOA

A
  • Increase endogenous insulin release
  • Decrease glucose levels
  • Increases sensitivity to insulin
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12
Q

Sulfonylureas MOA

A
  • Stimulate insulin release from pancreatic beta cells

- Indirectly potentiate action of insulin on target tissues

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13
Q

Sulfonylureas Adverse effects

A
  • All of these can cause hypoglycemia*
  • Some GI side effects (2nd gen better)
  • Weight gain*
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14
Q

Hypoglycemia from sulfonylureas

A
  • More in long lasting agents
  • 2nd gen agents typically better
  • Can be caused by drug interactions
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15
Q

Sulfonylureas contraindications/precautions

A
  • Severe renal dz or hepatic dysfunction

- Caution in patients w/allergies to sulfa drugs*

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16
Q

Sulfonylureas first generation

A
  • Tolbutamide
  • Chlorpropamide
  • Tolazamide
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17
Q

Tolbutamide

A
  • Rapid absorption
  • Half life: 4-5 hrs, infrequent hypoglycemia-LEAST OVERALL***
  • Safest in elderly***
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18
Q

Chlorpropamide

A
  • Half life 32 hours
  • Disulfiram-like effect
  • Worst hypoglycemia
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19
Q

Second generation sulfonylureas

A
  • Glyburdie
  • Glipizide
  • Glimepiride
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20
Q

Glyburide

A
  • 24h effect

- Hypoglycemia-worst of the 2nd gen***

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21
Q

Glipizide

A
  • Half life; 2-4 hours

- Least hypoglycemia of ends

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22
Q

Glimepiride

A
  • Once a day dosing

- Has little hypoglycemic effect

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23
Q

Meglitinides (Repaglinide, Nateglinide)

