Term
| Major concerns with androgen use for pubertal males is what? |
|
Definition
Stunting growth.
Androgens make long bones grow, but they close epiphyseal plate. NO MORE GROWTH. |
|
|
Term
| What type of drug is flutamide? |
|
Definition
| Androgen receptor blocker for metastatic prostatic cancer. |
|
|
Term
| What is the therapeutic use of flutamide? |
|
Definition
| Used as an adjunct thx with long acting GnRH agoinsts |
|
|
Term
| Why is flutamide used along with GnRH agonists?? |
|
Definition
To decrease the ADR associated with them.
When you first begin taking an GnRH agonist, you release a large amount of LH->Testosterone, and you will have ADR |
|
|
Term
| Rationale for flutamide w/ GnRH agoinst? |
|
Definition
| Block initial flare in cancer symptoms due to initial effect of GnRH analog to increase plasma testosterone of testicular origin. |
|
|
Term
Names of GnRH agoinsts
How are they given? |
|
Definition
Goserelin/Zoladex
Leuprolide/Lupron
SubQ injection q 3 months |
|
|
Term
| After a few weeks of using a gnrh agoinst, what happens to plasma levels. Do you continue flutamide? |
|
Definition
Testosterone decreases
You can DC flutamide |
|
|
Term
| Uses of finasteride? Doses? |
|
Definition
-BPH-5 mg
-Male Pattern Baldness- 1mg |
|
|
Term
| What type of drug is finasteride? |
|
Definition
5 alpha reductase inhibitor
Blocks conversion of testosterone to DHT |
|
|
Term
| What is finasteride used for? |
|
Definition
Symptomatic BPH (limited effect <=15% in symptoms score in BPH)
BPH Symptoms do NOT correlate w/ size/mass?? Maybe it is, maybe it's not. |
|
|
Term
| What is a side effect of finasteride when used for male pattern baldness? |
|
Definition
|
|
Term
| What is the effect of progesterone on the endometrium? Estrogen? |
|
Definition
Progestin-Anti-proliferative
Estrogen-Proliferative |
|
|
Term
| How does the effect of E2/LH change throughout the cycle? |
|
Definition
Prior to ovulation: Increase in estrogen was a + effect on pituitary, which releases LH
An increase in LH causes ovulation
Luteal phase: Corpus Luteum is formed, sustained levels of E2 and P from CL prevent another spike in LH |
|
|
Term
| How does clomiphene work? And what does it do? |
|
Definition
| It is a receptor antagonist of estrogen that is used to induce ovulation. It inhibits - FB of estrogen onto the pituitary |
|
|
Term
| If clomiphene inhibits -FB and you don't get LH, why does it lead to ovulation? |
|
Definition
| You start taking it on day 5 of your cycle, then when you stop, you ovulate because you will have a larger buildup of estrogen |
|
|
Term
| How is clommaphine used in males? |
|
Definition
Therapy for male infertility by blocking the negative feedback of the estrogens
Choronic administration may increase spermatogenesis by increasing gonadotropins by increasing gonadotropins
Testosterone is increased |
|
|
Term
| Concern for clomiphene abuse in males? |
|
Definition
Block -FB; Increase gonadotropins; Increase T
So you will have potential to increase muscle mass. |
|
|
Term
Effect of progestin of HDL/LDL/TG.
Effect of estrogen on HDL/LDL/TG |
|
Definition
Progestin: Decrease HDL/Increase LDL/ Increase TG??
