Pharmacology for Urology

When I was in Urology as a SHO (senior house officer), I have learned my cases and the medications that are used particularly in those urological conditions. So, I made a note for quick review and recall which could be helpful for other junior doctors like me.

First, the two most commonly used drugs in BPH are 5-alpha reductase inhibitors and the alpha blockers. 5-alpha reductase inhibitors have prostate volume reduction effect or apototic effect but the latter have not. However, it takes about 6 months to show the effect of 5-alpha reductase inhibitors and so alpha 1 blockers are used as first line symptomatic agents.

5-alpha reductase inhibitors

Dutasteride and Finasteride – inhibits the conversion of testosterone to dihydrotestosterone; used in combination with alpha-blockers in many cases

Dutasteride (Avodart)dual 5-alpha reductase inhibitor

– 0.5 mg po od

Finasteride (Proscar -5mg and Propecia-1mg) (type 2) 5-alpha reductase inhibitor

– 5mg po od; (1mg od is used in male pattern baldness MPB)

SE –
impotence (1.1% to 18.5%), abnormal ejaculation (7.2%), decreased ejaculatory volume (0.9% to 2.8%), abnormal sexual function (2.5%), gynecomastia (2.2%), erectile dysfunction (1.3%), ejaculation disorder (1.2%) testicular pain and depression. * ?increased risk of high-grade prostate cancer.

pregnancy category X – Mom ! don’t touch the pill, beware of blood transfusion

Alpha Blockers

Selective alpha-1 blockers – Doxazosin, Tamsulosin, Terazosin etc. – inhibits the binding of norepinephrine to the alpha-1 receptors on the membrane of vascular smooth muscle cells

Doxzosin mesylate ( Cardura, Carduran)

Dose: 1mg >>2mg>>4mg>> 8mg (max dose)/day.

Tamsulosin (Flomax, Flomaxtra, Contiflo XL and Urimax) 0.4mg >> 0.8mg od

Two major ADRs (Adverse Drug Reactions) :

  • Immunologic: contains sulfa moiety causing typical reactions to sulfa drugs.
  • Ophthalmologic: ” floppy iris syndrome” during cataract surgery.

Others : Retrograde ejaculation, dizziness and fainting due to BP drop.

N.B. Although prostate specific, it does not have the prostate apoptotic effects of other prostate drugs such as the 5 alpha-reductase inhibitors such as dutasteride and finasteride.

Trial

CombAT (Combination of Avodart and Tamsulosin) trial in 2008,- approved by the FDA on June 14, 2010

provides greater symptom benefits compared to monotherapy with either agent alone for treatment of benign prostatic hyperplasia.

Anticholinergics

Oxybutynin and Tolteredine

Oxybutynin – competitively antagonizes the M1, M2, and M3; also has direct spasmolytic effects on bladder smooth muscle as a calcium antagonist and local anesthetic in very high dose

– used in Overactive bladder/ urinary incontinence; possible treatment of hyperhidrosis

N.B. There was no difference in transdermal oxybutynin and extended-release oral tolterodine.

Contraindications

Untreated angle closure glaucoma and in patients with untreated narrow anterior chamber angles;  partial or complete bowel obstruction, hiatal hernia, GERD, paralytic ileus, intestinal atony of the elderly or debilitated patient, megacolon, toxic megacolon complicating ulcerative colitis, severe colitis and myasthenia gravis. It is also contraindicated in patients with obstructive uropathy and in patients with unstable cardiovascular status in acute hemorrhage.

Tolterodine (DetrolDetrusitol) – acts on M2 and M3

Hormone therapy

Cyproterone acetate CPA (Androcur or Cyprostat) – synthetic steroidal antiandrogen and also has progestogen and antigonadotrophic properties

Uses

1) in OC pills (2mg of CPA +35 or 50mg ehtinyestradiol),

2) hypersexuality, hirsutism, male-female transsexuals (25mg po.bd, up to 100mg/day)

3) metastatic Prostate CA (300mg/day), monitor LFTs, often co-administered with a GnRH agonist and a 5-alpha-reductase inhibitor

SE:  liver toxicity (dose dependent), adrenal suppression (so, monitor cortisol level and U&Es), often co-administered with a GnRH agonist and a 5-alpha-reductase inhibitor

Flutamide – oral, non-steroidal antiandrogen drug, has been largely replaced by Bicalutamide (Casodex, Cosudex, Calutide, Kalumid) –

Uses

1) stage D2 metastatic prostate cancer in combination with a LHRH analogue or as a monotherapy.

2) hirsutism, trials in Ovarian CA , also used in combination with castration

3) andogen receptor positive ER-/PR- metastatic breast cancer

Dose – 50mg po od (recommended same time each day)

Leuprolein or Leuprolide acetate -pituitary GnRH analogue

Pregnancy Category X

Uses: Hormone responsive cancers (Prostate CA, breast CA),

Use in Gynecology – precocious puberty, gender incongruency,  menorrhagia, endometriosis, adenomyosis, Uterine fibroids, in IVF(in vitro fertilization) – control of ovarian hyperstimulation,

Severe cases of CAH (congenital adrenal hyperplasia)

also, possible treatment for Paraphilia and Alzheimer’s dz

SE: s/s of hypo-estrogenism such as headache, hot flushes and osteoporosis

increased risk of heart problems by ~30% (when used for advanced CA Prostate)

Urinary Alkalinizing Agents

Potassium citrate (Cytra-K, Urocit K)

Urinary citrate <150 mg/day: 60 mEq/day PO (20 mEq with each meal) OR

Urinary citrate >150 mg/day: 30 mEq/day PO (10 mEq with each meal)

Maintenance –

  • Titrate dose to achieve urinary citrate 320-640 mg/day & urinary pH 6.0-7.0 (maximum dose 100 mEq/day)

Local Analgesic

Phenazopyridine – Azo dye; 100mg-200mg po tid (no more than 2 days)

used in severe dysuria;  post-procedures

Bleeding control

tranexamic acid (Cyklokapron, Lysteda) – Inhibits fibrinolysis through inhibition of plasminogen activator substances; also exhibits antiplasmin activity

used in conjunction with bladder irrigation in hematuria cases

Alright, I think you should be ready to go to urology unit by now. Good Luck!

N.B. I have also used Doxorubicin (Adriamycin) in many cases with TCC bladder; it is an Anthracycline that intercalates between DNA base pairs, impairs topoisomerase II function and inhibits replication & transcription

Add other drugs and noteworthy facts in the comments below please.

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