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Pharmacology3

Endrocrine

QuestionAnswer
Octreotide/Lantreotide are what type of drugs? What kind of side effects can they have? Somatostatin analogs Gallstones, GI disturbances, Abnormal cardiac conduction
GH is suppressed and antagonized by what five things? Somatostatin, Dopamine/Bromocriptine (only for GH tumors), Pegvisomant (GH-receptor antagonist), alpha blockers (Phentolamine), 5HT blockers (Cyproheptidine)
Mecasermin (Mecasermin rinfabate) is an analog of? An adverse affect may be: IGF-1. Hypoglycemia
Somatostatin blocks what 4 things? Insulin, Gucagon, GH, Gastrin (IG3)
Potent D2 agonists used to treat prolactinomas (3) Bromocriptine (also for acromegaly), Cabergoline, Pergolide
GH release is stimulated by and inhibited by: 5HT, Dopamine, B-blockers, Inhibited by alpha-blockers, somatostatin
These hormones are used for diagnostic purposes only: GHRH, CRH, ACTH, TRH, TSH
The only anterior pituitary hormone that does not regulate the production of other hormones by peripheral tissues: Prolactin
These four hormones are subject to feedback inhibition by the hormones whose production they control FSH LH ACTH TSH (FLAT)
In children, Somatotropin is used to treat these 5 diseases (3 are genetic). Side effects of GH in children GH deficiency (dwarfism), Chronic Renal Failure Genetic: Noonan's disease, Praeder Willi, Turner's Syndrome . Pseudotumor cerebri, slipped capital femorla epiphysis, scoliosis, edema, hyperglycemia, otitis media (in PW and T syndromes)
In adults, Somatotropin/GH is used for (5): Side effects (4): GH deficiency, AIDs-related wasting, post-GI resection malabsorption, anti-aging, boosting athletic performance. Myalgia, Arthralgia, Edema, INCREASED mortality
Gonadotropins are: Their functions in men and women LH and FSH. In males, FSH regulates spermatogenesis, LH stimulates androgen production in testes. In fmales, FSH stimulates follicle development, and FSH and LH regulate ovarian steroidogenesis. Used to treat infertiliy/anovulation
Ovulation induction protocol: What are the three steps? 1. Shut down endogenous gonadotropin production with GnRH agonist/antagonist 2. Daily injection of FSH for follicular development (menotropin/FSH derivative) 3. LH or hCG for final stage of oocyte maturation
2 Serious complications of ovulation induction 1. Multiple pregnancies 2. Ovarian hyperstimulation syndrome: large ovaries, ascites, hypovolemia, shock
Menotropins are Extracts of menopausal women's urine containing FSH and LH
LH analogs include (2) hCG and Lutropin alfa. The latter should only be used in combination with follitropin alfa for follicular develpment in infertile women with LH deficiency. NOT use to produce LH surge.
FSH analogs include (3) Urofollitropin (urine of postmenopausal women with LH activity removed by anti-hCG antibodies), Follitropin alfa/beta (synthetic rFSH)
Long acting GnRH agonists (5): Leuprolide, Goserelin, Histerelin, Nafarelin, Triptorelin
Antagonistic activity of long-acting GnRH agonists are useful in the treatment of(5): Side effects may include: Uterine fibroids, Endometriosis, Prostate cancer, Central Precocious Puberty, Early pubertal transgender adolescents . Side effects: Menopausal symptoms in females/males, bone loss, may initially exacerbate prostate cancer/central precocious puberty
GnRH antagonists and advantages (2): Ganirelix, cetorelix, (ovulation induction) degarelix (prostate cancer treatment). 1. No initial flare. 2. Less risk f ovarian hyperstimulation syndrome
Hyperprolactinemia's 2 major adverse effects: How is this condition treated? What 3 drugs may increase PRL secretion Infertility, Galactorrhea Bromocriptine (D2 agonist) Morphine, Endorphins, Anti-psychotics (D2 blockers - Clozapine/Haloperidol)
Oxytocin, a nonapeptide synthesized in ____nuclei of the hypothalamus and released from the _____ pituitary plays a role in ________ (2). Paraventricular. Posterior. Uterine contractions (inducing labor) and release of breastmilk
Atosiban is: Oxytocin-receptor antagonist. Acts as a tocolytic (prevents preterm labor).
