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Pharmacology Exam 3: Diuretics 2
diuretics 2
106
Anatomy
Graduate
03/10/2011

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Term
sympathetic to the bladder neck and destrussor does what?
Definition
sympathetics> alpha 1> contraction of bladder neck and urethra

sympathetics >beta 2 detrussor muscle> relaxation (no voiding)
Term
OAB:
Definition
overactive bladder

urgency without or without incontinenance, often frequency and nocturia
Term
Antimuscarinics are used to treat OAB b/c they ___ bladder capacity and ___ involuntary bladder contractions.
Definition
- increase
- inhibit
Term
side effects of antimuscarinic treatment for OAB:
Definition
dry mouth
constipation
visual changes
Term
What are the 4 Anticholinergic meds you need to know for OAB:
Definition
One Tall Tree Died.

- Oxybutynin
- Tolterodine
- Trospium
- Darifenicin
Term
Oxybutynin has an immediate and long lasting forms. The immediate for has ___ dosing. The long lasting one has dosing of __ to __ mg ___ a day. The side effects include ___ __, ___, and ___. This drug is approved for kids ___ and ___.
Definition
- tid
- 5-10 mg once a day
- dry mouth, headache, constipation
- 6 and older
Term
Oxybutynin can be given as a ___ patch. Patient would need __ ___ patches each week. The patch has less problems with __ __ but causes ___ and ___.
Definition
- transdermal
- 2 3.9mg
- less problems with dry mouth
- erythema/pruritis
Term
Tolterodine can be used for immediate or long lasting relief. The immediate dose is 2mg. The long lasting dose is 4 mg. Side effects are similar to Oxybutynin.
Definition
Term
Trospium chloride is a ___ ___ as opposed to a __ ___ so it does not cross the __ ___ ___ so it has fewer side effect. It is __ acting. It is NOT metabolized by the liver . 60% is excreted in the urine unchanged.
Definition
- quaternary amine
- tertiary amine
- does NOT cross blood brain barrier
- short
Term
Darifenacin is a __ ___ ___. Patient takes 7.5 mg or 15 mg ___ daily. Side effects include __ and __ __.
Definition
- M3 selective anticholinergic
- once
- constipation and dry mouth
Term
2 causes of urinary retention:
Definition
- outlet obstruction (benign prostate hyperplasia)
- impaired destrusor muscle response (postsurgical, neurogenic atony)
Term
Benign prostatic hyperplasia (BPH) is a ___ enlargement of the prostate gland caused by hyperplasia of both ___ and ___ cells and often leads to symptomatic lower urinary tract symptoms (LUTS).
Definition
- nonmalignant
- glandular and stromal
Term
Most common benign tumor in men that is NOT a precancerous condition:
Definition
BPH
Term
BPH symptoms:
Definition
- urgency
- strainging/difficulty urinating
- pause before flow begins
- very weak stream
- urine stream that starts and stops
- feeling of incomplete emptying of bladder
- frequency, especially at night
Term
lifestyle changes that help with BPH:
Definition
- enriched diet with fish, fresh fruits, vegetables
- reduce stress
- exercise on regular basis
- reduce weight
- limit fluid intake
- decrease bladder irritants- coffee, alcohol, AVOID ANTICHOLINERGIC DRUGS, NARCOTICS, AND SKELETAL MUSCLE RELAXANTS
Term
OAB you treat with anticholinergics b/c these patients want to pee less. BPH patients should not be on anticholinergics b/c this keeps them from peeing even more.
Definition
Term
In men with symptomatic BPH, progression is not inevitable and some men undergo spontaneous improvement or resolution of their symptoms
Men with moderate or severe symptoms can also be managed in this fashion if they so choose
Neither the optimal interval for follow-up nor specific enddpoints for intervention have been defined
Definition
Term
BPH can be treated with __ blockers, __ __ ___ inhibitiors, and __ ___.
Definition
- alpha blockers
- 5-alpha reductase inhibitors
- saw palmetto
Term
What are the 3 alpha blockers for BPH treatment you need to know?
Definition
- Doxazosin
- Terazosin
- Tamsulosin
Term
What are the 2 5-alpha reductase inhibitors that can be used to treat BPH:
Definition
- Finasteride
- Dutasteride
Term
List all the drugs you need to know for treatment of BPH:
Definition
Alpha 1 selective Blockers:
- Terazosin
- Doxazosin
- Tamsulosin

5-alpha reductase:
- Finasteride
- Dutasteride

Other
- Saw Palmetto
Term
Not everyone with BPH is symptomatic.
Definition
Term
Testosterone and other hormones play a __ role in BPH, they have to present for BPH to occur. But administering ___ ___ is not associated with increased risk of BPH symptoms.
Definition
- exogenous testosterone
Term
____ is a metabolite of testosterone and a major mediator of prostate growth. ___ is synthesized ___ __ ___ from circulating testosterone by the enzyme ___ __ ____.
Definition
- Dihydrotestosterone (DHT)
- DHT
- within the prostate
- 5-alpha-reductase
Term
Alpha blockers used to treat BPH are ___ ___ meaning they bind to the receptor but have __ ___ __. They produce their changes by interrupting __ __.
Definition
- competitive antagonists
- no intrinsic activity
- sympathetic tone
Term
Alpha adrenergic blockers block the effects of any compound acting at
receptors (whether that compound acts directly or
indirectly to activate the alpha receptor)

