PHARMACOLOGY 6.

03: Pancreatic hormones and Calcium Homeostasis

OVERVIEW Insulin
I. Pancreatic Hormones B. Nonhormonal
A. The Pancreas ● Bisphosphonates
● Cells and Secretions ● RANKL Inhibitor
● Insulin ● Fluoride
● Glucagon ● Calcimimetics
B. Diabetes Mellitus III. Clinical Correlation
● Medications for A. Hypercalcemia
Hyperglycemia B. Hypocalcemia
● Medications for DM2 C. Hyperphosphatemia
● Management of DM D. Hypophosphatemia
II. Bone & Mineral Homeostasis E. Primary Hyperparathyroidism
A. Hormonal F. Osteoporosis
● Parathyroid Hormone Figure 4. Effect of Insulin on Glucose Uptake
● Vitamin D
● Calcitonin
● Insulin binds to its receptor → GLUT4 is translocated to the plasma
● Estrogen
membrane → Glucose uptake from circulation
● Glucocorticoids
○ → ↓ Glucose concentration in the body (circulation) because it is
now stored in the cells
I.
PANCREATIC HORMONES
A. The Pancreas
● Has exocrine and endocrine functions

Figure 5. Action of insulin on other tissues

● Effect of insulin in:

● ↑ Protein synthesis, glycogen synthesis, glucose transport
Muscles
● ↓ Glucose levels (Used to perform mentioned fxns)
Adipose ● ↑ Triglyceride storage
Tissue ● Inhibit intracellular lipase
Figure 1. Anatomy of the Pancreas
● Inhibit glycogenolysis
Liver
● Inhibit conversion of fatty acids & amino acids → glucose
Cells and Secretions of the Pancreatic Islets

Glucagon
● Binds to Gs protein-coupled receptors on liver cells
○ ↑ cAMP that facilitates catabolism of stored glycogen and increase
gluconeogenesis and ketogenesis
➢ ↑ blood glucose levels
● Potent inotropic and chronotropic effect
● Relaxation of intestines
● Clinical use:
○ Emergency treatment of hypoglycemic reactions when IV glucose
treatment is not possible
○ Endoscopic retrograde cholangiopancreatography to relax the
sphincter of Oddi
● Recombinant glucagon: can be delivered via IV, IM or SC
● Contraindications: Pheochromocytoma and Insulinoma
Figure 2. Cells and Secretions of the Pancreatic Islets
(Last row, second column should be Ghrelin)
B. Diabetes Mellitus
● ↑ Blood glucose associated with absent or inadequate pancreatic
● Somatostatin: Also a pituitary, hypothalamic, & renal hormone.
secretions w/ or w/o impairment of insulin action
● Pancreatic polypeptide hormone & ghrelin: involved in hunger and appetite
● Types of diabetes mellitus:
DM Type 1 ● Selective beta cell destruction & severe insulin deficiency
Human pro-Insulin Structure
● Tissue resistance to the action of insulin combined with a
DM Type 2
relative deficiency in insulin secretion
● Abnormality of glucose levels noted for the first time
Gestational during pregnancy
Diabetes ● Returns to normal after giving birth but patient is
Mellitus (GDM) monitored because they are probably at risk for developing
DM later on

● Tests for diabetes mellitus:

○ Plasma or serum glucose: ≥ 126 mg/dL
○ Hemoglobin A1c: > 6.5%
➢ Plasma glucose control over 8-12 weeks
➢ Preferred test; can determine if patient is compliant with
medication
○ Oral Glucose Tolerance Test (OGTT)
➢ Intake of 75 mg of glucose, then blood glucose is measured at 0
and 120 minutes
○ Urine or blood ketone
Figure 3. Human pro-Insulin structure
➢ To check for diabetic ketoacidosis
➢ If high, requires hospitalization because it can become severe or
● Composed of an alpha chain, beta chain, C-peptide, and signal peptide
fatal
○ Activated to insulin when the C-peptide is cleaved off
○ Self-monitoring of blood glucose : Via capillary blood glucose
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 PCOL 6.03: Pancreatic hormones and Calcium Homeostasis

Medications for Hyperglycemia - Insulin Glucagon-like Peptide-1 (GLP-1) Receptor Agonists

