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Pharm Block 11
KYCOM Block 11
560
Pharmacology
Graduate
10/26/2013

Additional Pharmacology Flashcards

 


 

Cards

Term
what does HPA stand for
Definition
hypothalamic pituitary axis
Term
what does it mean when said HPA is dinural
Definition
higher activity in morning
Term
what can increase the HPA axis activity the best
Definition
stress, which can over ride normal feedback controls
Term
what does ACTH stand for, what is its job
Definition
adrenocorticotrophic hormones

stimylates adrenal cortex to secrete glucocorticoids, mineralcoricoids, weak androgens
Term
what are two weak androgens
Definition
andeostendione
dehydropiandrosteone
Term
what are the three zones of the adrenal cortex
Definition
zona glomerulosa - outer
zona fasculata - inner
zona reticularis - inner
Term
what enzymes does cortex outer zone have, what does it secrete
Definition
secretes aldosterone (mineralcorticoids) via aldosterone synthase
Term
how is mineralcorticoid production stimulated
Definition
ACTH acutely stimulates

angiotensin II receptors with Gs protein initiate it
Term
what happens to the cortex if it does not get enough stimulation
Definition
does not atrophy without pituitary stimulation
Term
what enzymes does the cortex inner zones have, what do they secrete
Definition
12-a-hydroxylase, 11-B0hydroxylase

secretes glyucocorticoids
Term
what stimulates inner cortex, what if there is too much stimulation
Definition
increases in ACTH cause hyperplasia, hypertrophy, increased cortisol and androgens
Term
what is steroidogenesis
Definition
ACTH increases due to impaired cortisol synthesis
Term
what happens if the inner cortex does not get stimulation
Definition
artophy
Term
what occurs in the acute phase of steroid production
Definition
within seconds increased supply of cholesterol to substrate (depends on amount of cholesterol)
Term
what occurs in the chronic phase of steroid production
Definition
within hours steridogenic enzyme transcription is increased
Term
where are most of the enzymes for steroid production
Definition
P450
Term
explain the process of steroid hormone production (3 steps)
Definition
1. cholesterol is turned into pregnilone via CHOLESTEROL SIDE CHAIN CLEVAGE ENZYME (P450 SCC) **RATE LIMIT

2. pregnilone is turned into cortisol, aldosterone, and adrenal androgens

3. products go to receptors and cause transcription. their structures are similar and they can activate e/o receptors
Term
how is production of cortisol stimulated
Definition
hypothalamus releases CRF and AVP which activate pituitary which releases ACTH which acrivates adrenal gland which releases cortisol
Term
what controls rate of cortisol production
Definition
ACTH release from pituitary corticotropes which are regulated by corticotropin releasing hormone (CRH)
Term
how is cortisol production/stimulation regulated (2)
Definition
ACTH can stimulate production but will burn out so it stops activity in hypothalamus

cortisol (glucocorticoids) stop activity in pituitary and hypothalamus
Term
cortisol and aldosterone bind same receptors for same affinity, how does the body discriminate
Definition
in mineralcorticoid (ALD) receptors it has enzyme barrier with 11-B-hydroxy DH that metabolizes cortisol to cortisone which cannot bind ALD receptor
Term
what are the 7 areas / systems that corticosteroids effects
Definition
carb and protein metabolism
lipid metabolism
cardiovascular
skeletal muscle
CNS
blood
immune supression/anti-inflammatory
Term
what do corticosteroids do to carb and protein metabolism
Definition
protect glucose dependent tissues from starvation (brain and heart)

glucogenolysis
glyconeogenesis
diminish glucose utilization in tissue

cause protein break down
Term
what do corticosteroids to to lipid metabolism
Definition
stimulate lipolysos
increase fat in neck (buffalo hump) and face (moon faces)
loss of fat in extremities
Term
what do corticosteroids to do skeletal muscle
Definition
needed for normal function
decreased muscle work due to adrenocorticol insufficiency (addison's disease)
hypercorticism: causes muscle wasting
Term
what effects do corticosteroids have on CNS (5)
Definition
mood, behavior, brain excitability

in cushings and addisons: neuroses, psychoses
Term
what does corticosteroids do to the immune system (7)
Definition
decreases cytokine production, lymphocyte response, histamines, leukotrienes, arachadonic acid release via phospholipase A2 inhibition
supress inflammation
decrease WBC circulation
Term
what are the HPA axis drugs (2)
Definition
ACTH and cosyntropin
Term
what are the short acting glyucocorticoids (2)
Definition
hydrocortisone
cortisone
Term
what are the intermediate acting glucocorticoids (3)
Definition
prednisone
methylprednisolone
triamcinolone
Term
what are the long acting glucocorticoids (2)
Definition
betamethazone
dexamethazone
Term
what are the corticosteroid inhibitors (3)
Definition
aminoglytethimide
ketoconazole
spironolactone
Term
what are the mineral corticoids
Definition
fludrocortisone
Term
MOA ACTH
Definition
high concentrations affect hypothalamus, stimulate corticoid and androgen receptors testing HPA axis
Term
MOA cosyntropin
Definition
tests HPA axis ysing synthetic ACTH residues 1-24
Term
side effects ACTH (2)
Definition
antigenic: comes from animals

vasopressin par causes hyponatremia
Term
short acting glucocorticoid MOA
Definition
metabolized via reduction in liver to 11-8-hydeoxyderivative to be active
Term
side effects of short acting glucocirticoids (4)
Definition
antiinflammatory
salt retension
minteral corticoid effects
less potent
Term
side effects of intermediate acting glucocorticoids (3)
Definition
more potent
low salt retension
low mineralcorticoid effect
Term
side effects of long acting glucocorticoids (3)
Definition
most potent
no salt retension
no mineralcorticoid effect
Term
shared side effects of all glucocirticoids (12)
Definition
withdrawl: flare of of disease
acute adrenal insufficiency
HPA supression
fluid and electrolyte imbalance
hypertension
hyperglycemia
fat redistribution
osteoperosis
myopathy
behavorial changes
cataracts
increased infection
Term
why do glucocirticoids cause acute adrenal insufficiency
Definition
due to rapid withdrawl after prolonged use
Term
who do glucocirticoids cause HPA supression
Definition
occurs with supraphysiologocal doses for 2wk +
Term
how do glucocirticoids cause osteoperosis
Definition
inhibit ostroblasts and decrease bone formation
Term
how are glucocirticoids administered (9)
Definition
oral, injected, inhaled, topical, optic, opthalamic, enema, rectal, retro rocket
Term
where are glucocirticoids metabolized and eliminated
Definition
metabolized in liver
excreted in kidney
Term
what affects the distribution of glucocirticoids
Definition
90% bound to proteins (corticosteroid binding globulin, transcortin, albumin)
Term
what are the clinical uses of glucocirticoids (15)
Definition
adrenal insufficiency
chronic primary adrenal insufficiency
congenital adrenal hypoplasia
RA
SLE
degrnerative joint
regional pain syndrome (injection)
allergies
asthma
PJP
influenza virus
ocular disease: supresses inflammation but increases IOP
cerebral edema
stroke
spinal cord injuty
Term
what are 2 diseases that cause chronic primary adrenal insufficiency
Definition
adrenal surgery

cortex lesion (addisons)
Term
MOA aminoglytethimide
Definition
inhibit P450 SCC
Term
aminoglytethimide clinical use
Definition
cushings
Term
ketoconazole MOA
Definition
inhibits C17-20 lyase
Term
ketoconazole clinical use
Definition
cushings
Term
spironolactone MOA
Definition
competes for mineralcorticoid receptor and stops Na reabsorption
Term
spironolactone clinical use
Definition
hyperaldosteronism
Term
fludorcortisone MOA
Definition
act on DCT to increase reabsorption of Na into plasma and excretion of K and H
Term
fludorcortisone clinical use (4)
Definition
addisons
severe salt loss
adrenogenital syndrome
orthostatic hypotension
Term
3 functions of FSH, which are the main ones
Definition
main: spermatogenesis in seminiferous tubules
regulate testicular growth
steroidogenesis
Term
what are the 4 functions of LH, which is the main one
Definition
main: regulate testosterone release from leydig cells
regulate resticular growth
steroidogenesis
spermatogenesis
Term
how is the release of testosterone regulated
Definition
it feeds back to hypothalamus and pituitary
Term
what is the process of testosterone production
Definition
cholesterol > progesterone > andostenedione or androstendione . testosterone
Term
what enzyme produces testosterone
Definition
12B-hydrosteroid dehydrogenase
Term
how is testosterone transported in the body
Definition
sex hormone binding globulin (can enter cell too may have role in action)

some on albumin

1-2% unbound
Term
what enzyme turns testosterone into DHT, where is it located
Definition
steroid 2a-reductase in non-genital skin and liver

steroid 5a-reductase in urogenital tract
Term
what is the difference between testosterone and DHT
Definition
DHT has a higher binding affinity
Term
what are the 6 general functions of testosterone
Definition
embryo: virilize urigenital tract of male

