Endocrine Drugs Flashcards
risks of tight glucose control
hypoglycemia
hypoglycemic coma
mechanism of action of insulin
binds insulin receptor, stimulates GLUT4 channel membrane proliferation (via exocytosis). GLUT4 channels allow glucose to enter the cell
end result: higher intracellular glucose, lower extracellular (plasma) glucose
do the various insulin formulation differ in their pharmacokinetic or pharmacodynamic principles?
pharmacokinetic
all are identical pharmacodynamically to endogenous insulin
actions of insulin
glycogenesis & cellular uptake of glucose
protein synthesis from amino acids
triglyceride production from fatty acids
(all anabolic actions)
Can you give insulin PO? IV?
Only SubQ or IV
Which type of insulin is closest to endogenous insulin (pharmacokinetically)?
regular insulin
list the rapid acting insulins
aspart
lispro
glulisine
How long after administration is the peak action of rapid acting insulin
30-60minutes
NPH is a ______-acting insulin.
intermediate
_______ is an insulin with no peak time of activity
glargine
which insulins can be mixed together in the same syringe?
NPH & short acting insulins
what medication class is metformin
biguanide (oral antidiabetic medication)
which two classes of oral antidiabetic medications carry a hypoglycemia risk when administered alone?
sulfonylureas
meglitinides
adverse effects of metformin
most common: GI upset
decreased B12 & folate absorption
lactic acidosis with toxicity
why do some oral antidiabetics carry a hypoglycemia risk and some don’t?
those that do promote insulin release
those that do not work via other mechanisms (decreased insulin resistance, decreased glucose absorption or glucose excretion)
when should metformin be held?
hypoperfusion states
such as sepsis, cardiac failure, renal failure, etc.
what is the difference between the meglitinides and the sulfonylureas?
meglitinides are shorter acting & only taken with meals
why do thiazolidinediones not work for type 1 diabetics?
insulin must be present since the drug works by increasing insulin sensitivity
mechanism of action of alpha glucosidase inhibitors?
inhibition of alpha glucosidase enzyme
results in delayed carbohydrate absorption
mechanism of action of sodium glucose cotransporter 2 inhibitors (SGLT2 inhibitors)?
inhibition of SGLT2 in renal tubules = increased renal excretion of glucose
SGLT2 is responsible for 90% of glucose reabsorption back into the plasma
actions of glucagon
glycogenolysis (increased free glucose)
decreases glyconeogenesis
stimulates glucose production from the liver
opposite of insulin
treatment for growth hormone deficiency?
exogenous growth hormone (somatotropin - identical to endogenous)
routes of administration for somatropin?
IM or SubQ
adverse effect of somatropin
hyperglycemia
treatment for prolactin excess?
dopamine agonists
i.e. cabergoline or bromocriptine
function of ADH
increase water reabsorption in the collecting ducts (preserves H2O & concentrates the urine)
at very high doses = vasoconstriction & GI smooth muscle contraction
Two ADH replacements?
vasopressin
desmopressin (DDAVP)
actions of vasopressin
vasoconstriction
smooth muscle contraction
actions of desmopressin (DDAVP)
anti-diuresis (H2O reabsorption in collecting ducts)
no vasoconstriction
route of administration of DDAVP
PO
intranasal
primary endogenous glucocorticoid?
cortisol
primary endogenous mineralocorticoid?
aldosterone
s/s cortisol deficiency
hypotension
hypoglycemia
cachexia
depression/lethary
s/s cortisol excess
HPA axis suppression
hypertension
hyperglycemia
fat redistribution (buffalo hump, etc.)
osteoporosis
menstrual irregularities
infection risk
CNS excitation
s/s aldosterone deficiency
hyponatremia
hyperkalemia
acidosis
cellular dehydration
late & untreated can lead to renal failure, CV collapse, death
s/s aldosterone excess
myocardial & vascular remodeling & fibrosis
SNS activation
baroreceptor reflex disruption
untreated this leads to decreased contractility, dysrhythmias, hypertension to heart failure & MI
how does ketoconazole treat glucocorticoid excess?
blocks glucocorticoid synthesis
What is the drug used for mineralocorticoid excess? What is the drug class?
spironolactone
potassium sparing diuretic
What time of day should adrenal hormone replacement therapy be administered?
morning
(mimics endogenous secretion)
Is the dose of gluco/mineralocorticoid HIGHER for replacement therapy or for anti-inflammation?
