Endocrine

Indication: Hypothyroidism
Replacement Therapy:
Levothyroxine T4
- Synthroid
Liothyronine T3
Liotrix mixture of
-T4 and T3 in a 4:1
-ratio
No drug interactions
No adverse effects

Indication: Hyperthyroidism
Drug is concentrated in thyroid, where the β particles destroy the gland
Adverse: Hypothyroidism

Indication: Hyperthyroidism
Inhibits thyroid peroxidase, an enzyme responsible for the synthesis of thyroid hormones
Surgery
Adverse Effect: Hypothyroidism

Class: Androgen
Indications:
delayed puberty in males
breast cancer
therapy after testicular cancer
Controversial indications:
enhancement of athletic performance
female hypo-gonadism
male contraception
catabolic and wasting states (cancer, AIDS)
blood dyscrasias
Adverse:
Hair growth, acne, baldness, virilization, gynecomastia
Dyslipidemia
Prostate hypertrophy, cancer
Jaundice
Osteoporosis
Behavioral effects: “Roid rage”

Class: Anti-androgen
5 α-reductase: enzyme testosterone to
dihydroxytestosterone
Mediator of the actions of the hormone
Testosterone can be aromatized to estrogen, DHT cannot
Competitive inhibitor of 5 α-reductase:
- Benign prostatic hypertrophy (Proscar),
-Alopecia (Propecia)

Indications:
Pre-menopausal women
-Birth control
-Adolescents when puberty is absent
Post-menopausal women
-Prevention of osteoporosis related fractures
-Vasomotor symptoms
-Controversial in women over 60: CVD, breast cancer, stroke, DVT

MOA: Inhibits the hypothalamus and pituitary from releasing LH and FSH which leads to ovulation
Monophasic: Fixed dose of hormones throughout month
Biphasic: Fixed dose of estrogen, progesterone dose increases during month
Triphasic: Varying amounts of hormones during the month
Progesterone is present to protect the endometrium from estrogen effects: endometrial cancer
Adverse:
Thromboembolic disorders and stroke
Possible increase of breast cancer
Gallbladder disease
Migraine
Endometriosis
Oral Contraceptives and Antibiotics:
Rifampin (for TB) induces enzymes in liver that metabolizes the hormones
Other antibiotics change intestinal flora and lead to enhanced excretion

Indication: Osteoporosis
MOA: increases calcium and phosphate levels by increasing bone resorption

Indication: Osteoporosis
MOA: Inhibits osteoclast activity and bone resorption

Indication: Osteoporosis
MOA: Facilitates absorption of calcium and phosphate from the small intestine

Indication: Osteoporosis
Facilitates absorption of calcium and phosphate from the small intestine
Some doubt about efficacy

Indication: Osteoporosis
Selective Estrogen Receptor Modulator (SERM)
Partial agonist: stimulates estrogen receptors in bone, but inhibits in other tissues
Effects on bone similar to estrogen:
-Decrease resorption of bone
-Decrease bone turnover
-Increase bone mineral density
Adverse:
Increased risk of deep vein thrombosis (DVT)
Contraindications:
Pre-menopausal
Pregnancy
Concurrent estrogen therapy
History of breast cancer

Indications:
Osteoporosis
- Decrease the incidence of fractures
Paget’s Disease
-Reduce bone turnover rate
-Slow disease progression
MOA:
Inhibition of farnesyl diphosphate synthase
Reduction of geranylgeranyl diphosphate
Decrease of GTPase prenylation
-Osteoclast inactivation
-Osteoclast apoptosis
-Inhibition of osteoclast formation
Adverse:
Osteonecrosis of the Jaw
-1st symptom - absent or delayed hard and soft tissue healing after extractions
-May remain asymptomatic - exposed bone in oral cavity becomes secondarily infected, trauma to soft tissues from the exposed bone
-Risk factors - dental extractions, infectious disease, ill-fitting dentures, bone manipulation, poor oral health, concomitant therapy with steroids, chemo, immunotherapy, 6% of patients on oral therapy
Types:
Alendronate (Fosamax)
Zoledronate (Zometa)
Ibandronate (Boniva) once a month
Risedronate (Actonel)
Pamidronate (Aredia)
Etidronate (Didronel)
Zoledronic Acid (Reclast) once a year 15 min infusion
Tiludronate (Skelid)