growth of testes, scrotum, penis

thicken and make skin more oily

increase height and muscle

axillary hair

larynd development
Term
what are the testosterone drugs (5)
Definition
testosterone aq
testosterone cypionate
fluxymesterone
testosterone gel (androgel)
danzol
Term
what are the anti-androgens (5)
Definition
spironolactone
flutamide
ketoconazole
cimetidine
finasteride
Term
what is used to treat impotence (3)
Definition
sildenafil
vardenaful
tadalafil
Term
MOA spironolactone (3)
Definition
stop androgen binding to receptor

stop synthesis of androgens

decrease p450enz 12a-hydroxylase C12-20 lyase complex which decreases testosterone
Term
MOA flutamide
Definition
non-steroid competitive inhibitor of DHT
Term
MOA ketoconazole
Definition
H2 receptor antagonist that competes for receptor
Term
finasteride MOA
Definition
5a-reductase competitive inhibitor of conversion enzyme of DHT to testosterone
Term
MOA impotence treatment
Definition
normally NO activates gyanulyl cyclase which causes smooth m. relaxation of corpus callosum letting blood in then phosphodiesterase (PDE) closes it off

drug inhibits PDE
Term
11 uses of all testosterone drugs
Definition
androgenic: hypogonadism, failure of hypo-pit-axis

anabolic: osteroperosis, burns, surgery recovery

counteract cortical hormone effects

growth: skeletal muscle growth in pre-pubescent boys and dwarfism

unapproved: increase lean body mass, muscle strength, agression
Term
clinical use of fluoxymesterone
Definition
more focused on anabolic effects of androgens (little androgenic effects)

osteoperosis, burns, surgurical recovery
Term
clinical use of danzol (3)
Definition
not very androgenic

endometrosis, fibrocystic breast disease, hereditary angioedema
Term
clinical use of spironolactone (2)
Definition
women: hirsutism
men: causes impotence
Term
clinical use of flutamide (1)
Definition
prostate cancer (with GnRH blocker or an estrogen)
Term
clinical use of ketoconazole (1)
Definition
prostate cancer (high dose)
Term
clinical use of cimetidine
Definition
women: histutism
Term
clinical use of finasteride (3)
Definition
prostatic hyperplasia

male pattern baldness (low dose)
Term
side effects flutamide (2)
Definition
hepatitis, anemia
Term
side effects ketoconazole
Definition
hepatotoxic
Term
side effect cimetidine
Definition
males with zollinger ellison get cynecomastia
Term
side effect finasteride
Definition
impotence
Term
side effects impotence treatment (6)
Definition
no effect in absence of stimulation

headache
flushing
dyspenia
change in color vision
decreased BP
Term
what is a major contraindication to impotence drugs
Definition
nitrates
Term
what is the longest lasting impotence drug, how long
Definition
36h
tadaladil
Term
side effects of all testosterone drugs in females only (8)
Definition
masculinization
acne
facial hair
deeper voices
male pattern baldness
muscle development
menstural irregularities
virilization of fetus
Term
side effects of all testosterone drugs in males only (5)
Definition
priapism
impotence
decreased spermatogenesis
gynecomastia
Term
side effects of all testosterone drugs in any sex or age (6)
Definition
increased LDL
decreased HDL
coronary artery disease
fluid retention
edema
PANCREATITIS
Term
side effects of all testosterone drugs in kids only (4)
Definition
abnormal sexual maturity
premature closure of epiphysis
hepatic abnormalities
psychosis
Term
side effect of testosterone gel
Definition
absorbed to skin, transfered to others on hands
Term
side effects of danzol
Definition
interacts with progesterone and androgen receptors and supresses pituitary-ovarian axis decreasing FSH and LH
Term
how are the 5 testosterone drugs administered
Definition
testosterone aq- IM
testosterone cypionate- IM
fluxymesterone- oral
testosterone gel- topical
danzol- oral
Term
where is testosterone gel metabolized and excreted
Definition
metabolized in liver
excreted in urine
Term
which testosterone has the shortest and longest half life, how long
Definition
testosterone aq: short 10-100 min
testosterone cypopnate: long 8d
Term
5 GnRH agonists
Definition
leuprolide
grosereline
nafarelin
histerlin
triptorelin
Term
4 GnRH Antagonists
Definition
ganirelix
cetorelix
abarelix
degarelix
Term
2 GH agonist
Definition
somatostatin
mecasermin
Term
2 GH antagonists / somatistatin agalons
Definition
octerotide
lanretoide
Term
1 GH blocker
Definition
pegvisomant
Term
1 FSH + LH drug
Definition
menotropins
Term
1 FSH drug
Definition
urofollitropin
Term
1 LH drug
Definition
Lutropin / recombinant hCG
Term
1 prolactin agonist
Definition
no such thing
Term
2 prolactin antagonist, 1 AKA
Definition
aka: dopamine agonist

bromocriptine
cabergoline
Term
2 vasopressin agonist and their receptors
Definition
8-L-arginine vasopressin (V1)

desmopressin (V2) (tetracycline antibiotic)
Term
3 vasopressin antagonists and their receptors
Definition
conivaptin (V1+V2)

tolvaptin (V2)

lithium (V2)
Term
MOA GnRH agonist
Definition
control FSH and LH release

pulsatile (replacement) therapy: increases release

continous (supression) therapy: inhibits release
Term
GnRH antagonist MOA
Definition
stops release of FSH and LH
Term
somatropin MOA
Definition
longitudinal growth via ILGF-1 and some ILGF-2
Term
mecasermine MOA
Definition
complex of ILGF-1 and ILGF binding protein 3 that causes growth
Term
GH antagonist MOA
Definition
somatostatin agonist stop GH, glucagon, insulin, and gastrin release
Term
GH blocker MOA
Definition
blocks GH receptors
Term
where do menotropins come from
Definition
postmenopausal urine
Term
where does urofollitropin come from
Definition
naturally modified
Term
where does lutropin come from
Definition
recombinant LH (identical to hCG so it can be used)
Term
what regulates prolactin
Definition
dopamine
Term
how does a prolactin antagonist work
Definition
dopamine agonist decreases prolactin release
Term
why would some have increased prolactin (2)
Definition
anti-psychotic drugs (dopamine receptor blockers)
prolactinoma
Term
what happens when prolactin is increased (4)
Definition
amenorrhea
no ovulation
galactorhea
breast tenderness
Term
oxytocin MOA
Definition
induces myometrial contraction by changing ion concentrations
Term
what does ADH to do V receptors (8), what type of receptor
Definition
Gq receptors

V1a: vasoconstriction, glycogenolysis, platelet aggregation, ACTH release

V1b: ant pituitary, pancrease, brain, adrenal medulla
Term
what tissues have V2 ADH receptors on them, what type of receptor is it
Definition
Gs receptor on aquaporin 2 on collecting duct cells
Term
GnRH agonist side effects
Definition
continous therapy gives flare in condition prior to supression (desensitization)
Term
GH antagonist side effects (5)
Definition
flatulence
steratorrhea
biliary sludge
gall stones
sinus bradycardia
Term
oxytocin side effects
Definition
simillar to ADH
water retension or intoxication (if on IV)
Term
lithium side effects
Definition
mimics nephrogenic diabetes insupidus
Term
how can GnRH be administered
Definition
pulastile: every 1-4 hours
continous
Term
why is administering GnRH different than just giving the hormone (gonadorelin)
Definition
the half life of the drug will be longer than administering the hormone
Term
what is the benifit of using a GnRH antagonist over agonist (2)
Definition
no flare in hormone levels before supression
more rapid onset
Term
what blocks oxytocin (3)
Definition
B blockers
Mg sulfate
inhaled anasthetics
Term
what is pulsatile GnRH used for (3)
Definition
infertility
delayed puberty
hypogonadism
Term
what is continous GnRH used for (4)
Definition
endometrosis
uterine fibroids
prostate cancer
central precoious puberity
Term
when do you decide to treat central precoious puberty
Definition
before 8 in girls and before 9 in boys
Term
how is prostate cancer treated (2)
Definition
GnRH agonist with androgen receptor blocker to inhibit flare
OR
GnRH antagonist
Term
what do GnRH antagonists treat
Definition
prostate cancer
ovarian hyperstimulation
prep for in vitro fertilization
Term
why is GnRH antagonist used for prep for in vitro fertilization
Definition
prevents premature LH surge
Term
what is somatropin used for (3)
Definition
GH deficiency (<4cm/y)

