UROLOGY PHARM Flashcards
ALPHA-1 BLOCKER DRUGS
Tamsulosin (Flomax) Terazosin (Hytrin) Doxazosin (Cardura) Alfuzosin (Uroxatrol) Silodosin (Rapaflo)
Combo 5-alpha reductase inhibitor-alpha-1 blocker
Dutasteride-Tamsulosin (Jalyn)
more effective than 5-alpha reductase inhibitors for short & long term symptom management
alpha-1 blockers
MOA OF ALPHA-1 BLOCKERS
relaxes smooth muscle in bladder neck, prostatic capsule, and prostatic urethra
where are alpha-1 receptors located
in the base of the bladder and in the prostate
which 2 alpha-1 blockers were more effective than finasteride (proscar)
doxazosin
terazosin
which alpha-1 blocker has equal efficacy with finasteride
Tamsulosin (Flomax)
MOST COMMON SE OF ALPHA-1 BLOCKERS
DIZZINESS
ORTHOSTATIC HYPOTENSION
which alpha-1 blockers cause more BP lowering effects than others
Doxazosin (Cardura) & Terazosin (Hytrin)
which alpha-1 blockers have less BP effects
Tamsulosin (Flomax)
Silodosin (Rapaflo)
Alfuzosin (Uroxatrol)
TSA! = less BP effects
how to start patients on alpha-1 blockers
generally start a small dose at bedtime and titrate up slowly over several weeks
⦁ ***Alpha-1 blockers = can cause severe hypotension if used with
PDE-5 inhibitors
***Alpha-1 blockers = can cause severe __________ if used with PDE-5 inhibitors
hypotension
SE OF ALPHA-1 BLOCKERS
- dizziness & hypotension….also
⦁ Asthenia (muscle weakness)
⦁ nasal congestion
⦁ problems with ejaculation
which alpha-1 blocker has the most problems with ejaculation
Tamsulosin (Flomax)
alpha-1 blockers problems with ejaculation
- can decrease volume of ejaculate by 90%
- 35% of patients may have no ejaculate
- up to 28% have retrograde ejaculation in Silodosin (Rapaflo)
which alpha-1 blocker causes retrograde ejaculation
Silodosin (rapaflo)
5-alpha reductase inhibitor drugs (5-ARI)
Finasteride (Proscar)
Dutasteride (Avodart)
he only agents that provide LONG TERM DECREASE IN PROSTATE SIZE and decreased need for prostatic surgery
5- ARIs
5-ARI MOA
- competitive inhibitor of both tissue & hepatic 5-alpha reductase
- 5- alpha reductase converts testosterone to dihydrotestosterone
- by inhibiting 5-alpha-reductase = blocks conversion of testosterone to dihydrotestosterone = suppresses serum dihydrotestosterone levels
⦁ serum dihydrotestosterone decreases by 70%
⦁ serum testosterone increases by 10% - This decreases prostate size
EFFICACY OF 5-ARIs
- may take up to a year to notice reduction in symptoms
⦁ reduction in obstructive symptoms = 23%
⦁ reduction in non-obstructive symptoms = 18% - increase in maximum urinary flow rate
- reduction in mean prostatic volume by about 18%
- decreased need for surgery
- decreased development of acute urinary retention
- the larger the prostate volume, the more effective the medication
- Dutasteride (Avodart) may be more potent than Finasteride (Proscar)
the larger the prostate volume, the more _____________________ (5-ARI)
effective the medication is
which 5-ARI is more potent than the other
- Dutasteride (Avodart) may be more potent than Finasteride (Proscar)
MAJOR SE OF 5-ARIs
⦁ decreased libido
⦁ ejaculatory or erectile problems (ED)
- may only have these SE for the first year of therapy
⦁ decreases serum PSA by 50%
- in the first 24 months of therapy = multiply PSA by 2 when interpreting results - after 24 months of therapy = multiply PSA by 2.5 when interpreting results
what classes/meds are used for treatment of BPH
⦁ Alpha-1 blockers
⦁ 5 alpha-reductase inhibitors
⦁ Combo = Dutasteride-Tamsulosin (Jalyn)
⦁ Tadalafil (Cialis) = 5PDE-inhibitor
PDE5-INHIBITORS SHOULD NOT BE USED WITH
nitrates
alpha-1 blockers
- can cause severe hypotension
MOA of Cialis (PDE5-inhbiitor) for BPH
Cialis blocks PDE5 in the prostate in bladder
- the mechanism of how cialis reduces BPH symptoms is not completely understood
takes ____________ to note symptom improvement with Cialis when used for BPH
2-4 weeks
PDE-5 INHIBITORS (phosphodiesterase inhibitors)
Tadalafil (Cialis)
Vardenafil (Levitra)
Sildenafil (Viagra)
Avanafil (Stendra)
prostaglandin injectable
Alprostadil (Caverject), Muse (pellets) = vasodilator
drug classes/meds used for ED
PDE-5 inhbiitors & prostaglandin injectables (alprostadil)
MOA OF ALPROSTADIL (prostaglandin injectable)
