HP axis Flashcards

1
Q

Somatropin, Somatrem

A
Somatropin = recombinant GH 
Somatrem = GH analog

Pharmacokinetics
• Active blood levels = persist for ~ 36 h
• Given subcutaneously 3-7 times a week

SE's
Children
• Generally well tolerated
• Hypothyroidism
• Intracranial hypertension (rare)
• Scoliosis (during rapid growth)
• Otitis media (increased risk for Turner Syndrome patients) 
• Pancreatitis, gynecomastia & nevus growth
• Diabetic syndrome (chronic use)

Adults
• Peripheral edema, myalgias & arthralgias (hands & wrists especially)
• Carpal tunnel syndrome
• Proliferative retinopathy (rare)

Contraindications
• Cytochrome P450 inducer
• Patients with a known malignancy

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2
Q

Sermorelin

A

• GHRH analog
• FDA approved for treatment of GH deficiency
• Generally well tolerated and less expensive than
somatropin (BUT less effective)
• Will not work in patients whose GH deficiency results from defects in anterior pituitary

Adverse Effects
• Same as recombinant GH

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3
Q

Mecasermin

A
  • IGF-1 analog. Complex of recombinant human IGF-1 and recombinant human IGF-binding protein-3. Small number of children with growth failure have IGF-1 deficiency
  • Causes: mutations in gene that encodes for GH receptor & development of neutralizing antibodies to GH

SE
• Hypoglycemia (eat 20 min before or after admin.) • Intracranial hypertension (rare)
• Asymptomatic elevation of liver enzymes (rare)

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4
Q

Pegvisomant

A

• GH rec antagonist. Prevents dimerization of GH recs -> no JAK signaling -> no GH signaling

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5
Q

Octreotide

A

• SST analog. Inhibits release of GH, glucagon, insulin, and gastrin

Clinical Applications
• Reduces symptoms caused by hormone-secreting tumors: acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, nesidioblastosis, watery diarrhea, hypokalemia, achlorhydria syndrome & diabetic diarrhea.
• Localizing neuroendocrine tumors
• Acute control of bleeding from esophageal varices

PK
• 45 x more potent than somatostatin
• 2 x more potent in reducing insulin secretion
• t 1⁄2 = ~ 80 min (30 x somatostatin)
• Octreotide acetate long-acting suspension can be given at 4 week intervals

SE
• Nausea, vomiting, abdominal cramps, flatulence, steatorrhea (with bulky bowel movements)
• Constipation
• Biliary sludge & gallstones (20-30% patients after 6 month use)
• Sinus bradycardia (25%) & conduction disturbances (10%)
• Vitamin B12 deficiency (may occur with long-term use)
• Pain at injection site = common (esp. with long-acting)

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6
Q

Bromocriptine, Cabergoline

A

Pharmacokinetics
• Oral or as vaginal inserts
• Bromocriptine t1/2 = ~7 h
• Cabergoline t1/2 = ~65 h

Clinical Applications
• Hyperprolactinemia. Standard treatment. Dopamine agonists shrink pituitary prolactin-secreting tumors, lower circulating prolactin levels, and restore ovulation in ~70% women with microadenomas & ~30% with macroadenomas
• Acromegaly. Alone or in addition to surgery, radiation or octreotide admin.

SE
• Nausea (bromocriptine>cabergoline), headache, light-headedness, orthostatic hypotension, fatigue
• Psychiatric manifestations occasionally occur
• High doses = cold-induced peripheral digital vasospasm
• Chronic high-dosage therapy = pulmonary infiltrates

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7
Q

Gonadotropin

A

Menotropins or human menopausal gonadotropins (hMG):
- Purified extract of FSH and LH

Purified FSH :

  • Follitropin a and follitropin B (rFSH): recombinant FSH
  • Urofollitropin (uFSH): purified human FSH extract

hCG
• Extracted and purified from urine (given IM)
• Choriogonadotropin a (rhCG): recombinant form (given SC)

Pharmacokinetics
• SC or IM injection (usually daily)

Women
• Ovarian hyperstimulation syndrome (ovarian enlargement, ascites, hydrothorax, and hypovolemia. Hemoperitoneum, fever & arterial thromboembolism can occur)
• Multiple pregnancies (15-20%)
• Headache, depression, edema, precocious puberty