Vasopressin V2 receptor function (2) 1. Insert water channels in apical membrane of collecting duct cell (reabsorb/antidiuresis) 2. Regulate release of coagulation factor VIII and Von Willebrand factor (binds to and prevents degradation of VIII)
Name a V2 agonist. Used to treat what 3 diseases? Desmopressin. Von Willebrand's disease, Hemophilia A, Pituitary Diabetes Insipidus
V1 vasopressin receptor types and functions (2) V1a: Vasoconstriction V1b: ACTH release
Vasopressin receptor antagonists: Conivaptan, Tolvaptan
GH and prolactin act through what kind of receptors JAK STAT
TSH, FSH and LH are dimeric proteins that act through what kind of receptors. They have ___ and ___ chains G-protein coupled
Three things that inhibit TRH stimulation of TSH release and one thing that activates release: Thyroid hormone, Glucocoritcoids, Somatostatin Estrogen
Thyroid hormones (T3 and T4) inhibit the release of (2) TSH and prolactin
TRH can stimulate the release of GH in what 4 disease states? Acromegaly, Depression, Anorexia, Uremia
Agonistic effects of GnRH treatment (2) Idiopathic hypogonadism, Hypothalamic amenorrhea
CRH release is activated by (2): and inhibited by (3): (2): 5HT and ACh (3): NE, melatonin, GABA
In Early Follicular phase, does estrogen increase or decrease LH/FSH release by GnRH? Decrease
In Late Follicular phase, does estrogen increase or decrease LH/FSH release by GnRH? Increase
In Post-Menopausal women, does estrogen increase or decrease LH/FSH release by GnRH? Decrease
In males, does testosterone increase or decrease LH/FSH release by GnRH? Decrease
Finasteride does what? Blocks 5a-reductatase, reducing synthesis of Dihydrotestosterone from Testosterone. This can reduce prostate hyperplasia and balding and treats hirsutism in women
Flutamide/Nilutamid are: Anti-androgens (blocks receptors).
GH must either be derived from ______ or a synthetic analog may be used humans
How does IGF-1 differ from insulin? Shows Non-Suppressible Insulin-like activity (not suppressed by antibodies against insulin)
Compare and contrast GH and IGF1 in terms of protein synthesis, lipolysis, and blood sugar levels GH: increases protein synthesis/muscle mass, lipolysis and causes hyperglycemia (Reduces insulin sensitivity and causes hyperinsulinemia) IGF1: increases protein synthesis, reduces lipolysis and causes hypoglycemia (insulin-like)
In children/infants, lack of GH results in ________, where as lack of thyroid hormone results in ________. Dwarfism. Cretinism.
Excess of GH in children/adolescents leads to _______ and in adults leads to ________ Gigantism, Acromegaly
Pegvisomant is: (Bonus: How does it work?) GH Receptor antagonist. It is a mutated version of GH that activates only one of the two receptors, which allows for receptor dimerization but does not cause the conformation changes needed for signaling
Synthetic somatostatin analogs offer what advantages? Compared to somatostatin, octreotide is only 2x as active in inhibiting insulin-like effects whereas 45x as active in blocking GH effects. It also has a 30x longer half life (90min compared to 3).