Anti-inflammation
for replacement therapy, we just give the dose that results in the patient having normal hormone levels (not suppressing inflammation). Only higher doses (i.e. putting the patient in “excess”) result in decreased inflammation & infection risk
How much higher dose is a stress dose
up to 10x
Which glucocorticoid is identical to cortisol?
hydrocortisone
what does fludrocortisone do?
exogenous mineralocorticoid
(fluid retention, potassium excretion)
Does dexamethasone have more glucocorticoid or mineralocorticoid activity?
glucocorticoid. very little mineralocorticoid
What two hormones does the thyroid gland release?
T3 & T4
Which is more physiologically active, T3 or T4?
T3
A high TSH indicates a _____(low/high) T3 and/or T4 level?
low
Which thyroid hormone has a longer half life?
T4
(7 days vs. 1 day T3)
Which thyroid hormone is more potent?
T3
actions of thyroid hormone
increased basal metabolic rate (increased O2 consumption & heat production)
increased HR & contractility (increased CO & myocardial O2 demand)
promotion of growth & development
How many half lives does it take for a drug to reach a plateau level in the body?
4
How long does it take levothyroxine to reach steady state
approximately one month
Routes of administration of levothyroxine?
primarily PO
IV in emergency
levothyroxine is taken 30mins before meals because:
absorption is reduced by food
treatment for thyrotoxic crisis (thyroid storm)?
medications to suppress thyroid hormone synthesis & release (thionamides)
supportive care:
- beta blockers to attenuate tachycardia
- sedation
- cooling
- fluids
mechanism of action of thionamides?
inhibit peroxidase, which results in decreased thyroid hormone synthesis
onset of action of thionamides
Only decrease synthesis of NEW thyroid hormone. So already synthesized hormone isn’t affected
Thus, full effect can take 3-12 weeks
methimazole is preferred over PTU because:
- longer 1/2 life
- more potent
- the serious adverse effects are less common
adverse effects of methimazole & PTU (thionamides)
pruritic rash with initial therapy
arthralgias
rare: agranulocytosis, hepatotoxicity, vasculitis
overdose = hypothyroid symptoms
which thionamide is preferred in 1st trimester pregnancy and why?
PTU
less placental crossing
adverse effect of radioactive iodine (iodine 131)
bone marrow depression (results in low RBC, WBC, platelet counts)
care precautions for the nurse when caring for a patient taking radioactive iodine
less than 30mins per day of patient contact
follow facility protocols for disposal of body wastes
high doses of lugol solution can result in
hyperthyroid symptoms
use for lugol solution
rapid and temporary decrease in thyroid hormone
how is estrogen metabolized & excreted?
hepatic metabolism (CYP450), renal excretion
how is progesterone metabolized & excreted?
hepatic metabolism (CYP450) & renal excretion
non-reproductive effects of estrogen
- maintain bone density & mass
- vasodilation, decrease LDL, increase HDL
- increase coagulation & fibrin breakdown
- CNS protection
- glucose homeostasis
adverse effects of exogenous estrogen administration
endometrial CA (d/t hyperplasia)
breast CA
CV thromboembolic events
gall bladder disease
non-reproductive effects of progesterone
constipation
maternal immune suppression
growth/proliferation of breast ducts
adverse effects of exogenous progesterone administration
breast tenderness
headache
abdominal discomfort
naturally, which hormone is increasing during the proliferative phase of the menstrual cycle
estrogen
thus, it should make sense that exogenous estrogen can result in strong endometrial proliferation & thus endometrial CA
effects of menopause - i.e. why do women seek treatment?
vasomotor symptoms
sleep disturbances
urogenital atrophy
altered lipid metabolism
changes in cognition & sexual response
why is hormone therapy for menopause controversial?
risk of increased thromboembolic events (CV events like blood clots, MI, CVA, etc.)
