Urology Medications Flashcards
Name 4 PDE-5 inihibitors
Sildenafil–Viagra
Tadalafil–Cialis
Vardenafil–Levitra and Staxyn
Avanafil–Stendra
How do PDE-5 inhibitors help with ED (this is their MOA)
They breakdown the isoenzyme that breaks down cGMP. cGMP is responsible for relaxing smooth muscle in the corpus cavernosum so that there is more blood flow
Sildenafil is known as
viagra
Sildenafil (Viagra)
PDE-5 Inhibitor
-PO
-onset 60 minutes
-1/2 life 3-4 hrs
-take with food
-take on empty stomach
-metabolized by CYP3A4
-do not take with NITRATES, VASODILATORS, OR ALPLHA BLOCKERS b/c can cause hypotension
-taken on empty stomach 1 hour before sex
ADE: disturbances in perception of blue and greens, sudden transient hearing loss d/t vasodilation, priapism
Tadalafil is known as
cialis
Tadalafil (Cialis)
PDE-5 Inhibitor
- PO
- onset 120 minutes
- 1/2 life 18 hours
- *also approved for BPH
- metabolized by CYP3A4
- take with or without food
- ***caution with alpha blockers
Vardenafil is known as
Levitra; Staxyn
Vardenafil (Levitra; Staxyn)
PDE-5 Inhibitor
- PO
- onset 60 min
- 1/2 life 4-5 hrs
- food doesn’t matter but CAN’T TAKE WITH WATER
Avanafil is known as
Stendra
Avanafil (Stendra)
PDE-5 Inhibitor
- PO
- onset 30-45 minutes
- 1/2 life 5 hr
- food doesn’t matter
What is a synthetic prostoglandin E1 use for ED?
Alprostadil
Alprostadil
Synthetic prostaglandin E1
In the penile tissues, PGE1 allows relaxation of the smooth muscle of corpus cavernosum
Given intraurethral [supp] or intrapenile [injection]
Can be used 1st line—but most often used in those who are not candidates for oral agents
Acts locally, which decreases chance of ADEs
MOA—smooth muscle relaxants, exact physiological mechanism is unknown
Systemic absorption is minimal
Onset 5-10” [supp] or 2-25” [injection]—effects last 30-60”
ADEs—rare; hypotension, headache have been reported; local effects—penile pain, urethral
pain, testicular pain
Priapism may occur
What 3 types of drugs can be used for BPH
- alpha blockers
- 5 alpha reductase inhibitors
- PDE 5 inhibitor
MOA of alpha blockers in BPH
Blocking Alpha1A & Alpha1B receptors in the prostate cause the smooth muscles in the gland to relax, which leads to improved urine outflow Selective agents only block Alpha1B—have no BP effects— nonselective ones decrease peripheral vascular resistance and lower BP Five agents in this class approved for BPH, a sixth one may be used but not FDA approved 4 nonselective and 2 selective alpha blockers—real prototype drug hard to identify
MOA of 5 alpha reductase inhibitors o BPH
inhibit 5 alpha reductase—which converts
testosterone to dihydrotestosterone[DHT], the more
potent, active compound that stimulates the prostate
to grow. By decreasing DHT the gland shrinks and urine
outflow improves.
MOA of PDE-5 inhibitors on BPH
-inhibition of PDE 5 allow vasodilation and relaxation of smooth muscles of the prostate and bladder-which improves the symptoms of BPH
Name 4 nonselective alphablockers
- Terazosin- Hytrin
- Alfuzosin- Uroxatral
- Prazosin- Minipress
- Doxazosin-Cardura
Terazosin-Hytrin
Alpha blocker
Trade name: Hytrin FDA approved for BPH: yes NONSELECTIVE alpha blocker NO food effect Metabolized in liver but not CYP450
Alfuzosin-Uroxtral
Alpha blocker
Trade name: Uroxatral FDA approved for BPH: yes NONSELECTIVE alpha blocker Food HELPS with absorption CYP450 substrate **can prolong QT interval
Prazosin- Minipress
Alpha blocker
Trade name: minipress FDA approved for BPH: NOOOO NONSELECTIVE alpha blocker No effect with food CYP450: yes
Doxazosin-Cardura
Alpha blocker
Trade Name: cardura FDA approved for BPH: yes NONSELECTIVE alpha blocker No food effecr CYP450 metabolism? yes
2 selective alpha blockers
- Tamulosin (Flomax)
2. Silodosin (Rapaflo)
Tamulosin (Flomax)
Alpha blocker
Trade name: Flomax FDA approved for BPH: yes SELECTIVE alpha blocker Food helps with absorption CYP450 metabolism: yes
Silodosin (Rapaflo)
Alpha blocker
Trade name: rapaflo FDA approved for BPH: Yes SELECTIVE alpha blockers Food helps with absorption CYP450: yes** (also substrate for P-glycoprotein)
Name 2 - 5 alpha reductase inhibitors
- Finastride (Proscar)
2. Dutasteride (Avodart)
FINASTERIDE (Proscar)
Food does not affect absorption
½ life 6-12 hours [terminal ½ life of Avodart is 5 weeks, once the steady state is reached in 6 months]
ADEs—decreased ejaculate, decreased libido, ED, gynecomastia, oligospermia
All drugs in this category are teratogenic for women—those of child bearing age or those that are pregnant should not handle or ingest 5 alpha reductase inhibitors as they may lead to birth defects in the
genitalia of male fetus
Rare drug interactions
Finasteride is used [in small doses] for alopecia—
reduces DHT in scalp and serum which prevents hair
loss
Dutasteride (Avodart)
-more potent than proscar and causes greater reduction in DHT
What is finasteride use more for now days?