Growth failure: prader willi, turner syndrome, AIDS wasting

idiopathic short stature
Term
what is mecasermin used for
Definition
patient is deficient in ILGF-1 and exogenous GH isnt working
Term
GH antagonist uses (3)
Definition
DOC for acromeagly and gigantism

hormone secreting tumors

bleeding esophageal varices
Term
what causes acromeagly and gigantism
Definition
GH secreting adenoma
Term
what are 4 GH secreting tumors
Definition
gastrinoma
glucagonoma
carcinoid secreting tumors
carcinoid syndrome
Term
what is carcinoid syndrome
Definition
carcinoid tumor with liver metastasis and serotonin secretion
Term
what is the use for pegvisomant
Definition
acromeagly third alternative
Term
use of FSH and LH drugs
Definition
induce spermatogenesis or ovulation in infertility
Term
use of prolactin antagonist (2)
Definition
hyperprolactinemia

bromocriptime: acromeagly 2nd alternative
Term
oxytocin use (3)
Definition
lactation in natural doses

pharmacological doses: control post partum hemorrhage, induce labor but causing uterine contraction
Term
uses of a V1 agonist (3)
Definition
vasoconstriction stops bleeding esophageal varicies, post-op ileus, abdominal distension
Term
uses of V2 agonist (2)
Definition
central diabetes insipidus
SIADH
Term
use of V1/V2 antagonist (2)
Definition
euvolumeic or hypervolemic hyponatremia
SIADH
Term
what is diabetes insipidus
Definition
increased ADH due to pituitary or hypothalamus trauma or tumor
Term
what is nephrogenic diabetes insiputis
Definition
broken V2 receptors on nephron
Term
what categories of drugs are hypothalamic hormone drugs (2)
Definition
GnRH/gonadorelin agonist

GnRH antagonist
Term
what categories of drugs are anterior pituitary hormone drugs (8)
Definition
GH agonist
GH antagonist
GH blocker
FSH + LH
FSH
LH
prolactin agonist
prolactin antagonist
Term
what categories of drugs are the posterior pituitary hormone drugs (4)
Definition
oxytocin
vasopressin agonist
vasopressing antagonist
lithium
Term
explain thyroid hormones from ingestion of iodine to T3/4 production and storage (7 steps)
Definition
1. ingest iodine
2. TSH stimulates iodine uptake and hormone production
3. iodine active transport into thyroid
4. activated with THYROID PEROXIDAZE (using Hb and H2O2)
5. monotyrostol and diiodotyrosyl are produced
6. THYROID PEROXIDASE links AA making T3 and T4 in a 1:4 ratio
7. T3 and T4 are stored in thyroglobulin
Term
explain thyroid hormone release from thyroglobulin to arrival at the tissues (7 steps)
Definition
1. thyroglobulin fuses with lysoosme

2. proteolytic enzymes break it into...
- monotyrosyl and dioxotyrosyl which stay in thyroid
- T3/T4 which go into blood
- excess iodine which stays in thyroid

3. T3/4travel in blood on thyroxine binding globulin and albumin

4. T3/4 are released at tissues
Term
what motifications occur to T3/4 at the tissues (2)
Definition
diodinase enzymes remove 5' outer ring...

- 5-DI and 5-DII turn T4 to T3 (41% of T3)

- 5-DIII turns T4 into reverse T3
Term
where are T3 and T4 degraded
Definition
liver
Term
what are the differences in T3 and T4 elimination
Definition
T3 is eliminated in 2 d due to increased protein binding increasing hald life

T4 is eliminated in 6-7d
Term
how does iodine regulate thyroid hormone production
Definition
decreased iodine decrease thyroid hormones which stimulate TSH causing thyroid hypertrophy (gioter) and selective T3 formation
Term
how does the production of thyroid hormone reulate itself
Definition
it doesnt

it stops TSH production but increases thyrotropin releasing hormone (TRH) production which cancel
Term
what is the difference in tissue binding and activity of T3 and T4
Definition
T3 binds with 5x higher affinity

T4 binds with lower affinity
Term
what are the 6 areas in general thyroid hormones affect
Definition
growth and development
basal metabolic rate
released when cold to regulate body temp
heart
CNS
cholesterol metabolism
Term
how does the thyroid effect growth and development (5)
Definition
differentiation and myelination of cnS

potentiation of GH, PTH, and calcitonin
Term
in what organs does the thyroid hormone effect on basal metabolic rate have the most effect (4)
Definition
heart, muscle, liver, kidney
Term
what changes do thyroid hormones cause in the heart (4)
Definition
sensitize it (synergistic)
increase CO, HR, contractility
Term
what effects do thyroid hormones have on the CNS
Definition
sensitize catecholamine receptors (synergistic)
Term
what does thyroid hormone do to cholesterol metabolism
Definition
stimulates metabolism of cholesterol to bile acids

important! lack can cause hypercholesterolemia
Term
what is the name for adult hypothyroidism
Definition
myexedema
Term
what is the name for child hypothyroidism
Definition
cretinism
Term
what are the 9 signs of child hypothyroidism
Definition
impaired growth
mental retardation
pot belly
dwarfism
lethargy
hypothermia
slow HT
poor appetite
death if untreated
Term
what are the 8 signs of adult hypothyroiodism
Definition
pallid expression
blank expression
dry skin
brittle nails
weakness
reduced CO
fatigue
cold intolerence
Term
what are two diseases of hyperthyroidism
Definition
graves and plummers disease
Term
what are 7 characteristics of graves disease
Definition
diffuse toxic goiter
exophthalmos: big eyes
hot moist skin
forced rapid heart beat
angina
arrhythmia
heart failure
Term
what are 4 causes of graves disease
Definition
autoimmune: IgG bind to TSH receptor

chorionic: placental secretion of TSG stimulates receptors in pregnancy
Term
what are 6 signs of plummer's disease
Definition
toxic nodular goiter
hot moist skin
forced rapid heart beat
angina
arrhythmia
heart failure
Term
what are 5 general signs of hyperthyroidism
Definition
hot moist skin
forced rapid heart beat
angina
arrhythmia
heart failure
Term
what are the 3 treatments for hyperthyroidism
Definition
surgical removal of thyroid
local radiation with radioactive iodine
anti thyroid agents
Term
what causes a thyroid storm (7)
Definition
complication of hyperthyroidism triggered by stress, thyroid surgery, trauma, diabetic ketoacidosis, labor, heart disease, radioactive iodine
Term
what are the 7 treatments of a thyroid storm
Definition
fluids
anti-pyretics
cooling blankets
propylithiouracil in large doses
iodates
B blockers and Ca can control tachyarrhytima
dexamethasone
Term
what are the three thyroid hormone drugs, what hormone is each
Definition
desiccated thyroid - T3 and T4
levothyroxine - T4
liothyroxine - T3
Term
what are the advantages of using liothyronlne over levothyroxine (4)
Definition
liothyroline does not have to be converted for full potential, fast onset, good absorption, good when someone has problem with T4 to T3 conversion enzyme
Term
what is the clinical use for thyroid hormones (3)
Definition
hypothyroidism
non-toxic goiter
replacement therapy
Term
what are the contraindications to thyroid hormones (3)
Definition
acute MI

increase anticoagulant effects

reduce digitalis effects
Term
what are the 3 side effects or problems with desiccated thyroid
Definition
antigenic because it comes from pork

highly variable biological activity

religous objections to treatment
Term
what are the two anti-thyroid or thiroureylenes
Definition
propylthiouracil and methimazole
Term
MOA of anti-thyroids
Definition
stop iodiniation of throsyl in thyroglobulin

block thyroid peroxidae inhibiting coupling reaction

prophylthiouracil- blocks conversion of T3 to T4
Term
what are the three side effects of anti-thyroids
Definition
agranulocytosis

marrow aplasic (improves on DC)

secreted into breast milk
Term
what can anti-thyroids be used to treat (7)
Definition
graves disease
small goiters
mild hyperthyroidism

deplete thyroid hormone before radiation hyperthyroidism in elderly

after radiation

prethyrodectomy- prevent surge in surgery

thyroid storm - prophylthiouracil due to T3 to T4 ability
Term
iodine MOA
Definition
saturated potassium iodide prevents thyroid hormone release

inhibits hormone synthesis by decreasing TSG and blcking its action (wolff chickoff effect)
Term
4 side effects of iodine
Definition
rebound hyperthyroidism

angioedema

hypersensitivity

iodism
Term
what is iodism, what are 7 signs
Definition
chronic intoxication of iodine

burning bouth, throat, eyes, headache, productive cough, gastric irritation, skin lesions
Term
what are the three uses of iodine
Definition
reduce vascularity and increase gland firmness

thyroid storm prevention

pre surgery
Term
MOA radioactive iodine
Definition
gets trapped in thyroid and B-rays destory parenchyma
B-rays only destory bad tissue
Term
what are three side effects of radioactive iodine
Definition
cannot use in pregnancy

delayed hypothyroidism

chromosomal abberations (cannot use in kids and pregnancy)
Term
what is the half life of radioactive iodine
Definition
8d
Term
what is the use of radioactive iodine
Definition
safe after surgery
Term
what is another name for radioactive iodine
Definition
iodine 131
Term
define modeling
Definition
growth and development of endochondral bone
Term
define remodeling, when does it occur
Definition
continoous process of breakdown and renewal
final option after linear growth in finished
Term
what are the three steps in remodeling
Definition
IL-1 and IL-6 released from osteoblast stimulate osteoclast to reabsorb tunnels in corticoid bone or scallops in trabecular bone