A

-They are NOT sulfonamides-can be used in SA allergy

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24
Q

Meglitinides therapeutic effects

A
  • Decrease postprandial serum glucose** (euglycemia)
  • Rapid short action-mimics insulin better** (euglycemia)
  • Less hypoglycemia than sulfonylureas** (euglycemia)
  • Decrease HbA1C
  • Not much effect on weight
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25
Meglitinides MOA
bind to receptors on potassium channels on beta cells --> increase insulin release
26
Meglitinides pharmacokinetics
- Administered orally, preprandially (1-10 min) - Rapid action, half life: 1 hour - Liver metabolism-CYP3A4
27
Meglitinides adverse effects
Hypoglycemia (slight)
28
Meglitinides contraindications/precautions
- Not to be used in combination w/sulfonylureas - Caution in liver impairment - Hypoglycemia (better than 2nd gen. sulfonylureas)
29
Metformin (Glucophage)
-Does NOT release insulin
30
Metformin MOA
- Increases glucose uptake (increases insulin action in muscle and fat) - Decreases glucose absorption from the GI - Decreases glucagon - Decreases gluconeogenesis
31
Metformin therapeutic effects
- Overall effect: decreases glucose levels-->euglycemia** - Decreased plasma triglyceride levels (15-20%) - Does not increase body weight** (DOC+lifestyle changes) - Decreases macro vascular events**(DOC +lifestyle changes) - Safe for use in children >10 yo (Glucose is not lowered in normal subjects; decreases postprandial hyperglycemia)
32
Metformin pharmacokinetics
- Oral administration | - Extended release available for once/day dosing
33
Metformin adverse effects
- Lactic acidosis** (rare but may be lethal), dose dependent | - Diarrhea**, anorexia, nausea vomiting (30%-get better over time)
34
Metformin contraindications/precautions
-Lactic acidosis conditions** (renal dz, hepatic dz, alcoholism, disease predisposing to tissue hypoxia such as CHF, COPD, etc.)
35
Thiazolidinediones (Pioglitazone, Rosiglitazone)
-"Insulin sensitizers"--> specifically target insulin resistance
36
Thiazolidinediones MOA
- Ligands of the nuclear PPAR gamma receptor which can cause post-receptor insulin-mimetic action** - Increases glucose transporter synthesis in adipose - Onset and offset of action can take weeks to months - They do stimulate insulin secretion
37
Thiazolidinediones therapeutic effects
- Lowers insulin resistance** - Decrease triglycerides in long-term use - Slight increase in HDL - Potential for reducing the development of type 2 DM-->prophylactic use** - Improved glycemic control (decreases fasting plasma glucose, modest decrease of HbA1c glycosylation)
38
Thiazolidinediones pharmacokinetics
- Administered orally, once or twice a day - The plasma half life=103-158 hours - Metabolized by the liver
39
Thiazolidinediones adverse effects
- Weight gain** (might be edema) - Back pain, fatigue, HA - Hypoglycemia (slight) - Edema-increased risk of heart failure in CHF patients (prone to it)***
40
Rosiglitazone
- Meta-analysis found almost 2x increased incidence of MI and angina - Black label warning** - Newer studies do not show this effect
41
Thiazolidinediones contraindications/precautions
- Hepatic disease (troglitazone-->hepatotoxicity) ** | - CHF**
42
Alpha-glucosidase inhibitors (acarbose, miglitol)
- Reduce glucose absorption | - Non-FDA approved use in Type 1 DM
43
Alpha-glucosidase inhibitors MOA
-Inhibit alpha-glucosidases in small intestine --> delayed CHO digestion and absorption
44
Alpha-glucosidase inhibitors therapeutic effects
- Effectively decrease postprandial serum glucose - Minimal effects on fasting glucose - Modest decrease in HbA1C levels - No significant effects on weight
45
Alpha-glucosidase inhibitors pharmacokinetics
- Administered orally - Metabolized by intestinal digestive enzymes and microorganisms - Half life ~2 hours
46
Alpha-glucosidase inhibitors adverse effects
- Frequent GI effects (flatulence**) | - Elevated hepatic enzymes, jaundice
47
Alpha-glucosidase inhibitors contraindications/precautions
- GI disease, GI obstruction, ileus, inflammatory bowel disease, hiatal hernia - Hepatic disease - Renal impairment
48
Incretin mimetics (Exenatide, Liraglutide)
- Synthetic version of exendin-4 (GLP-1 analog from Gila monster saliva) - Resistant to enzymatic degradation by DPP-IV**
49
Incretin mimetics pharmacokinetics-Exenatide
- Morning and evening S.C. injections-60 min before 2 main meals** - Half life is about 2 hours - Eliminated by the kidney - New formulation-->one/week injection
50
Incretin mimetics pharmacokinetics-Liraglutide
- A single daily S.C. injection** | - Half life is about 12-13 hours
51
Incretin mimetics therapeutic effects
- Effectively lowers postprandial AND fasting serum glucose - Promotes better glycemic control - Modest decrease in HbA1C - Potential increased beta cell number and function** - Slows gastric emptying-patients eat less - Weight loss**
52
Incretin mimetics adverse effects
-Acute pancreatitis potentially** -Hypersensitivity reactions -Hypoglycemia in combo therapy (GI disturbance, nausea, etc.)
53
Incretin mimetics contraindications/precautions
- Slow GI problems, GI disease - Oral medications that cannot be exposed to stomach acid too long - Renal impairment - Thyroid cancer-->liraglutide-->black box warning**
54
Dipeptidyl-peptidase-IV (DPP-IV) inhibitors (Sitagliptin, Saxagliptin, Linagliptin, alogliptin) MOA
- DPP-IV inhibitors | - Potentiates the effects of the incretin hormones** by inhibiting their breakdown by DPP-IV
55
DPP-IV inhibitors therapeutic effects
- Effectively lower postprandial AND fasting serum glucose - Causes modest decrease in HbA1C glycosylation - Has no significant effects on weight**
56
DPP-IV inhibitors pharmacokinetics
- Administered orally**, once/day - Eliminated by the kidney - Half life is about 12 hours
57
DPP-IV inhibitors adverse effects
- Hypersensitivity reactions - Sitagliptin may be associated w/acute pancreatitis as well as pancreatic CA*** - Other adverse effects are similar to placebo
58
DPP-IV inhibitors contraindications/precautions
- Slow GI problems | - Renal impairment
59
Amylin-like peptide (Pramlintide)
- Only an adjunct to insulin therapy in type 1 and type 2 DM** - Synthetic analog of amylin, a hormone co-secreted w/insulin**
60
Amylin-like peptide MOA
- Works w/insulin to regulate postprandial glucose by: - Decreasing gastric emptying w/o altering the overall absorption of the nutrients - Suppression of postprandial glucagon secretion - Centrally mediated modulation of appetite--> decreases caloric intake
61
Amylin-like peptide therapeutic effects
- Modest decrease in HbA1C glycosylation | - Weight loss**
62
Amylin-like peptide pharmacokinetics
- S.C. injection, 3x per day (w/meal bolus of insulin) - Eliminated by the kidney - Half life ~48 min., therapeutic effects ~3 hrs.
63
Amylin-like peptide adverse effects
- GI disturbance - Hypoglycemia in combo w/insulin - Injection site lipodystrophy
64
Amylin-like peptide contraindications/precautions
Slow GI problems
65
Bromocriptine (cycloset) MOA
- Dopamine agonist - Augments low hypothalamic dopamine levels--> inhibits excessive sympathetic tone within the CNS-->decreases post meal plasma glucose levels due to enhanced suppression of hepatic glucose production**
66
Bromocriptine (cycloset) indications/therapeutic effects
- Improves glycemic control - Decreases fasting and postprandial free fatty acid and triglyceride levels** - Modest decrease in HbA1C - Weight neutral - Potentially reduces the cardiovascular end point problems in diabetics** (mechanism unknown)
67
Bromocriptine (cycloset) pharmacokinetics
- Oral, within 2 h of awakening - Cycloset different from other bromocriptines-->quick release - Eliminated by the biliary system
68
Bromocriptine (cycloset) adverse effects
- Mild and transient (nausea, weakness, constipation, dizziness) - Non-cycloset: psychotic disorders, hallucinations, and fibrotic complications
69
Bromocriptine (cycloset) contraindications/precautions
-Pregnant and nursing women
70
Colesevelam (WelChol)
-Bile acid binding resin
71
Colesevelam (WelChol) MOA
Unknown
72
Colesevelam (WelChol) indications/therapeutic effects
- Further decreases fasting plasma glucose and HbA1C in combo w/other anti diabetic agents - Beneficial effects for hyperlipidemia
73
Colesevelam (WelChol) adverse effects
- Relatively safe | - Most common toxic effects are constipation and bloating**
74
SGLT2 inhibitors (Canagliflozin, dapagliflozin)
-Newest class of anti diabetic drug
75
SGLT2 inhibitors MOA
-inhibits the sodium-glucose-co-transporter 2 (SGLT2) in the kidney
76
SGLT2 inhibitors indications/therapeutic effects
Modest decreases in HbA1C
77
SGLT2 inhibitors pharmacokinetics
oral
78
SGLT2 inhibitors adverse effects
- Common: female genital mycotic infections, UTIs, and increased urinary freq. - Osmotic diuresis (postural dizziness, orthostatic hypotension, syncope, and dehydration) - Renal problems (increased serum creatinine, decreased GFR, rare is renal impairment and acute renal failure) - Hyperkalemia - Increased LDL-C
79
SGLT2 inhibitors contraindications
- Severe renal impairment or dialysis | - Prone to UTIs or other genitourinary infections

Pharm Exam III (11 decks)

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