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Pharm Exam III > Insulin an other anti diabetic agents > Flashcards

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
Q

Meglitinides MOA

A

bind to receptors on potassium channels on beta cells –> increase insulin release

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26
Q

Meglitinides pharmacokinetics

A
  • Administered orally, preprandially (1-10 min)
  • Rapid action, half life: 1 hour
  • Liver metabolism-CYP3A4
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27
Q

Meglitinides adverse effects

A

Hypoglycemia (slight)

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28
Q

Meglitinides contraindications/precautions

A
  • Not to be used in combination w/sulfonylureas
  • Caution in liver impairment
  • Hypoglycemia (better than 2nd gen. sulfonylureas)
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29
Q

Metformin (Glucophage)

A

-Does NOT release insulin

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30
Q

Metformin MOA

A
  • Increases glucose uptake (increases insulin action in muscle and fat)
  • Decreases glucose absorption from the GI
  • Decreases glucagon
  • Decreases gluconeogenesis
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31
Q

Metformin therapeutic effects

A
  • 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)

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32
Q

Metformin pharmacokinetics

A
  • Oral administration

- Extended release available for once/day dosing

33
Q

Metformin adverse effects

A
  • Lactic acidosis** (rare but may be lethal), dose dependent

- Diarrhea**, anorexia, nausea vomiting (30%-get better over time)

34
Q

Metformin contraindications/precautions

A

-Lactic acidosis conditions** (renal dz, hepatic dz, alcoholism, disease predisposing to tissue hypoxia such as CHF, COPD, etc.)

35
Q

Thiazolidinediones (Pioglitazone, Rosiglitazone)

A

-“Insulin sensitizers”–> specifically target insulin resistance

36
Q

Thiazolidinediones MOA

A
  • 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
Q

Thiazolidinediones therapeutic effects

A
  • 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
Q

Thiazolidinediones pharmacokinetics

A
  • Administered orally, once or twice a day
  • The plasma half life=103-158 hours
  • Metabolized by the liver
39
Q

Thiazolidinediones adverse effects

A
  • Weight gain** (might be edema)
  • Back pain, fatigue, HA
  • Hypoglycemia (slight)
  • Edema-increased risk of heart failure in CHF patients (prone to it)***
40
Q

Rosiglitazone

A
  • Meta-analysis found almost 2x increased incidence of MI and angina
  • Black label warning**
  • Newer studies do not show this effect
41
Q

Thiazolidinediones contraindications/precautions

A
  • Hepatic disease (troglitazone–>hepatotoxicity) **

- CHF**

42
Q

Alpha-glucosidase inhibitors (acarbose, miglitol)

A
  • Reduce glucose absorption

- Non-FDA approved use in Type 1 DM

43
Q

Alpha-glucosidase inhibitors MOA

A

-Inhibit alpha-glucosidases in small intestine –> delayed CHO digestion and absorption

44
Q

Alpha-glucosidase inhibitors therapeutic effects

A
  • Effectively decrease postprandial serum glucose
  • Minimal effects on fasting glucose
  • Modest decrease in HbA1C levels
  • No significant effects on weight
45
Q

Alpha-glucosidase inhibitors pharmacokinetics

A
  • Administered orally
  • Metabolized by intestinal digestive enzymes and microorganisms
  • Half life ~2 hours
46
Q

Alpha-glucosidase inhibitors adverse effects

A
  • Frequent GI effects (flatulence**)

- Elevated hepatic enzymes, jaundice

47
Q

Alpha-glucosidase inhibitors contraindications/precautions

A
  • GI disease, GI obstruction, ileus, inflammatory bowel disease, hiatal hernia
  • Hepatic disease
  • Renal impairment
48
Q

Incretin mimetics (Exenatide, Liraglutide)

A
  • Synthetic version of exendin-4 (GLP-1 analog from Gila monster saliva)
  • Resistant to enzymatic degradation by DPP-IV**
49
Q

Incretin mimetics pharmacokinetics-Exenatide

A
  • 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
Q

Incretin mimetics pharmacokinetics-Liraglutide

A
  • A single daily S.C. injection**

- Half life is about 12-13 hours

51
Q

Incretin mimetics therapeutic effects

A
  • 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
Q

Incretin mimetics adverse effects

A

-Acute pancreatitis potentially**
-Hypersensitivity reactions
-Hypoglycemia in combo therapy
(GI disturbance, nausea, etc.)