osteoclasts replaces bone areas with collagen, osteocalcin, and protein

mineralization occurs after osteoblasts achieve 20 microns of thickness
Term
what are three problems with bone remodeling
Definition
deficits occur after each cycle

deficits increase with age

can never get back to origional bone mass after remodel
Term
what three things can alter remodeling
Definition
diet
hormones
drugs
Term
what hormones alter remodeling (5)
Definition
thyroid
PTH
vitamin D
glucocorticoids
estrogen
Term
6 functions of Ca
Definition
neuron excitability
neurotransmitter release
muscle contraction
membrane integrity
blood coagulation
secondary messenger for hormones
Term
where is Ca stored
Definition
skeleton in a pool exchangable with interstitial fluid
Term
what is stored in bone (5)
Definition
Ca
Na
K
Mg
flouride
Term
how do people obtain Ca
Definition
75% is from dairy intake
adults 45-50 yo should have supplement with vitamin D
Term
how does Ca get into the body
Definition
facilitated diffusion through SI
Term
how much Ca is absorbed
Definition
inversly proportional to intake
(not as good as we age)
Term
where and how much Ca is excreted
Definition
150mg is loss via billiary and intestinal sloughing
9mg is secreted in kidney but 98% is reabsorbed
Term
what do loop diruetics do to Ca excretion
Definition
act on ascending limg to cause increased Ca loss (but its a better diruetic)
Term
what do thiazida diruetics do to Ca excretion
Definition
uncouple Na and Ca excretion causing reduced Ca loss
Term
where is phosphate located in the body
Definition
80% in bone
15% in soft tissue
Term
what are 5 functions of phosphate
Definition
membrane phospholipids
modifies Ca
role in renal H excretion
secondary messenger
energy metabolism
Term
where, how, and how much phosphate is absorbed in the gut
Definition
active transport and vit D stimulate absorption
2/3 is absorbed
Term
where is phosphate is excreted, how much
Definition
excreted in urine
80% is reabsorbed
Term
how is PTH made
Definition
prehormone is cleaved in ER and in golgi it makes PTH which lives in secretory granules until secreted. if not secreted soon enough they undergo proteolysis and the gland gets hypertrophy and hyperplasia
Term
what is the half life of PTH
Definition
2-5 min
Term
how does PTH act on target cells
Definition
G protein
Term
what are the functions of PTH (4)
Definition
increase Ca and P absorption in intestines by activating vitamin D

increase bone reabsorption bia osteoblast action on osteoclast

increase Ca reabsorption in kidney

inhibit kidney phosphate reabsorption
Term
how is calcitonin made
Definition
parafollicular C cells in thyroid release it when plasma Ca is high
Term
what are the two actions of calcitonin
Definition
inhibition of osteoclast bone reabsorption

increased urinary Ca and P excretion
Term
what are the two types of viramin D and where are they made
Definition
D2: yeast
D3: animals and higher plants
Term
how is vitamin D made
Definition
in the bodycholesterol is reduced and is converted by UV into D3 hich is procesed in liver to calcifediol and then to calcitrol in kidney
Term
what are 4 pieces of evidence suggesting vitamin D is a hormone
Definition
made in body in skin
not needed in diet (in theory)
transported in blood to distant sites
specific receptors in target tissues on DNA
Term
how does vitamin D affect the body
Definition
increases absorption of P and Ca in SI

increases mobalization of P and Ca from bone with PTH help

decreases P and Ca excretion in kidney
Term
how is PTH made
Definition
prehormone is cleaved in ER and in golgi it makes PTH which lives in secretory granules until secreted. if not secreted soon enough they undergo proteolysis and the gland gets hypertrophy and hyperplasia
Term
what is the half life of PTH
Definition
2-5 min
Term
how does PTH act on target cells
Definition
G protein
Term
what are the functions of PTH (4)
Definition
increase Ca and P absorption in intestines by activating vitamin D

increase bone reabsorption bia osteoblast action on osteoclast

increase Ca reabsorption in kidney

inhibit kidney phosphate reabsorption
Term
how is calcitonin made
Definition
parafollicular C cells in thyroid release it when plasma Ca is high
Term
what are the two actions of calcitonin
Definition
inhibition of osteoclast bone reabsorption

increased urinary Ca and P excretion
Term
what are the two types of viramin D and where are they made
Definition
D2: yeast
D3: animals and higher plants
Term
how is vitamin D made
Definition
in the bodycholesterol is reduced and is converted by UV into D3 hich is procesed in liver to calcifediol and then to calcitrol in kidney
Term
what are 4 pieces of evidence suggesting vitamin D is a hormone
Definition
made in body in skin
not needed in diet (in theory)
transported in blood to distant sites
specific receptors on DNA
Term
what are three things vitamin D does in the body
Definition
absorption of Ca and P in SI

increase mobalization of Ca and P from bone with PTH help

decrease P and Ca excretion in kidney
Term
5 symptoms of hypocalcemia
Definition
parasthesia
increased neuromuscular excitability
laryngospasm
muscle cramps
tonic clonic convulsions
Term
2 symptoms of hypercalcemia
Definition
diverse clinical conditions
dehydration due to compormised renal concentration
Term
4 symptoms of hypophosphatemia
Definition
malaise
muscle weakness
osteomalacia
decreases RBC ATP and 2,3-BPG causing hemolytic anemia and impaired oxygenation - rare
Term
what are 4 causes of hypercalcemia
Definition
increased intake of Ca in hypothyroid pt

familial benign hypercalcemia

vitamin D toxicity

milk alkali syndrome
Term
what is used to treat hypercalcemia
Definition
calcitonin
IV bisphosphate
corticosteroids - vitamin D toxicity
Term
what is wrong in familial benign hypercalcemia
Definition
parathyroid cannot sense Ca so it increases PTH
Term
how can you get vitamin D toxicity
Definition
overuse of hyperparathyroid drugs
Term
what is used to treat vitamin D toxicity
Definition
calcitonin
IV bisphosphate
corticosteroids
Term
what causes milk alkali syndrome
Definition
milk alkali powder increases Ca reabsption
Term
what are two conditions that cause hypercalcemia and hypophosphatemia
Definition
hyperparathyroidism
PTH secreting tumor
Term
what is used to treat hypercalcemia and hypophosphatemia
Definition
calcitonin
IV bisphosphate
IV/oral phosphate - hyperparathyroid
corticosteroids - PTH tumor
Term
how does hyperparathyroid cause problems, what are two complications
Definition
increases PTH secretion
renal stones, peptic ulcers
Term
what type of cancer is a PTH secreting tumor
Definition
squamous or epithelial cell
Term
what is used to treat PTH secreting tumor
Definition
calcitonin
IV bisphosphate
corticosteroids
Term
what is used to treat hyperparathyroidism
Definition
calcitonin
IV bisphosphate
IV/oral phosphate
Term
what causes paget's disease, 6 symptoms
Definition
excessive remodeling
weak, mishape, painful bones
deafness
cord compression
cardiac failure
Term
what is used to treat paget's disease
Definition
calcitonin
IV bisphosphate
Term
what are two conditions that cause hypophosphatemia
Definition
aluminum antacid toxicity
normal children: mild childhood anemia due to decreased affinity of Hb to O2
Term
what is used to treat hypophosphatemia
Definition
IV/oral phosphate
Term
what three conditions can cause hypocalcemia and hypophosphatemia
Definition
familial benign hypophosphatemia
rickets/osteomalacia
hypophosphatemia
Term
what is used to treat hypocalcemia and hypophosphatemia
Definition
IV/oral phosphate
vitamin D - rickets/osteomalacia
Term
what is wrong in familial benign hypophosphatemia, what is a complication
Definition
impaired vitamin D production causes increased PTH which depletes bone of Ca and P

