Pancreatic Hormones & Diabetic Drugs Flashcards
(57 cards)
1
Q
Which diabetes has more of a genetic predisposition
A
Type II
2
Q
Which diabetes has insulin deficiency
A
Type 1
3
Q
Which diabetes has a loss of beta cells
A
Type 1
4
Q
Which diabetes is more prone to ketoacidosis
A
Type 1
5
Q
Which diabetes is prone to a non-ketototic hyperosmolar coma
A
Type II
6
Q
K+/ATP and Insulin:
Open state of K+/ATP channel
A
hyperpolarize the cell by causing outflow of K+ and inhibit insulin release
7
Q
K+/ATP and Insulin:
Closed state of K+/ATP channel
A
depolarize the cell and insulin released.
8
Q
Insulin Receptor signaling:
A
insulin binding to alpha subunit regulates beta subunit activity –>
autophosphorylation of beta subunit –>
increase tyrosine kinase activity –>
phosphorylation of other substrates –>
activation of phosphoinositide 3-kinase
9
Q
Effects of insulin on the liver
A
Stimulates:
- glycogen synthesis
- triglyceride synthesis
Inhibits:
- glycogenolysis
- ketogenesis
- gluconeogenesis
10
Q
Effects of insulin on skeletal muscle
A
Stimulates:
- glucose uptake
- protein synthesis
- glycogen synthesis
Inhibits:
- Protein degradation
- Glycogenolysis
11
Q
Effects of insulin on adipose tissue
A
Stimulates:
- Glucose uptake
- Triglyceride storage
Inhibits:
- lipolysis
12
Q
Overall, insulin stimulates ____and inhibits ____
A
Promotes anabolic processes and
Inhibits catabolic processes
13
Q
advantages to recombinant DNA insulin
A
- Less insulin resistance
- Less allergy
- Less lipodystrophy
14
Q
Rapid/ short-acting insulin:
onset and duration
A
Onset: 5-15 min
Duration: 3-5 h
15
Q
Rapid insulin
A
- Insulin lispro, aspart, glulisine given s.c
- Inhaled human insulin - Indicated only in adults,
- Contraindicated- children, asthma, bronchitis, smokers
16
Q
short-acting insulin
• duration
• what? method given?
• use?
A
- Duration: 5-8h
- Regular insulin given s.c and i.v.
- Use in diabetic ketoacidosis and other emergency situations
17
Q
intermediate-acting insulin: • onset • duration • what? •
A
- onset: 2-5h
- duration: 4-12h
- Lente insulin, NPH insulin (Neutral protamine Hagedorn or isophane) mixture of insulin with protamine (basic substance obtained from fish sperm)
18
Q
Ultra-long acting insulin
• onset
• duration
• what?
A
- onset: slow
- duration: 20-24h
- Ultra lente, Insulin glargine, Insulin detemir
- Peakless, given once daily
19
Q
Hypoglycemia
• S/Sx
• Tx
A
- Sympathetic signs (tachycardia, sweating, palpitations, tremors) parasympathetic signs (nausea, hunger)
- Treatment : Glucose or glucagon treatment
20
Q
Allergy and resistance to insulin
A
- Local cutaneous reactions or systemic
* Human insulin are less antigenic than insulin from animal sources
21
Q
lipodystrophy
A
- Atrophy of fatty tissue at the site of injection
* Never seen since the development of highly purified insulin
22
Q
Treatment of Type II DM includes
A
• Diet • Exercise • Wt reduction • Step wise approach to drug treatment • Patient education ➢ Oral drugs for reduction of blood glucose • Used only in the Rx of Type II DM • Oral medication is initiated when 2-3 months of diet and exercise alone are unable to achieve or maintain their optimal plasma glucose levels
23
Q
Insulin secretogogues
A
- Sulfonyureas
* Meglitinides
24
Q
Oral Hypoglycemics
A
1. Insulin secretogogues • Sulfonyureas • Meglitinides 2. Biguanides 3. Thiazolidinediones 4. Alpha glucosidase inhibitors
25
First Generation Sulfonylurea
* Chlorpropramide
* Tolbutamide
* Tolazamide
26
2nd Generation Sulfonuylurea
* Glipizide
* Glyburide
* Glimepiride
27
Mechanism of action of Sulfonylurea
* Block ATP sensitive K+ channels in pancreatic beta cells --> Inhibits the efflux of K+ resulting in depolarization
* Opening of voltage gated Ca influx --> release of preformed insulin -->
* Increase the sensitivity to insulin by increasing number of insulin Receptors
28
Chloropropamide (Diabinese)
* Long acting for 32 hours
* Can cause prolonged hypoglycemia in elderly patients (contraindicated age)
* Slowly metabolised in liver, so Contraindicated in patients with hepatic disease
29
Tolbutamide (Orinase)
* Rapidly metabolised in liver
| * Short half life - safest SU in elderly
30
2nd generation SU drugs:
* glipizide (glucotrol)
* glyburide (micronase, glynase prestab)
* glimepiride
➢ Second generation drugs commonly prescribed agents because of fewer side effects and drug interactions
31
glipizide (glucotrol)
* 2nd generation SU drug.
* commonly prescribed agents because of fewer side effects and drug interactions
* Half-life - 2 to 4 hours
* Potency – High (2.5 to 40 mg/d)
* 90% is oxidized to inactive metabolites in liver
* Contraindicated in patients with hepatic disease - can cause hypoglycemia
32
Glyburide (Micronase, Glynase PresTab)
* 2nd generation SU drug.