Estrogen: Increase HDL/Decrease LDL/Increase TG |
|
|
Term
| What is the origin of premarin? |
|
Definition
|
|
Term
| Is premarin orally active? |
|
Definition
|
|
Term
| What medications are in oral contraceptives? |
|
Definition
EE 20-50 mg daily
Progestins
Exhibit leass perturbation in LDL/HDL |
|
|
Term
OC Regimens (days)
-Fixed
-Phasic
-Sustained
-Transdermal patch
-Vaginal Ring |
|
Definition
Fixed 21 days on; 7 days off
Phasic: established daily dose or increments @ time intervals during cycles
Sustained: 3 and 12 month regimens
Transdermal Patch (1/week *3, 1 week off)
Vaginal ring (1 ring in place for 3 weeks, 1 week off) |
|
|
Term
| Rationale for estrogen in OC's? |
|
Definition
1. Prevent ovulation by decrasing FSH, follicular development, and surge in endognous E2/LH spike
2. Phenotypic sexual characteristics--growth @ target tissues
3. Increase progestin receptor |
|
|
Term
| Rationale for progestin in OC? |
|
Definition
Prevents ovulation by decreasing LH, engogenous E2, and ovulation
Anti-prolieferative effect in E2 aimed tissues. |
|
|
Term
| What is one of the main effects of progesterone? What causes it? |
|
Definition
| Anti-proliferative effect will result in no breakthrough bleeding. |
|
|
Term
| What was the first use for "oral contraceptives"? |
|
Definition
|
|
Term
| How do OC work for dysmenorrhea? |
|
Definition
Prosteglandins are released with endometral shedding, and this can cause pain.
Prog. in OC will decrease endometrium and therefore decrease pain |
|
|
Term
| Rationale for OC for use with acne/hirsuitism? MOA?? |
|
Definition
Abnormal increase in ovarian androgens
No rationale for adrenal androgens are causing the problem because they are regulated by ACTH, and not GNRH.
A decrease in ovarian steroidogenesis, including abnormal androgen synthesis, by decreasing FSH and LH |
|
|
Term
| Toxicities in COC in pre-menopausal females? What is the main one?? --Estrogens |
|
Definition
**Thromboembolism
Diabetogenic
Fluid retention (wt gain)
FI if tumor of estrogen sensitive tissue |
|
|
Term
| What are some toxicities of COC's in pre-menopausal females? What one is worse than others? -progestins |
|
Definition
Thromboembolism
Depression, Headache
**LDL/HDL (age and smoking)
acne, hirsuitism
Increase appetite and weight gain |
|
|
Term
| What factor can cause an increase in chance for MI in COC us? |
|
Definition
|
|
Term
| At what age are COC's CI for smokers? |
|
Definition
|
|
Term
| What are the two main factors that contribute to CHD in patients taking OC's? |
|
Definition
Increased platelet aggregation and blood clots
Effects on plasma lipids |
|
|
Term
| Which has a greater risk for VTE, patch or pill OC? |
|
Definition
|
|
Term
| What is the strategy to prevent fetal abnormalities from occurring while taking COC's?? |
|
Definition
Initiate after menses
Evaluate if you do not have a withdrawal bleed |
|
|
Term
|
Definition
Mental Depression/Fatigue/Drowsy/Migrane/Headache/Anxiety
Cholestatic Jaundice |
|
|
Term
| How long does it usually take ovulation to return after completing therapy? What if it doesn't return? |
|
Definition
Usually 3 months
If it doesn't return, consider hyperprolactinemia |
|
|
Term
| Potential Benefits associated w/ COC? |
|
Definition
-Inhibition of ovulation
-Anti-proliferative effect of prog
-Increased cervical mucous viscosity |
|
|
Term
| Things that progesterone is used for along? |
|
Definition
Dysfunctional uterine bleeding
Contraceptive
-post coital
-mini pill
-sub dermal implant
-long acting injectables for contraception
-IUD |
|
|
Term
| What are some advantages/disadvantages to the minipil OC? What does this product contain? |
|
Definition
P only.