Men
• Gynecomastia

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8
Q

GnRH and analogs

A

• Gonadorelin = gonadotropin-releasing hormone
• Goserelin, leuprolide, nafarelin = gonadotropin- releasing hormone analogs

• GnRH binds to GPCRs on gonadotroph cell membranes
• Pulsatile GnRH secretion is required to stimulate release of LH and FSH
• Sustained nonpulsatile admin. of GnRH inhibits FSH and LH release (men & women) leading to hypogonadism

Chemical Structure
• Gonadorelin = acetate salt of synthetic human GnRH
• Analogs = D-amino acids at position 6 and (apart from nafarelin) have ethylamide substituted for glycine at position 10
• All analogs are more potent & longer-lasting than GnRH / gonadorelin

PK
• Gonadorelin = IV or SC
• Analogs = SC, IM, nasal spray (nafarelin) or as SC implant
• Gonadorelin t1/2 = 4 min 
Analog t1/2’s = ~3 h

Administration
Continuous administration gives biphasic response:
• First 7 days = agonist response ‘flare’,
• Chronic effects (> 1 week) = inhibitory action (due to receptor down-regulation & changes in signaling pathways)

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9
Q

GnRH and analogs clinical applications

A

Stimulation
• Female infertility: Use is uncommon (inconvenient & costly)
• Male infertility: In men with hypothalamic hypogonadotropic hypogonadism (pulsatile gonadorelin)
• Diagnosis of LH responsiveness: Whether delayed puberty is due to constitutional delay or hypogonadotropic hypogonadism

Suppression
Agents are more commonly used for suppression of gonadotropin release
• Controlled ovarian hyperstimulation (leuprolide, nafarelin): Critical to suppress endogenous LH surge that could prematurely trigger ovulation
• Endometriosis (leuprolide, goserelin, nafarelin): Pain often decreased by abolishing exposure to cyclical changes in estrogen & progesterone concentrations during menstrual cycle. Treatment limited to 6 months
• Uterine Leiomyomata (fibroids) (leuprolide, goserelin, nafarelin): Can reduce fibroid size and combined with supplemental iron can improve anemia
• Prostate Cancer (leuprolide, goserelin): Combined therapy with continuous GnRH agonist and an androgen receptor antagonist is effective as castration in reducing serum testosterone
• Central Precocious Puberty (leuprolide, nafarelin): Must confirm diagnosis before treatment begins
• Advanced Breast & Ovarian Cancer
• Treatment of Amenorrhea & Infertility in women with Polycystic Ovary Disease
• Thinning of Endometrial lining: Preparation for endometrial ablation procedure in women with dysfunctional uterine bleeding

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10
Q

Gonadorelin SE

A
  • Headache, light-headedness, nausea, flushing
  • Swelling at SC injection site
  • Generalized hypersensitivity dermatitis (long-term admin.)
  • Rare acute hypersensitivity reactions
  • Sudden pituitary apoplexy & blindness (reported in patients with a gonadotropin-secreting pituitary tumor)
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11
Q

GnRH analogs - SEs in continuous treatment

A

Women
• Menopausal symptoms (hot flushes, sweats, headaches)
• Depression, diminished libido, generalized pain, vaginal dryness & breast atrophy can occur
• Ovarian cysts (generally resolve)
• Reduced bone density & osteoporosis (long treatment)

Contraindications
• Pregnant and breast-feeding women

Men
• Hot flushes, sweats, edema, gynecomastia, decreased libido, decreased hematocrit, reduced bone density, asthenia, & injection site reactions

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12
Q

Certrorelix, Ganirelix

A

• Competitive antagonists of GnRH recs

Clinical Applications
• Suppression of Gonadotropin Production: Prevent LH surge during controlled ovarian hyperstimulation

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13
Q

Corticotropin, Syntropin

A

• ACTH analogs
• Limited utility as a therapeutic agents (less predictable and convenient than corticosteroid therapy)

• Act via MC2R (GPCR -> increased cAMP) to stimulate adrenal cortex to secrete glucocorticoids, mineralocorticoids & androgen precursor
• ACTH normally released from pituitary in pulses with highest concentration at ~ 6am and lowest in evening. Secretion also stimulated by stress
• Cortisol suppresses its release (-ve feedback)