Prenatal growth is ____ (GH/IGF-1) dependent and ____(GH/IGF-1) independent. Postnatal growth after 1 year of age is ___ dependent. IGF-1, GH, GH
3 Categories of Dwarfism include: How are they treated? Laron's Disease (unable to synthesize IGF-1 even with GH administration), Praeder-Willi Syndrome, Turner Syndrome. Laron's is treated by Mecasermin (IGF-1 analog) and the latter two diseases are treated with GH analogs or GHRP(GH releasing peptide)
3 GHRH derivatives: Sermorelin, Hexarelin, GHRP2/6
Octreotide is: Side effects include: Before giving a long-acting form: A somatostatin analog. GI events, (cramps/nausea/vomiting/flatuence/steaorrhea), gallstones, sinus bradycardia, pain at site of injection, Vitamin B12 deficiency with long term use Test with a short acting form to see if it's tolerated
In female follicular stage, ___ in the theca cells produces _____, and _____ in granulosa cells converts it to ______. In the luteal stage, ____ is responsible for production of ____ and ______ LH, Testosterone, FSH, Estrogen LH, estrogen progesterone
hCG is most similar to ____ and works through the same receptors. LH
In males, ____ assists in spermatogenesis in ______ cells, and ______ produces androgens in ______ cells. ____ also converts androgens to estrogens in ______ cells. FSH, Sertoli, LH, Leydig FSH Sertoli
L-Dopa is commonly used to treat ________ disease (CNS). A side effect may be that it lowers ___ levels in the blood. Parkinson's. Prolactin
Infertility in men is treated with: Spermatogenesis occurs in ____ months What is ICSI hCG, then hMG 4-6 months Intracytoplasmic Sperm Injection: more efficient
What class of testosterone is Testosterone Cypionate How is this class of drugs administered and what is it used for? Aromatizable or no? Crosses BBB? Class 1 IV or transdermal patch. To treat hypogonadism. Aromatizable. Yes
What class of testosterone is Nandrolone Decanoate How is this class of drugs administered and what is it used for? Aromatizable or no? Crosses BBB? Class 2 IM (Long acting). Out of clinic Aromatizable. Yes
What class of testosterone is 17a-methyltestosterone/ stanozolol/ oxyandrolone? How is this class of drugs administered and what is it used for? Aromatizable or no? Crosses BBB? Class 3 Oral administration, many uses Non-aromatizable. Acts mostly on periphery
AAS can be used to treat (9): "muscle growth provides happiness to most boys of all ages" 1. Malnutrition 2. hypoGonadal men 3. delayed male Puberty 4. HIV patients to gain muscle mass 5. female to Male Transgenders 6. Mood disorders 7. Breast engorgement 8. Anemia 9. Aging
Describe regimen to treat hypopituitarism in puberty/adulthood: Long/Short acting agents, How is it administered, Use long acting agents: Tes. Enanthate/Cypionate via IM injections (50mg) and decrease interval time and increase dose to mimic what happens in puberty. In adults, use 200mg at 2 wk intervals
Adverse effects of AAS in women and men acne, deep voice, enlarged clitoris, risk for atherosclerosis, altered serum lipids, progestational activity (endometrial bleeding), affects fetus in pregnancy, liver/kidney damage, jaundice (raised bilirubin), prostate hyperplasia in men
How does Ketoconazole (anti-fungal) impact the Estrogen/Testosterone ratio? Adverse effects? Steroid synthesis inhibitor. Synthesis of testosterone is lowered, but conversion rate to estrogen using aromatase in not inhibited, raising the Estrogen to Testosterone ratio. Toxic to women, gynecomastia in men
Cyproterone is: an anti-androgen (androgen receptor blocker), It suppressed LH and FSH feedback. Used to treat excess libido in men and hirsutism in women.
Bicalutamide is used for: Nilutamide is used for: Reducing prostate tumor flares in addition to GnRH analog Surgical castration
Spironolactore, an aldosterone antagonist, can also compete for ____ receptors and lowers serum Testosterone levels by reducing the enzyme _______. It is used to treat __________ in women. androgen (competes with DHT) 17a-hydroxylase hirsutism
Two methods of chemical contraception in males: 1) Testosterone enanthate with progestins to reduce adverse effects of testosterone aromatization to estrogen 2) Testosterone with GnRH antagonists
Exogenous testosterone has ________ effects, but shuts down the ___________ Peripheral, HPG
3 patterns of AAS abuse Shotgunning, Cycling, Pyramiding
AAS abuse is usually combined with ____, ____ or _____. Antiestrogens, Competitive aromatase inhibitor, hCG/LH (to maintain endogenous testosterone production/testes size)
Aminogluthethemide and Anastrozole are examples of competitive aromatase inhibitors
Dietary Supplements that are used as ergoenic agents incliude: hGH (may cause acromegaly), Androstenedione, Creatine (pure protein)
AAS Drug Test Techniques (2): EMIT (enzyme immunoasay) and GC/MS (gas chromatography/massspec)
Time for detection of 1) oral AAS 2) Injected AAS 1) 3-6 weeks 2) 6-8 months
AAS effects on 1. 5HT 2. Dopamine 3. Glutamate 4. Vasopressin 1. Lowers 5HT (depression) 2. Increases Dopamine (reward) 3. Increases Glutamate (aggressive/anxious) 4. Increases vasopressin (memory)
Estrogen-like compounds in our daily lives include soybean, BPA, PCBs
Estrogen can (increase/decrease) clotting factors, (increase/decrease) plasma renin substrate, (increase/decrease) bone resorption, (increase/decrease) endometrial proliferation. increase, increase, decrease (oppose PTH), increase
Estrogen (does/does not) pass through breast milk. Progesterone (does/does not). does does not.