It may cause irregular and unpredictable menses
There is less of a risk of thromboembolism than estrogen containing OC
You can use these post partum. |
|
|
Term
| What was a major side effect of Norplant? what is this drug? |
|
Definition
Headache, 24% incidence. Withdrawn from market
Subdermal implant |
|
|
Term
| Side effects of subdermal P implants? |
|
Definition
Irrgular periods
HE, Weight gain, Acne, Abdominal pain, Anxiety, depression, infection, androgenic SE |
|
|
Term
| What is medroxyprogesterone acetate? |
|
Definition
"The shot"
Injected IM preparation. |
|
|
Term
| How does depoprovera work? What is a SE of this drug? |
|
Definition
-Decreases gonadotropins, which decreases ovarian function and atrophic endometrium
-Possible infertility for up to 2 years after cessation of thx. |
|
|
Term
|
Definition
Works as an anti-fertility drug
Local anti-proliferative effect on endometrium, no fertilization, no ovum |
|
|
Term
| How do progesterones work as OC? |
|
Definition
They are anti-proliferative which shows effect on endometrium
Also increase in mucous viscosity
Possible systemic effects |
|
|
Term
| What is mifepristone/RU-486? How does it work? |
|
Definition
Anti-glucocorticoid, anti-progestin and incrase prostaglandins
Abortive drug
Potential vasoconstriction |
|
|
Term
|
Definition
| Prevents LH surge to prevent ovulation |
|
|
Term
|
Definition
| Increase ova transport, decrease implantation, luteolysis |
|
|
Term
| What happens to estrogen and fsh levels in menopause? How is menopause diagnosed? |
|
Definition
Estrogen levels decrease
FSH levels increase
Amnorrhea |
|
|
Term
| What are the therapeutic uses of E+P in post-menopausal women? |
|
Definition
-Symptomatic menopause
-Osteoporosis |
|
|
Term
| Common regimen of E+P in post menopausal women?? |
|
Definition
|
|
Term
| What is the significance of taking a progestin along with an estrogen? |
|
Definition
| Progestin's are anti-proliferative, so they will stop growth of the endometrium, which will suppress the growth provided by estrogen alone (also why you decrease chance of cancer with this combo) |
|
|
Term
| What is the rationale for both E/P in post-menopausal women? |
|
Definition
E-Vasomotor symptoms, Boneloss
P-Protect against endometrial cancer w/ estrogen (no need for this if no uterus) |
|
|
Term
| What women are at risk for estrogen related OP? |
|
Definition
At age 30, start to lose bone.
Up to age 65, you lose more..
Up to 125/year in the two years following post-ovariectomy
30% of women @ risk for fracture |
|
|
Term
| Reversal vs Prevention of post-menopausal OP? |
|
Definition
| can't reverse it very well.. Use prophylactic thx to prevent further progression. |
|
|
Term
| How long are most women left of E+P for prevention of OP? |
|
Definition
| Most 4 years or less.. Some think lifetime thx is best bc fracture risk increases when you stop. |
|
|
Term
| OP estrogen fractures in E2 vs Control? |
|
Definition
E2=0 fractures/1428 patients
Control=19 fractures/5380 patients |
|
|
Term
| Coronary artery disease related to estrogen therapy: Rationale/Effects of E |
|
Definition
|
|
Term
| What diseases does estrogen therapy increase/decrease? (Breast cancer/MI/Hip Fracture/Endometrial cancer/Stroke/CAD/Life Expectancy |
|
Definition
Decrease MI/Hip fracture/Life Expectancy
Increase: Breast/Endometrial/Stroke/CAD |
|
|
Term
| WHI Study w/ E+T in women with an intact uterus: (CHD, Breast C/A, Fractures) |
|
Definition
Increase CHD/CA
Decrease fractures |
|
|
Term
| WHI Treatment of post menopausal women w/ premarin alone? (Stroke, Heart disease, Breast cancer, fractures, dimentia) |
|
Definition
Slight Incrase in stroke
Heart disease, Breast cancer*** stay the same
Decrease fractures
Possible increase in dementia >>65 |
|
|
Term
| CHD with estrogen treatment usually effected what group of women specifically |
|
Definition
| Those in the 7th generation of life |
|
|
Term
| Current "safety" issue with prempro use for breat cancer and HRT? |