Clinical Applications
• Diagnostic tool for differentiating between primary adrenal insufficiency (Addison’s disease) and secondary adrenal insufficiency (inadequate ACTH secretion)
• Infantile spasm (West Syndrome) treatment

Adverse Effects
• Similar to glucocorticoids

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14
Q

Oxytocin

A
  • Acts on GPCRs -> stimulates release of prostaglandins & leukotrienes that augment uterine contraction
  • Small doses increase force & frequency of contractions
  • Higher doses evoke sustained contractions. Weak antidiuretic & pressor activity (vasopressin R activation)
  • Contraction of myoepithelial cells surrounding mammary alveoli -> milk ejection

Pharmacokinetics
• IV used for initiation & augmentation of labor
• IM used for control of postpartum bleeding
• t1/2 = 5 min

Clinical applications
• Labor Induction: When early vaginal delivery is required (Rh problems, maternal diabetes, preeclampsia, ruptured membranes)
• Augment Normal Labor: When labor is protracted or displays arrest disorder
• Control of uterine hemorrhage

SE
• Severe toxicity is rare
• Excessive stimulation of uterine contractions: Fetal distress, placental abruption, uterine rupture
• Inadvertent activation of vasopressin receptors: Excessive fluid retention, water intoxication -> hyponatremia, heart failure, seizures, death
• Bolus injections can lead to hypotension: Administer IV as dilute solution at a controlled rate

CI
• Fetal distress
• Prematurity
• Abnormal fetal presentation
• Cephalopelvic disproportion
• Uterine rupture predisposition
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15
Q

Atosiban

A

• Oxytocin antagonist. Used for treatment of preterm labor (NOT in US)

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16
Q

Vasopressin, Desmopressin

A

Desmopressin
• Long-acting synthetic analog of vasopressin
• Minimal V1 activity (as opposed to vasopressin) -> little vasopressor activity
• Antidiuretic-to-vasopressor ratio 4000 x vasopressin

Pharmacodynamics
• 2 GPCRs activated
• V1R = vascular smooth muscle -> vasoconstriction
• V2R = renal tubule cells -> increased water permeability & water reabsorption

Pharmacokinetics
• Vasopressin: IV, IM (t1/2 = ~15 min)
• Desmopressin: IV, SC, intranasally or orally (t1/2 = 1.5-2.5 h)

Clinical applications
• Drugs of choice for Diabetes Insipidus
• Vasopressin: Esophageal variceal bleeding & colonic diverticular bleeding
• Desmopressin: Coagulopathy treatment in Hemophilia A and von Willebrand’s disease

SE
• Headache, nausea, abdominal cramps, allergic reactions
• Overdosage = hyponatremia & seizures

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17
Q

Conivaptan

A

• Vasopressin antagonist. Approved for use in patients with hyponatremia (due to elevated vasopressin)
• Conivaptan has high affinity for V1 & V2 R’s

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18
Q

Cortisol (Hydrocortisone) metabolic effects

A

Metabolic Effects
• Stimulates and is required for gluconeogenesis & glycogen synthesis (which maintains hepatic glycogen availability) in fasting state
-> increase serum glucose levels (thus leading to stimulation of insulin release) & inhibiting uptake by muscle cells
• Stimulates lipolysis (leading to fat deposition and redistribution & increased release of fatty acids & glycerol)
• Stimulates protein catabolism & release of amino acids

Net Result: Maintenance of an adequate glucose supply to brain (most apparent in fasting state)

Catabolic Effects
• In addition to protein catabolism, cortisol also has effects in lymphoid and connective tissue, muscle, peripheral fat and skin (wasting occurs at high concentrations)
• Catabolic effects on bone = osteoporosis
• In children = growth retardation

Both are major limitations in long-term treatment with glucocorticoids.

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19
Q

Cortisol (Hydrocortisone) other effects

A

Immunosuppressive Effects
• Effects on leukocytes
• Increased neutrophils (increased influx into blood & decreased migration from blood vessels)
• Decreased lymphocytes (T and B cells), monocytes, eosinophils and basophils (movement from vascular bed to lymphoid tissue)
• Vasoconstriction due possibly to suppression of mast cell degranulation
• Decreased histamine release and capillary permeability

Anti-inflammatory Effects
• Inhibition of phospholipase A2 (through induction & activation of annexin I) which blocks arachidonic acid release (major precursor of prostaglandins).
• Cyclooxygenase-2 synthesis is reduced (through inhibition of NF-kB).
• Induction of MAPK phosphatase I (inhibits MAPK activated proinflammatory signaling pathways).

