Week 1 Drugs Flashcards
Constriction of the smooth muscles (Trigone and sphincter) occurs when NE binds to ____ receptors due to sympathetic activity
So if you have a problem with urine flow, you can give someone an alpha 1 adrenergic ANTAGONIST, to compete with NE and promote muscle relaxation to improve the flow
There are various subtypes of A1 receptors and include _____ for the blood vessels, ____ for the prostate, _____ for the detrusor and spinal cord
Alpha 1 adrenergic receptors
A1b, A1a, A1d
Alpha 1 adrenergic antagonists has a ___ action (within a few days) and work to relax muscle tone aka DYNAMIC remedy
Which A1 antagonists are non-specific for the A1 subtypes (aka these bind to Alpha1 all subtypes)
Which ones are specific for A1a and A1d?
^** Therefore these 2 are the important ones for dealing with lower UT symptoms
Take these ___ a day, ORALLY, for PBH
Fast
TAD (Terazosin, Alfuzosin, and Doxazosin)
Tamsulosin and Silodosin
Once
Terazocin and Doxazosin like we said, have no uroselectivity and will cause ___tension and has drug interactions with ____
Tamsulosin and Silodosin like we said, have Uroselectivity for A1a and A1d (and NOT A1b which is involved with blood vessels), and therefore is the best drug of choice for a patient with hemodynamic insufficiencies since it won’t affect blood pressure
^** One adverse effect to remember from these two drugs is ____, and reduced ejaculation and drug interactions are with ____
Alfuzosin causes adverse effect is ____ and while it does not have uroselectivity for A1 subtypes, it is considered ____ selective since by molecular makeup, it tends to concentrate in the ____
Hypotension, PDE5-Inhibitors
IFIS (Intraoperative floppy iris syndrome), CYP450
QT prolongation, Functionally, prostate
Steroid 5-alpha reductase inhibitors have a ___ action (3-6 months) that prevents prostate enlargement and shrinks the prostate aka STRUCTURAL remedy
As you get older, your prostate enlarges and this is due to the action of adrongenic steroids, ____ and ____ which allow the epithelium to survive and grow
^** DHT is much more potent than T, and usually T is converted to DHT via ____ types 1 and 2, and often hypertrophic prostates have excess SAR type ___
So the idea is that if you inhibit this enzyme, you no longer get T -> DHT conversion and this can help by not allowing the epithelium to survive and grow aka epithelial atrophy, shrinkage, and gradual relief
Which two drugs can accomplish this?
Also realize since your’e inhibiting SAR 2, you will get ____ DHT levels and ___ Testosterone levels for the direct effects
Also realize the decreased serum PSA is a way to show that prostate volume has also decreased
Slow
Testosterone and DHT
SAR (Steroid 5 alpha reductase), type 2
Finasteride and Dutasteride
Decreased, increased
____ is a specific inhibitor for SAR 2 and ____ is a dual inhibitor for SAR 1 and SAR 2
^***** KNOW THIS IT WILL BE ON THE TEST
Finasteride, Dutasteride
^** FI-nasteride = speciFIc
DU-tasteride = DUal inhibitor
******The only PDE-5 inhibitor approved for BPH (Benign Prostatic Hyperplasia) is ____**
Tadalafil
The corpus ____ is involved in maintaining and erection, NOT the spongiosum and an erection occurs with the smooth muscles relax, blood fills the sinusoids, and the organ becomes rigid
**In order to modulate smooth muscle tone, ____ is produced by ____ neurons in the ____ cells, which interacts directly with _____ and that stimulates GTP -> ____ conversion, which then blunts ____ and leads to smooth muscle relaxation, vasodilation, and an erection***
^*** KNOW THIS ****
The enzyme that converts active cGMP back to GMP is ____ so if you inhibit this enzyme via drugs, it keeps the cGMP active in order to maintain them at higher levels so a patient can get an erection
Cavernosum
NO, NANC (NonAdrenergicNonCholinergic), endothelium, Guanylate cyclase, cGMP, Ca2+
PDE-5
Which 3 drugs are included in the PDE-5 inhibitor class?
Which drug lasts for 36 hours since its half life is 18 hours compared to the other 2 that have a half life of 4 hours?
