Endocrine Pharmacology

Front 1

What is the treatment strategy for Type 1 Diabetes?

Back 1

Low-Carb diet

Insulin Replacement

Front 2

What is the treatment strategy for type 2 Diabetes?

Back 2

• Dietary Modification and Exercise for weight loss
• Oral agents
• Non-insulin injectables
• Insulin Replacement
  

Front 3

Treatment strategies for gestational diabetes

Back 3

• Dietary modifications
  
• exercise
• insulin replacement if lifestyle modification fails

Front 4

Aspart

Glulisine

Lispro

Back 4

Rapid acting Insulin

Given as Bolus

Action: Binds insulin receptor (tyrosine kinase)

Liver: ↑ glucose stored as glycogen

Muscle: ↑ glycogen, protein synthesis; ↑ K uptake

Fat: ↑ TG storage

Clinical Use: Type 1/2 DM and GDM (postprandial control)

Tox: Hypoglycemia, rare hypersensitivity Rxn

Hint 4

Class

Action

Clinical Use

Toxicities

Front 5

Regular Insulin

Back 5

Insulin Short Acting

Given as Bolus

Clinical Use: Type 1 DM, Type 2 DM, GDM, DKA (IV), Hyperkalemia (+ glucose), Stress hyperglycemia

Front 6

NPH

Back 6

Insulin, Intermediate Acting

Basal Insulin

Clinical Use: Type 1/2 DM

GDM

Front 7

Detemir

Glargine

Back 7

Insulin, Long Acting

Basal Insulin

Clinical Use: Type 1/2 DM

GMD ( basal glucose control)

Front 8

Metformin

Back 8

Oral Hypoglycemic - Biguanides

Action: Works in mitochondria to ↓ hepatic glucose output.

• ↓ gluconeogenesis
  
• ↑ glycolysis
• ↑ Peripheral glucose uptake
• ↑ insulin sensitivity

Front 9

Metformin - Clinical Use

Back 9

• Oral
  
• 1st line therapy in Type 2 DM
  
• Causes modest weight loss
  
• Can be used in patients without islet function
  

Front 10

Metformin- Toxicities

Back 10

• GI Upset
  
• Lactic Acidosis (contraindicated in renal insufficiency) - monitor Creatinine

Front 11

Chlorpropamide

Tolbutamide

Back 11

Oral Hypoglycemics- 1st Generation Sulfonyureas

Close K+ channel in ß-cell membrane → cell depolarizes → insulin release via ↑ Ca2+ influx

(stimulates endogenous insulin release inside pancreatic ß-cell.

Front 12

Glimepiridine

Glipizide

Glyburide

Back 12

Oral Hypoglycemics- 2nd Generation Sulfonyureas

Close K+ channel in ß-cell membrane → cell depolarizes → insulin release via ↑ Ca2+ influx

(stimulates endogenous insulin release inside pancreatic ß-cell.

Front 13

Sulfonylureas - Clinical Use

Back 13

Stimulate release of endogenous insulin in type 2 DM

Require some islet function - therefore useless in Type 1 DM

Front 14

Sulfonylureas- Toxicities

Back 14

Risk of hypoglycemia ↑ in renal failure

1st Generation: Disulfiram like effects

2nd Generation: Hypoglycemia

Front 15

Pioglitazone

Rosiglitazone

Back 15

Oral Hypoglycemic- Glitazones/ Thiazolidinediones

↑ insulin sensitivity in peripheral tissue

Binds to PPAR-y nuclear transcription factor

Takes days to weeks to see effects

Front 16

Clinical Use

Pioglitazone

Rosiglitazone

Back 16

Used as monotherapy in Type 2 DM

Or combined with other agents

Front 17

Toxicities

Pioglitazone

Rosiglitazone

Back 17

• Weight Gain (from fluid retention)
  
• Edema
• Hepatotoxicity
• Heart Failure
• ↑ Risk of Fractures

Front 18

Exenatide

Liraglutide

Back 18

Oral hypoglycemics -GLP-1 Analogs

↑ Insulin and ↓ glucagon release - Effect entire body

Front 19

Clinical Use

Exenatide

Liraglutide

Back 19

Type 2 DM

Front 20

Toxicities

Exenatide

Liraglutide

Back 20

Nausea

Vomiting

Pancreatitis

Weight Loss

Front 21

What is the function of GLP

Back 21

GLP stimulates insulin secretion in a glucose dependent manner

Front 22

Lingalipin

Saxagliptin

Sitagliptin

Back 22

Oral-hypoglycemics -DPP-4 inhibitors

↑ insulin and ↓glucagon release

• Incretin enhancers
• inhibit the breakdown of GLP and GIP

Front 23

Clinical Use

Lingalipin

Saxagliptin

Sitagliptin

Back 23

Type 2 DM

Front 24

Toxicities

Lingalipin

Saxagliptin

Sitagliptin

Back 24

• Mild urinary and respiratory infections
• Rash

Front 25

Pramlintide

Back 25

Oral hypoglycemic- Amylin Analog

↓ Gastric emptying ↓ glucagon

(Amylin is normally co-secreted with insulin)