Other Effects
• CNS: behavioural changes (insomnia, euphoria leading to depression)
• Increased intracranial pressure: large doses
• Suppression of release of ACTH, growth hormone, thyroid-stimulating hormone & luteinizing hormone: chronic use
• Peptic Ulcers: Stimulation of gastric acid. Suppression of immune response to H.pylori?
• Increase platelets & RBCs
• Renal function: is impaired with cortisol deficiency
• Development of fetal lungs

PK
• Relatively short duration of action
• Diffuses poorly across skin (unless inflamed) 
• Diffuses well across mucous membranes
• Some salt-retaining effects
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20
Q

Synthetic glucocorticoids

A
  • Prednisone, Methylprednisolone, Dexamethasone, Beclomethasone, Triamcinolone
  • Rapidly and completely absorbed orally
  • Selected compounds can also be given IV, IM, topically, intra-articularly & by aerosol
  • Long t1/2’s
  • Reduced salt-retaining effects
  • Prednisone = prodrug (rapidly converted to active prednisolone)
  • Beclomethasone = short t1/2 & penetrates airway mucosa (low systemic toxicity)
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21
Q

Fludrocortisone

A

• Synthetic mineralocorticoid. Most commonly prescribed salt-retaining hormone

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22
Q

Clinical applications of synthetic corticosteroids

A

Adrenocortical Insufficiency
a. Chronic (Addison’s disease)
• Characterized by weakness, fatigue, weight loss, hypotension, hyperpigmentation, inability to maintain blood glucose levels during fasting

Treatment
• Daily hydrocortisone (increase dose during stress) + mineralocorticoid (fludrocortisone)
• DO NOT administer long-acting glucocorticoids or ones lacking salt-retaining effects

Adrenocortical Insufficiency
b. Acute
• Associated with life-threatening shock, infection or trauma

Treatment
• Start treatment immediately
• Large amounts of parenteral hydrocortisone + correction of fluid & electrolyte abnormalities
• Can administer salt-retaining hormone once hydrocortisone levels are reduced (~ 5 days)

Adrenocortical hypo- and hyperfunction
a. Congenital Adrenal Hyperplasia
• Caused by defects in cortisol synthesis (either in CRH production by hypothalamus or in corticotropin production by pituitary)
• Decreased steroid levels lead to an increase in ACTH production and hyperplasia of adrenal gland
-> increased amounts of cortisol precursors that are diverted to the androgen pathway

Treatment
• Glucocorticoid admin. leads to suppression of ACTH
• Treat initially as an acute adrenal crisis
• Once stabilized: oral hydrocortisone or prednisone + fludrocortisone
• Fetus can be protected in high-risk pregnancies by dexamethasone admin. to mother

b. Cushings Syndrome
• Usually result of bilateral adrenal hyperplasia secondary to an ACTH-secreting pituitary adenoma
• Manifestations associated with chronic presence of excessive glucocorticoids

Treatment
• Surgical removal of tumor, irradiation of pituitary tumor, or resection of one or both adrenals
• Patients must receive high doses of cortisol before and after surgery
• Dose has to be slowly decreased to prevent withdrawal

Adrenocortical hypo- and hyperfunction
c. Aldosteronism
• Primary aldosteronism usually results from excessive production by adrenal adenoma (can be from malignant tumor)

Symptoms: result from renal loss of K+ (hypokalemia, alkalosis & elevation of serum Na+)

Diagnosis and Treatment
Spironolactone

Diagnostic Purposes
Dexamethasone Suppression Test
• Cushing’s syndrome: dexamethasone suppresses cortisol release in individuals with pituitary- dependent Cushing’s syndrome (not released from adrenal tumors)
• Depressive psychiatric states

Stimulation of Lung Maturation in Fetus
• Fetal lung maturation is regulated by cortisol secretion
• If premature delivery is expected, treatment of the mother with large doses of glucocorticoids reduces incidence of respiratory distress syndrome
• IM steroids are used (usually dexamethasone)

