Drugs Flashcards
3 SERMS
- Tamoxifen, Raloxefene, Chlomiphene
PK, PD, Uses and AEs
For Tamoxifen
PK- Oral available
PD- Partial Agonist effects in endometrium and bone
Uses- Used to treat breast cancer in post-menopausal women and adjuvant with lumpectomy
AEs- Due to partial agonist effects in endometrium associated with higher incidence of endometrial cancer. Hot flushes, n/v in 25%
PK, PD, Uses and AEs
For Raloxefene
- PK- High first pass metabolism, large Vd and long half life once daily for prevention of post menopausal osteoporosis
- PD- Antagonist at the breast and endometrium, agonist at bone
- Uses- Prevention of post-menopausal osteoporosis delays or prevent bone regression does not increase endometrial cancer, prophylactic use for high risk breast cancer
Chlomiphene
PK, PD, Uses and AEs
- PK- Orally available, once daily for 5 days, dose must be repeated each month as it induces one ovulation
- PD- Antagonist in the hypothalamus and anterior pit gland, partial agonist in ovaries. Causes negative feedback inhibition by estrogen blackade, causing increase in GnRH, LH and FHS release, triggers ovulation. Stimulates ovulation in women with oligomenorrhea and ovulatory dysfunction
- Uses- Treat disorders of ovulation in women wanting to become pregnant not useful for ovarian or pituitary failure
- AEs- Mild menopausal type Rxn like hot flushes, occasional eye involvement, intesified and prolonged after images, HA, Constipation, allergic skin rxns, reversible hair loss, can cause multiple folicles to grow leading to increased incidence of multiple births 10%
- Ovarian enlargement due to developments of multiple follicles
- Hormone change SEs- N/V, depression, fatigue, breast soreness
3 third gen SERMs
- Bazedoxifene
- Lasofoxifene
- Ospemifene
What are SERMs
What is their basis for tissue selectivity? 3 things
Estrogenic agents often mixed agonists and antagonists dependent on tissue examined
- estrogen receptor subtype expression
- expression of co-activators
- expression of co-repressors
SERMs and Tissue
Know where the agonists and antagonists are
All of the ones we went over
What do SERMs take advantage of to give them there selectivity?
- Tissue specific receptor expression
- Transcription factor recruitment to estrogen receptor is specific to tissues
Bazedoxifene
Used in combination with?
Approved for the tx of?
Agonist where? What does this reduce?
No increase in what type of cancer?
No increase in ____ and reduction in?
Bazedoxifene with conjugated estrogens approved for the treatment of moderate to severe vasomotor symptoms and prevention of osteoporosis
- Reduces fractures
- no increase in breast cancer
- no increase in endometrial thickness and reduction in endometrial cancer
Ospemifene
Used to treat what?
PK?
Agonist effects? But is not associated with strong?
AEs? 4 Kind of serious ones
- Moderate to severe dysparenuria
- Oral
- Effects vaginal epilthelium but not associated with strong endometrial stimulation
- lots of vasomotor symptoms, sweating, stroke, blood clots
Lasofaxifene
Approved in europe for?
Increases, and reduces?
Increases endometrial _____ but no increase in?
AEs? 1
- Post-menopausal osteoporosis
- Increases bone density, reduces fracturs
- Reduces risk of breast cancer
- Increases endometrial thickness bit no increase in endometrial cancer
- AEs- PRominent vasomotor symptoms
Aromatase Inhibitors 3 but really only have to remember 1
- Anastrozole
- Letrozole
- Exemestane
PD of Aromatase inhibitors?
Anastrozole, Letrozole-
Exemestane -
Uses
AEs
- Competitive inhibitors of aromatase
- Irreversible inhibitors via covalent binding
- Estrogen is synthesized from androgens by aromatase is its blocking that
- Treat estrogen dependent tumors, especially metastic breast cancer with surgical and radiation therapy
- AEs- Increased risk of osteporosis associated fractures
Endometriosis
Growth of endometrial tissue where?
____ growth in areas surrounding 4 areas?
Etiology
- Outside of the uterus
- fallopian tube, ovaries, rectovaginal pouch and unterine ligaments
- Retrograde migration of endometrial tissue via fallopian tube, metastic growth from peritoneum
- This shit increase aromatase activity in the endometrial tissue.
Progesterone antagonists
1
mifepristone RU486
PD and Uses of the one progesterone antagonist
AEs
What is it used in combination with?