Front 26

Clinical Use

Pramlintide

Back 26

Type 1 DM

Type 2 DM

Front 27

Toxicities

Pramlintide

Back 27

Hypoglycemia

Nausea

Diarrhea

Only given during meals

Front 28

Canagliflozin

Back 28

Oral Hypoglycemic -SGLT-2 Inhibitor

Blocks reabsorption of glucose in PCT

Front 29

Canagliflozin - Clinical Uses

Back 29

Type 2 DM

Front 30

Canagliflozin - Toxicities

Back 30

• Glucosuria
• UTIs
• Vaginal yeast infection

Front 31

Acarbose

Miglitol

Back 31

Oral Hypoglycemics- α-glucosidase inhibitors

Reversibly inhibit intestinal brush border α-glucosidases.

Delayed carbohydrate hydrolysis and glucose absorption → ↓ postprandial hyperglycemia

Front 32

Clinical Use

Acarbose

Miglitol

Back 32

• Used as monotherapy in Type 2 DM or as a combination drug
  

• Skip meal → Skip dose

Front 33

Toxicities

Acarbose

Miglitol

Back 33

GI disturbances (due to bacterial breakdown of carbs in the gut)

Front 34

Propylthiouracil

Back 34

• Dosing 3-4X a day
• Dual mechanism

Block thyroid peroxidase, inhibiting the oxydation of iodide and the organification (coupling) of Iodide → inhibition of thyroid hormone synthesis

Also blocks 5'-deiodinase → ↓ peripheral conversion of T4 to T3

Front 35

Methimazole

Back 35

• Dosing is 1-2x a day

Block thyroid peroxidase, inhibiting the oxydation of iodide and the organification (coupling) of Iodide → inhibition of thyroid hormone synthesis

Front 36

Clinical Use

Propylthiouracil

Methimazole

Back 36

Hyperthyroidism

PTU blocks Periferal conversion, used in Pregnancy

Front 37

Toxicity

Propylthiouracil

Methimazole

Back 37

• Skin Rash
  
• Agranulocytosis (rare) but need to monitor white blood cell counts
• aplastic anemia
• hepatotoxicity (propylthiouracil)
• Possible Teratogen (methimazole)

Front 38

Levoyhyroxine (T4) and Triiothyronine (T3)

• Mechanism
• Clinical Use
• Toxicity

Back 38

Control bodies metabolism

• Thyroid hormone replacement (T4 used more)

• Hypothyroidism, myxedema. Used off lable as weight loss supplement

• Tachycardia, heat intolerance, tremors, arrhythmias

Front 39

Nateglinide

Repaglinide

Back 39

Non-sulfonylurea insulin secretors

Rapid stimulation of pancreatic insulin secretion. Bind same receptor but adjacent to sulfonylurea site

More glucagon dependent

Skip meal → skip dose

Front 40

Conivaptan

Tolvaptan

Back 40

ADH- Antagonist

Use: SIADH - block action of ADH at V2-Receptor

Front 41

Desmopressin Acetate

Back 41

Use: Central diabetes insipidus (not nephrogenic)

Front 42

Gonadotropin Hormone (GH)

Back 42

Use: GH deficiency, Turner syndrome

Front 43

Oxytocin

Back 43

Use: Stimulates labor, uterine contractions, milk let down.

Controls uterine hemorrhage

From posterior pituitary

Front 44

Somatostatin (octreotide)

Back 44

Use:

• Acromegaly
• Carcinoid syndrome
• gastrinoma
• glucagonoma
• esophageal varices

Front 45

Demeclocycline

• Mechanism
• Clinical Use
• Toxicity

Back 45

• ADH antagonist (member of tetracyclin family)
  
• SIADH
• Nephrogenic DI (kidney's cause diabetes), photo-sensitivity, abnormalities of bone and teeth
  

Can bind cations so avoid taking with antiacids, dairy, and iron

Front 46

Glucocorticoids

Back 46

see page 340

Front 47

Cinacalcet

• Mechanism
• Clinical Use
• Toxicity

Back 47

• Sensitizes Ca2+ sensing receptor (CaSR) in parathyroid gland to circulating Ca2+ → ↓PTH

• Hypercalcemia due to primary or secondary hyperparathyroidism

• Hypocalcemia