- causes vasodilation by directly acting on vascular & smooth muscle. Relaxes trabecular smooth muscle by dilation of cavernosal arteries when injected along the penile shaft –> allows blood flow to the penis and entrapment of blood flow through veno-occlusive mechanism
onset/duration of action of alprostadil
- Onset = 5-20 minutes
- Duration = < 1 hour
CONTRAINDICATIONS TO PROSTAGLANDIN INJECTABLES (alprostadil)
⦁ conditions that predispose the patient to priapism (painful erection > 4 hrs)
⦁ anatomic or fibrotic conditions of the penis
⦁ For the pellets (Muse) = urethral stricture or perineal pain
SE OF PROSTAGLANDIN INJECTABLES
⦁ syncope
⦁ priapism
⦁ may cause BP lowering
MOA OF PDE-5 INHIBITORS
- For an erection to occur, nitric oxide (NO) is released in the corpus cavernosum during sexual stimulation
- Nitric Oxide (NO) then activates the enzyme guanylate cyclase –> results in increased levels of cGMP (cyclic guanosine monophosphate) –> produces smooth muscle relaxation and inflow of blood to the corpus cavernosum (erection)
- PDE-5 degrades cGMP in the corpus cavernosum, so PDE-5 inhibitors enhance the effect of NO by inhibiting PDE-5 from degrading cGMP = leads to maintained erection
PDE-5 inhibitors Do not directly cause penile erections
they increase the potential for this, but still needs the stimulus like they normally would…still need to be aroused
CONTRAINDICATIONS TO PDE-5 INHIBITORS
⦁ men taking nitrates
⦁ caution with alpha-1 blockers due to risk for severe hypotension
ADVERSE REACTIONS OF PDE-5 INHIBITORS
⦁ severe hypotension (with nitrates or alpha-1 blockers)
⦁ common = flushing, headaches, dyspepsia
⦁ visual effects = transient blue vision with sildenafil (viagra), may increase risk for nonarteritic ischemic optic neuropathy
⦁ Hearing loss
⦁ Priapism
which PDE-5 inhibitor can cause transient blue vision
sildenafil (Viagra)
common adverse reactions with PDE-5 inhibitors
- flushing
- headaches
- dyspepsia
DRUG INTERACTIONS with PDE-5 inhibitors
- CYP3A4 inhibitors may increase the serum concentration of PDE-5 inhibitors
ADMINISTRATION
- in general = take 1 hour before sex
- Vardenafil (Levitra) & Avanafil (Stendra) = have a quicker onset of action (30 minutes)
- Food & Alcohol delay the onset of action in Sildenafil (Viagra) & Vardenafil (Levitra)
- Daily dose Tadalafil (Cialis) is available
- average duration of action = 8-12 hours
- Tadalafil (Cialis) average duration of action = 36 hours
For Levitra & Viagra = have to wait 24 hours before taking Nitrates
For Cialis = have to wait 48 hours before taking Nitrates
which PDE-5 inhibitors have a shorter onset of action of 30 minutes rather than 1 hour
Vardenafil (Levitra) & Avanafil (Stendra)
which PDE-5 inhibitor has a daily dose available
Tadalafil (Cialis)
which PDE-5 inhibitors have a delayed onset of action with food & alcohol
Sildenafil (Viagra) & Vardenafil (Levitra)
which PDE-5 inhibitor has a duration of action of 36 hours (instead of 8-12 hours)
Tadalafil (Cialis)
For Levitra & Viagra = have to wait ______ before taking Nitrates
For Cialis = have to wait _______before taking Nitrates
24 hours
48 hours
which PDE inhibitors have SE of visual abnormalities
Viagra & levitra
which PDE inhibitor has SE of myalgias / back pain
cialis
primary vs secondary hypogonadism
⦁ Primary hypogonadism = testes fail to produce testosterone
⦁ Secondary hypogonadism = pituitary or hypothalamus malfunction
treat with testosterone
MOA of testosterone replacements
- direct action by binding to androgen receptor
- acts on tissues that express the enzyme 5-alpha reductase
⦁ converts to dihydrotestosterone, which binds more readily to the androgen receptor than testosterone - can act as an estrogen after converting to estradiol via an aromatase and bind to the estrogen receptor
symptoms that are treated with testosterone replacement
decreased libido decreased AM erections loss of body hair low bone density gynecomastia small testes decreased muscle mass
- need 3-6 months of therapy to note improvement in symptoms - need 2 years for improvement of BMD (bone mineral density)
⦁ do NOT use testosterone replacement to treat impaired
impaired spermatogenesis
- testosterone therapy suppresses pituitary gonadotropin secretion and leads to more impairment of spermatogenesis
PRIOR TO STARTING TESTOSTERONE THERAPY
- need to screen for…….