- PR bloackade destabolizes the unterine lining resulting in detachment of the blastocyct from the uterus
- Postcoital contraceptice within 72 hours
- Induce abortion in the first trimester, used with misoprostol a prostaglandin analogue to induce uterine contraction
- Aes- Vomiting/Di, ab or pelvic pain, lots of vag bleeding
Testosterone
PK, uses, AEs
- Not orally effective due to high first pass, available as transdermal patch and tompical gel, tablet for sublingal
- Uses- Androgen replacement therapy, for hypogonadalmales, anabolic
- Masculinizing effects in women and children, sodium retention and edema, hepatic dysfunction common and proportional to dose, Acne, sleep apnea, erythrocystosis, gynecomastia, azespermia
Androgen Antagonists
2
Flutamide
Spironolactone
What are these and what are their uses?
Flutamide
Spironolactone
- Androgen Antagonists
- Flutamide- Tx of metastic prostate cancer and used for tx of BPH
- Spiron- aldosterone antagonist and androgen receptor antagonists used for the tx of hirsutism in women
5 alpha reductase inhibitor 1
Finesteride
Finesteride
What is it?
PK, Uses, AEs
- Orally available
- Rapid onset of action
- Uses- BPH, prostate cell dependent on androgen for survival, slows growth of prostate tissue, 1 year reduced 25%, bald
- AEs- Decreased libido, and ED, depression
Anterior Pituitary
Growth Hormones Def
- How can this type of def occur? 2 ways
- What characteristics in children?
- Generalized _____, reduce ____ ____, _____ and reduced ____ in adults,
- What are the types of defs?
- Growth Hormone Deficiency
- What is the synthetic GHRH?
- How is administered what form?
- What does it treat?
- AEs?
- Genetic or acquired
- Short stature with mild adiposity in children
- Generalized obesity, reduced muscle mass, asthenia and reduced cardiac output in adults
- GH insensitivity, secondary, tertiary
- Semorelin- Parenteral Admin only, Used to tx GHRH def, Flushing, chest tightness, injection site rxns, and development of antibodies
Growth hormone replacement what are the drugs 2? need to know one what form?
- Somatropin- Recombinant GH
- Somatrem not recombinant
- Parenteral only
IGF-1 Drug
What is it?
Tx?
AEs
- Mescasermin, non responsive to GH
- Used to treat pts with GH insensitivity, GH insufficiency, or GH antibodies
- AE of HYPOGLCEMIA
Excess in GH
This is a sustained release formulation for SC injection
and what is it exactly?
Ocreolide
- Somatostatin analogue- inhibits the release of GH, decrease growth of somatotroph adenomas
Excessive GH
Dopamine analogues
only one
Bromocriptine
Dopamine analogue only one
PK
AEs
- Bromocriptine
- Orally available, or long acting IM injection
- AE- N/V
GH competitive Antagonists
Pegvisomat
GH competitive Antagonists
Only one
Uses-
PK-
AEs-
Pig Afro
- Pigevisomant
- Acromegaly- reduced tumor size
- Increases liver enzymes
Prolactin
Hyperprolactinemia
Dopamine receptor agonists 1
uses
- Cabergoline
- Shrink pituitary tumors secreting prolactin and reuce prolactin levels, restore ovulation
What is Cabergoline?
What is it used for?
What is Bromocriptine?
- Dopamine Agonist- Shrinks pituitary tumors, decreases prolactin, restores ovulation
- Dopamine analogue- comes in oral or LA Injection - N/V
Gonadotropins
FSH Analogues
1 what is it?
What is FSH?
Folliropin alpha- recombinant form of FSH
Its a gonadotropin, Follicle stimulating hormone
LH analogues
Lutropin
Lutropin
What is it? What does it treat? Only used in combination with?
PK? Formulation is all
- Recombinant LH used only in combination with follitropin alpha to stimulate follicle development in severe LH def to treat infertility
Uses for purified gonadotrophins
AEs?