causes dwarfism
Term
what is wtong in rickets
Definition
impaired vitamin D production causes increased PTH which deplates bone of Ca and P
Term
what are signs of rickets in kids (2)
Definition
soft bones
deformities
Term
what are signs of rickets in adults
Definition
painful bones
weak muscles
Term
what are three conditions that cause hypocalcemia and hyperphosphatemia
Definition
hypoparathyroidism
pseudohypoparathyroidism
renal disease
Term
what is wrong in hypoparathyroidism , what is the cause
Definition
decreased release o f PTH due to thyroid or neck surgery, autoimmune or genetic disease
Term
how is hypoparathyroidism treated
Definition
Ca replacement
vitamin D
Term
what is wrong in pseudohypoparathyroidism, what other symptoms are there
Definition
body does not respond to PTH
short stature, metacarpals, metatarsals
Term
what is the treatment for pseudohypoparathyroidism
Definition
Ca replacement
Term
what does renal disease do to Ca and P
Definition
Ca excretion
P retention
Term
how do we treat the Ca and P effects of renal disease
Definition
aluminum antacids
calcitriol
Term
calcitonin MOA
Definition
acts on osteoclast to inhibit bone reabsorption
rapid Ca reduction
Term
limit in calcitonin use
Definition
in hypercalcemia body will become sensitized in a few days
Term
what are 4 uses of calcitonin
Definition
hypercalcemia
hypercalcemia + hyperphosphatemia
paget's disease
osteoperosis
Term
what are the 2 IV bisphosphates
Definition
alendronate
pamidronate
Term
what is the MOA of IV bisphosphate
Definition
inhibit osteoclast bone reabsorption
reduction of Ca over several days
Term
what 4 things for IV bisphosphates treat
Definition
hypercalcemia
hypercalcemia + hyperphosphatemia
paget's disease
osteoperosis
Term
MOA corticosteroids
Definition
takes 1-2 days to reduce Ca
Term
what two things do corticosteroids treat
Definition
lymphoma (PTH secreting tumor)
vitamin D toxicity caused hypercalcemmia
Term
IV/oral phosphate MOA
Definition
increases plasma phosphate levels
Term
what are 3 side effects of IV/oral phosphate
Definition
mild laxative
if not needed is rapidly excreted (no storage)
excess can reduce Ca via percipitation in soft tissue and be toxic
Term
4 uses of IV/oral phosphate
Definition
hypophosphatemia
hypocalcemia + hypophosphatemia
hyperparathyroidism
mild laxative
Term
MOA vitamin D analogs
Definition
supression of PTH decreases bone turn over
Term
side effects of vitamin D analogs
Definition
possible vitamin D toxicity
Term
4 uses of vitamin D analogs
Definition
rickets / osteomalacia
osteoperosis
treat hypoparathyroidism due to thyroid or parathyroid operation
renal failure 0 calcitrol
Term
what are the three types of vitamin D analogs and their administration
Definition
ergocalciferol: oral, iv, im
dihydrotachysterol: oral
calcitrol: oral, iv
Term
what molecule is ergocalciferol
Definition
pure vitamin D2
Term
what molecule is dihydrotachysterol
Definition
reduced vitamin D2
Term
what are the three types of Ca analogs and their administeration and why
Definition
Ca chlorida: IV (IM causes vasodilation and burning)

Ca glyconate IV (IM causes abscess)

CA gluceptate IV or IM (IM causes some irritation)
Term
what are two uses of calcium analogs
Definition
hypocalcemia + hyperphosphatemia
malabsorption or malnutrition of Ca
Term
aluminum antacids MOA
Definition
decrease plasma phosphate by decreasing phosphate absorption
Term
aluminum antacids side effects
Definition
hypophosphatemia
Term
aluminum antacids clinical use
Definition
clearance of phosphate in kidney failure
Term
define osteoperosis, who is it normally seen in
Definition
low bone mass and microfractures with minimal trauma in older women
Term
what are the types of osteoperosis
Definition
primary type 1
primary type 2
secondary
Term
what is the cause of osteoperosis primary type 1
Definition
loss of trabecular bone due to estrogen lack at menopause
Term
what is the cause of osteoperosis primary type 2
Definition
loss of cortical and trabecular bone in men and women due to remodeling inefficiency, diet, activation of parathyroid axis with age
Term
what is the cause ot secondary osteoperosis
Definition
systemic illness
medication: glucocorticoids, phenytoin
Term
what are the three regulators of bone density
Definition
physical activity
endocrine status
Ca intake
Term
what is the trend in bone density over time
Definition
stable until 50 then progressivel decline
Term
what are 8 drugs that treat osteoperosis, state if they are for a specific kind or patient
Definition
calcitonin
IV bisphosphate
vitamin D analogs
Ca carbonate
estrogen - post menopause osteoperosis
raloxifene
thiazide diruetuc
testosterone - hypogonadal males
Term
what is a side effect of Ca carbonate
Definition
constipation when >2000 mg/d
Term
what estrogen is used for osteperosis
Definition
conjugated equine estrogen without progesterone
Term
side effect of raloxifene
Definition
anti-estrogen in breast tissue
Term
MOA of raloxifene
Definition
selective estradiol receptor modulator

agonist in liver and bone
Term
how do thiazidie diruetics help osteoperosis
Definition
reduce Ca excretion
Term
what is the main way to distinguish between diabetes mellitus and insipidus
Definition
melllitus has glucose in the urine
Term
why is the glucose in the urine in diabetes
Definition
glucose in the blood exceeds capacity for reahsption so it is excreted in the urine
Term
what is the cause of type I diabetes (3)
Definition
B cells cant make enough insulin, destoried B cells dont respond to glucose, B cell lesions and necrosis
Term
what are 5 signs of type I diabetes
Definition
polydipsia
polyphagia
polyuria
ketoacidosis
hyperglycemia
Term
describe the typical type I diabetes patient
Definition
onset in childhood
looks undernourished
Term
does diabetes have a genetic predisposition
Definition
type II more than type I. but yes
Term
what is the treatment for type I diabetes
Definition
exogenous insulin
Term
describe the typical type II diabetes patient
Definition
over 30yo
obease
Term
what is the cause of type II diabetes
Definition
insulin resistant and inabilit to make enough insulin
can progress to be like type I
Term
what is the treatment for type II diabetes
Definition
weight reduction, exercise, dietary modification
oral hypoglycemics
last resort: exogenous insulin
Term
what are 6 complications of diabetes
Definition
hyperglycemia
increased BP
neuropathy
proteinuria
cardiovascular disease (more type II)
diabetic retinopathy
diabetic neuropathy
Term
what is the treatment for neuropathy and proteinuria
Definition
ACE inhibitor
Term
what is the treatment for diabetic cardiovascular disease
Definition
statins lower lipid and cholesterol, stop smoking
Term
what is the treatment for diabetic neuropathy
Definition
foot care, ulcer care, erythromycin for vagus neuropathy causing GI immotility
Term
what are the two types of diabetes insipidus, what causes each
Definition
central: deficiency in ADH
nephrogenic: lack of response to ADH
Term
how can you distinguish between central and nephrogenic diabetes insipidus
Definition
demopressin replaces ADH so if urine production decreases they have central
Term
how does diabetes insipidus cause disease (no matter which type)
Definition
causes lack of reabsorption of water in the CD
Term
where is insulin made
Definition
B cells of islets of langerhans
Term
what are normal fasting insulin levels
Definition
80-120 mg/dL
Term
what occurs in fasting metabolism
Definition
adipose releases FA which is processed in liver to glucose
pancreas releases glucagon which signals to the liver to make glucose
glucose is first used in the brain then other major organs
Term
what are normal prandial insulin levels
Definition
<180 mg/dL
Term
what occurs in prandial metabolism
Definition
carbs are ingested and turned into glucose which is ingested and distributed to the organs
pancreas releases insulin which tells the liver, muscle, and adipose to store glucose
Term
how does glucose get into the cell
Definition
insulin turns on GLUT facilitated diffusion transporters which activate TK which intrinsically phosphorlyates various substrates

insulin stimulates translocation of GLUT4 transporters to the membrane allowing for glucose to get into the cell
Term
how are B cells activated to release insuln
Definition
glucose comes through GLUT2 receptors and glucokinase phosphorlyates it so it can stay in the cell.

G6P is shuttled to ATP production which increases ATP in relation to ADP

ratio switches on K channel and cell moves from basal state (hyperpolarized and inhibited) to depolarized

this causes Ca cannels to open and Ca moves in stimulating release of insulin
Term
how is insulin made
Definition
single chain precursor called preproinsuln (A and B chains connected by C peptide) is cleaved in ER to proinsulin, processed in golgi to insulin, and released with C peptide
Term
what is the clinical significance of C peptide
Definition
helps determine if insulin levels are due to edogenous (no C) or endogenous (has C) insulin
Term
what is the best determinant of insulin levels, why
Definition
HBA1C because it shows BG over several months
Term
what is the cycle of insulin
Definition
increases after a meal and is at low basal levels between meals
Term
where is insulin made
Definition
B cells of islets of langerhans
Term
what are normal fasting insulin levels
Definition
80-120 mg/dL
Term
what occurs in fasting metabolism
Definition
adipose releases FA which is processed in liver to glucose
pancreas releases glucagon which signals to the liver to make glucose
glucose is first used in the brain then other major organs
Term
what are normal prandial insulin levels
Definition
<180 mg/dL
Term
what occurs in prandial metabolism
Definition
carbs are ingested and turned into glucose which is ingested and distributed to the organs
pancreas releases insulin which tells the liver, muscle, and adipose to store glucose
Term
how does glucose get into the cell
Definition
insulin turns on GLUT facilitated diffusion transporters which activate TK which intrinsically phosphorlyates various substrates

insulin stimulates translocation of GLUT4 transporters to the membrane allowing for glucose to get into the cell
Term
how are B cells activated to release insuln
Definition
glucose comes through GLUT2 receptors and glucokinase phosphorlyates it so it can stay in the cell.

