Week 12: GU Pharm Flashcards by Laura Viel

Proliferation of prostate cells leading to enlargement and partial blockage of the urethra.

BPH

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Etiology not completely understood, multi-factoral, hormones play a role.

Androgrens, estrogen
Genetics, susceptibility

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Urinary frequency, urgency, weak/intermittent stream, needing to strain, sense of incomplete emptying, nocturia

BPH Symptoms

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Fluid restriction, prior to bed esp.
Limiting caffeine and alcohol intake
Double voiding
Seated voiding
Minimizing diuretics use

non-pharm treatment BPH

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Decision to treat based on

International Prostate Symptom Score (IPSS) or American Urology Symptom Index

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Over the past month, how often have you…
- had a sensation of incomplete emptying
-had to urinate again less than 2 hours after last void
-stopped and started again several times
-found it difficult to postpone urination
-had a weak urinary stream
-how many times do you get up in the middle of the night to urinate

IPSS

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0-7 mild
8-19 moderate
20-35 severe
- start medications for bothersome moderate-severe symotoms

Treatment based of off IPSS score

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Alpha 1 blockers (alpha 1 adrenergic antagonist)
-Monotherapy in mild-moderate cases,
-Combined w/ 5 alpha reductase inhibitor in severe cases.

BPH Treatment Pharm, 1st line treatment

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5 alpha reductase inhibitors
-anticholinergic agents
PDE-5 inhibitors

Severe Cases BPH.

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alfuzosin 10mg/ day
receptor sensitivity , no generic
-doxazosin 1-8mg/ day
yes
-sicodosin 8mg/day
+ no
-tamulosin 0.4-0.8mg/day
+ yes
-terazosin 1-10mg/day
yes

FDA approved meds to treat BPH
ALPHA ANTAGONISTS

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-dutasteride 0.5mg/day
+ receptor sensitivity, no generic
-finasteride 5mg/day
+yes

FDA approved meds to treat BPH
5 alpha reductase inhibitors

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MOA- blocks alpha 1 receptors in the vasculature resulting in arterial and venous dilation.
-alpha 1 receptors are densely located in the bladder neck and prostate. Relaxation of the smooth muscle and decreased urethral resistance.

Alpha Blockers

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Major SE: hypotension; potentiated by PDE-5 inhibitor use. Space dosing by at least 4 hours.
Other SE: headache, dizziness, nasal congestion, fluid retention, impotence, palpitations and drowsiness.

Alpha Blockers

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Not recc as monotherapy for treatment of hypertension. Increase HF risk.

Alpha Blockers

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inexpensive and equally as effective as the newer alpha blockers

doxazosin, terazosin

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Initiate dosing at bedtime d/t risk of orthostatic hypotension w/ 1st dose.

Alpha Blockers

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newer, more uroselective, less risk for hypotension, no dose titration needed

Alfuzosin, Tamulosin and Sildosin.

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Risk of intraoperative floppy ins syndrome.
highest incidence of ejacualtory dysfunction

Tamulosin (flomax)

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lowers incidence of hypotension

Alfuzosin

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off label- doxazosin, tamulosin and terazosin

Adjunct therapy for renal stones

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-converts testosterone to dinhydrotestosterone (DHT).
-DHT stimulates proliferation of prostate cells and decreases prostate cell apoptosis.
-by inhibiting the conversion of testosterone to DHT the size of the prostate is decreased.

5 alpha reductase inhibitors

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finasteride (proscar)
- propecia (for hair loss)- lower dose
dutasteride (avodart)

5 alpha reductase inhibitors

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daily dosing, no titration
3-6 months for max effect
-will decrease serum PSA by 50%- important if you are monitoring changes
-can be used in combination of alpha blocker
SE: decreased libido, impotence, decrease semen quantity.

Dutasteride (avodart)
5 alpha reductase inhibitors

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-Alpha blockers: improve symptoms BPH and increase urinary flow rate by relaxing prostatic and bladder neck smooth muscle through sympathetic activity blockade.
-5 alpha reductase inhibitors: improve symptoms, improve urinary flow rate and prevent BPH outcomes by reducing prostate enlargement through hormonal mechanisms.