Hormone Replacement Therapy reduces risk of __________ but raises risk of ____ and ______, the latter of which may be avoided if HRT is used in combination with _________. osteoporosis, breast cancer, endometrial cancer, progestins
If HRT does not work, a different therapy involves the use of ______ Clonidine
After 4 months of continuous use, HRT be cause _____ amenorrhea
Diethylstilbestrol (DES), a synthetic estrogen used to maintain pregnancy, may cause _______________. Now it is only used to _______ and as __________l. Vaginal adenocarcinoma in offspring Treat cancer, morning after pill
Metabolic effects of progesterone (on fat/glycogen) include (3): Fat deposition by lipoprotein lipase, glycogen storage by facilitating effects of insulin (may lead to diabetes type 2), Ketogenesis
Progesterone's effects on 1) body temperature 2) Na retention 3) bodily changes 4) urinary nitrogen excretion 5) blood pressure 6) HDL 1) increases body temp 2) decreases Na retention (competes with aldosterone) 3) alveolobular/secretory breast development 4) increases nitrogen excretion 5) increases BP 6) reduces HDL
Describe types of contraception: Oral: monophasic (constant dose), biphasic, triphasic (dose of one or both changed through cycle), progestin only (minipill) Implantable: etonogestrel Vaginal rings or IUDs
For breastfeeding mothers, what kind of oral contraceptives are allowed to be used? Progestin-only (minipill) - does not go into breastmilk like estrogen
On CNS, Estrogen ____ excitability and Progesterone _____ it. Increases, Decreases
Estrogen ____ TG, HDL, and cholesterol and Progesterone _____. Increases, decreases
L-Norgestrel is commonly used as The morning after pill ("Plan B")
Mifepristone (RU486) is an antagonist or what receptor(s)? What is it used for? Progesterone and Glucocorticoid Terminating pregnancy (before 7 weeks gestation), Cushing's diseases
Danazol is an ______ derivative with weak ___, ___, and ____ activities. It prevents midcycle ________, and is used to treat ____ (4) Eristerone (synthetic steroid) Weak P, androgenic, GC activities Prevents LH/FSH surges Treats endometriosis, hemophilia, fibrocytic breast disease, angioedema,
Describe and state the uses for: 1. Anatrozole/Letrozole 2. Exemestane 3. Fadrozole All aromatase inhibitors. 1. Anastrozole: Non-steroidal. Used when tamoxifen is ineffective 2. Exemestane: Steroidal, irreversible. Used for advanced breastcancer 3. Fadrozole: Non-steroidal. Used to treat precocious puberty/excessive aromatase syndrome
Fulvesant is: a pure estrogen receptor antagonist; inhibits ER complex from binding DNA - used when pt is resistant to tamoxifen
Desribe 3 SERMs. Tamoxifen (breast cancer) Raloxifen (long acting >24 hrs, prophylactic use for breast cancer/osteoporosis), Clomiphene (ER partial agonist,inhibits negative feedback, increases gonadotropins, used in ovulation induction)
In Sertoli cells, activin and inhibin respectively increase and decrease _____ Sertoli cells also convert ____ to ______ FSH Testosterone to estradiol
SHBG is increased by ____ and ______ SHBG is reduced by _____, _____ and ______ Estrogen and thyroid hormone Androgens, Insulin, Growth Hormone
Testosterone can _____ HDL, _____ renal erythropoietin, ______ clotting actors, ______ the action of hepatic TG lipase lower, increase, increase, increase
Describe ovarian hyperstimulation syndrome Ovarian enlargement, hydrothorax, hemoperitoneum, arterial thromboembolism, shock
In male or female infertility, what GnRH analog is first administered and how? Gonadorelin - delivered by pump every 90 minutes (pulsatile)
Delayed onset of puberty may be caused by (2): 1. Constitutional delay (impending puberty) 2. Hypogonadism (LH levels <15.6mIU/mL after GnRH administration)
Why is a GnRH analog used in controlled ovarian hyperstimulation? To prevent endogenous LH surges that may prematurely trigger ovulation