- and make sure __________ is being treated if present
PRIOR TO STARTING TESTOSTERONE THERAPY
- screen for prostate cancer in men > 50 or men > 40 who have any risk factors
- screen for erythrocytosis
- if sleep apnea is present, make sure it is being treated!
REDUCES SERUM PSA
INCREASES SERUM PSA
5-ARI
testosterone replacement
SIDE EFFECTS OF TESTOSTERONE REPLACEMENT
⦁ polycythemia (which is why screen for erythrocytosis)
⦁ worsening of BPH
⦁ acne
⦁ increase in PSA (unlike 5-ARI)
⦁ oral & prolonged IM doses = associated with multitude of liver issues (jaundice, hepatitis, elevated LFTs)
⦁ increased risk of prostate cancer (screen for prostate cancer >50/> 40 with risk factors)
⦁ decreased spermatogenesis (so don’t use for impaired spermatogenesis!)
⦁ fluid retention
⦁ worsening of sleep apnea (so need to have treatment for sleep apnea prior to tx)
⦁ possible increased risk of cardiovascular events
CONTRAINDICATIONS TO TESTOSTERONE THERAPY
⦁ known prostate cancer
⦁ known breast cancer (can be converted to estradiol)
⦁ severe lower urinary tract symptoms
⦁ HCT > 50% (because of polycythemia)
⦁ untreated severe sleep apnea (because it worsens sleep apnea)
⦁ PSA > 4.0 or PSA > 3.0 with any prostate cancer risk factors (increases prostate CA risk)
hepatic SE (jaundice, hepatitis, elevated LFTs)
testosterone (oral & prolonged IM doses)
LABS - prior to initiating testosterone therapy
- serum testosterone
- hematocrit
- PSA
good 1st choice of testosterone therapy
transdermal gel
⦁ well tolerated
⦁ achieves normal testosterone levels in most
⦁ the testosterone patch is another option
⦁ educate patients about the transfer of gel onto others
testosterone gels
- AndroGel = comes in pumps or packets
- Testim = tubes
- Fortesta = pump - apply to front & inner thighs
- Axiron = pump - apply to each underarm
testosterone patch
androderm
- worn on the arm or torso
- can cause significant skin irritation - 1/3 of men discontinue patch due to this SE
IM testosterone
⦁ Testosterone enanthate (Delatestry)
⦁ Testosterone cypionate (Depo-Testosterone)
- Gluteal injections once weekly (50-100mg) or once every 2 weeks (100-200mg)
MONITORING WITH TESTOSTERONE THERAPY
- serum testosterone
- serum LH if primary hypogonadism
- bone density
- PSA & DRE
- HCT
⦁ check serum testosterone - 2-3 months after starting or changing dose
⦁ if primary hypogonadism, check for normalization of serum LH (with primary hypogonadism in which testes aren’t responding, LH would by really high)
⦁ check Bone density - recheck every 2 years until normalizes or stabilizes
⦁ check PSA & DRE - 3-6 months after starting treatment, then yearly
- problematic if prostate nodule present, if PSA increases > 1.4 in a year, or PSA velocity > 0.4 per year x 2+ years
⦁ check HCT - 3-6 months after starting therapy, then yearly
- D/C if HCT >/= 54
urinary tract analgesic drugs
⦁ Phenazopyridine (Pyridium)
⦁ Pentosan (Elmiron)
OTC = Azo-Gesic, Baridium
INDICATIONS OF URINARY TRACT ANALGESIC DRUGS
Symptomatic relief of urinary burning, itching, frequency and urgency associated with UTI or post urologic procedures
do not urinary tract analgesic drugs if
GFR < 50
turns urine bright orange, turns skin/sclera yellow
phenazopyridine (pyridium)
urinary tract analgesics
urinary tract analgesic considerations