G6P is shuttled to ATP production which increases ATP in relation to ADP

ratio switches on K channel and cell moves from basal state (hyperpolarized and inhibited) to depolarized

this causes Ca cannels to open and Ca moves in stimulating release of insulin
Term
how is insulin made
Definition
single chain precursor called preproinsuln (A and B chains connected by C peptide) is cleaved in ER to proinsulin, processed in golgi to insulin, and released with C peptide
Term
what is the clinical significance of C peptide
Definition
helps determine if insulin levels are due to edogenous (no C) or endogenous (has C) insulin
Term
what is the best determinant of insulin levels, why
Definition
HBA1C because it shows BG over several months
Term
what is the cycle of insulin
Definition
increases after a meal and is at low basal levels between meals
Term
what are the short acting insulins (4)
Definition
insulin lispro
insulin aspart
insulin glulisine
insulin regular
Term
what are the long acting insulins (2)
Definition
insulin glargine
insulin detemir
Term
what are the insulin AA combinations (3)
Definition
lispro + protamine
asprt + protamine
NPH + R
Term
what insulins have the best HBA1C control
Definition
short acting
Term
what are the side effects of all insulin medications (2)
Definition
hypooglycemia
lipodystrophy
Term
what are the ratings of the hypoglycemic effects of the different types of insulin
Definition
short acting has most
long acting is second
no peak insulin has no effect
Term
what are three sources of insulin, which is used today
Definition
beef - outdated
pork - outdated
E. coli produces human insulin
Term
how is insulin administered (2)
Definition
subcutaneous
IV (emergency)
Term
which type of insulin is the most rapidly absorbed
Definition
short acting
Term
how well is insulin absorbed
Definition
depends on prep
human is absorbed the best and most quickly
Term
where is insulin metabolized and by what
Definition
metabolized to be inactive in liver and kidney by insulinase
Term
how long does it take for short acting insulin to kick in, how long does it last
Definition
onset <15 min
duration 3-6 hours
Term
why is long acting insulin long acting, what is the duration
Definition
NPH (insulin isophane suspension complexed with zinc) allows slow release
12-18h
Term
which insulin has slow release and rapid onset, how does it work
Definition
insulin combined with AA

onset <10min because insulin dosent stick together due to AA substitution and is more free for use
Term
how long does no peak insulin last
Definition
24 hours of consistant plasma levels
Term
how is a pregnant woman with diabetes treated
Definition
insulin!
Term
how do insulin pumps work
Definition
uses short acting insulin on continous infusion to provide steady basal insulin level and bolus injections depending on size and time of meal
Term
when is IV insulin used
Definition
emergency, when someone needs insulin fast
ketoacidosis
Term
what is a non-intensive diabetes treatment
Definition
NPH with lispro at breakfast and dinner
Term
what are the two most populat insulin redigmen, which is bettwe
Definition
glargine x2 and lispro x4
or
insulin pump

best one depends on pt
Term
what is the general pathway in diabetes treatment
Definition
diet and exercise (if type II)

check liver function - if abnormal use insulin

check kidney function (Cr)- if not abnormal use metformin

if still hyperglycemic- try sulfonylurea

if still hypoglycemic- try combo meal time + basal medication)

if still hyperglycemic- use insulin
Term
what drug is contraindicated with oral hypoglycemics
Definition
salicylates
Term
what drugs antagonize insulin or oral hypoglycemics (4)
Definition
corticosteroids, estrogen, thyroid hormones
thiazides
Term
what are the 4 sulfonylureases
Definition
gen 1: chlorpropamide

gen 2: glipizide, glyburide, glomepiride
Term
what are the two thiazolidiendiones
Definition
pioglitazone
rosiglitazone
Term
what are the two aa derivatives
Definition
metaglinide
repaglinide
Term
what are the two a-glycosidase inhibitors
Definition
acarbose
miglitol
Term
what drug is a biguanide
Definition
metformin
Term
what drugs mimic incretin (2)
Definition
exenatide
liraglutide
Term
what drugs inhibit DPP-4 (3)
Definition
stilagliptin
saxagliptin
linagliptin
Term
what drug is synthetic amylin hormone
Definition
pramlintide
Term
what drig is a SGLT2 inhibitor
Definition
canaglifolozin
Term
what is used as a anti-hypoglycemic (2)
Definition
glucagon
glucose tablets
glucose source - grape juice
Term
what are the 5 categories of oral hypoglycemics
Definition
sulfonylureases
thiazolidiendiones
AA derivatives
a-glucosidase inhibitors
biguanides
Term
MOA solfonylureases (3)
Definition
bind and block K channel on B cells depolarizing, opening Ca channel letting it in and causing insulin release

reduce glucagon (indurect due to insulin decrease)

increase insulin blocking (maybe increasing receptors)
Term
MOA thiazolidiendiones (3)
Definition
increase sensitivity to insulin in tissues

decrease hepatic glucose output

use PPARy in adipose to increase insulin receptors
Term
AA derivative MoA
Definition
same as sulfonulureases
Term
a-glucosidase inhibitor MOA
Definition
inhibit enzyme in SI brush border decreasing sugar absorption
prevents post-prandial rise in glucose
Term
metformin MOA
Definition
inhibits gluconeogenesis
stimulates glucolysis
increases glucose uptake in tissues
Term
exenatide and liraglutide MOA
Definition
mimics incretins

incretins are released from intestines in response to food and increase insulin secretion
Term
sitagliptin, saxagliptin, linagliptin MOA
Definition
inhibit dipeptitdyl peptidase 4 (DPP-4) so incretin cannot be degradedand insulin increases
Term
pramlintide MOA
Definition
synthetic amylin hormone

normally made in pancreas after meal to slow rate of food absorption in intestines and reduce appetite
Term
SGLT2 inhibitor MOA
Definition
blocks Na/glucose cotransporter 2 in PCT preventing reabsorption
Term
glucagon MoA
Definition
stops active hypoglycemia
Term
side effects sulfonylureases (4)
Definition
all cause hypoglycemia

mostly 1st gen causes: hyponatremia, disulfram, hypotension (so basically don't use in old people)
Term
thiazolidiendione side effects (2)
Definition
hypoglycemia

MI and other cardio events - dont use with CHF pt (especially rosiglitazone)
Term
AA derivative side effects
Definition
low hypoglycemia risk
Term
a-glucosidase inhibitor side effects (3)
Definition
flatulence
diarrhea
abdominal cramps
NO hypoglycemia
Term
metformin side effect
Definition
lactic acidosis in pt with renal or heart failure

NO hypoglycemia
Term
exenatide, liraglutide side effects (5)
Definition
liragltide; weight loss

hyoiglycemia: low risk

nausea, vomiting, diarrhea
Term
sitagliptin, saxagliptin, linagliptin side effects (2)
Definition
URI
nasopharyngitis
Term
pramlintide side effects (3)
Definition
weight loss
nausea
hypoglycemia
Term
SGLT2 inhibitor side effects (3)
Definition
increased K
female GU infections
Term
how is glucagon administered
Definition
SU,IV, IM
Term
how is canaglifolozin administered
Definition
oral once a day before first meal
Term
how is pramlintide administered
Definition
SC before meals
Term
how is sitagliptin, saxagliptin, linagliptin administered
Definition
oral
Term
how is exenatide, liraglutide administered
Definition
SC
Term
what is sitagliptin, saxagliptin, linagliptin used for
Definition
type II diabetes - need functioning B cells
Term
what is exenatide, liraglutide used for
Definition
type II diabetes - need functioning B cells
Term
what is pramlintide used for
Definition
adjunct to insulin in type I or II diabetes (lower insulin though)
Term
where is metformin metabolized and excreted
Definition
not metabolized
excreted in urine
Term
what plasma protein is metformin bound to
Definition
none
Term
which oral hypoglycemic has the shortest half life
Definition
AA derivatives
Term
how are thiazolidiendiones used
Definition
with insulin or in another combo (not enough alone)
Term
where are sulgonylureases metabolized and excreted
Definition
liver

excreted in kidney
Term
which drug should you never use in pregnant diabetic patients, why
Definition
thiazolidiendiones
can cross placenta and deplete fetal pancreas of insuln
Term
what are the 4 main uses for estrogen or progesterone drugs
Definition
hormone replacement therapy / post-menopause