What is endometriosis and what are 3 treatment methods? Estrogen sensitive endometrium-like tissue that grows outside the uterus. 1. Contraceptives 2. GnRH analogs (may cause bone loss over time) 3. Danazol (not first choice - has many side effects, DO NOT TAKE when pregnant)
What are uterine fibroids and how are they treated? Estrogen-sensitive fibrous growths in uterus that may cause menorrhagia and anemia, treated with GnRH analogs for 3-6 months (often supplemented with iron to reduce anemia)
Prostate cancer is treated with what regimen? Continuous GnRH with flutamide (Androgen Deprivation Therapy) or surgical castration
Central Precocious Puberty is treated with? GnRH analogs
Cetorelix and Ganirelix are used in _____ Degrelix is used in _____ Collectively these drugs are known as: Controlled ovarian hyperstimulation Prostate cancer GnRH antagonists (inhibits FSH/LH secretion)
Prolactin is secreted from the ______ and its levels rise at the end of pregnancy when the levels of progesterone ______. Hyperprolactinemia may cause _________, and is treated with ______ Anterior pituitary, Decrease Galactorrhea and amenorrhea in women, erectile dysfunction in men. Treat with Dop-agonists (Bromocriptine)
Bromocriptine and Quinagolide _______ levels of GH in patients with acromegaly. Decrease
Dopamine agonists can cause _________ in early weeks of pregnancy and ________ in post partum women sponataneous abortions stroke/coronary thrombosis
Oxytocin's functions (4) 1. Mammary gland contraction (milk release) 2. Uterine contractions (induce labor/terminate pregnancy) 3. Control post-partum bleeding 4. Weak anti-diuretic by activating ADH receptors
Atosiban is: Oxytocin antagonist used to prevent pre-term labor
Diabetes may cause 4 conditions: 1. Retinopathy, 2. Kidney Damage 3. Vascular Damage 4. Neuronal damage
Fasting glucose should be less than ____ mg/dL HbA1C measure blood glucose levels over _____ period and normal should be lower than ___%. 100 3 month 6%
Glucose metabolism is mediated by the GI enzymes ___ and ___. GIP and CCK
Insulin levels are increased by ___ and ___ receptors and decreased by ____ receptors. B-adreneric & Muscarinic increase alpha-adrenergic decrease
Stimulation of ventro_____ hypothalamus (parasympathetic) increases insulin whereas ventro______ hypothalamus (sympathetic) decreases it. lateral = increase medial = decrease
Insulin is a peptide, and therefore must be administered ____ IV
What are the two major types of Primary Diabetes 1. Insulin-dependent 2. Insulin-independent (insulin insensitivity)
Oral hypoglycemic agents are only used to treat Type ___ diabetes 2
Ketoacidosis is always found with Type ___ diabetics 1
High plasma glucagon is suppressible or non-suppressible in Type 2 diabetics? Non-suppressible
Type 2 diabetics have 3 classifications - what are they? 1. Non-obese 2. Obese 3. MODY (maturity onset diabetes of the young)
Secondary causes of Diabetes Mellitus (5) 1. Chronic Pancreatitis (alcoholism) 2. Hormonal (Pheochromo, Cushing's, Acromegaly - all cause hyperglycemia) 3. Drug-induced: Streptozotocin kills beta cells 4. Insulin receptor abnormalities 5. Myotonic Dystrophy - impairs beta-cell activity
Does insulin stimulate or inhibit: 1. Glycogen synthase 2. Glucokinase 3. Glycolysis 4. Glyceraldehyde Phosphate Dehydrogenase 5. Phosphorylase A 6. Gluconeogenesis 7. PEPCK 8. Pyruvate Carboxylase 9. 1,6 Fructose Bisphosphatase Stimulates 1-4. Inhibits 5-9
Oral hypoglycemic agents include: (7) 1. Sulfonylureas 2. Biguanides 3. Thiozoinediones (Rosiglitazone) 4. Glucosidase inhibitors (Acarbose/Miglitol) 5. DPP-blockers (Gliptins) 6. Pramintide (Amylin analog) 7. Exenatide (GLP1 analog)
How does Sitagliptin work? Decreases DPP (dipeptidyl dipeptidase) which normally breaks down GLP-1.