- don’t use for more than 2 days
- can turn skin and/or sclera YELLOW
- turns urine bright orange
- Only used for symptom relief….does NOT treat the infection
adverse reactions to urinary tract analgesics
- headache
- dizziness
- stomach cramps
INDICATIONS FOR PENTOSAN
cystitis
low molecular weight heparinoid
pentosan - so can cause significant blood thinning
MOA of Pentosan
drug adheres to the bladder wall mucosa and acts as a buffer to protect the tissues from irritating substances in the urine
SE OF PENTOSAN
o CNS
⦁ headache
⦁ dizziness
o Derm
⦁ Alopecia
⦁ rash
o GI ⦁ rectal hemorrhage ⦁ diarrhea ⦁ nausea ⦁ abdominal pain ⦁ dyspepsia
o Hepatic
⦁ LFT abnormalities
MUSCARINIC ANTAGONISTS/ANTISPASMODIC DRUGS
⦁ Oxybutynin (Ditropan) (Ditropan XL) (Oxytrol transdermal patch) ⦁ Tolterodine (Detrol) (Detrol LA) ⦁ Trospium (Sanctura), (Trospium XR) ⦁ Solifenacin (Vesicare) ⦁ Darifenacin hydrobromide (Enablex) ⦁ Fesoterodine (Toviaz)
indications for muscarinic antagonists/antispasmodic drugs
for treatment of urgency / urgency predominant mixed or overactive bladder symptoms
do NOT use muscarinic antagonists/antispasmodic drugs in patients with
dementia
CONTRAINDICATIONS FOR muscarinic antagonists/antispasmodic drugs
gastric retention
angle closure glaucoma
dementia
MOA OF MUSCARINIC ANTAGONISTS/ANTISPASMODIC DRUGS (oxybutynin / Detrol)
- increases bladder capacity
- blocks basal release of acetylcholine during bladder filling, resulting in decreased urgency
FACTS ABOUT MUSCARINIC ANTAGONISTS/ANTISPASMODIC DRUGS
**Extended release = have lower rates of adverse effects than immediate release agents
- start with lowest available dose; evaluate response in 4-6 weeks
- on average, takes at least 4 weeks to peak efficacy
- reduce starting dose in age 60 or older
- may respond to one agent and not another, so okay to try others in the same class***
ADVERSE EFFECTS OF MUSCARINIC ANTAGONISTS/ANTISPASMODIC DRUGS
(high discontinuation rate due to SE) ⦁ dry mouth ⦁ constipation ⦁ blurred vision to near objects ⦁ tachycardia ⦁ drowsiness ⦁ decreased cognitive function ⦁ dizziness
CONSIDERATIONS FOR PRESCRIBING
- hepatic metabolism at CYP450 - many interactions - except for Trospium
- renal failure
- hepatic failure
- cognitive impairment
- combinations to avoid
- adverse effects to avoid
*Generally prescribe extended release (less SE) or transdermal formulations
AVOID MUSCARINIC ANTAGONISTS/ANTISPASMODIC DRUGS WITH THESE DRUGS
- 1st generation antihistamines, muscle relaxants, some antipsychotics, TCAs, ipratropium, Spiriva, Cholinesterase inhibitors, Trospirum & ETOH within 2 hrs of each other, Mirabegron, Metoprolol & Darifenacin, Grapefruit juice with any…
COMMON ANTIBIOTICS FOR UTIs
Ciprofloxacin Trimethoprim/sulfamethoxazole (Bactrim/Septra) Nitrofurantion (Macrodantin) Amoxicillin Ampicillin
CIPRO
- class
- MOA
- pregnancy category
- BBW
- indications
Class = fluoroquinolone MOA = inhibits DNA topoisomerase Pregnancy category = C Black box warnings (2) = tendon rupture; may exacerbate myasthenia gravis Adjust dose based on renal function Urologic indications ⦁ Cystitis ⦁ UTI ⦁ Prostatitis
BACTRIM
Class = Sulfonamides MOA = inhibits folic acid synthesis - avoid in pregnancy! Pregnancy category = X - 2nd best coverage for MRSA after Vanco - oral tx for MRSA