● Amplify the glucose-induced insulin secretion
TG Note: Dr. Remonte said she will not dwell on this. She just wanted to show there are ● Stimulate insulin release and lowers glucose levels
many types of insulin. Insulin is used for T1DM and late T2DM MOA
● Suppress glucagon secretion, delay gastric emptying,
reduce apoptosis of human islets
● Human insulin: Regular; Neutral protamine Hagedorn (NPH)
● Exenatide ● Dulaglutide
● Animal insulin: Isophane; Neutral; Lente Example
● Liraglutide ● Semaglutide
● Short acting
○ Regular human insulin and 3 rapidly acting analogs ● Nausea, vomiting, diarrhea
○ Hypoglycemic effects within 30 mins after SC injection, peak at 2 ● Contraindicated in patients with past medical or family
Side effects
hours, lasts for 5-7 hours history of medullary thyroid cancer or multiple
● Rapidly acting insulin analogs (Humalog) endocrine neoplasia (MEN) syndrome type 2
● Long acting Dipeptidyl Peptidase 4 (DPP-4) Inhibitors
○ NPH - intermediate, onset 2-4 hours, peak, 6-7 hours, duration ● Inhibit the degradation of the incretins, glucagon-like
10-20 hours peptide-1 (GLP-1) and glucose-dependent
MOA
● Insulin glargine - soluble, peakless insulinotropic peptide (GIP)
● Insulin detemir - duration 17 hours ● Increase post-prandial insulin
● Insulin degludec - duration is more than 42 hours PD ● Excreted in the urine
● Mixture of insulin - 70/30 ● Sitagliptin
● Alogliptin
Example ● Saxagliptin
Medications for Diabetes Mellitus Type 2 ● Vidagliptin
● Linagliptin
Table 1. Medications for DM 2
● Predisposition to nasopharyngitis or URTI
Sulfonylureas Side effects
● Hypersensitivity reactions
● Bind to sulfonylurea receptor that is associated with
Sodium-Glucose Co-Transported 2 (SGLT2) Inhibitors
beta-cell inward rectifier ATP-sensitive potassium
● Inhibits glucose reabsorption in the kidneys inducing
MOA channel
glucosuria & lower blood glucose levels
● Opens the voltage-gated calcium channel → calcium MOA
● Weight loss, lower blood pressure, diuresis
influx and release of preformed insulin
● Reduces progression of albuminuria
PD ● Metabolized in the liver
● Dapagliflozin ● Canaliflozin
● Tolbutamide (1st generation) Example
● Empagliflozin ● Ertugliflozin
○ Associated with high mortality, hence it is not
● Increase genital fungal infection and UTI
Example available anymore
○ Urine becomes a culture ground
● 2nd generation
Side effects ● Glycosuria can cause intravascular volume contraction
○ Glyburide, Glipizide, Glimepiride, Gliclazide
and hypotension
● Hypoglycemia
Side effects ○ Patient should drink plenty of fluids
● Weight gain
Others ● Preferred in DM with chronic renal insufficiency
Meglitinide Analogs
Islet Amyloid Polypeptide (IAPP, Amylin) Analog
● Regulating potassium efflux through the potassium
MOA ● Negative feedback on insulin secretion
channel
MOA ● Reduces glucagon secretion and slow gastric emptying
● Rapid onset of action (within 1 hour)
PD ● Centrally decreases the appetite
● Metabolized in the liver
Example ● Pramlintide
● Repaglinide ● Nateglinide: D-phenylalanine
Example ● Hypoglycemia
● Mitiglinide derivative Side effects
● GI symptoms
Side effects ● Hypoglycemia
● Cannot be mixed with insulin – a separate syringe
● No sulfur - Can be used in patients with an allergy to Others
Others should be used
sulfur or sulfonylurea
Bile Acid Sequestrant
Biguanides
● Interruption of enterohepatic circulation and decrease in
MOA ● Reduce hepatic gluconeogenesis
farnesoid X receptor (FXR) activation
PD ● Metabolized in the liver MOA ● FXR has effects on cholesterol, glucose, and bile acid
Example ● Metformin metabolism
Side effects ● Interferes with Vit. B12-intrinsic factor complex ● Lowers HgbA1c
● No sulfur - Can be used in patients with an allergy to Example ● Colesevelam hydrochloride
Others
sulfur or sulfonylurea ● GI symptoms
Thiazolidinediones Side effects
● Exacerbation of hypertriglyceridemia
● Decrease insulin resistance Dopamine Agonist
● Ligands of peroxisome proliferator-activated receptor ● Not known
gamma (PPAR-γ) → sensitization of tissues to insulin, MOA
● Lowers HgbA1c
MOA plus ↓ hepatic gluconeogenesis & triglycerides and ↑ Example ● Bromocriptine
insulin receptor numbers
● Nausea, fatigue, dizziness
● ↑ glucose transporter expression, decrease free fatty Side effects
● Vomiting, headache
acid levels, decrease hepatic glucose output
*Receptor of TZD is PPAR-γ but was spelled as PPAR-f in the PPT.
PD ● Metabolized in the liver
● Pioglitazone: lowers TGA, increases HDL Management of Diabetes Mellitus
Example ● Rosiglitazone: increases total, HDL, and LDL cholesterol ● Diet
without any effect on TGA ○ Limit the carbohydrate intake to 40%
● Increased risk of angina pectoris or MI ● Education
Side effects ● Fluid retention ○ Lifestyle changes
● Heart failure ○ How to use insulin injection
Alpha-Glucosidase Inhibitors ● Glycemic targets
● Inhibit alpha-glucosidase enzymes and reduce ○ HbA1c less than 7%
post-meal glucose excursions by delaying the digestion ○ Pre-meal glucose level of 90-130 mg/dL
MOA
& absorption of starch & disaccharidases ○ Peak post-prandial glucose less than 180 mg/dL
● Lowers postprandial glucose levels by 30-50% ● Treatment
PD ● Not metabolized, but cleared by the kidney ○ Should be individualized and based on the patient’s condition,
Example ● Acarbose, Miglitol, Voglibose preference, and lifestyle
● Flatulence ○ Type 1: Insulin
Side effects ● Diarrhea ○ Type 2: Medical therapy with lifestyle
● Abdominal pain