contraception

health benifits of contraception

receptor antagonist: breast cancer, infertility
Term
what is another name for the follicular phase, how long is it
Definition
proliferative phase, length varies
Term
what are the two phases of the menstural cycle
Definition
follicular
luteal
Term
what is another name for the lutela phase, how long is it
Definition
secretory
14 days
Term
explain the process of hormone production in the follicular phase
Definition
pulses of GnRH cause release of LH and FSH
estrogen increases reduce LH and FSH release
inhibin is mad ein ovary and causes feedback decreasing FSH
mid cycle estrogen reaches peak for 36 hours and stops inhibiting gonadotropins and causes surge instead
Term
what happens in the luteal phase
Definition
corpus luteum secretes progesterone (estrgen levels stay elevated)
if pregnancy does not occur corpus luteum regresses due to lack of LH and progesterone and falls so endometrium sheds causing menstural discharge
Term
what does progesterone do for the baby/uterus
Definition
stops endometrium proliferation
helps with implantation and growth of blastocyst
causes growth of endometrial vessels
Term
what is the general structure of estrogen
Definition
18C with an aromatic phenolic acid ring (required for selective high affinity binding)
Term
what is the natural form of estrogen, where is it made in men and women
Definition
17B estradiol

women: ovarian granulosa cells
men and post-menopause; adipose tissue viea DHEA from adrenal cortex
Term
what stimulates for estrogen release
Definition
gonadotropins stimulate aromatase
Term
what are precursors for estrogen
Definition
androstendione
testosterone
Term
estrogen needs aromatic ring to work, how does it get it
Definition
aromatase using NADPH and O
Term
where are estrogen receptors located
Definition
ovarian granulosa, sertoli and leydig cells, stroma of adipose, placenta, blastocyte, brain
Term
how is estrogen converted between its different forms
Definition
estradiol oxidized to esterone via 12-hydroxysteroid DH

estradiol and esterone converted to estriol
Term
what is the down side of using natural progesterone
Definition
large first pass effect
Term
what are the two types of synthetic progesterone
Definition
21C progesterone skeletons
19-nortestosterone
Term
what is 19-nortestosterone
Definition
progesterone without C19, 20, 21
resembles testosterone more so has effects of both
Term
where is progesterone made, when
Definition
made in testis, adrenal cortex, placenta, and ovary corpus luteum

begins being made in follicular phase and increases in luteal phase later in pregnancy
Term
what is the relationship between progesterone and the cns
Definition
increases body temp 1 deg midcycle until onset of menstural flow (ovulation)
Term
what is the down side to using estrogen alone in hormone replacement
Definition
risk of endometrial carcinoma due to hyperplasia of the endometrium
Term
what is the benifit of combined estrogen progesterone therapy in hormone replacement
Definition
estrogen receptors dont get out of hand because it has to make some progesterone receptors too
Term
how is a post-menopausal women with a uterus treated forr hormone replacement
Definition
progesterone/estrogen combination
Term
what are contraindications to progesterone/estrogen hormon replacement
Definition
unable to tolerate progestins
risk of cardiovascular disease
poorlipoproteins use estrogen alone
Term
how is a post-menopausal women with a hysterctomy treated for homeone replacement
Definition
estrogen alone, no where for it to cause carcinoma
Term
what are 4 ways to administer hormone replacement therapy
Definition
cyclic
continous
transdermal patch
vaginal ring
Term
what is the redigmen for cyclic hormone replacement
Definition
estrogen 15d
estrogen and progesterone 10d
repeat
Term
what is the redigmen for continous hormone replacement
Definition
estrogen and progesterone daily
OR
estrogen and progesterone 10d
esteogrn 15d
repeat
Term
what are the contents of combination oral contraceptives
Definition
estrogen: ethinyl estradiol or mestraol
progesterone: norethindrone or norgestrel
Term
what are the three types of oral contraceptives
Definition
monophasic
biphasic
triphasic
Term
how are monophasic oral contraceptives administered
Definition
same amount of estrogen and progesterone in each tablet for 21d
Term
how are biphasic oral contraceptives administred
Definition
two tablets with different amounts for 21 days
Term
what is the benifit of biphasic oral contraceptives
Definition
reduce steroids administred because it approximates estrogen to progesterin ratio of menstural cycle
Term
how are triphasic oral contraceptives administered
Definition
three tablets with different amounts for 21 days
Term
what is the general MOA of contraceptives
Definition
estrogen supresses FSH and stops follicular development
proteitiating action of progestrin which stops LH surfe
progesterin stops ovulation, thickens cervical mucous, and causes endometrial atrophy
estrogen stabilizes endometrial lining (bleeding control)
Term
what are 4 contraindications to oral contraceptives
Definition
thrombotic disease
over 35 and smoking
hormone sensitive tumor (breast canceR)
pregnancy
Term
what are the 4 forms of estrogen, talk about the bioavailability and blood distribution of each
Definition
natural: 12B estradiol, esterone, estriol: poor oral bioavailability high first pass effect

17B estradiol estrace: microcrystaline form, reduced first pass
Term
what are the benifits of a transdermal estrogen patch
Definition
slow release
increased bioavailability
constant blood levels
Term
what are the 4 types of synthetic estrogens
Definition
conjugated
ethinyl estradiol
menastrol
estradiol cruptionate
Term
what is conjugated estrogen made of where does it come from
Definition
many conjugated estrogen metabolites
pregnant mares
Term
what is the structure of ethinyl estradiol
Definition
ethinyl group on C17 of estrace nucleus
Term
how is mestranol metabolized
Definition
prodrug
converted to ethinyl estradiol
Term
what is a non-steroidal estrogen agonist
Definition
diethylstilbesterol
Term
what is the MOA of oestrogen contraceptives
Definition
passivly diffuse into cell

bind nuclear receptors in genital, breast, HPA, bone, and liver

interact with estrogen response elements (ERE) which alter transcription

supress FSH stopping follicle development and stabilizing endometrial lining (bleeding control)
Term
what are the 12 negative side effects of estrogen contraceptives
Definition
elevated TG
decrease bile acid (due to cholesterol secretion)
removal: hot flashes, chills, sweating, parasthesia

nausea
cramping
fluid retention
dizzy
headache
breast tenderness
Mi or thrombosis in women >35 who smoke
Term
what are the good side effects of estrogen contraceptives (and natural functions) (14)
Definition
decrease cholesterol
increase HDL
decrease LDL

growth of uterus, vagina, fallopian tubes, breast, ducts, sexual development

fat distribution, growth spurt, fusion of epiphysis

increase plasma binding proteins

prevent bone loss: block reabsorption

decrease endometrial and ovarian cancer

decrease fibroadenomas, fibrocysts, PID

decrease blood loss and cause cycle regularity
Term
why are esgtrogen contraceptives used (7)
Definition
contraception
replacement
fibroadenomas
fibrocysts
PID
cycle regularity
failure of ovarian development
Term
what are three diseases that include failure of ovarian development
Definition
dwarfism
turner syndrome
hypopituitarism
Term
what is the administration of the 4 estrogen contraceptives
Definition
conjugated: oral active
ethinyl estradiol: oral active
mestranol: not for replacement
estradiol crypionate: long acting given IM
Term
how are estrogen drugs excreted
Definition
in urine with glucourindes and sulfate conjugates
Term
what are the side effects of diethylstilbesterol
Definition
congenital abnormalities in fetus
Term
why would you use diethylstilbesterol
Definition
prostate cancer
Term
what are the three antiestrogen drugs
Definition
chlomiphene
tamoxifen
raloxifene
Term
clomiphene MOA
Definition
competitive agonist of estrogen binding

stimulates ovulation in women with normal HPA and estrogen levels by opposing negative feedback increasing gonadotropin pulse amplitude (not frequency)
Term
tamoifen MOA
Definition
competitive antagonist of estrogen binding
antagonizes receptor
Term
raloxifene MOA
Definition
partial agonist effect on bone reabsorption and plasma lipoproteins
NO effect on reproductive tissues
selective estrogen receptor modulator
Term
what is the structure of clomiphene
Definition
mixed isomeres
cis has estrogenic activity
trans has anti-estrogenic activity
Term
what is the structure of tamoxifen
Definition
pure trans isomere (only the useful part of clomiphene)
Term
why would you use clomiphene
Definition
infertility
Term
why would you use tamoxifen
Definition
block hormone induced breast tumors

adjunct with surgery or chemo
Term
why would you use raloxifene
Definition
osteoperosis post-menopause
Term
what are the side effects of clomiphene (6
Definition
ovarian hyperstimulation
increased multiple births
ovarian cysts
anti-estrogenic: follicle, endometrium, cervical mucous (counter active)
Term
what are the side effects of tamoxifen (3)
Definition
decrease tumor development in other breast
endometrial carcinoma
hormone independent breast tumors
Term
how is clomiphene administered, half life, where metabolized, where excreted
Definition
oral
t.5 = 5-7d
hepatic metabolism
GI excretion
Term
tamoxifen: aministration, metabolism, excretion
Definition
oral
hepatic metabolism
Gi excretion
Term
explain how tamoxifen is eliminated
Definition
phase 1: 4-11d
phase 2: 4d (hydroxytamoxifen)
Term
what are the two aromatase modifying drugs
Definition
amastrazole
exemestane
Term
amastrazole MOA
Definition
selective aromatase inhibitor stops conversion of androgens to estrogens
reversible
Term
esemestane MOA
Definition
aromatase inactivastor acts as false substrate for enzyme and intermediate irreversibly binding to acrive site (suicide inhibition) stopping conversion of androgens to estrogens

irreversible
Term
what is the clinical use of amastrazole
Definition
post-menopausal hormone dependent breast cancer
Term
what is the use of exemestane
Definition
post-menopausal hormone dependent breast cancer
Term
what is an anti-progesterin drug, what progesterin structure family is it from
Definition
mifepristone