BPH Medical therapy

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-tricyclic antidepressants -anticholinergics -decongestants -antihistamines -antipsychotics -muscle relaxants -amphetamines -hormones: estrogen, progesterone, testosterone

Common Meds that can exacerbate BPH symptoms

multifactoral -Vascular: uncontrolled DM, Vascular disease, hypertension -Neurogenic: spinal cord injury, neurogenic dx. - Hormonal: decreased testosterone, hypothyroid (rare), BPH -Medications: antidepressants, antihypertensives (esp. Beta Blockers, but also thiazides, ACE), alcohol -Psychogenic *initial workup is to ID an organic cause.

Erectile dysfunction

MOA- PDE-5 converts to cGMP to GMP. PDE inhibitors stop this process resulting in increase levels of cGMP. cGMP is necessary for erection to occur.

Erectile Dysfunction

-Sildenafil (Viagra) -Tadalafil (Cialis) -Vardenafil (Levitra) -Avanafil (Stendra) generally effective regardless of the cause of ED. Require sexual stimulation for effect.

PDE-5 inhibiors

-longest duration -36 hours compared to 4 hours -Sometime daily dosing used (2.5mg) -no affected by food or alcohol Sildenafil and Vardenafil should be taken on an empty stomach. Alcohol and fatty food will delay absorption -take 30 to 60 minutes before intercourse

Tadalafil

-anyone taking nitrates -MI/ stroke or life threatening arrythmia within the last 6 months -use caution with HF, Hypo or uncontrolled hypertension, unstable angina, prolonged QT, alpha use.

PDE-5 inhibitor containdications

Priapism, visual disturbances, hearing loss, flushing, headaches, blue hue to vision (can last several weeks)

PDE-5 inhibitor Side Effects

-BPH also regulates smooth muscle tone in the prostate, tadalafil is approved for this indication. -Pulmonary HTN- cGMP also dilates blood vessels in the lungs. -PDE-5 inhibitors aide in dilating those vessels reducing pulmonary hypertension. ex: Sildenafil (Revatio): 20mg daily dosing. *chart on phone*

PDE-5 inhibitor Other Interactions

-sudden, strong urge to urinate w/or w/o the involuntary leakage if urine. -often accompanied by nocturia and urinary frequency -believed to be from detrusor muscle overactivity (the bladder tells the brain you need to urinate when it is not full).

Overactive Bladder/ Urge Incontinence

-behavior modification 1. education 2. pelvic floor muscle exercises 3. reinforcement 4. bladder retraining 5. timed voiding

Non Pharm Treatment for Overactive Bladder/ Urge Incontinence

Anticholinergics (mainstay of treatment). They inhibit detrusor muscle contraction.

Pharm Treatment for Overactive Bladder/ Urge Incontinence

- Oxybutynin (Ditropan) -Tolterofine (Detrol) -Solifenacin (Vesicate) -Datifenacin (Enalbrex) -Trospium (Sanctura) -Fesoterodine (Tovidz)

Anticholinergics for Overactive Bladder/ Urge Incontinence

-urinary retention -dry mouth * -constipation - dizziness -blurry vision -tachycardia -drowsiness Contraindicated in narrow angle closure glaucoma, uncontrolled tachycardia and increased dementia risk. XR formulations are prefered, fewer and less side effects.