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 PCOL 6.03: Pancreatic hormones and Calcium Homeostasis

Algorithm of DM 2 Treatment ● Teripateriparatide

○ A recombinant truncated form of PTH for parenteral
Drug products treatment of osteoporosis
● Natpara
○ approved for hypoparathyroidism
Side effects ● Dizziness, bone pain, heartburn, cramps
Vitamin D
● Skin: Vitamin D can be synthesized from
7-dehydrocholesterol
○ Under the influence of ultraviolet light
○ Absorbed from the diet in the natural form (vitamin D3,
cholecalciferol) or the plant form (vitamin D2,
Forms
ergocalciferol).
● Active metabolites are formed in the:
○ Liver: 25-hydroxyvitamin D or calcifediol
Figure 6. Algorithm of DM 2 Treatment ○ Kidney: 1,25-dihydroxyvitamin D or calcitriol (plus
Table 2. Treatment of Type 2 Diabetes Mellitus other metabolites)
Monotherapy Add Add ● Causes net increase in serum concentrations of calcium
Exenatide or insulin or and phosphate by:
Obese Metformin Sulfonylurea ○ ↑ intestinal absorption
glitazone MOA
○ ↑ bone resorption
Non- Sulfonylurea or Metformin or Exenatide or insulin or
○ ↓ renal excretion
obese metformin sulfonylurea glitazone
● Also increase urinary calcium
Low dose Switch to simple
Elderly ● Similar to calcium
secretagogue insulin regimen
● If high concentration → bone resorption, hypercalcemia,
Sulfonylurea or insulin or Effects
Asians Glitazone Metformin hyperphosphatemia
exenatide
● If low intermittent doses → bone formation
*For symptomatic patients, they may initially use secretagogue or insulin to rapidly decrease
glucose. ● Nutritional deficiency, intestinal osteodystrophy, chronic
**Exenatide not approved for use with glitazone kidney or liver disease, hypoparathyroidism, and nephrotic
syndrome
Clinical
II. CALCIUM HOMEOSTASIS ● Prevention of osteoporosis
uses
A. Bone and Mineral Homeostasis ● Treatment of psoriasis (topical form)
● Supplements such as calcium carbonate also has vitamin
D
● Less hypercalcemia, less calciuria
● Doxercalciferol and Paricalcitol
Drug products ○ Hypoparathyroidism in CKD
● Calcipotriene
○ Topical treatment of psoriasis
Side effects ● Hypercalcemia, hyperphosphatemia, and hypercalciuria
Calcitonin
Source ● Secreted by thyroid gland
Figure 7. Bone and mineral homeostasis ● Decreases serum calcium and phosphate by:
MOA ○ inhibiting bone resorption
● Bone - main organ abundant in calcium
○ inhibiting renal reabsorption
● Composed of two elements (hormonal and nonhormonal)
● Conditions in which an acute reduction of serum calcium
○ Calcium - not only for the skeleton but also important in the normal
Clinical uses is needed (eg, Paget’s disease, hypercalcemia)
function of many cells in the body
● Osteoporosis
Table #. Hormonal and nonhormonal regulators of bone homeostasis
● Salmon calcitonin – more often used than human
Hormonal Nonhormonal Drug products calcitonin
● Parathyroid hormone* ○ Administered through IV or nasal spray
● Biphosphonates
● Vitamin D* ● Nausea, stomach pain, arthralgia
● Fluoride Side effects