GLP-1 effects include (4) 1. Central anorexia 2. Slow gastric emptying 3. Insulin release 4. Glucagon suppression
Biguandies have an adverse side effect of: Lactic acidosis
How do sulfonylureas work First generation sulfonylureas include: Second generation: Adverse effects: Inhibit ATP-sensitive K+ channels, depolarize cell, allow calcium inflow,/ stimulate insulin secretion 1: Chlorpropamide, Tolbutamide, Tolazamide, Acetohexamide 2: Glyburide, Glipizide Adverse effects: Hypoglycemia, CV events
Thiozolidinediones (glitazones) work through: Adverse effects are: nuclear PPARy receptors that increase insulin sensitivity. Adverse effects: water retention, weight gain
Biguanides include: Metformin, Buformin
Acarbose and Miglitol are: Glucosidase Inhibitors: block the degradation of complex carbohydrates in the gut. They have no effect on absorption of simple sugars
List the 4 types of Insulin preparations: Rapid acting (Lispro, Aspart, Glulisine) Short acting (Novolin, Humulin) Intermediate acting (Neutral Protamine Hagedorn) Long acting (Detemir (myristic acid added), Glargine)
Thiocyanate and Perchlorate inhibit what function Uptake of Iodide into thyroid gland
PTU and Methimazole inhibit what function: Iodination of tyrosine and coupling of Di-iodotyrosin and Mono-iodotyrosine to form thyroid hormones PTU also inhibits T4 to T3 conversion
Iodides inhibit what function: Colloidal reabsorption and proteolysis
Dinitrotyrosine does what? Inhibits de-iodination
The 3 main agents for hyperthyroidism are: PTU, Methimazole, Iodides
T4 binding to TBG is ______ by estrogen and _______ by androgens and glucocorticoids increased, decreased (facilitates excretion)
Thryoid hormone can be displaced from TBG by (2) Salicylate and Furosemide
TRH secretion is inhibited by ___ and ____ and its action on receptors on the pituitary is inhibited by _____ Somatostatin, Dopamine Glucocorticoids
Lithium inhibits what process in T4 production Colloidal resorption
Drugs that induce HYPOthyroidism (2) Lithium, Phenylbutazone (NSAID)
What happens in thyroiditis? Differentiate between acute and chronic: Inability to store T3/T4 Acute: Excessive free thyroid hormone (hyperthyroidism) Chronic: Hypothyroidism
Hashimoto's Disease occurs due to: Autoimmune destruction of enzymes needed for tyrosine iodination (peroxidase)
Grave's disease occurs due to: Thyroid stimulating immunoglobulin binding and resulting production of excessive thyroid hormone
In hyperthyroidism, cardiovascular issues may occur due to upregulation of __ receptors, which may be prevented by using _____ and _____ Beta Adrenergic B-Blockers, Ca-Channel Blockers
ADH release is stimulated by Beta and Muscarinic receptors
Glucocorticoid effect on ADH stimulation (2) 1. raises threshold of osmo-sensitivity 2. less renal tubules less permeable to water (diuresis)
ADH stimulatory drugs include (9) CNS: Nicotine, Barbiturates, Morphine Anti-Cancer: Vinblastine Vincristine Cyclophosphamide Etc: Clofibrate, Chlorpropamide (diabetes), TCA
ADH inhibitory drugs include: Anti-narcotics, Ethanol, Chlorpromazine
Desmopressin, compared to aqueous vasopressin has what sort of activity profile 3000:1 ratio of ADH:vasocontrictive activity, longer half life
Leukopenia is an adverse side effect of which antithyroid drugs: PTU and Methimazole.
Created by: dainnwoo