|
Definition
No increased incidence if less than 2 years of thx
Increased significantly and substancially if within 3 years |
|
|
Term
| What has been a notable finding relating to the use of progestins and development of breast c/a? Which specific progestin? |
|
Definition
MPA function as a tumor promoter for rat mammary cancer
Other progestins are fine |
|
|
Term
| What are the toxicities of E+P use in post menopausal women? |
|
Definition
Nausea, Bloating, slight weight gain, breast tenderness, depression, irritability
Exacerbation of migranes
Increased TG
incrased CHD/VTE/Stroke (only in 7th decade of life) |
|
|
Term
| What is the suggested "culprit" in E+P therapy that increases chance of breast cancer risk? |
|
Definition
|
|
Term
| SERM/Raloxifene effects on bone/lipids/breast/uterus tissue? How do these mixed actions happen? |
|
Definition
Beneficial effect on the bones/lipids
Anti-estrogen effect in the breast/uterus
These different actions happen because there are 2 forms of the estrogen receptor |
|
|
Term
| HDL effect of raloxifene compared to MPA+Premarin? |
|
Definition
| Raloxifene is not as good |
|
|
Term
|
Definition
Hot flashes
Leg cramps
Thromboembolism |
|
|
Term
PremPro vs Raloxifene:
-Hot Flash
-OP
-Endometrial Cancer
-Breast Cancer
-Thromboembolism |
|
Definition
Prempro: decreases; effective;prevents w/ progestin; increase; increase
Raloxifene:
Worsens;Benefit; No effect on cancers
Increase TE |
|
|
Term
| What is more effective for OP treatment: raloxifene or bisphosphonates? |
|
Definition
|
|
Term
| Which is more effective: raloxifene or tamoxifen for prevention of high risk breast cancer? |
|
Definition
About equally effective
Raloxifene has less SE, however (this is because tamoxifen is a weak estrogen and can increase incidence of endometrial cancer) |
|
|
Term
| What are aromatase inhibtitors used for? |
|
Definition
| Treatment of breast ancer in post menopausal females |
|
|
Term
| How do aromatase inhibitors work? |
|
Definition
| Block the conversion of androgens to estrogens |
|
|
Term
| What is the difference between tamoxifen and raloxifene? |
|
Definition
Tamoxifen is a partial estrogen agonist in the uterus/breast
Also has increased endometrial cancer and thromboembolism |
|
|
Term
Anastrozole.
Compared to tamoxifen
MOA.
Toxicity |
|
Definition
Better w/ more efficacy than tamoxifen
Aromatase inhibtior: blocks androgen to estrogen formation
Can increase OP risk. |
|
|
Term
| What type of therapy do type 1 diabetics receive? Why? |
|
Definition
| Therapy with insulin. Bc they don't make it bc destruction of B cells. |
|
|
Term
| What do you treat type 2 diabetics with? Why? |
|
Definition
Insulin sensitizers (bc they are resistant)
Therapy with secretogogues bc they can't release enough insulin and this actually decreases over time. |
|
|
Term
| What results for the differences in duration from sc injection of insulin? |
|
Definition
|
|
Term
| What is the effect of exercise on insulin perfusion? |
|
Definition
| If someone exercises, they can have increased absorption of their insulin. This can result in a hypoglycemic event. |
|
|
Term
|
Definition
Short acting insulin
Not made from humans
Solution for injection |
|
|
Term
Exubera
-Administered?
-Onset? |
|
Definition
Inhaled insulin
Similar in onset/duration to ultra short/rapid insulin |
|
|
Term
| Why are insulin's such as lispro important? Why do they have this effect? |
|
Definition
More rapid onset, for instances such as mealtime.
Shorter duration, so less post-prandial hypoglycemia
This insulin retains greater solubility in the sc fat, so it's absorbed more quickly |
|
|
Term
| What are the specific targets of type 1 insulin dependent therapy? |
|
Definition
Maintain Basal Level
Meals
"dawn effect" |
|
|
Term
| What is the dawn effect? What causes it? Why does your body do this? |
|
Definition
Secondary to normal increase in GH and cortisol @4-6AM, raises blood sugar and antagonizes insulin.