- Stim ovulation secondary to hypogonadsim, polycystic ovarian syndrome, obesity in women that fail in other txs
- To control ovarian hyperstimulation for assisted reproductive proceduresm male infertility with hypogonad
- HA, depression, edema, ovarian stim syndrome, gynecomastia
Gonadotropin releasing hormone (GnRH)
Short- t1/2 One
Long 1
- Gonadorelin- Acetate salt of synthetic GnRH
- Leuprolide
Uses for Gonadorelin and Leuprolide
PD
AEs
complex dose-response relationships that change during life-time
- Pulsatile release of GnRH stimulates LH and FSH release which is simulated with gondaorelin administration iv every 1-4 hours
- Constant administration of any GnRH analogue causes increase in gonadal hormones for 7-10 days then a prolonged inhibitory response
Uses
Occasionally for stimulating gonadotropin release
- Can be used to treat male and female infertility but due to expense and need for long term iv infusion not commonly used
- Diagnosis of LH responsiveness- to determine if delayed puberty in a hypogonadotropic adolescent is due to hypogonadotropism or if puberty is impending
- Commonly used to suppress gonadotropin release
- controlled ovarian hyperstimulation:
- GnRH is used to suppress the LH surge that triggers ovulation to provide multiple mature oocytes for assisted reproduction
- endometriosis:
- Inhibits cyclical changes in estrogens to reduce pain caused by estrogen-sensitive endometrial-like tissues outside of the uterus; use limited to 6 mos. due to bone density related problems
- uterine fibroids
- Reduce fibroid size for benign estrogen-sensitive fibrous growths in the uterous
- prostate cancer
- Used in combination with androgen receptor antagonist to reduce serum testosterone and its effects, during initial 7-10 days a worsening due to “flare” can be prevented by treatment with an androgen receptor antagonist
- -central precocious pubertyUsed for treatment of the onset of puberty before age 8 in girls and 9 in boys, must rule out adrenal hyperplasia and tumors as cause
AEs:
Headache, light-headedness, nausea, flushing
Rare acute hypersensitivity reactions such as anaphylaxis and bronchospasm
Long-term in women- typical menopausal symptoms, ovarian cysts, decreased bone density
Contraindicated in pregnancy and breast feeding
Long-term in men- androgen deprivations symptoms such as gynecomastia, hot flushes, sweats, decreased bone density,
Long –term in children- well tolerated after initial surge exacerbating problems
GnRH Receptor Antagonists
2
Both end in?
Ganirelix
Abarelix
Ganirelix
Abarelix
What are they?
PK
PD
Uses
AEs
- GnRH receptor Antagonists
- SC or Injecton
- Inhibits LH and FSH secretion in a dose dep manner
- Uses
- Ganirelix and cetrorelix approved for controlled ovarian hyperstimulation
- Better than GnRH agonists because no initial surge and shorter treatment times needed but slightly lower pregnancy rates than with agonists
- Aberelix and degarelix approved for advanced prostate cancer
- Better than GnRH agonists because no initial surge, used in men with severe initial surge
- Abarelix- Immediate onset allergic rxn including skin rxn, hypotension, syncope, symptoms of androgen deprivation
- Ganirelix and cetrorelix approved for controlled ovarian hyperstimulation
Thyroid Hormones
What do they do? Via?
What regulates calcium metabolism?
- Regulate growth, development, body temp, enery levels via T3 and T4
- Calcitonin
Hypothyroid
1 drug
- Levothyroxine- Synthetic T4
- T4-T3 in cells
Hyperthyroid Thiomides 1
PD
- Methimazole
- Inhibits hormone synthesis and blocks iodine organification. Slow onset since synthesis is blocked not release
Posterior Pituitary
2 Types of places I guess
Oxytocin (pitocin)- Induces labor and control post-partum bleeding
ADH- Antidiuretic Hormone
Posterior Pituitary
ADH
1 Agonist
1 Antagonists, uses and AEs
- Desmopressin- ADH Analogue with longer T1/2 for V2 receptors resulting in selective antidiuretic effects rather than vasocontricting effects via V1
- Conivaptan- Tx-HTN, HF, counteracts high ADH in SIADH (syndrome of inacppropriate ADH Secretion)
- AEs- Infusion site Rxn, hypernatremia
Anatomy, physiology, and pathophysiology of bone mineral homeostasis
- Two main cell types which do what?
- What are the 6 signaling pathways that bone remodeling relies on?
Bone remodeling (metabolism) is a life long process where mature bone tissue is removed from the skeleton and new bone is added
- What are the 3 distinct stages of this?
- What do osteclasts and blasts do and how do they do it?
- WHat is a major activator of osteoclasts?
- Osteoclasts (break down grap them)
- Blasts- formation of new bone
- Calcium and phosphate
- PTH
- Vit D
- GH
- Steroid
- Calcitonin
- Calcium and phosphate
- Stages- Resorption, Reversal, Formation
- Clasts- stick to matrix and form lacunae, secrete enzymes to degrade osteoid which increases extracellular calcium and phosphate concentrations
- Blasts- Responsible for bone matrix proteins (fibronectin, collagen) leading to minerlization (hydroxylapatite crystals=Ca and P
- Activator of Clasts is RANK Ligand or RANKL
Anatomy, physiology, and pathophysiology of bone mineral homeostasis
10 disorders of Bone Mineral Homeostasis
- Osteoporosis
- Chronic Renal failure
- Primary hyper parathyroidsim
- Hypoparathyroidism
- Osteomalacia and Riskets
- Intestinal osteodystrophy
- Hyper and hypo calcemia
- Idiopathy hyper cal
- paget
- hyper/hypophos
Know the biosyn physiological effects and clinical uses of calcium
- What needs to be balanced to maintain calcium balance?
- How do you correct total calcium levels?
- What 3 levels does calcium regulation take place?
- What are the 3 metabolic regulators of calcium? These affect it by either increasing or decreasing it.