Non-Adrenal Disorders
• Numerous immunological inflammatory conditions: asthma, collagen vascular disorders (Rheumatoid arthritis), ocular diseases (uveitis, optic neuritis, exopthalmos),
• Allergic reactions (contact dermatitis, urticaria etc) • Hodgkin’s lymphoma (prednisone)
• Cerebal Edema (dexamethasone)
• Chemotherapy-induced vomiting

  • Hematologic disorders (anemia, leukemia etc)
  • Organ transplants (prevention of rejection)
  • Renal disorders (nephrotic syndrome)
  • Hypercalcemia
  • Mountain Sickness
  • Inflammatory bowel disease etc.
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23
Q

Corticosteroid SEs, CIs

A

• Peptic ulcers
• Clinical findings of certain disorders (particularly bacterial & mycotic infections) may be masked by steroid use
• Myopathy (part. with long-acting steroids)
• Nausea, dizziness, weight loss
• CNS (euphoria, psychosis, depression)
• Increased intraocular pressure (glaucoma)
• Posterior subcapsular cataracts
• Sodium & fluid retention, loss of potassium
• Growth retardation (children)
• Adrenal suppression

Use with caution in patients with:
• Peptic ulcers
• Heart disease or hypertension with heart failure 
• TB, varicella zoster infections
• Psychoses
• Diabetes
• Osteoporosis
• Glaucoma
24
Q

Spironolactone

A

• Acts by competing with aldosterone for its receptor (decreasing its effect peripherally)

Clinical Applications:
• Aldosteronism (diagnosis & treatment)
• Hirsutism in women (acts as androgen antag.)
• Diuretic

SE
• Hyperkalemia, cardiac arrhythmia, menstrual abnormalities, gynecomastia, sedation, headache, GI disturbances, skin rashes

25
Q

Glucocorticoid antagonists

A

Mifepristone
• Antagonist at glucocorticoid & progesterone receptors
Clinical Application:
• Inoperable patients with ectopic ACTH syndrome or adrenal carcinoma

Aminoglutethimide
Blocks conversion of cholesterol to pregnenolone -> reduces synthesis of all hormonally active steroids
Clinical Application:
• Adrenal cancer (+ hydrocortisone or dexamethasone)

Ketoconazole
Potent & non-selective inhibitor of adrenal & gonadal steroid synthesis
Clinical Applications:
• Cushings syndrome
• Prostate cancer

Metyrapone
Relatively selective inhibitor of steroid 11- hydroxylation (interferes with cortisol & corticosterone synthesis)
Clinical Applications:
• Tests of adrenal function
• Treatment of pregnant women with Cushing’s

SEs
• Salt & water retention 
• Hirsutism
• Transient dizziness
• GI disturbances
26
Q

Raloxifene

A

• Raloxifene: Antagonist at breast and but agonist at bone. No estrogenic effect on endometrium.
• No increased risk of endometrial cancer
• Uses:
– Prophylaxis against breast cancers (in high risk patients)
– Prevention of osteoporosis.

27
Q

Fulvestrant

A
  • ER antagonist in all tissues. Used in the treatment of breast cancer in tamoxifen-resistant patients.
  • A.E: Hot flushes, injection site reactions & headache
28
Q

Aromatase inhibitors

A

• Inhibits conversion of androgens to estrogen
- Letrozole - reversible non-steroidal inhibitor
- Anastrozole - reversible non-steroidal inhibitor
- Exemestane – steroidal irreversible aromatase inhibitor
• Used in treatment of breast cancer as 2nd line drugs after tamoxifen.
• Oral administration
• A.E: hot flushes, decreased bone mineral density.

29
Q

Clomiphene

A

• Acts as estrogen antagonist in hypothalamus and anterior pituitary
• Prevents feedback inhibition of GnRH release by hypothalamus
• Continued release of GnRH from hypothalamus
LH and FSH from the pituitary
• Ovulation

•  Used in treatment of infertility.
•  Side effects:
–  Ovarian hypermenstruation syndrome 
–  Ovarian enlargement 
–  Multiple pregnancy
–  Visual disturbances
30
Q

Mifeprostone

A

• Competitive inhibitor of progesterone &
glucocorticoid receptors.
• Controversial morning after drug used as an
abortifacient.
• It is given concomitantly with PG-E or PG-F to
increase myometrial contraction.
• Adverse effects: Excessive bleeding, gastrointestinal effects as nausea, vomiting, anorexia and abdominal pain.