Endogenous agonists (epinephrine; norepinephrine). Note: blockade of sympathetic tone explains why antagonists produce effects.
Definition
Term
The human prostate and bladder sphincter contain __ __ ___. These smooth muscle cells ___in response to alpha agonists and ___ urination.
Definition
- alpha 1 adrenoreceptors
- contract
- prevent
Term
More specifically, the prostate and bladder sphincter contain ___ receptor.
Definition
alpha1A
Term
remember to pee the destrusor has to contract (DC), and the sphincter has to relax (SR)
Definition
Term
Alpha 1 Selective Blockers Side Effects:
Definition
- reflex tachycardia may occur, signifiantly less than with non-selective blockers
- syncope, especially when first administered
Term
Alpha 1 Selective Blocker first dose phenomenon:
Definition
- some component of postural hypotension
- caution patients to avoid sudden postural changes
Term
Doxazosin is an __ ___ selective blocker. It is a popular treatment for __. ___ a day dosing. Start with __ dose due to __ __ syncope. It may lower ___. One adverse effect includes ___ ___. It causes little tachycardia.
Definition
- alpha 1 selective blocker
- BPH
- once
- low
- first dose
- may lower LDL
- stuffy nose
Term
what alpha 1 selective blocker may lower LDL?
Definition
Doxazosin
Term
Terazosin is ___ ___ and has more ___ side effects than Doxazosin.
Definition
- long acting
- more severe (hypotension)
Term
Tamsulosin is a selective __ blocker. It binds ___ and __ and a little ___. It is __ __ in treating BPH. It has very little __ ___. It is well tolerated. Effectiveness is maintained for ___, meaning tolerance does not develop. But it is MORE EXPENSIVE.
Definition
- alpha1A
- alpha1A
- alpha1D
- alpha1B
- highly efficacious
- very little vascular effects
- effectiveness maintained for years
Term
Tamsulosin side effects:
Definition
- 4-18% had ejaculatory problems
- rate rises to 30% with long term use
- mild nasal stuffiness
- asthenia not related to orthostatic hypotension
Term
The 2 isozymes of 5 alpha reductase are __ _ and __ _. It is controversial if either one is more important in BPH. Originally Type 2 was thought to be more important, but recent data is not entirely supportive.
Definition
- Type 1
- Type 2
Term
2 5-alpha reductase inhibitors:
Definition
Finasteride
Dutasteride
Term
5 alpha reductase inhibitors prevent ___ from being made into ____.
Definition
- testosterone
- dihydrotestosterone
Term
Finasteride is selective for ___ __ of the 5-alpha reductase. This ___ __ result in negative feedback of testosterone synthesis. __ __ of thereapy is required to see maximum effect.
Definition
- type 2
- does not
- six months
Term
With Finasteride, you see about ___ reduction in size of prostrate. This is __ and __. You will see improvement of urine flow and retention problems. ___ onset- often needs __ months to see full effect.
Definition
25% reduction
safe and efficacious
slow
six
Term
Other uses of Finasteride:
Definition
- alopecia
Term
Finasteride problems:
Definition
- 5% ejaculation problems
- 10% erection problems
- 5% libido problems
Term
Finasteride decreases __ by ___. The __ test is still valid it just has to be interpreted differently. Get a __ before starting Finasteride.
Definition
- PSA by 50%
- PSA
Term
Dusasteride inhibits __ isozymes of __ __ ___. It has a slow onset of __ months. Side effects are similar to Finasteride, though Dutasteride may also cause ___. This is approved by for BPH, but not yet for alopecia.
Definition
- both isozymes
- 5-alpha reductase
- gynecomastia
Term
which 5 alpha reductase inhibitor may cause gynecomastia?
Definition
Dusasteride
Term
Precautions with 5-alpha reductase inhibitors:
Definition
- WOMEN SHOULD NOT HANDLE 5ALPHA REDUCTASE INHIBITORS> BIRTH DEFECTS

- PATIENTS CANNOT DONATE BLOOD UNTIL 6 MONTHS AFTER THE LAST DOSE

- MEN MAY EXPERIENCE DECREASED LIBIDO AND EJACULATION PROBLEMS
Term
Which type of drugs for BPH can you not donate blood until being off the med for at least 6 months?
Definition
5 alpha reductase inhibitors
Term
Before starting 5 alpha reductase inhibitors, patients should be assessed to rule out other urological disorders, including prostate cancer, check PSA prior to prescribing these agents.
Definition
Term
Saw palmetto is from berries of the ___ ___ dwarf palm tree. It is ___. Its mechanism is not clear. Must be taken at least __ __ to see onset of positive effects.
Definition
- Serona repens
- OTC
- 6 weeks
Term
Saw palmetto studies: Significant improvement in urinary symptom scores and nocturia, resembling the effects of finasteride
Definition
Term
most frequent side effect seen with saw palmetto:
Definition
erectile dysfunction
Term
Drugs that aggravate BPH:
Definition
- Adrenergic agonists: pseudoephedrine and any other alpha agonist
- Antimuscarinics - atropine/scopolamine- prevent voiding