19-nortestosterone derivative
Term
MOA mifepristone
Definition
potent competitive inhibitor of progesterone and glucocorticoids

decrease in progesterone cause abortion by detaching blastocyst

myometrial contraction and cervical softening allow for expulsion
Term
mifpristone use
Definition
administer up until 49 days after pregnancy
abortion pill
Term
what are the 4 progesterone contraceptives and their progesterone structure family
Definition
norethindrone: 19-nortestosterone
norgestrel: 19-nortestosterone
mexroxyprogesterone acetate: 21C progesterone
progestasert
Term
what is the admnistration of the 4 progesterone contraceptives
Definition
norethindrone: oral
norgestrel: oral, subdermal (5y)
mexroxyprogesterone acetate: IM (3mo)
progestasert: intrauterine
Term
MOA progesterone contraceptives
Definition
supresses LH surge
thickens cervical mucous
decreases endometrial proliferation
stops ovulation
Term
where are progesterone receptors
Definition
genital, mammary, CNS (hypothalamus)
Term
what is the role of progesterone in pregnancy
Definition
maintains it
supresses mensturation and uterine contraction
proliferation of mammary acini
Term
why not use a progesterone contraceptive all alone
Definition
slightly less effective
Term
what are the uses of progesterone contraceptives
Definition
ovarian supression: dysmenorrhea, endometrosis, histurism, uterine bleeding

hormone replacement: combined with estrogen

fibroadenomas
fibrocysts
PID

cycle regulation
Term
in general why is progesterone added to estrogen contraceptives, why aernt progesterone side effects a big deal
Definition
avoid side effects of estrogen

progesterone side effects usually go away after 1 year
Term
what are the side effects of progesterone contraceptives (11)
Definition
spotting
amenorrhea
decreased HDL
increased LDL
edema
weight gain: fat deposition
bloating
acne
histuism

impaired glucose tolerance: longer term, short term increases basal insulin

MI and thrombosis in women >35 who smoke
Term
MOA of the morning after pill
Definition
combination oral contraceptive in a high dose
Term
administration of the morning after pill
Definition
taken within 72 hours of intercourse
ineffective after 7 days (cannot un-implant)
Term
what is the 21 patch made of
Definition
ethinyl estradiol norelgestromin
Term
administration of 21 patch
Definition
1 patch for 3 weeks
Term
use of 21 patch
Definition
contraception
Term
define agonist
Definition
drug that binds to the same site as the ligand and makes the same signal
Term
define allosteric agonist
Definition
drug that binds to different site than drug making no signal but causing drug to be more effective
Term
define partial agonist
Definition
drug produces lesser response than the ligand and competes for ligand site
Term
define competitive agonist
Definition
drug binds reversibly to receptor but increase in ligand can overcome it
Term
define non-competitive agonist, what are the two types
Definition
binds to receptor and prevents agonist from producing max effect

irreversible: more common, same receptor
allosteric: different receptor
Term
how can you tell if something on a graph is more potent or effective
Definition
moving left on the X axis is more potent
moving up on the Y axis is more effective
Term
what does a partial agonist graph look like compared to agonist
Definition
less effective
shorter, less high on the Y axis
Term
what does a allosteric agonist graph look like compared to agonist
Definition
same effectiveness (height on Y axis)
increased potency (more left on X axis)
Term
what does a non-competitive agonist graph look like compared to agonist
Definition
very short, sinking
less effective (height on Y axis)
less potent (more right on X axis)
Term
what does a antagonist graph look like compared to agonist
Definition
same effectiveness (height on Y axis)
less potency (more right on X axis)
Term
how does a Gs protein work
Definition
activates cAMP which increases PKA
Term
how does a Gi protein work
Definition
decreases cAMP which decreases PKA
Term
how does a Gq protein work
Definition
releases IP3 and DAG
IP3 releases Ca
DAG and Ca activate PKC
Term
what is the point of equal ionization
Definition
pKa
Term
what happens to an acid and base if you put it in stuff that is lower (more basic) than the pKa
Definition
acid will ionize
base will not ionize
Term
what happens to an acid and base if you put it in stuff that is higher (more acidic) than the pKa
Definition
acid will not ionize
base will ionize
Term
what form of a drug is best excreted
Definition
WA will be excreted beter in a basic enivornment

WB will be excreted better in an acidic enivornment
Term
what form of a drug is best distributed in the body
Definition
the same form

WA likes acid
WB likes base
Term
what is used to fix and WB or WB drug OD
Definition
NaHCO3 is used to alkalize urine and fix WA OD

NH3CL is used to acidify urine and fix WB OD
Term
define inducer
Definition
increases gene expression of P450 metabolizing enzymes which decreases the plasma level of the drug making it less effective and decreasing presence of symptoms
Term
what are 5 examples of inducers
Definition
rifampin, bensopyrine, chronic ethanol, phenytoin, barbituates
Term
define inhibitor
Definition
decrease gene expression for metabolizing P450 enzymes increasing plasma concentration of the drug which increases symptoms
Term
what are 4 examples of inhibitors
Definition
cimetidine, erythromycin, ketonazole, grapefruit
Term
define first order metabolism
Definition
rate of drug metabolism is proportional to concentration of the free drug
constant fraction of drug is metabolized per unit time
Term
define zero order metabolism
Definition
drugs with large doses saturate metabolizing enzymes
constant amount of drug is metabolized per unit time
Term
what are 3 examples of drugs with zero order kinetics
Definition
aspirin, ethanol, phenytoin
Term
what is a maintience dose for, how is it calculated
Definition
adjust rate so input equals rate of loss to keep a steady plasma level

(Cs)(Cl)/(F)
Term
what is loading dose for, how is it calculated
Definition
load initial volume of drug needed

(Cp)(Vd)/(F)
Term
how long does it take to get to steady state, what is it dependent on(2)
Definition
4-5 half lives
depends on half life and steady state is determined by first order kinetics
Term
NRTI: name 3 drugs
Definition
zidovudine
lamivudine
entricitabine
Term
NRTI MOA
Definition
host adds 3P then drug terminates DNA elongation
Term
NRTI side effects (3)
Definition
peripherial neuropathy
lactic acidosis
marrow supression - zidovudine
Term
NTRTI drug name
Definition
tenofovir
Term
NTRTI MOA
Definition
host adds 2P, drug terminates DNA elongation
Term
NNRTI drug name
Definition
enfavirenz
Term
NNRTI side effects
Definition
maculopapular rash
CNS effects - enfavirenz
Term
NNRTI MOA
Definition
binds reverse transcriptase causing inactivation
Term
name a protease inhibitor, what is the MOA
Definition
ritonavir
inhibits protease stopping viral replication
Term
protease inhibitor side effects (5)
Definition
central fat deposition
insulin release
hyperglycemia
P450 inhibitor - increased in infants
Term
how is ritonavir used
Definition
in combination with out PI because it is an extra good P450 inhibitor
Term
name an integrase inhibitor
Definition
raltegravir
Term
integrase inhibitor MOA
Definition
inhibits viral genetic integration into host chromosomes
Term
name three anti-herpes drugs
Definition
acyclovir
gencyclovir
foscarnet
Term
acyclovir MOA
Definition
TK adds 1P, host adds 2P, DNA chain termination
Term
acyclovir side effects (4)
Definition
delerium
tremor
seizure
nephrotoxicity (crystal urea, drink water)
Term
gencyclovir MOA
Definition
TK adds 1P, host adds 2P, DNA chain termination
Term
gencyclovir side effects
Definition
marrow supression
Term
foscarnet MOA
Definition
stops reverse transcriptase and DNA polumerase
Term
fascarnet side effects (2)
Definition
nephrotoxicity
altered Ca and P balance
Term
what two herpes drugs treat CMV
Definition
foscarnet, gencyclovir
Term
name and influenza a and b drug
Definition
oseltamivir
Term
oseltamivir MOA
Definition
neuroaminidase inhibitor that stopps viral budding
Term
name two TB drugs
Definition
isoniazid
rifampin
Term
isoniazid MOA
Definition
stops mycolic acid assembly
Term
isoniazid side effects
Definition
peripherial neuritis (take B6 to fix)
Term
isoniazid clinical use
Definition
only TB
Term
rifampin MOA
Definition
stops RNA polymerase
Term
rifampin side effects (5)
Definition
P450 inhibitor
pseudomembrane colitis
renal failure
anemia
red/orange urine
Term
rifampin clinical use
Definition
broad
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