● Calcitonin* ● Allergic reaction
● Calcimimetics
● Estrogen & Glucocorticoid
Estrogen
MOA ● inhibition of PTH-stimulated bone resorption
*TG Note: Doc mentioned these are the three main hormonal regulators of bone
homeostasis. Estrogen & glucocorticoids only have secondary roles. ● Prevent or delay bone loss in post-menopausal women
Clinical ○ They give estrogen supplements to post-menopausal
uses women and calcium supplements to menopausal
Hormonal women[Doc Remonte]
Parathyroid Hormone ● Estrogen
Table 2. Parathyroid Hormone Drug products ● Selective estrogen receptor modulators (SERMs):
Parathyroid Hormone Raloxifene
● Acts on membrane G protein-coupled receptors to ● Breast tenderness, nausea, vomiting, bloating, stomach
increase cyclic adenosine monophosphate (cAMP) in cramps, headaches, wt gain, hyperpigmentation of skin,
bone and renal tubular cells. Side effects
hair loss, vaginal itching, abnormal uterine bleeding
● In the kidneys: ● Long term use not recommended
○ Inhibits calcium excretion Glucocorticoids
MOA ○ Promotes phosphate excretion
● Alter bone mineral homeostasis by:
○ Stimulates the production of active vitamin D
○ Antagonizing Vitamin D–stimulated intestinal calcium
metabolites
MOA transport
● In the bone:
○ Stimulating renal calcium excretion
○ Promotes bone turnover by increasing the activity of
○ Stimulating bone resorption (initially)
both osteoblasts and osteoclasts
● Reverse hypercalcemia associated with lymphomas and
● If high concentration → bone resorption, hypercalcemia, Clinical
granulomatous diseases
Effects hyperphosphatemia uses
● Vitamin D intoxication
● If low intermittent doses → bone formation
Drug products ● Prednisone, methylprednisolone, hydrocortisone
Clinical
uses
●
●
Osteoporosis
Hypoparathyroidism
Side effects ● Osteoporosis ⭐
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 PCOL 6.03: Pancreatic hormones and Calcium Homeostasis

Nonhormonal B. Hypocalcemia

⭐
Table 3. Nonhormonal regulators of bone mineral homeostasis Table 7. Hypocalcemia
Bisphosphonates Hypocalcemia
● Inhibit osteoclastic bone resorption by attaching to ● Tetany
hydroxyapatite binding sites on bony surfaces, especially ● Paresthesia
MOA
surfaces undergoing active resorption. Symptoms ● Laryngospasm
● Slows down bone loss ● Muscle cramps
● Management of hypercalcemia associated with some ● Seizure
malignancies (i.e. Paget’s disease). ● Hypoparathyroidism
Clinical uses
● Chronic bisphosphonate therapy to prevent and treat all ● Vit D deficiency
Causes
forms of osteoporosis ● Chronic kidney disease
● Etidronate (least potent) ● Malabsorption
● Alendronate 1. Calcium gluconate or calcium chloride IV; calcium
Drug
● Ubandronate carbonate, calcium lactate (oral)
products Management
● Pamidronate (available in IV) 2. Vitamin D
● Zoledronic Acid (Available in IV) ● Calcitriol
Side effects ● Gastric and esophageal irritation
RANKL ligand inhibitors C. Hyperphosphatemia
● Binds the cytokine RANKL (receptor activator of NFκB Table 8. Hyperphosphatemia