alopecia
What PDE-5 inhibitor is also used for BPH
Tadalafil-Cialis
Inhibition of PDE-5 allow vasodilation and
relaxation of smooth muscles of the
prostate and bladder—which improves
the symptoms of BPH
Anticholinergics are also called…
antimuscarinic
Drug of choice for overactive bladder (incontinence/loss of bladder control)
Antimuscarinic meds
How do antimuscarinic/anticholingerics work on bladder
Acetylcholine is the primary contractile neurotransmitter in the human detrusor, and antimuscarinics exert their effects on OAB/DO by inhibiting the binding of acetylcholine at muscarinic receptors M(2) and M(3) on detrusor smooth muscle cells and other structures within the bladder wall.
Meds for detrusor over activity
- Propantheline (Pro-Banthine)
- Dicyclomine (Bentyl)
- Tricyclic antidepressants (TCAs)
Antimuscarinic Medications—
Prototype—Oxybutynin (ditropan)
4 formulations:
- Immediate release: 2.5–5 mg BID–QID, up to 20 mg/day
- Extended release (ER) (Ditropan XL): 5–20 mg/day
- Topical patch (Oxytrol): 3.9 mg, applied 2x/week
- Topical gel (Gel): 1 gram applied every 24 hours
• Side effects (less frequent with ER and topical): Dry mouth Blurry vision Constipation Possibly cognitive
Interactions with CYP34A and 2D6
• Monitor PVR if UI worsens
Antimuscarinic Medications—
Tolterodine [Detrol]
Initial dose: 1–2 mg BID immediate release, 2–4 mg
QD for ER (Detrol LA)
Side effects similar to those of oxybutynin-ER; possible decreased xerostomia (dry mouth)
Interactions with CYP34A and 2D6
Antimuscarinic Medications—
Trospium [Sanctura]
Dose is 20 mg twice daily; can dose once daily in elderly because of renal clearance
Does come in an extended release form—Santura XR 60 mg daily
Must be taken on an empty stomach
Associated with 56%–60% reduction in weekly urge incontinence episodes
No data in long-term-care populations
Adverse events: dry mouth, constipation, headache, abdominal pain
Antimuscarinic Medications—
Darifenacin [Enablex]
Dose is 7.5 or 15 mg/day
Median reduction in weekly UI episodes 55%–58% in patients on 7.5 mg and 60%–70% in patients on 15 mg
No data in long-term-care populations
Adverse events: dry mouth, constipation; may have limited cognitive effects
Interactions with CYP34A and 2D6
Antimuscarinic - Fesoterodine [Toviaz]
Atropine like agent that is used to treat OAB—this quaternary amine has the fewest cholinergic effects—working mostly on muscarinic and nicotonic receptors in the detrusor
Increases bladder capacity
For those on drugs that may increase
cholinergic neurotransmitters [agents
for dementia]—this is one of the DOC (drug of choice)
for OAB in those individuals
**first line for person with cognitive deficits
β 3 Agonist (NOT an antimuscarini)—Mirabergron [Myrbetriq]
This agent relaxes the detrusor smooth muscle and increases bladder capacity
Used for OAB [in patients that have failed other agents or have a contraindication to the use of the anticholingergics
Myrbetriq 25-50 mg daily
- Can increase BP [this effect is more marked at lower doses]
- It increases digoxin levels; can decrease Metoprolol levels; can inhibit CYP2D6
- If GFR is <30 cc/min—use the 25 mg dose
What can be used for stress incontinence?
- estrogens-has a enhancing effect on the vaginal and urethral mucosa, and the pelvic floor muscles, rejuvenating the tissues and making them more elastic.
- alpha agonist-results in contraction of the internal urethral sphincter and increases the urethral resistance to urinary flow.
- ⍺ adrenergic agonist-stimulate urethral smooth muscle contraction