The idea is to inhibt PDE5, but sometimes one can get blue vision disturbances since there is some blockage of PDE__ which is located in the retina and this can happen with the drugs ___ or ____
The main contraindication is to not take these drugs with ____ since it can cause extreme ____ or the Non-specific Alpha1 adrenergic antagonists like Doxazosin/Terazosin
Sildenafil, Vardenafil, and Tadalafil
PDE6, Sildenafil or Verdenafil
Organic nitrates, hypotension
CAVERJECT is another possible drug for treating ED via intracavernosal injection of vasoactive drugs such as ___ which acts via the cAMP pathway to cause smooth muscle relaxation
^** PGE1 works via activating ____ to convert ATP -> ____ and therefore cause smooth muscle relaxation
Prostaglandin E1
Adenylate cyclase, cAMP
For the hypothalamic-pituitary-gonadal axis, ___ from the hypothalamus acts on the ____ pituitary causing LH or FSH to be releases (realize these are PULSATILE in nature)
LH stimulates ___ cells, which produces ____
Then, the testosterone + FSH stimulates the ___ cells to produce sperm maturation
The sertoli cells also contain ___, which converts testosterone into ____
Also realize the the leydig cells contain the ____ enzyme that converts T to DHT
**LH is needed to be released in pulsatile manners, but if there is CONTINUOUS high concentrations of LH, it actually causes ____ secretion of testosterone due to down-regulation of LH receptors
GnRH, anterior
Leydig, testosterone (which is a type of androgen)
^** Think LLLLLLh = LLLLLLeydig cells
Sertoli
Aromatase, estradiol (estradiol is a type of estrogen)
Steroid 5alpha reductase
DECREASED
Androgens cause prostate cancer cells to grow… So if you stop androgen production, you can shrink or cause the cells to grow more slowly…. Some drugs that can do this include
1) ____ is a GnRH ANTAGONIST
^** The problem with this is that the adrenal gland still produces some
2) ____ is a GnRH AGONIST and this works via desensitizing the receptors for GnRH but realize you obviously get a testosterone SURGE
1) Degarelix (Think DEGarelix = DEGradtes aka antagonist)
2) Leuprolide
Like we said, leuprolide will cause a testosterone flair, and one way to stop this from occurring is to give ANTI-androgen drugs (aka androgen receptor ___nists) so that even though there is a flair of androgens (testosterone) at first, they can’t bind to their receptors so no harm done
The 3 important androgen receptor antagonists include ____, ____, and ____
^** Note these are almost ALWAYS used with leuprolide, and not by themselves
Take Bicalutamide ___ a day ORALLY, and take Flutamide ____ a day ORALLY
ANTAGONISTS
Bicalutamide, Flutamide, and Nilutamide
BiNF
1 (qd), 3 (tid)
Like we also said the problem with GnRH antagonists and even agonists will eventually stop testosterone synthesis due to the hypothalamic-pituitary-gonadal axis, but the problem is that other organs make androgens still (like the prostate cancers themselves, or the adrenal glands)
The two drugs to help with this problem is
1) ____, which blocks CYP___ in the ADRENAL glands
^** Note that CYP17 is made up of ___ and ___ so if a question asks which one it will inhibit… Realize it inhibits ALL of those
2 problems occur from blocking the adrenal glands
1) Also note that since you are inhibiting the adrenal glands, you are also inhibiting steroid synthesis since not only do the adrenals make testosterone, but also steroids so it is used WITH ____ or other corticoids to help this problem
2) Also realize since you blocked the pathway to make DHEA and Androstendedione and eventually testosterone…. You now get a build up of Pregnenolone and Progesterone, which turn into ___ and therefore another side effect is excess aldosterone accumulation
^** So to recap, Abiraterone’s side effects are Aldosterone accumulation and Cortisol deprivation
**Ketoconazole is another drug similar to abiraterone, but is has hepatotoxicity so it isn’t often used anymore
Abiraterone, CYP17
17alphahydroxylase and 17,20 lyase
Prednisone
Aldosterone
In PRIMARY male infertility, if a patient has a low T or sperm count, then you administer them ____, which is an LH analog
^** Has a longer half life and less expensive, which is why its better than injecting LH or FSH
Male infertility can also be due to SECONDARY causes like secondary hypogonadism due to the fact that to MUCH androgens (aka taking to much testosterone aka steroids) cause excess estrogens to be accumulated, which feeds back to the brain and decreases testosterone from being made and now you have a lot more estrogen and this leads to infertility and shrink your gonads
^** So distortion of estrogen synthesis can occur in ____
*** So if you see decreased testosterone in the urine, increased estrogen, or just look for the steroid itself then the patient is ABUSING steroids
^** In order for these steroid abusers to decrease the effects of estrogen, they take ___ which is a selective estrogen receptor modulator (SERM) aka an ___onist that acts on the ____ to make it seem like there is no negative feedback loop (so the drug occupies the estrogen receptor binding sites but does NOT activate them) and that helps hid man boobs etc since testosterone levels are continuously being made… Or you can take ___ inhibitors like ____ or ____
HCG
Secondary hypogonadism
Clomiphene, antagonist, hypothalamus
Aromatase inhibitors, Anastrazole or Letrazole