Anticholinergics for Overactive Bladder/ Urge Incontinence Side Effects

-Mirabegron- beta 3 adrenoreceptor agonist: promotes beta receptor stimulation in the detrusor muscle causing smooth muscle relaxation typically fewer side effects than the anticholinergics contraindicated in sever and uncontrolled hypertension -Botox injection into the detrusor muscle: avoid in history of urinary retention or recurrent UTI

Overactive Bladder Treatment Pham 2nd and 3rd line

two formulations of estrogen are available in contraceptives

ethinyl estradiol and mestranol

norethindrone, norethindrone acetate and ethyriodiol diacetate

1st generation progestins

norgestrel and levonorgestrel

2nd generation progestins

desogestrel and norgestimate

3rd generation progestins

drospirenone (spironolactone derivative) dierogest (19-nortestosterone derivative)

4th generation progestins

-Progestins are primarily responsible for the contraceptive effect -Progestins exhibit a negative effect in the hypothalamic-pituitary-ovarian axis. -Progestins cause atrophy of the endometrium and preventing implantation -The estrogen component improves efficacy by suppressing FSH release. -Estrogen provides cycle control

Mechanisms of Pregnancy Prevention

-CV risk -concurrent medications -allergies -smoking -HTN -Migraines

Rational Drug Selection; Eval prior to initiation of contraceptives

- VTE risk (2-9x w/ oc use) -cholestatic, jaundice, benign hepatic neoplasms and neurological migraines

ADR's contraceptives

-metabolism of oc accelerated by phenobarb, phenytoin, griseofulvin, rifampin, St. John's wart. Progestin only contraceptives have fewer contraindications than estrogen containing products.

Contraceptives drug interactions

- reduced risk of cervical CA -decreased dysmenorrhea, menstrual irreg., and menstrual blood loss -reduced pain related to endometriosis -reduced endometrial hyperplasia -reduced pelvic inflammatory disease -rapid return to fertility

Non contraceptive benefits for IUD users

-less acne and hirsutism -fewer ovarian cysts -reduced risk of endometrial/ ovarian cancer -lower incidence of benign breast conditions such as fibrocystic changes and fibroadenoma. -increases bone density -suppression of endometriosis for women who do not currently desire pregnancy.

Non contraceptive benefits of OC

-intrauterine progestin -mirena IUD releases 14-20mcg of levonorgestrel daily -can be left in place for 3-8 years -only small levels of systemic circulating hormone -changes in menstrual bleeding, amenorrhea.

Progesterone only contraceptives

-etonogestrel implant-one rod containing 68mg of etonogestrel provides contraception for up to 3 years

Progestin Implants

-depot medroxyprogesterone acetate is a long-acting, injectable progestin- only contraceptive. -one injection suppresses ovulation 12-13 weeks. -changes in bleeding patterns -weight gain

Injectable progestins

-used when estrogen is contraindicated -norethindrone 0.35mcg, drospirenone 4mg -contraceptive effect is through thickening of cervix mucus ad prevention of sperm penetration -users must take dose at the same time -if a pill is a few hours late, backup method is recc for 48 hours.

Progestin only oral drugs

Nuvaring is a flexible plastic ring releasing 15mcg of estrogen and 120mcg of etonogestrel daily. - ring in for 3 weeks, then remove for 1 week -better cycle control, decreases breakthrough bleeding, less exposure to estrogen vs OC. Annovera is a silicone based ring delivering 0.15mg segesterone acetate and 0.013 etonogestrel daily

Vaginal Ring

Xulane: 20mcg of estrogen and 150mcg norelgestromin -patch applied weekly for 3 weeks, then1 week off -start on 1st day of menses. -can start other days if backup method is used -ADR's similar to OC -Decrease efficacy in obese women

Topical patch

should be implemented within 72 hours of unprotected intercourse -may be initiated up to 120 hours after -suppress ovulation

Emergency Contraception (Plan B)

-combined OC -Progestin only ie- Ella (ulipristol acetate)

Methods of emergency contraception

close monitoring of DM and seizure dx.

Copper IUD

replenishes women with hormones diminished during the natural menopausal transition. Traditional HRT is combined with estrogen, progesterone Addition of progesterone helps prevent endometrial hyperplasia in those with an intact uterus.

HRT

-menopausal transition -premature ovarian insuff -hormone replacement therapy -prevent osteoporosis

HRT indications

-conjugated equine estrogens (Premarin) -esterified estrogens estradiol ethinyl estradiol -phytoestrogens soybeans, soy products, flax seeds, red clover, hops, fruits and vegetables.