ligand), an essential factor initiating bone turnover Hyperphosphatemia

MOA ● Cramps
● RANKL inhibition blocks osteoclast maturation, function,
and survival, thus reducing bone resorption Symptoms ● Tetany
Clinical uses ● Osteoporosis ● Perioral numbness (signs of hypocalcemia)
Drug products ● Denosumab - subcutaneously every 6 months ● Renal failure
● Less gastrointestinal side effects ● Hypoparathyroidism
Causes
Side effects ● But more risk for infections ● Vit D intoxication
○ Due to the association of RANKL with immune system ● Tumor calcinosis
Fluoride ● If emergency, dialysis or glucose infusions
● Restrict dietary phosphate and give phosphate binding
● Accumulates in bones and teeth and stabilize the Management
gels
MOA hydroxyapatite crystals
● Sevelamer or lanthanum carbonate
● Protective MOA only
● Studied for use in osteoporosis but failed to demonstrate
D. Hypophosphatemia
Clinical uses reduction in fractures and increase in bone mineral
Table 9. Hypophosphatemia
○ Not recommended
Hypophosphatemia
Side effects ● Nausea, vomiting, GI blood loss
● Loss of appetite
Calcimimetics
Symptoms ● Body weakness
● Lowers PTH by activating the calcium-sensing receptor in
MOA ● Bone pains
the parathyroid gland
● Primary hyperparathyroidism
● Secondary hyperparathyroidism in chronic kidney disease
Clinical uses Causes ● Vitamin K deficiency
● Hypercalcemia in parathyroid carcinoma
● Idiopathic hypercalciuria
Drug
● Cinacalcet ● Should be avoided when using forms of therapy that can
products Management
Side effects ● Hypocalcemia and adynamic bone disease lead to it

E. Primary Hyperparathyroidism
III. CLINICAL CORRELATION Table 10. Primary hyperparathyroidism
A. Hypercalcemia Primary Hyperparathyroidism
Table 6. Hypercalcemia ● Hypercalcemia
Hypercalcemia ● Hypercalciuria
Symptoms
● CNS depression ● Osteoporosis
Symptoms
○ Coma ● Kidney disease
Causes ● Adenoma – most common cause
● Thiazide therapy
● Hyperparathyroidism ● Surgical removal of parathyroid
Management
Causes ● Cancer ● Cinacalcet
● Hypervitaminosis D
● Milk-alkali syndrome F. Osteoporosis

1. Saline hydration & diuresis w/ Furosemide ⭐ Table 11. Osteoporosis

Osteoporosis
2. Bisphosphonates ● Back pain
● Pamidronate & Zoledronate (for hypercalcemia Symptoms
● Loss of height
due to malignancy)
● Associated with loss of gonadal function in menopause
3. Calcitonin (Calcimar) Causes
● Effect of longer term steroid treatment
● Has a very small effect
● Parathyroid hormone and Vitamin D
4. Gallium nitrate (for hypercalcemia due to malignancy)
Management ● Bisphosphonates
● Inhibits bone resorption
● Raloxifene
5. Phosphate
Management ● Teriparatide
● Fastest way but dangerous.
● Romosozumab
● Possible rapid hypocalcemia, ectopic calcification,
● Calcitonin
hypotension, acute renal failure
● Denosumab
6. Glucocorticoids (for chronic hypercalcemia of sarcoidosis,
Vit D intoxication)

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 PCOL 6.03: Pancreatic hormones and Calcium Homeostasis

REVIEW QUESTIONS

PANCREATIC HORMONES REFERENCES

● Mary Antonette Y. Remonte, MD, FPCP, FPCCP. Notes from Pancreatic
_____1. Which of the following cells are matched INCORRECTLY with their secretion? Hormones
A. Delta cell - Ghrelin
B. Epsilon cell - Ghrelin
C. Alpha cell - Glucagon
D. Beta cell - Insulin

Diabetes Mellitus Type 2

_____2. Which of the following drugs contain no sulfur and can be used in patients allergic
to sulfur or sulfonylurea?
A. Glipizide
B. Tolbutamide
C. Repaglinide
D. Glyburide

_____3. Which of the following is NOT TRUE about Metformin?

A. It is metabolized in the liver
B. It reduces hepatic gluconeogenesis
C. It interferes with Vitamin B12 intrinsic factor complex
D. It cannot be used in patients with an allergy to sulfur or sulfonylurea
_____4. What are the glycemic targets for the management of diabetes mellitus?
A. HgbA1c less than 7%
B. Pre-meal glucose level of 90-130 mg/dL
C. Peak post-prandial glucose less than 180 mg/dL
D. AOTA

Bone and Mineral Homeostasis

_____5. The following hormones promote bone resorption and increase serum calcium
levels, EXCEPT:
A. Parathyroid hormone (PTH)
B. Vitamin D
C. Calcitonin
D. Glucocorticoids

_____6. Bisphophonates inhibit osteoclastic bone resorption by attaching to hydroxyapatite

binding sites on bony surfaces, especially surfaces undergoing active resorption. Less
gastrointestinal side effects can be experienced but can predispose one to more risk for
infections.
A. First statement is true. Second statement is false.
B. First statement is false. Second statement is true.
C. Both statements are true.
D. Both statements are false.