- net intestinal absorption must be balanced by urinary excretion
- based on albumin levels
- Osteoclasts
- Distal Renal Tubules
- Intestinal epithelium
- Increase PTH, Increase Vit D, Decreased calcitonin
Know the biosyn physiological effects and clinical uses of calcium
- Calcium is a major extracellular?
- What does it give bone?
- Fundamental for many intra and extra cellular processes 3
- Mechanism is by voltage calcium channels
- divalent cation
- strength and rigidity
- Muscle contraction, NT release, blood coagulation
Know the biosyn physiological effects and clinical uses of calcium
Clinical uses
- Can be used in the treatment and prevention of
- Low?
- Along with ____ for _____ caused by corticosteroids
- Oral calcium carbonate acts as an antacid for indegestion
- Oral calcium reduces ___ ______ and ____ ___ levels due to kidney failure
- What can IV calcium gluconate do?
- Precautions and Contra: Consider total calcium intake so no hypercalcemia, avoid if they have shitty kidney function or PTH disorder, Avoid IV 48 hours after ceftriaxone because it damages the lungs and kidneys
- Low calcium levels
- Vit D tx osteoporosis cause by corticosteroids
- Blood phosphate and PTH levels
- can reverse excess blood potassium
Hormonal and Nonhormonal regulators of Bone Min Homeo
- Hormonal:
- PTH (Major hormone for the regulation of serum calcium, binds to osteoblasts increasing RANKL and decreasing osteoprotegerin expression, causes an overal increase in serum Ca and decrease in P, Secretion if any mineral decreases)
- VIt D
- Calcitonin
- Estrogen
- Glucocorticoids
- Non:
- Bisphosphonates
- Fluoride
- Calcimimetics
Know the Biosynth, physiological effects and clinical use of PTH
Major?
Synthesized by? Metabolized?
Binds to? and increases expression of?
Causes and overall increase in? and Decrease?
Secretion is stimulated by?
Action on the bone?
Action on Kidney
Intestine first activation of? Which causes?
Clincal use
- Major hormone for the regulation of serum calcium
- Synthesized by the chief cells of PTH gland fast metabolism
- Binds to osteoblasts increasing RANKL and decreasing osteoprotegerin expression
- Causes an overal increase in serum Ca and decrease in P, Secretion if any mineral decreases
- Increase resorption increase Ca and P release
- Decrease P, increase Ca reabsorption
- Activation of Vit D– which causes increase Ca abs
- Teriparatide- Anabolic effect on bone increase bone density
Sources physiological effects and clinical uses of Vit D
Sources of Vit D
Stimulus for Secretion?
Action on bone?
Kidney
Intestine?
Overall on Ca and P
Increases expression of what is osteoblasts?
- Fatty Fish
- Liver
- Egg Yoke
- Only if you sont have sun exposure
- Milk unless fortified isnt good source
Clinical Uses:
Calcidediol, Calcitriol, Cholescalciferol
Used for the prevention adn tx of:
- Rickets and Osteomalacia, disease resulting in Vit D def
- Weak bones
- Bone loss and hypocalcemia in people with hyper PTH
- Psoriasis
- Muscle pain from statins
Biosynth, physiological effects and clinical use of secondary hormonal regulators (calcitonin, estrogen, glucocorticoids)
What does OPG do?
- Calcitonin is secreted by the parafollicular cells of the thyroid and secretion is stimulated by a increase in serum calcium, this has the opposite effect of other regulators causing a overall decrease in Serum calcium, it does this by decreasing resorption and increasing deposition in the bone this causes and overal decrease in Ca and P release. It also works in the kindeys by decreasing absorption of both P and C. In the intestine it decreases absorptionof calcium overal decrease in Ca dont know with P. Calcitonin and Salcatonin (salmon) Are used to treat hypercalcemia and they do this by inhibiting osteoclastic bone resorption Its what calcitonin does
- Estrogen is synth and secreted by the ovaries in women and covnerted from testosterone in men (bone interity in women) . Estrogen increases osteoclast apoptosis, decreases cytokines that recruit osteoclasts and decreases RANKL increase OPG production Raloxifene Tx of osteoporosis stops everything for osteoclasts
- Glucocorticoids- Prednisone- Decreases calcitriol production
Non hormonal Regulators
3
Which one shouldnt be taken with antacid?
- Bisphosphonates (dont take on antacid, stand up after taking, long ass half life, Osteo, take on empty stomach,pagets, hypercal)
- Inhibits osteoclast activity through: Accelerate osteoclast apoptosis (formation of nonfunctional molecule), disrupts cytoskeletal osteoclasts, inhibits differentiation of the precursors)
- Fluoride (Osteoblasts, for pagets and osteoporosis)
- Calcimimetics (Secondary hyper PTH in CKD, parathyroid carcinoma)
Therapeutic Strats for Disorders of bone min homeostasis