* commonly prescribed agents because of fewer side effects and drug interactions
* Half-life - 6 hours
33
Glimepiride
* Approved for once-daily use
| * Potency – Highest (1 to 8 mg/d)
34
Clinical uses of Sulfonylureas
* Hypoglycemic agents for treatment of Type 2 DM
* Act by increasing endogenous insulin secretion \ not indicated for Type 1
* Most effective when ß cell function has not been severely compromised
* Increased insulin secretion favors lipogenesis
* Suitable drug in non obese diabetics
35
A/E in Sulfonylureas
* Severe hypoglycemia
* Most common with glyburide and chlorpropramide in elderly patient
* Weight gain
* Erythema, skin reactions
* Disulfiram like reaction with alcohol (chlorpropramide)
36
Contraindications for Sulfonylureas
* Pregnancy
* Surgery, Severe infections
* Severe stress or trauma
* Severe hepatic or renal failure
* Insulin therapy should be used in all of these
37
Meglitinides:
Repaglinide and Nateglinide
38
```
Meglitinides
• MOA
• DOA
• use
• a/e
```
➢ Insulin secretogogues….same as sulfonyl ureas
➢ Rapid onset and short duration of action
• Suitable for controlling postprandial hyperglycemia
➢ Approved for used alone or with biguanides
➢ Common adverse effect is Hypoglycemia
39
Biguanides
Metformin
40
Biguanides (Metformin) MOA
Antihyperglycemic:
• Increases peripheral insulin sensitivity
• Inhibits hepatic gluconeogenesis & glucose absorption from GI tract
• Reduction of plasma glucagon levels
• "Euglycemic", no hypoglycemia. *
• Does not alter insulin secretion *
41
Clinical use of Biguanides (Metformin)
* They are Insulin sparing agents
* Do not produce hypoglycemia
```
Secondary beneficial effects on lipids:
• Reduced triglycerides
• Reduced total cholesterol
• Reduced LDL
• Increased HDL
• Does not increase Weight
```
Use:
• Appropriate for obese Type 2 diabetics
• Other use: Polycystic ovarian syndrome - lowers the serum androgens and restores normal mentrual cycles and ovulation
42
used to control postprandial hyperglycemia
Meglitinides: Repaglinide and Nateglinide
43
Metformin A/E and contraindications
Adverse effects:
• *Gastrointestinal – anorexia, nausea, vomiting, diarrhea
• Lactic acidosis (increased risk in alcoholics & in Pts with hepatic impairment)
• Vitamin B 12 defeciency
Contraindications:
• Alchoholism, renal and hepatic disease- risk of lactic acidosis
44
Thiazolidinediones
Pioglitazone, Rosiglitazone
45
Thiazolidinediones MOA
➢ Mechanism: Stimulate the nuclear peroxisome proliferator-activating receptors (PPAR's) involved in transcription of insulin-responsive genes --> Increase the glucose uptake in muscle and adipose tissue & decreases hepatic gluconeogenesis
• They reduce plasma glucose and Triglycerides
46
Thiazolidinediones A/E
Adverse effects:
• Do not cause hypoglycemic, earlier drugs were hepatotoxic (troglitazone)
➢ Adverse effects
• Troglitazone*:
• Hepatotoxicity- Withdrawn from market
* Rosiglitazone, Pioglitazone*:
* No evidence of drug-induced hepatotoxicity
* Peripheral Edema, anemia
* * Are hepatic enzyme inducers
* TZDs- euglycemics
47
troglitazone
(Thiazolidinedione)
hepatotoxic--withdrawn from office
48
* Rosiglitazone, Pioglitazone*:
* No evidence of drug-induced hepatotoxicity
* Peripheral Edema, anemia
* * Are hepatic enzyme inducers
* TZDs- euglycemics
* No evidence of drug-induced hepatotoxicity
* Peripheral Edema, anemia
* Are hepatic enzyme inducers
* TZDs- euglycemics
49
Alpha glucosidase inhibitors
Acarbose, Miglitol
50
Alpha glucosidase inhibitors MOA
* Competitive and reversible inhibitors of a glucosidase in the small intestine
* Delay carbohydrate digestion and absorption
* Reduction in postprandial hyperglycemia
51
Alpha glucosidase inhibitors clinical use
* Individuals with significant postprandial hyperglycemia
| * Monotherapy or in combination with other oral hypoglycemics
52
Alpha glucosidase inhibitors A/E
* Flatulence, Nausea, Diarrhea
* Due to increased fermentation of unabsorbed carbohydrate by colonic bacteria
* Do not produce hypoglycemia, lactic acidosis, or significant weight gain
53
Pramlintide
* Administered s.c
* Synthetic analog of amylin, supress glucagon release
* Targets post prandial blood sugar levels
54
Exenatide
(1st incretin therapy to be approved for DM)
* Administered s.c
* Synthetic glucagon like polypeptide (GLP-1)
* Potentiates insulin secretion
55
Sitaglyptin
Inhibitor of dipeptidyl peptidase-4-enzyme that degrades GLP-1
56
Glucagon effects
➢ The primary counter-regulatory hormone
• Effects are generally opposite those of insulin:
• Stimulates glycogenolysis, ketogenesis, and gluconeogenesis
• Inhibits glycogen synthesis and lipogenesis
• Increased hepatic glucose output
• Increased blood glucose level
➢ Other effects
• Inotropic and chronotropic effects on heart
• Relaxation of intestinal muscle
57
Glucagon clinical uses
* Severe hypoglycemia
* Overshooting in insulin therapy
* Hypoglycemia from long-acting oral agents
* Relaxation of the GI tract for X-ray and magnetic resonance visualization
* Inotropic effect on heart- can be used to reverse effects of ß-blocker overdose