31
Q

Danazol

A

• An inhibitor of P450 in gonadal steroid synthesis.
• Partial agonist of progestin, androgen and glucocorticoid receptors.
• Used in endometriosis and fibrocystic disease of breast.
• AE: hepatitis–abnormal liver function tests and drug interaction due to P450 inhibition.
It is a modified testosterone shows some signs of masculinising effects –acne, hirsutism, menstrual disturbances.

32
Q

Synthetic androgens

A

• Oxandrolone, Stanozolol, Fluoxymesterone, Oxymetholone, Nandrolone

Clinical uses:
• Substitution therapy in hypogonadism
• Increases bone density (for osteoporosis), could be used in increasing muscle mass (+ve nitrogen balance)
• Some cases of aplastic anemia.
• Administration: Transdermal, buccal, subcutaneous implant

•  Adverse effects:
–  Overmasculinization
–  In women could lead to hirsutism, suppression of menses, acne, and clitoral enlargement.
–  Hepatic adenomas
–  Cholestatic jaundice (elevated serum
transaminations)
–  Prostatic hypertrophy
–  Premature closure of epiphysis
•  Ironically, excessive use results in feminization (gynecomastia, testicular shrinkage, infertility) as a result of feedback inhibition & conversion of exogenous testosterone into estrogen.
33
Q

Androgen receptor antagonists

A
  • Flutamide, Bicalutamide, Nilutamide

• Primarily used in conjunction with GnRH (to ↓ initial tumor flareups).

34
Q

5-a reductase inhibitors

A
- Finasteride (PROPECIA), Dutasteride (Newer analog)
•  Oral administration
•  Inhibit conversion of testosterone to
dihydrotestosterone.
•  Use: BPH 
•  AE: gynecomastia and impotence
35
Q

Antiandrogen steroid synthesis inhibitor

A
  • Ketoconazole – oral administration
    Use: advanced prostate cancer that are resistant to 1st line drugs
    AE: May have drug interactions with other steroids due to P450↓
36
Q

GnRH analogs

A
  • Leuprolide
  • Gonadorelin
    • Continuous dose (not pulsatile dose) will produce reversible medical castration.
37
Q

Other drugs with antiandrogen action

A
  • Spironolactone
  • Cimetidine
  • Cyproterone acetate
  • Abarelix & Degarelix are GnRH antagonists
38
Q

Use of anti androgens

A
  1. Leuprolide and Flutamide used in prostatic cancer.
  2. Abarelix & Degarelix: are GnRH antagonists are used in advanced prostate cancer.
  3. Spironolactone and cyproterone: used in treatment of hirsutism.
    Cyproterone is a common component in hormonal therapy of male-to-female transsexual people.
  4. Finasteride: used in the treatment of BPH and male patern baldness
  5. Ketoconazole: Treatment of Cushing’s disease and metastatic prostatic cancer.
39
Q

Other antithyroid drugs 2

A

A few drugs may provoke autoimmune or destructive inflammatory thyroiditis, inducing hypothyroidism.
1. Amiodarone: has structural similarity with thyroxine.
(a) Iodine associated hyperthyroidism may occur – can be treated with thiamides.
(b) Autoimmune mediated inflammatory version treated with steroids.
(c) Hypothyroidism due to blockade of T4 to T3.
2. IFN-a & Interleukin G2
3. Lithium -> inhibits release of hormones (hypothyroidism) and thyroid enlargement.
4. Goitrogens: 
 

• Cabbage (contain thiocyanate)

• Cassava –contains carbohydrates + thiocyanate

Drugs that inhibits conversion of T4 to T3
1. Corticosteroids 
2. Propranolol 
3. Amiodarone

40
Q

Teriparatide

A
  • Recombinant PTH
  • Useful in treatment of osteoporosis
  • Pulsatile doses stimulate bone formation – an intermittent S.C. injection.
  • Whereas in excess causes resorption
  • AE: may cause hypercalcemia & hypercalciuria
41
Q

Denosumab

A
  • RANK Ligand (RANKL) inhibitor
  • It is a monoclonal antibody. It binds with RANKL and prevents it from stimulating osteoclast differentiation and function.
  • Inhibit bone resorption
  • Used in osteoporosis
  • AE: increased risk of infections
42
Q

Vitamin D

A
  • Calcitriol - treatment of secondary hyperparathyroidism in patients with chronic renal disease and liver disease.
  • Calcipotriol - treatment of psoriasis (topical application).
  • Vitamin D supplements are used in osteoporosis, chronic renal failure, nutritional rickets due to inadequate dietary intake, chronic liver disease.