Why is progesterone added to HT and oral birth control?
to prevent endometrial CA
(estrogen only = unopposed proliferation of the endometrium!)
**no uterus, no need to add progesterone!
absolute contraindications to HT or hormonal birth control
pregnancy
breast or endometrial CA
acute liver disease
uncontrolled hypertension
thrombosis (DVT, MI, CVA)
undiagnosed vaginal bleeding
Is a 40 year old heavy smoker a good candidate for hormonal birth control?
no (increased risk for thromboembolic events)
but it is not absolutely contraindicated
what does SERM stand for and what does it mean?
selective estrogen receptor modulator
agonize some estrogen receptors, antagonize others - attempts to provide benefits w/out risks
what is the main difference between tamoxifen & raloxifene?
raloxifene doesn’t result in endometrial proliferation (i.e. no endometrial CA risk)
risks of SERM therapy?
endometrial CA risk (only tamoxifen)
increased hot flashes
increased thromboembolism risk
benefits of SERM therapy?
breast CA prevention
osteoporosis prevention
improved lipid profile
why do some women get HT for osteoporosis prevention and others don’t?
those that are very high risk for osteo require lifelong therapy.
it is not standard for all women because of the high risk for thromboembolic events as one ages
Which hormones are in oral contraceptives?
estrogen AND progesterone
or
just progesterone
mechanism of action of combination oral contraceptives?
suppression of ovulation: high estrogen provides negative feedback to suppress FSH (follicle cannot mature, no ovulation occurs)
also alters cervical mucus & endometrium
mechanism of action of minipills?
cervical secretion changes
what are minipills?
progestin-only OCs
how many days in a cycle for minipill administration?
n/a - this medication is taken continuously throughout the cycle (no placebo)
list several other formulations of contraceptives
transdermal patch
vaginal ring
subdermal implants
IM/subQ injections
IUDs
which two drugs are used for medical abortion?
mifepristone (antiprogestin)
misoprostol (prostaglandin)
mechanism of action of mifepristone w/ misoprostol
mifepristone blocks progesterone receptors, which results in detachment of conceptus as well as cervical softening/dilation
misoprostol is a prostaglandin that directly stimulates uterine contractions
what percent of infertility is due to the female?
50%
mechanism of action of clomiphene
blocks estrogen receptors in hypothalamus & pituitary
normally estrogen binds these receptors & provides negative feedback, leading to decreased LH & FSH
when receptors are blocked, LH & FSH continue to be secreted = ovulation
what is ovarian hyperstimulation syndrome (OHSS)
exogenous hormone administration for infertility leads to exaggerated response –> ovaries swell, leak fluid, & are painful.
Can be dangerous - fluid can collect in abdomen/chest, electrolyte disturbances can occur, blood clots, renal failure, etc.
how do menotropins work?
they are a 50/50 mixture of LH/FSH. So just work like endogenous LH/FSH –> result in follicular maturation & ovulation
adverse effect of menotropins
OHSS
when should exogenous hCG be administered during fertility treatmnets?
after clomiphene or menotropin
(those drugs are for follicular growth, hCG is for ovulation - commonly called “trigger shot”)
list four classes of tocolytics
beta 2 agonists
calcium channel blockers
COX inhibitors
oxytocin receptor blockers
what are tocolytics?
drugs that suppress uterine contractions
what is terbutaline & how does it work?
B2 agonist
agonizes B2 on uterine smooth muscle, resulting in decreased contractions
adverse effects of terbutaline?
pulmonary edema
hypotension
hyperglycemia
tachycardia
what is indomethacin & how does it suppress uterine contractions?
COX inhibitor
inhibits prostaglandin synthesis, which results in decreased contractions via cAMP-mediated pathway
adverse effects of indomethacin
nausea
gastric irritation
increased postpartum bleeding
why is magnesium sulfate given for premature labor?
fetal neuroprotective effects
adverse effects of magnesium sulfate administration?
hypotension
flushing
headache & dizziness
SEVERE: hypothermia, paralytic ileus, pulmonary edema
fetal effects of magnesium sulfate administration? (i.e. when baby is born, what do you expect?)
hypotonia
sleepiness
associated w/ increased infant mortality
what drug is indicated to PREVENT preterm labor before it starts?