Clincal Correlation of Calcium Homeostasis

_____7. Which of the following symptoms can be seen in patients with hypercalcemia
A. Coma
B. Loss of appetite
C. Cramps
D. Seizure

_____8. A patient was rushed to the emergency department. According to the attending
doctor, she has hyperphosphatemia which needs to be corrected immediately. Which of
the following should be done?
A. “Si OA!”
B. Give Vitamin D
C. Restrict dietary phosphate
D. Give glucose infusions

ANSWERS
1: A 2: C 3: C 4: D 5: C 6: B 7: A 8: D
RATIONALE
1: Recall.
2: Recall.
3: Recall.
4: Recall.
5: Explanation 5
6: Explanation 6
7: Recall
8: Recall

Q&A Portion:
(Questions and some of doc’s answers were not audible or clear enough, so some parts
from the lecture were not included. Please be guided.)
● One complication of diabetes affects the renal system
○ One of its early manifestations would be albuminuria
○ If the Micral test is significant, the patient is started on SGLT2 on top of other
drugs (Can detect microalbuminuria, unlike the urine dipstick which shows (+)
protein at higher albumin / protein levels)

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 PCOL 6.03: Pancreatic hormones and Calcium Homeostasis

SUMMARY TABLES

Pancreas
EXAMPLES CLASS MOA SIDE EFFECTS
● Tolbutamide (1st gen) ● Bind to sulfonylurea receptor that is associated with ● Hypoglycemia
○ Associated w/ high beta-cell inward rectifier ATP-sensitive potassium channel ● Weight gain
mortality → not available ● Opens voltage-gated calcium channel → Results in
anymore Sulfonylureas calcium influx and release of preformed insulin
● 2nd generation ● Metabolized in the liver
○ Glyburide, Glipizide,
Glimepiride, Gliclazide
● Repaglinide ● Regulating potassium efflux through the K+ channel ● Hypoglycemia
● Mitiglinide ● Rapid onset of action (within 1 hour)
● Nateglinide - Meglitinide Analogs ● Metabolized in the liver
D-phenylalanine derivative ● Structure: No sulfur → Can be used in Pxs allergic to
sulfur or sulfonylurea
● Metformin ● Reduce hepatic gluconeogenesis ● Interferes with VB12 intrinsic factor
Biguanides
● Metabolized in the liver complex
● Pioglitazone: lowers TGA, ● ↓ insulin resistance ● Increased risk of angina pectoris or MI
increases HDL ● Ligands of peroxisome proliferator-activated receptor ● Fluid retention
● Rosiglitazone: increases gamma (PPAR-f) → sensitization of tissues to insulin, ● Heart failure
total, HDL, and LDL plus ↓ hepatic gluconeogenesis & triglycerides and ↑
Thiazolidinediones
cholesterol without any insulin receptor numbers
effect on TGA ● ↑ glucose transporter expression, ↓ free FA levels, ↓
hepatic glucose output
● Metabolized in the liver
● Acarbose ● Inhibit alpha-glucosidase enzymes and reduce post-meal ● Flatulence
● Miglitol glucose excursions by delaying digestion & absorption of ● Diarrhea
Alpha-Glucosidase
● Voglibose starch & disaccharidases ● Abdominal pain
Inhibitors
● Lowers postprandial glucose levels by 30-50%
● Not metabolized, but cleared by the kidney
● Exenatide ● Amplify glucose-induced insulin secretion ● Nausea, vomiting, diarrhea
● Liraglutide ● Stimulate insulin release → ↓ Glucose levels ● Cx: Patients with past medical or
Glucagon-Like Peptide-1
● Dulaglutide ● Suppress glucagon secretion, delay gastric emptying, family history of medullary thyroid
(Glp-1) Receptors Agonists
● Semaglutide reduce apoptosis of human islets cancer or multiple endocrine
neoplasia (MEN) syndrome type 2
● Sitagliptin ● Inhibit degradation of incretins, glucagon-like peptide-1 ● Predisposition to nasopharyngitis or
● Saxagliptin (GLP-1) and glucose-dependent insulinotropic peptide URTI
Dipeptidyl Peptidase 4
● Linagliptin (GIP) ● Hypersensitivity reactions
(Dpp-4) Inhibitors
● Alogliptin ● ↑ post-prandial insulin
● Vidagliptin ● Excreted in the urine
● Dapagliflozin ● Inhibits glucose reabsorption in the kidneys inducing ● Increase genital fungal infection and
Sodium-Glucose
● Empagliflozin glucosuria & lower blood glucose levels UTI
Co-Transported 2 (Sglt2)
● Canaliflozin ● Weight loss, lower blood pressure, diuresis ● Glycosuria can cause intravascular
Inhibitors
● Ertugliflozin ● Reduces progression of albuminuria volume contraction and hypotension
● Pramlintide ● Negative feedback on insulin secretion ● Hypoglycemia
Islet Amyloid Polypeptide ● Reduces glucagon secretion and slow gastric emptying ● GI symptoms
(Iapp, Amylin) Analog ● Centrally decreases appetite
Note: Can’t be mixed w/ insulin – use a separate syringe
● Colesevelam hydrochloride ● Interruption of enterohepatic circulation and decrease in ● GI symptoms
farnesoid X receptor (FXR) activation ● Exacerbation of hypertriglyceridemia
Bile Acid Sequestrant ● FXR has effects on cholesterol, glucose, and bile acid
metabolism
● Lowers HgbA1c
● Bromocriptine ● Not known ● Nausea, fatigue, dizziness
Dopamine Agonist
● Lowers HgbA1c ● Vomiting, headache