53
Q

Incretin mimetics contraindications/precautions

A
  • 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
Q

Dipeptidyl-peptidase-IV (DPP-IV) inhibitors (Sitagliptin, Saxagliptin, Linagliptin, alogliptin) MOA

A
  • DPP-IV inhibitors

- Potentiates the effects of the incretin hormones** by inhibiting their breakdown by DPP-IV

55
Q

DPP-IV inhibitors therapeutic effects

A
  • Effectively lower postprandial AND fasting serum glucose
  • Causes modest decrease in HbA1C glycosylation
  • Has no significant effects on weight**
56
Q

DPP-IV inhibitors pharmacokinetics

A
  • Administered orally**, once/day
  • Eliminated by the kidney
  • Half life is about 12 hours
57
Q

DPP-IV inhibitors adverse effects

A
  • Hypersensitivity reactions
  • Sitagliptin may be associated w/acute pancreatitis as well as pancreatic CA***
  • Other adverse effects are similar to placebo
58
Q

DPP-IV inhibitors contraindications/precautions

A
  • Slow GI problems

- Renal impairment

59
Q

Amylin-like peptide (Pramlintide)

A
  • Only an adjunct to insulin therapy in type 1 and type 2 DM**
  • Synthetic analog of amylin, a hormone co-secreted w/insulin**
60
Q

Amylin-like peptide MOA

A
  • 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
Q

Amylin-like peptide therapeutic effects

A
  • Modest decrease in HbA1C glycosylation

- Weight loss**

62
Q

Amylin-like peptide pharmacokinetics

A
  • S.C. injection, 3x per day (w/meal bolus of insulin)
  • Eliminated by the kidney
  • Half life ~48 min., therapeutic effects ~3 hrs.
63
Q

Amylin-like peptide adverse effects

A
  • GI disturbance
  • Hypoglycemia in combo w/insulin
  • Injection site lipodystrophy
64
Q

Amylin-like peptide contraindications/precautions

A

Slow GI problems

65
Q

Bromocriptine (cycloset) MOA

A
  • 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
Q

Bromocriptine (cycloset) indications/therapeutic effects

A
  • 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
Q

Bromocriptine (cycloset) pharmacokinetics

A
  • Oral, within 2 h of awakening
  • Cycloset different from other bromocriptines–>quick release
  • Eliminated by the biliary system
68
Q

Bromocriptine (cycloset) adverse effects

A
  • Mild and transient (nausea, weakness, constipation, dizziness)
  • Non-cycloset: psychotic disorders, hallucinations, and fibrotic complications
69
Q

Bromocriptine (cycloset) contraindications/precautions

A

-Pregnant and nursing women

70
Q

Colesevelam (WelChol)

A

-Bile acid binding resin

71
Q

Colesevelam (WelChol) MOA

72
Q

Colesevelam (WelChol) indications/therapeutic effects

A
  • Further decreases fasting plasma glucose and HbA1C in combo w/other anti diabetic agents
  • Beneficial effects for hyperlipidemia
73
Q

Colesevelam (WelChol) adverse effects

A
  • Relatively safe

- Most common toxic effects are constipation and bloating**

74
Q

SGLT2 inhibitors (Canagliflozin, dapagliflozin)

A

-Newest class of anti diabetic drug

75
Q

SGLT2 inhibitors MOA

A

-inhibits the sodium-glucose-co-transporter 2 (SGLT2) in the kidney

76
Q

SGLT2 inhibitors indications/therapeutic effects

A

Modest decreases in HbA1C

77
Q

SGLT2 inhibitors pharmacokinetics

78
Q

SGLT2 inhibitors adverse effects

A
  • 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
Q

SGLT2 inhibitors contraindications

A
  • Severe renal impairment or dialysis

- Prone to UTIs or other genitourinary infections

Pharm Exam III (11 decks)

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