Pharmacology of Male GU Disorders Flashcards
What inhibits dihydrofolate reductase directly? What inhibits it indirectly?
Directly: Trimethoprim
Indirectly: Sulfamethoxazole (competes with PABA)
(TMP-SMX)
What are the common symptoms of LUTS (lower urinary tract symptoms)
- Interrupted stream/dribbling
- frequency
- urgency
What are the α1 adrenergic receptor antagonists used in the treatment of BPH (benign prostatic hypertrophy)
- Terazosin
- Doxazosin
- Alfuzosin
- Silodosin
- Tamsulosin
What is the MOA of α1 adrenergic receptor antagonists?
relax muscle tone —> rapid relief of symptoms (days)
What are the adrenergic subtypes? Which are specific to the prostate?
α1B - peripheral vascular resistnace
α1A - Prostate SM
α1D - detrusor muscle
α1D - spinal cord control of urinary function
What normal physiologic action occurs with α1A receptor stimulation by NE?
Prostate smooth muscle contraction
bladder outlet obstruction
What normal physiologic action occurs with α1D receptor stimulation by NE?
Detrusor instability
What occurs with pharmacologic antagonism of α1 receptors?
- reduces bladder spasm
- promotes muscle relaxation
- improves urine flow
antagonists will be agents that compete with normal physiologic NE
Describe the effects of terazosin, doxazosin, tamsulosin, silodosin, and alfuzosin on α1 adrenergic receptors
Antagonists
Alfuzosin (α1 adrenergic receptor antagonist) has functional uroselectivity. What does this mean? What are the recommendations for taking this medication?
the drug distributes into the prostate more than the serum
- Avoid in those with hepatic impairment
- take immediately after the same meal every day
What medication types can be used in the treatment of BPH?
- α1 adrenergic receptor antagonists
- steroid 5α-reductase inhibitors
- PDE-5 inhibitors
What mediation types can be used in treating erectile dysfunction?
- PDE-5 inhibitors
- PGE1 agonists
What are the steroid 5α reductase inhibitors used in the treatment of BPH?
- Finasteride
- Dutasteride
How quickly do steroid 5α reductase inhibitors (finasteride, dutasteride) take effect?
delayed action, promotes shrinkage of prostate and symptom relief over the course of 3-6 months
what factors cause hypertrophy of the prostate in BPH?
Aging and dihydrotestosterone (DHT)
DHT 10x > T
What are the direct/indirect effects of Steroid 5α reductase inhibitors?
Direct Effects:
- T accumulation
- DHT depletion
Indirect Effects:
- Androgen receptor not occupied
- no gene transcription
What is the MOA of Steroid 5α reductase inhibitors (finasteride, dutasteride)?
inhibit SAR-1 and SAR-2
SAR-2 converts testosterone (T) to dihydrotestosterone (DHT)
DHT is 10x more potent than T and is responsible for hypertrophy of the prostate
Finasteride: specific inhibitor of SAR-2
Dutasteride: Dual inhibitor of SAR-1 & 2
Explain what occurs with prostate DHT, PSA, Serum T, and Serum DHT with finasteride and dutasteride treatment
Prostate DHT - 90% decreased
PSA - 50% decreased
Serum T - 15-20% increased
Serum DHT:
- Finasteride - 70% decreased
- Dutasteride - 90% decreased (SAR-1 & 2)
What are the AE of Steroid 5α Reductase Inhibitors?
- Erectile dysfunction
- Gynecomastia
- Depressed libido
- Ejaculation disturbances
There are no dosage adjustments for age or renal insufficiency nor are there any significant drugs interactions with Steroid 5α Reductase Inhibitors (finasteride, dutasteride) what is one caution that must be considered with these drugs?
Use w/ caution in patients with liver abnormalities
drug is metabolized by CYP3A
What is the one PDE-5 Inhibitor approved by the FDA for the treatment of BPH and erectile dysfunction?
Tadalafil
What is the MOA of PDE-5 inhibitor?
cGMP is converted to 5’-GMP by PDE-5 which ends the erection
What are the PDE-5 Inhibitors?
- Sildenafil (viagra)
- Vardenafil (Levitra)
- Tadalafil (Cialis) - action of 36 hours (18 hr half-life)
- Avanafil (Stendra) - can be taken 15 minutes prior
Which PDE-5 Inhibitor has the longest duration of action and half-life?
Tadalafil (Cialis)
36 hours of action
18 hour half-life