Calcium Homeostasis
Hormonal Regulators
Drug Products CLASS MOA and EFFECTS CLINICAL USES and SIDE EFFECTS
● Teripateriparatide ● Acts on membrane G protein-coupled receptors to ● Osteoporosis
○ a recombinant truncated increase cyclic adenosine monophosphate (cAMP) in ● Hypoparathyroidism
form of PTH for bone and renal tubular cells. ● Dizziness, bone pain, heartburn, cramps
parenteral treatment of ● In the kidneys:
osteoporosis ○ Inhibits calcium excretion; Promotes phosphate
● Natpara excretion
○ approved for ○ Stimulates the production of active vitamin D
Parathyroid
hypoparathyroidism metabolites
hormone
● In the bone:
○ Promotes bone turnover by increasing activity of
both osteoblasts and osteoclasts
EFFECTS
● High concentration → bone resorption,
hypercalcemia, hyperphosphatemia
● If low intermittent doses → bone formation

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 PCOL 6.03: Pancreatic hormones and Calcium Homeostasis

● Less hypercalcemia, less MOA EFFECTS - Similar to calcium ● Nutritional deficiency, intestinal osteodystrophy,
calciuria ● Causes net ↑ in Ca & ● If high concentration → chronic kidney or liver disease, hypoparathyroidism,
● Doxercalciferol and phosphate by: bone resorption, and nephrotic syndrome
Paricalcitol ○ ↑ Intestinal hypercalcemia, ● Prevention of osteoporosis
Vitamin D
○ hypoparathyroidism in absorption hyperphosphatemia ● Treatment of psoriasis (topical form)
CKD ○ ↑ Bone resorption ● If low intermittent doses ● Supplements such as ca carbonate also has vitamin D
● Calcipotriene ○ ↓ Renal excretion → bone formation ● Hypercalcemia, hyperphosphatemia, and
○ topical tx of psoriasis ● ↑ urinary calcium hypercalciuria
● Salmon calcitonin – more ● Decreases serum calcium and phosphate by: ● Used in conditions in which an acute reduction of
often used than human ○ inhibiting bone resorption serum calcium is needed (eg, Paget’s disease and
calcitonin ○ inhibiting renal reabsorption hypercalcemia)
○ Administered IV or by Calcitonin ● Osteoporosis
nasal spray ● Nausea, stomach pain, arthralgia
● Allergic reaction
● Estrogen ● Inhibition of PTH-stimulated bone resorption ● Prevent or delay bone loss in postmenopausal
● Selective estrogen receptor women( They give estrogen supplements to
modulators (SERMs): post-menopausal women and calcium supplements to
Raloxifene menopausal women)[Doc Remonte]
Estrogen ● Breast tenderness, nausea, vomiting, bloating,
stomach cramps, headaches, weight gain,
hyperpigmentation of the skin, hair loss, vaginal
itching, abnormal uterine bleeding
● Long-term use not recommended
● Prednisone ● Alter bone mineral homeostasis by: ● Reverse hypercalcemia associated with lymphomas
○ antagonizing Vitamin D–stimulated intestinal and granulomatous diseases