ADR: chronic over dose leads to hypercalcemia and hyperphosphatemia

43
Q

Sevelamer

A

• Phosphate-binding drug used to prevent hyperphosphatemia in patients with chronic renal failure. Binds to dietary phosphate and prevents its absorption.

44
Q

Ca2+

A

• Oral: Ca2+ carbonate, Ca2+ citrate, and Ca2+ lactate
• I.V. Ca2+ gluconate for the treatment of
hypocalcimic tetany
• Used to counteract overdose of Magnesium sulfate used in eclampsia.
• AE: I.M. inj may cause necrosis and abscess formation. I.V. can result in thrombophlebitis.

45
Q

Calcitonin

A
  • A peptide hormone
  • Approved for the treatment of osteoporosis and has been shown to increase bone mass and reduce spine fractures.
  • Salmon calcitonin has a longer half life and greater potency.
  • Available as injection and nasal spray.
46
Q

Bisphosphonates

A

Etidronate (i.v), Alendronate, Pamidronate (i.v), Ibandronate, Risedronate, Tiludronate & Zoledronic acid (i.v)

• MOA: Inhibit osteoclastic activity via ↓ farnesyl pyrophosphate synthesis by disrupting mevalonate pathway ↓ osteoclast H+ ATPase.
1) Reduce resorption and
2) Helps formation of hydroxyapatite.
Oral bioavailabality less than 10%

  • Useful in treatment of osteoporosis, malignancy associated hypercalcemia, Paget’s disease of bone.
  • Paget’s disease of bone - ↑ turnover with extreme bone resorption and excessive bone formation.
  • H/O aching bone or joint pain or fractures.
  • It is suspected to be due to latent viral infection and linked to hyperparathyroidism.

ADR: 
1. Erosive esophagitis due to direct irritation to esophageal lining. Prevented by upright position after taking medication and Increasing fluid intake

  1. Decreased bone cell activity (adynamic bone
    disease) .
  2. Osteonecrosis of jaw & fractures
47
Q

Cinacalcet

A

Activates the calcium sensing receptors in parathyroid cells. Leading to suppression of PTH synthesis and release.

  • Used in secondary hyperparathyroidism in chronic renal disease and hyperparathyroidism in patients with parathyroid carcinoma.
  • Adverse effects: Nausea, hypocalcemia
48
Q

Fluoride

A

– Chronic exposure can lead to new bone synthesis which is denser but brittle.

49
Q

Gallium nitrate

A

– Inhibits bone resorption, useful in cancer-related
hypercalcemia
– Nephrotoxic

50
Q

Plicamycin (Mithracin)

A

– Cytotoxic anticancer drug
– Useful in cancer-related hypercalcemia
– ADR: Thrombocytopenia, Hepatic and renal toxicity

51
Q

Strontium renelate

A

– Promotes apoptosis of osteoclast useful in treatment of osteoporosis.

52
Q

Drugs causing osteoporosis/osteomalacia

A
Drugs causing osteoporosis 
– Corticosteroids  
– Heparin 

– Lithium 

– Anastrazole 
– Alcohol    

Drugs causing osteomalacia
– Phenytoin

– Etidronate (More than 12 months use)

53
Q

Drugs preventing calcium excretion

A

• Thiazide diuretics decreases the excretion of calcium by increasing reabsorption.
• Useful in prevention of renal stone formation

• Treatment of hypertension in osteoporosis patient.

54
Q

Treatment of hypercalcemia

A
  • Furosemide and saline infusion
  • Bisphosphonates
  • Calcitonin
  • Parathyroidectomy, if patient is symptomatic.
55
Q

Treatment of osteoporosis

A
  • Stop smoking, alcohol abuse and corticosteroid
  • HRT –in symptomatic perimenopausal period
  • Calcium & Vitamin D supplementation
  • Bisphosphonates
  • SERMs
  • Teriparatide