Estrogens

-increase bone density -affect lipid levels -reduce bowel motility -enhance coagulation of blood -cause edema (action on the renin-agiotensisn-aldosterone system, mainstay of thermoregulation center.)

Effects of Estrogen

- well absorbed oral, transdermal and parental admin routes. -transdermal formulations avoid hepatic 1st pass -single dose of IM estradiol valerate or estradiolcypionate is absorbed over several weeks. -metabolized in the liver

Estrogen

-used after cophorectomy, in natural menopause for vasomotor symptoms, and as a component of hormonal contraception.

Estrogen Pharmacotherapeutics

estrogen-only products are contraindicated. in women w/ an intact uterus, history of estrogen-dependent cancer, unexp vaginal bleeding, DVT, severe hepatic dx., history of CVA.

Estrogen Precautions and Contraindications

-dose related -CV and hematological: MI, HTN, Thromboembolism

Estrogen ADR's

-anticoag -tricyclic antidepressant -barbituates -anti TB drugs -corticosteroids -antiseizure meds

Estrogen Drug Interactions

-relief of peri and post menopausal symptoms -start on the lowest dose for the shortest duration -avoid unopposed estrogen in women w/ a uterus micronized estradiol (estrace) oral 0.5 to 2mg doses conjugated estrogen A : oral 0.3mg to 1.25mg conjugated estrogen B: oral 0.3mg to 1.25mg -reduced risk of colon cancer -prevention and treatment of osteoporosis (estrogen not for primary treatment) -contraception (ethinyl estradiol and mestranol) -previous management of vulvovaginal atrophy and dyrness -vaginal estrogen cream, tablets or rings -estrogen agonist- antagonist- ospemsfene 60mg

Estrogen Clinical use and dosing

-oral formulations are the most common -transdermal -vaginal instillation other than oral, most expensive

cont. Estrogen Clinical use and dosing

-Promethrium -Progesterone in oil -crinone -Prochieve -Medroxyprogesterone acetate (Provera) -Depoprovera -Norethinadrone (Dygestin) -Megestrol acetate (megace)

Progesterones

post menopausal therapy when the uterus is intact

Progesterones

progestin only pills = norethindrone medroxyprogesterone acetate (depo provera)

Progestin only contraception

absorbed rapidly any route PO progesterone rapidly metabolized in 1st pass through the liver excreted in kidneys and feces onset, peak and duration vary by form of progesterone

Progesterone

Progestin implanted intrauterine device

Mirena

Precautions and Contraindications of Progesterone

- clots -breast CA -Impaired liver -depression -disorders that worsen with fluid restriction -avoid first trimester of pregnancy -norethindrone acetate avoid in pregnancy!

selective antagonist of progesterone , w/o progesterone to maintain the pregnancy, termination results

Mifepristone/ Misoprostol

will act as an abortifacient when used in conjunction with misoprostol during the 1st 7-10 weeks of pregnancy

Mifepristone

absorption- rapidly absorbed, and peak plasma concentrations are attached 90 minutes after administration distribution- high plasma protein binding (98%) it binds to albumin and alpha 1 acid glycoprotein Mifepristone can cross the blood brain barrier metabolism- metabolized by CYP3A4, CY2C8, CYP2C9 and CYP2B6; it forms pharmacologically active metabolites. elimination- half life is 18 hours in a single dose, excreted in feces

Pharmacokinetics

if prescribed by clinician should be enrolled in REMS confirm gestational age admin inititally in a 200mg tablet PO on day 2 or 3 misoprostol should be placed in the buccal pouch as 4 200 tablets , kept in cheek for 30 minutes

Mifepristone

CYP3A4 inhibitors of CYP3A (AZOLES) like ritonavir can increase the concentration of M. dose should not exceed 600/day avoid concurrent use w/ CYP3A4 inducers like phenobarb, dilantin, carbamezepine... risks severe infection and severe bleeding.

Mifepristone/ Misoprostol Drug interactions