⭐
Glucocorticoids calcium transport ● Vitamin D intoxication
○ stimulating renal calcium excretion ● Osteoporosis
○ stimulating bone resorption (initially)
Non-Hormonal Regulators
Drug Products CLASS MOA CLINICAL USES and SIDE EFFECTS
● Etidronate (least potent) ● Inhibit osteoclastic bone resorption by attaching to ● Management of hypercalcemia associated with some
● Alendronate. Ubandronate. hydroxyapatite binding sites on bony surfaces, malignancies (i.e. Paget’s disease)
Bisphos-
●
●
Pamidronate (available in IV)
Zoledronic Acid (Available in
phonates ⭐ especially surfaces undergoing active resorption.
● Slows down bone loss
● Chronic bisphosphonate therapy to prevent & treat all
forms of osteoporosis
IV) ● Gastric and esophageal irritation
● Denosumab - ● Binds the cytokine RANKL (receptor activator of ● Osteoporosis
subcutaneously every 6 NFκB ligand), an essential factor initiating bone ● Less gastrointestinal side effects
RANKL ligand
months turnover. ● But more risk for infections
inhibitors
● RANKL inhibition blocks osteoclast maturation, ○ Due to association of RANKL with immune system
function, & survival, thus, reducing bone resorption
● Accumulates in bones and teeth and stabilizes the ● Studied for use in osteoporosis but failed to
hydroxyapatite crystals demonstrate reduction in fractures and increase in
- Fluoride
● Not recommended bone mineral
● Nausea, vomiting, GI blood loss
● Cinacalcet ● Lowers PTH by activating the calcium-sensing ● 2ndary hyperparathyroidism in chronic kidney disease
Calcimimetics receptor in the parathyroid gland ● Hypercalcemia in parathyroid carcinoma
● Hypocalcemia and adynamic bone disease

Clinical Correlations
Case Symptoms Causes Management
Hypercalcemia ● CNS depression ● Thiazide therapy ● Saline hydration & diuresis with ● Phosphate
○ Coma ● Hyperparathyroidism Furosemide ○ Fastest way but dangerous.
● Cancer ● Bisphosphonates ○ Possible rapid hypocalcemia,
● Hypervitaminosis D ○ Pamidronate & Zoledronate ectopic calcification,
● Milk-alkali syndrome (hypercalcemia due to malignancy) hypotension, acute renal failure
● Calcitonin (Calcimar) ● Glucocorticoids (for chronic
● Gallium nitrate (hypercalcemia due to hypercalcemia of sarcoidosis, Vit
malignancy)- Inhibits bone resorption D intoxication)
Hypocalcemia ● Tetany, Paresthesia ● Hypoparathyroidism ● Calcium gluconate or calcium chloride IV; calcium carbonate, ca lactate (oral)
● Laryngospasm ● Vit D deficiency ● Vitamin D
● Muscle cramps ● Chronic kidney disease ● Calcitriol
● Seizure ● Malabsorption
Hyperphosphatemia ● Signs of ● Renal failure ● If emergency, dialysis or glucose infusions
hypocalcemia: ● Hypoparathyroidism; Vit D ● Restrict dietary phosphate and give phosphate binding gels
Cramps, Tetany, intoxication ● Sevelamer or lanthanum carbonate
Perioral numbness ● Tumor calcinosis
Hypophosphatemia ● Loss of appetite ● Primary hyperparathyroidism ● Should be avoided when using forms of therapy that can lead to it
● Body weakness ● Vitamin K deficiency
● Bone pains ● Idiopathic hypercalciuria
Primary ● Hypercalcemia; ● Adenoma – most common ● Surgical removal of parathyroid
Hyperparathyroidism Hypercalciuria cause ● Cinacalcet
● Osteoporosis;
Kidney disease
Osteoporosis ● Back pain ● Associated w/ loss of gonadal ● Parathyroid hormone ● Raloxifene ● Romosozumab
● Loss of height function in menopause and Vitamin D ● Teriparatide ● Calcitonin
● Effect of longer-term steroid tx ● Bisphosphonates ● Denosumab

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