MOA: Insulin binds to tyrosine kinase growth factor receptor
Kinase cascade causes translocation of glucose transporter
Glucose transporter fuses with the membrane
Increased glucose uptake
Effects:
Carbohydrates
-Increase glucose transport
-Increase glycogen synthesis
-Increase glycolysis
-Inhibits gluconeogenesis
Proteins
-Increase protein synthesis
-Increase amino acid transport
Fats
-Increase lipoprotein lipase activity
-Increase fat storage
-Inhibits lipolysis
-Increase hepatic lipoprotein synthesis
-Inhibits fatty acid oxidation
Adverse:
Hypoglycemia (sweating, weakness, tremor, confusion, blurred vision, altered behavior)
Weight Gain

MOA: Identical to regular human insulin, except for transposed lysine and proline in B chain
Hexamers and dimers bind 300 times weaker
Use: Injected 15 minutes before eating
Peak action in minutes rather than 2 hours (advantage over regular)
Duration of action is less than one hour instead of several hours as with regular
Reduces after meal hyperglycemic episodes and hypoglycemia later

Use:
Human insulin that binds to albumin (serum protein) via a fatty acid linkage
Slow absorption and longer duration of action (up to 24 hours)
Indicated for basal therapy in type 1 with a once or twice daily dosing and as add on therapy in type 2
No drug interactions with other protein bound drugs because it is tightly bound

pH=4
Use:
Causes more pain at injection site
Acidic solution is neutralized in body
Insulin slowly precipitates into crystals
Slowly absorbed over 24 hours
Given once daily at bedtime

Synthetic analog of amylin
Use:
Used only in combination with insulin in type I and type II diabetes
Decreases glucose levels in the 3 hours after meals
Provides a more “tight” control of glucose levels
Given by injection before meals
Patients have to be motivated
-Test glucose before and after every meal and at bedtime
-Participate in diabetes education
-Understand how to adjust dose of both insulin and Symlin

Class: Incretin Mimetic
Synthetic analog of GLP-1
Effects: Slows gastric emptying- drug interactions
Used only in Type 2 Diabetes
1st phase insulin response

Class: Sulfonylurea
Mechanism: Stimulate insulin release by blocking ATP dependent K+ current in pancreatic β cells
Adverse Effects: Hypoglycemia, Nausea and vomiting, weight gain
Interactions:
Increase Effect
-Azole antifungals
-Salicylates, ASA
-Sulfonamides
-NSAIDS
-Tricyclic Antidepressants
Decrease Effect
-Corticosteroids

Class: Biguanide
Pharmacological Effects:
Decrease hepatic gluconeogenesis
Improve tissue sensitivity to insulin
Decrease peripheral glucose uptake
Decrease intestinal absorption of glucose

Class: Thiazolidinedione
Mechanism: Post-receptor insulin mimetic activity affecting insulin receptor kinase activity and insulin receptor phosphorylation
Pharmacological Effects: Increase insulin sensitivity of tissues
Metabolized by p450s, interact with ketoconazole
Black box warning:
Increase a person's risk of CHF
83,000 major heart problems since 1999
Might be taken off market
Increase the body's tendency to accumulate fluids due to inadequate pumping from the heart

Class: Thiazolidinedione
Mechanism: Post-receptor insulin mimetic activity affecting insulin receptor kinase activity and insulin receptor phosphorylation
Pharmacological Effects: Increase insulin sensitivity of tissues
Metabolized by p450s, interact with ketoconazole
Black box warning:
Increase a person's risk of CHF
83,000 major heart problems since 1999
Might be taken off market
Increase the body's tendency to accumulate fluids due to inadequate pumping from the heart

Class: α glucosidase inhibitor
MOA: Competitive and reversible inhibitor of α glucosidase, hydrolase, pancreatic α amylase
Delay in the breakdown of carbohydrates to glucose

Class: Dipeptidyl peptidase 4 (DPP-4) Inhibitor
MOA: Slows the inactivation of incretin (stimulator of insulin secretion, glucose dependent synthesis of insulin, inactivated by DPP-4hormones) by inhibiting DPP-4

Indications:
-Look for Whipples Triad
1.blood sugar <65
2.symptoms of Catecholamine release
3.improvement of symptoms with glucose administration
-Hypoglycemia (<30mg/dL )is immediately life-threatening – “hypoglycemic encephalopathy”
Use:
Need Emerg Kit: 1 mg Glucagon , Can give IM, works rapidly(within 4 min) to raise blood sugar
Watch closely those people who have had frequent lows over the past several weeks