Genitourinary

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5-α Reductase Inhibitors

IND: BPH w/ enlarge prostate (>40mL). MOA: Inhibits conversion of testosterone to DHT which shrinks prostate. EVD: Lowers PSA level ~50%. AE: sexual dysfunction, breast tenderness. Warning: Pregnant women shouldn't touch the pills. PK: Onset=3-6 months.
dutasteride=Avodart: DI: diltiazem, ketaconazole and ritonavir. PK: t1/2=5wks. F=60%. Met by 3A4. DOS: 0.5mg/d.


finasteride=Proscar: IND: Also marketed as Propecia for hair loss. DI: No significant DIs. PK: t1/2=4.5h. DOS: 5mg/d.


 

α1 Adrenergic Antagonists

IND: BPH. MOA: Relaxes prostate muscles surrounding urethra. EVD: 60% of pts will see effect. ADM: T at bedtime. AE: dizziness15%, congestion10%, headache15%, weak/lethargic10%. DI: BP lowering meds, phosphodiesterase inhibitors. PK: Onset: 1-2w. OTH: aka alpha blockers. Won’t affect PSA or cause sexual dysfunction. Efficacy doesn’t depend on prostate size.

SELECTIVE

AE: Typically fewer AE vs non-selective. COS: More expensive vs non-selective.


tamsulosin=Flomax: AE: Retrograde ejaculation7%. PK: t1/2=6h (IR), 12h (CR). F=90%. Met by 3A4 and 2D6. DOS: 0.4mg/d.


silodosin: AE: Retrograde ejaculation28%.


NON-SELECTIVE
IND: Also used to lower BP. DOS: Start w/ low dose then increase.
doxazosin=Cardural: PK: t1/2=17h. F=65%. Met by 3A4>2D6>2C19 DOS: 1-12mg qHS.


prazosin: PK:F=90%. t1/2=3h (short acting).
terazosin=Hytrin: PK: t1/2=12h. F>90%. DOS: 1-10mg qHS.


 

Abortion Drugs

Mifegymiso=mifepristone+misoprostol. AVL: Myfegymiso kit= mifepristone (PO1x200mg tab) + misoprostol (buccal4x200ug tabs). MOA: Mifeprstone is a selective progesterone receptor modulator (SPRM) aka anti-progestin. It works by inducing progestin blockade, causing endometrial degeneration, uterine contractility, resumption of prostaglandin production, and decreased βhCG. It also contributes to cervical softening and dilation via a non-prostaglandin pathway (increase of the matrix metalloproteinase-2 expression). Misoprostol is a potent synthetic prostaglandin E1 (PGE1) that induces cervical ripening and uterine contractions. EVD: Three Phase 3 trialsn=146, 214, 551 of Mifegymiso showed efficacy=95.2%-98%. There is slightly higher efficacy and less AE for buccal misoprostol vs PO when combined w/ mifepristone. Mifegymiso is 87-98% effective up to 70d gestational age (off label use). ADM: Can T 63d into Pregnancy. Mifepristone (1 PO tab) taken first then misoprostol (4 buccal tabs) taken 24-48h after. Buccal tabs: hold 4 tabs between cheek and gums for 30min then swallow any remaining fragments. Once mifepristone is taken misoprostol must be taken as well. AE: >10%: Naus, vom, diar, abdominal pain, headache, vaginal bleeding (heavier than period), uterine cramping, fatigue, chills, fever, dizziness. 1-10%: Prolonged bleeding, breast tenderness, endometreitis. <1%: rupture of ectopic pregnancy (severe bleeding and cramping), toxic shock syndrome, hot flush, hypotension, arrhythmia, bronchospasm, rash. mortality risk (4 in 1,000,000) usually from infection or undiagnosed ectopic pregnancy. CI: AnemiaHgb<9.5g/dL (less blood loss w/ surgical abortion), recent bleeding or pelvic pain, ectopic pregnancy, uncontrolled astma, IUD in place. PRG: Mifepreistone alone possibly not teratogenic (rarely studied alone). Misoprostol has been linked to teratogenicity. LAC: <1.5% of dose found milk. Breastfeeding is likely safe in lactation. DI: Mifepristone: 3A4 inducers (Rifampin, SJW etc.), 3A4 inhibitors (Ketoconazole, GFJ etc). PK: mifepristone: t1/2=83-90h. Tmax=1-2h. PB=94-99%. Met by 3A4. Irreversibly inhibits 3A4, and to a lesser extent 1A, 2B, 2D6, 2E1. Excretion is primarily fecal (<10% in urine). misoprostol: t1/2=20-40min. Tmax=30min. Not met by CYPs. Rapidly de-esterified in liver. SL Tmax=30min. Buccal: contractions in ~67min w/ sustained action 90min later and declines at 5h. Vaginal: first contractions in ~98min. Sustained action at 128min and contractions declines at 5h. Moistened tabs may increase AUC when administered vaginally. COS: $350.62 for 1 pack2017 (Covered completely in NS through MSI). DOS: Less than 1% of active misoprostol metabolite is excreted in urine, and renal dosing is generally not required. OTH: Partner’s consent is also not necessary. Pt doesn’t have to attend abortion clinic to get prescribe Myfegymiso. Ovulation possible 8d after abortion. COCs patches, rings can be inserted on the same day or day after abortion. IUDs can be inserted at 1w follow up. Misoprostol is unstable outside blister pack. Doesn’t affect future fertility or rate of complications. PhC can’t prescribe mifegymiso. Blood levels for mifepristone are similar after 100-600mg doses leading Canada to have a lower dose vs USA. Misoprostol:

 

Anticholinergic/Antispasmodics

IND: Overactive bladder. MOA: Competitive antagonist of acetylcholine which relaxes bladder smooth muscles.
oxybutynin=Oxytrol: AVL: PO, patch. IND: Urge incontinence, urgency, and frequency. ADM: T w/ or without food. Patch can be applied to abdomen, hip, or butt. AE: Dry mouth/eyes/skin, sedation, dizziness, blurred vision, Naus, Vom, Com, Diar, headache, unusual taste, application site itch/redness. CI: <5yo PK: Racemic mixture of R and S enantiomers (R=most active). DOS: BID or TID.


 

Contraceptives (IM injections)

Depo-Provera: EVD: Effective immediately if given within first 5d of menses. ADM: Don’t rub injection site. AE: Typical weight gain (5ibs per year). Decrease in BMD (reversible). Irregular bleeding, headache, may take a few months to become fertile. DOS: 1 injection q3 months.

 

Contraceptives (IUDs)

Mirena: MOA: Thickens cervical mucus, stops endometrial perforation, may inhibit implantation, may inhibit ovulation. EVD: Takes 7d to be effective unless started within first 7d period. Fertility can return immediately after removal. Has less bleeding and cramps vs copper IUDs. MON: Check strings after each period. OTH: Progestin only IUS. 50% of pts will stop having period.

 

Contraceptives (oral)

Plan B: AVL: 1 pill as a high dose of progesterone. EVD: Possibly less effective if obese. ADM: Take w/ food.
Micronor: MOA: Doesn't always stop ovulation. Thickens cervical mucus. ADM: Need to take same time every day. No pill free interval. Start on day 1 of menses. OTH: Progestin only pill. Takes 48 hours to work. Good option for smokers.


 

Contraceptives (other)

Evra patch: ADM: Change patch weekly. Use backup contraception for first 7d. If patch is off >24hrs use backup for 7d. CI: Pts >90kg OTH: Fold into itself to dispose. Should not smoke.
NuvaRing: ADM: Insert on first day of period. Leave in for 3w. AE: Vaginal irritation, breakthrough bleeding, foreign body sensation. PK: Combination estrogen and progestin.


 

Phosphodiesterase inhibitors (PDE5I)

IND: Erectile disfunction (ED), pulmonary HTN. MOA: Inhibits the enzyme that degrades cGMP in the corpus carvenosum. cGMP is a molecule that dilates the blood vessels leading to the penis. Warning: See Dr. for erection lasting >4h. DI: Nitrates, alpha blocker (hypotension), 3A4 inducers/inhibitors. COS: Typically not covered by insurance. OTH: Won’t increase sex drive.

sildenafil=Viagra: AVL: PO (tabs25,50,100mg). IND: ED, pulmonary HTN. ADM: T ~1h (30min-4h) before sexual activity. AE: Headache15%, flushing10%, upset stomach6%, indigestion7%, vision changesrare. CI/Warning: Wait >24h to give nitrates. PK: t1/2=3-5h. Tmax=30-120min. Met by 3A4(major) and 2C9(minor). Excreted 80% in feces and 13% in urine. COS: 4 tabs (1box)2017: 25mg generic=$48.41. 50mg generic=$50.93. 50mg brand=$54.00. 100mg generic=$52.52. 100mg brand=$55.71.
DOS: Start=25mg. OTH: Doesn’t increase MI or death. Drops BP by 8.3/5.3 mmHg at peak 1-2h after dose.


tadalafil=Cialis: IND: Also used w/ alpha blockers (if dose is stabilized) for BPH. ADM: Can be taken 0.5-36h before sexual activity. AE: Headache11%, indigestion7%, back/muscle pain4%, flushing4%, dizziness1.7%, vision changesrare. CI: Wait >48h to give nitrates. Not studied <18yo. PK: t1/2=17.5h. Met by 3A4. COS: 4 tabs (1 box)2017: 10mg generic=$64.81. 10mg brand=$64.97. 20mg generic=$66.77. 20mg brand=$66.91. DOS: 2.5mg or 5mg daily for daily dosing. 10mg or 20mg for prn dosing.


vardenafil=Levitra: AVL: PO (tab5,10,20mg). ADM: T 25-60min before sexual activity. Can T w/ food but will delay effect. AE: Headache10%, Naus1.2%, nasal congestion4%, flushing11.3%, indigestion2.5%, hearing lossrare, priapismrare. minor QT prolongation. PK: t1/2=4-5h. F=15%. PB=high. Met by 3A4 (main), 3A5, 2C9. DOS: >65yo start=5mg. Adult start=10mg. Max=20mg. OTH: Only avail as Brand2017. Decreases BP by 7/8 mmHg.


 

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