hydroxyprogesterase caproate
contraindications of induction of labor
umbilical cord prolapse
transverse fetal position
active genital herpes
h/x c-section or myomectomy
placenta previa
what are prostaglandins used for in an induction of labor?
ripen cervix primarily, but can also contribute to uterine contractions
how to administer dinoprostone?
transvaginally
nursing consideration when administering prostaglandin for induction of labor?
monitor fetal heart rate & contractions
fetal distress can occur, tachysystole (rapid contractions) can occur
what is oxytocin?
endogenous hormone
exogenous version is identical to endogenous
effects of oxytocin?
uterine stimulation
milk ejection
water retention
besides induction of labor, when else is oxytocin given?
augmentation of spontaneous labor
postpartum bleeding
abortion
most common cause for postpartum hemorrhage?
uterine atony (80%)
drug of choice for postpartum hemorrhage due to uterine atony?
oxytocin
besides oxytocin, what else can be given for postpartum hemorrhage?
misoprostol (Cytotec)
caboprost tromethamine (Hemabate)
methylergonovine (Methergine)
mechanism of action of caboprost tromethamine (Hemabate)
prostaglandin that results in uterine contractions and INTENSE vasoconstriction
contraindications of caboprost tromethamine (Hemabate)
pelvic inflammatory disease
cardiac disease
pulmonary disease
renal disease
liver disease
caution in asthma, hypertension, diabetes
adverse effects of caboprost tromethamine (Hemabate)
abdominal pain, nausea/vomiting due to smooth m stimulation
hypertension
bronchoconstriction
adverse effects of methylergonovine (Methergine)
HTN (severe!)
nausea, vomiting
headache
dangerous –> only give in emergencies!
how does tranexamic acid work?
inhibits plasmin
thus the fibrin mesh doesn’t dissolve (hemostasis is preserved)
serious adverse effect of tranexamic acid (TXA)?
thrombosis (can lead to PE, MI, CVA)
adverse effect of 17-alpha-alkylated compounds?
hepatotoxicity
medical uses for exogenous testosterone?
- male hypogonadism
- testosterone replacement therapy (TRT)
- delayed puberty
- menopause symptoms (for women)
- cachexia
- anemias
- transgender men
why is PO testosterone not preferred?
because both formulations are 17-alpha-alkylated compounds and risk hepatotoxicity
caution with transdermal testosterone therapy?
drug transfer with skin-to-skin contact (especially think with women or children)
adverse effects of testosterone therapy?
hepatotoxicity
virilization (male characteristics)
premature epiphyseal closure
atherosclerosis
edema
abuse
in high doses = sterility
psychologic effects
what drug class does sildenafil belong to?
PDE5 inhibitor
how do phosphodiesterase 5 inhibitors work?
inhibit PDE5 = increase cGMP. Thus with stimulation, erection can occur
adverse effects of PDE5 inhibitors
hypotension
priapism
increase OSA
HA
flushing
contraindications of PDE5 inhibitors
MI, unstable angina
hypotension
heart failure
NITROGLYCERIN! (require 24hrs between doses)
what can occur with concurrent administration of sublingual nitroglycerin and sildenafil?
severe hypotension
how do the injectable ED (erectile dysfunction) drugs work?
vasodilation that allows rapid inflow of arterial blood
list two main pharmacologic interventions for premature ejaculation
selective serotonin reuptake inhibitors (SSRIs)
local anesthetics
what medication class is finasteride?
5-alpha-reductase-inhibitor
how do 5-alpha-reductase inhibitors work?
inhibit 5-alpha-reductase, which is the enzyme that converts testosterone to DHT (the active form in the prostate)
thus, regression of prostate epithelial tissue & decreased mechanical obstruction occurs
adverse effects of 5-alpha-reductase inhibitors
decreased libido
gynecomastia
how do alpha1 adrenergic antagonists work in treating BPH?
relax smooth muscle & decrease dynamic obstruction
some are selective for the receptors on the prostate = less adverse effects
adverse effects of nonselective a1 adrenergic antagonists?
hypotension
dizziness
nasal congestion
**hypotension can be severe with other drugs that can decrease BP