Your body does this bc it wants to ensure that it has enough glucose to get through the night. |
|
|
Term
| What are the toxicities of insulin? Explain what happens here? |
|
Definition
Hypoglycemia--stimulate movement of glucose into muscle and fat cells; stimulation of hepatic glycogen synthesis from plasma glucose
Increase or decrease fat @ injection site--absorption varies
Tempoary visual disturbances |
|
|
Term
| What does amylin do? What is the drug analog for this? |
|
Definition
| It is usually co-secreted w/ insulin and suppresses glucagon (by going over alpha cells). Pramintide is the drug name |
|
|
Term
| How is amylin messed up in diabetics? How does pramlintide differ? |
|
Definition
| If you don't secrete glucose, amylin is not co-sereted. Therefore, you must give premlitide..It's injected sq however, and doesn't have the same effects bc it doesn't cross the alpha cells. |
|
|
Term
| What does amylin suppress? |
|
Definition
|
|
Term
| Pramlintide approved in what type of diabetes? |
|
Definition
|
|
Term
| What effects does pramlintide have on the body? |
|
Definition
-Slows gastric emptying (satiety)
-Inhibits glucagon release
-May inhibit glucose induceed insulin release
-10% hypoglycemic risk (w/in 3 hours)
-Less weight gain relative to insulin alone
-Self limiting nausea |
|
|
Term
| What can propranolol do in type 1 diabetes? |
|
Definition
Blocks countre regulatory effect of epinephrine to cause live glycogenolysis after insulin regulation
-Also blocks some symptoms of hypoglycemia |
|
|
Term
| Which medications are secretogogues and which are sensitizers? (metformin, glitazones, sulfonylureas, incretin analog) |
|
Definition
Sulfonylureas and incretin analogs are secretogogues
Metformin and glitazones are sensitizers |
|
|
Term
| Explain the incretin effect. Does it happen with oral glucose or IV glucose? |
|
Definition
| Increases vagal ach, which enhances 1st phase. Stimulates beta cells, and induced release of incretines from intestine, glucose induced insulin release. |
|
|
Term
| Where is the site for secretogogue drug action? (which phase of insulin release_ |
|
Definition
|
|
Term
| MOA of sulfonylurea drugs: |
|
Definition
Give a rise in ATP/ADP ratio
Closes the K channel, and causes depolarization.
Calcium channels open, and stimulates insulin release |
|
|
Term
Glyburide:
DOA
Protein binding?
Excretion
Features |
|
Definition
18-24 hours--long
>>98% protein bound. nonionic. moderately active
excretion: 50% urinary and fecal
micronized formulation enhances bioavailability with similar effects on glycemic control |
|
|
Term
| Toxicity of sylfonylureas. Which are the main ones? |
|
Definition
-Hypoglycemia*** (caution, potential for irreversible or fatal CNS damage bc long DOA)
-Weight gain***
-Decrease in renal fxn
-Elderly who are somnolent and may have poor/irregular nutrition
-Alcohol or drugs displacing protein bound drug |
|
|
Term
| What two drugs are among the type 4 classes causing ADR? |
|
Definition
Insulin and hypoglycemica
Heparin and anti-cogaulants there also |
|
|
Term
| Sulfonylureas related to cardiac death: Explain significance |
|
Definition
two types of SUR receptors, SUR-1 in pancreas SUR-2 in the coronary circulation and myocardium (K channels that open during ischemia and cause violation (blocked by SUR agonsits)
--Lancet 2998 says NOT associated. |
|
|
Term
| Glyburide vs. Glimepiride in association with sudden cardiac death: |
|
Definition
Glyburide: SUR1 and SUR2 agonist/ greater risks of hypoglycemia
Glimepiride: SUR1 ONLY; less hypoglycemia action. |
|
|
Term
| What is exenatide, and how does it work? |
|
Definition
It is an incretin analog. (GLP-1) derived from gila monster venom
GLP-1 is ach induced analog from intestinal L cells. (glucose induced insulin release)--decrease glucagon. |
|
|
Term
| What are some other effects of exenatide? |
|
Definition
Increase number of beta cells
Decreased gastric emptying, and decreased appetite--weight loss*** |
|
|
Term
| Does exenatide cause glucose induced insulin release? |
|
Definition
| NO!! It just facilitates the process! |
|
|
Term
| What are some toxicities of exenatide? |
|
Definition
Pancreatitis***
Immunological reactions
Diarrhea/Malaise/Edema
Hypoglycemia
Dose dependent N/V |
|
|
Term
DPP-4 inhibitors:
-name
-administration/frequncy
-MOA
-Effect on insulin/glucagon |
|
Definition
Januvia
PO qd
Increase GLP-1 @ meals by preventing hydrolysis
-Minimize post-prandial hyperglycemia
-incraese insulin and decrease glucagon |
|
|
Term
| What is the main advantage of sitagliptin/januvia? |
|
Definition
| Decrease risk of hyperglycemia w/ minimal SE (no weight gain, GI, or pancreatitis) |
|
|
Term
| What is the purpose of insulin sensitizers in type 2 diabetics?? |
|
Definition
| They make the body respond to insulin better. |
|
|
Term
|
Definition
| Decrease liver production of glucose by inhibiting glycogenolysis and gluconeogenesis (the things that make glucose) |
|
|
Term
| What drug is usually first line in type 2 diabetics? |
|
Definition
|
|
Term
| What is a major side effect of metformin? How does this happen? |
|
Definition
| Aerobic lactic acidosis because metformin blocks gluconeogenesis, high increases pyruvate and therefore lactate |
|
|
Term
| What is the mortality rate of aerobic lactic acidosis which is assocated with metformin? |
|
Definition
|
|
Term
| What are contraindications with metformin to decrease lactic acid acidosis? |
|
Definition
DC if hypoxemia
Avoid with low renal function
Excessive alcohol intake (inhibits gluconeogenesis)
Avoid w/ CV or pulmonary disease |
|
|
Term
| What are the SE of metformin? Main one** |
|
Definition
Weight loss*
Transient metallic taste
N/V/D in initial pts |
|
|
Term
| How do the glitazones work? |
|
Definition
| They increase insulin sensitivity in adipose tissue by agonizing the PPAR and retinoid recepotr |
|
|
Term
| Side effects w/ glitazones? |
|
Definition
Liver toxicity- rare but bad.
Peripheral edema
Non-fatal MI ONLY w/ rosiglitazone (black box warning, only last resort, off market in europe)
Weight gain
Decreased efficacy of OC (bc hepatic enzyme induction)***
OP |
|
|
Term
| Drug interaction between metformin and acarbose? |
|
Definition
No. Both cause excessive GI effects
Acarbose can decrease metformin absorption. |
|
|
Term
| When should insulin be used in a type 2 diabetic? |
|
Definition
If diet/exercise/oral hypoglycemics don't work.
If surgery, fever, infection, pregnancy, or predisposing conditions/toxicity to agent |
|
|
Term
| What is the first line thx in type 2 diabetes, what comes next if this doesn't work. Why? |
|
Definition
1. Metformin
2. Add exenatide
Both can increase weight loss |
|
|
Term
| Why can ACE inhibitors be useful in diabetes? Type one or type 2 diabetes? |
|
Definition
| Because narrowing of vesssels in the kidney often cause nephropathy in these patients, so ACE decrases tone in the efferent arteriole, so nephropathy is decreased |
|
|
Term
| Why should diabetics not consume ethanol? |
|
Definition
| Chronic food deprivation and alcohol hypoglycemia secondary to decreased gluconeogenesis. Symptoms of intoxication may mask symptoms of hypoglycemia. |
|
|