- Antihistamines- H1 antagonists, particularly first generation drugs b/c these also have antimuscarinic effects
Term
Common complication of inguinal hernia repair?
Definition
post-op urinary retention
Term
what med do you use for post-op urinary retention?
Definition
Bethanechol- cholinergic agonist- makes detrussor muscle contract
Term
you use bethanechol to treat urinary retention b/c this a __ __ that causes the __ muscle to contract so you can pee.
Definition
- cholinergic agonist
- detrussor
Term
Bethanechol is a ___ aka ___ aka __ ___ aka ___ __. It does NOT affect __ receptors. It is ___ ___ effectively by ___ so it has a ___ duration of action.
Definition
- parasympathomimetic aka vagomimetic aka muscarinic agonist aka cholinergic agonist
- does NOT affect nicotinic receptors
- NOT hydrolyzed by cholinesterases
- long duration
Term
Behanechole uses:
Definition
- neurogenic atony of bladder (DM)
- post-op urinary retention
Term
potential side effects of bethanicol? TEST
Definition
- diaphoresis
- GI upset
- diarrhea
- miosis
Term
Contraindications to bethanechol: TEST
Definition
- Asthma
- Bradycardia
- Peptic Ulcers
- Epilepsy
- Parkinsonism
Term
Erection is due to ___ of the penile erectile tissue from vasodilation of the ___ ____ in the __ ___.
Definition
- engorgment
- central artery
- corpora cavernosa
Term
During sexual excitement, a ___ reflex is activated and causes dilation of arterioles. The dilation is caused by release of __ ___.
Definition
- parasympathetic
- nitric oxide
Term
With erection the vascular spaces of the ___ ___ fill with blood causing penis to become large and rigid.
Definition
- corpora cavernosum
Term
With erection, the expansion of erectile tissue __ the veins and ___ outflow of blood.
Definition
- compresses
- reduces
Term
Erection:

nerve releases NO> causes guanylyl cyclase to make cGMP> cGMP cauases smooth muscle relaxation in arterioles> erection
Definition
Term
PDE 5 inhibitor reduces destruction of ____ which causes ___ ___ which allows for more smooth muscle relaxation and blood flow for erection.
Definition
- reduces destruction of cGMP
- increased cGMP
Term
PDE-5 isoenzyme (phosphodiesterase 5) is the __ __, ___, __, __, __, ___ ___, ___, ___, __, and __. PDE-6 isoenzyme is in the ___.
Definition
PDE-5: corpus cavernosum, platelets, bladder, urethra, heart, leg muscle, lung, brain, kidney,liver

PDE-6: retina
Term
Mechanism of Action:
PDE inhibitors work through increasing cGMP that promotes and sustains smooth muscle relaxation. They reduce the metabolism or breakdown of cGMP
Definition
Term
PDE-5 inhibitors do NOT cause a chemical erection. Sexual stimulation is still necessary to cause initial release of ___ ___, which stimulates the synthesis of ___.
Definition
- nitric oxide
- cGMP
Term
PDE-5 inhibitors (3):
Definition
- Sildenafil (Viagra)
- Vardenafil (Levitra)
- Tadalafil (Cialis)
Term
Sildenafil takes ___ hour to work and has a half life of __ hours.
Definition
- one
- four
Term
Vardenafil takes __ ___ ___ to and has half life of __ hours.
Definition
-30-45 minutes
- 6 hours
Term
Tadalafil takes __ hours to work and has a half life of __ hours.
Definition
2 hours to work
18 hour half life
Term
Erectile dysfunction PDE inhibitors adverse effects:
Definition
- Headache (15%)
- flushing
- dyspepsia
- nasal congestion
- visual disturbances (Sildenifil- bluish vision)
- Priapism
- Back ache
Term
Absorption of Sildenafil is decreased by ___ __ ___. It is best taken on an __ ___. This drug works in __ of men, ___ have suboptimal effects. This can cause a bright blue-green halo around vision.
Definition
- high fat meal
- empty stomach
- 70%
- 10%
Term
Diabetics and patients who have had post-radical-nerve-sparing prostatectomy have a higher incidence of success with ____.
Definition
Vardenafil
Term
Vardenafil absorption is also inhibited by __ __ intake, but not as much so as Sildenafil is.
Definition
high fat
Term
In Europe vardenafil is considered a 24 hour agent but drug insert in US – no duration of action
Definition
Term
Tadalafil is the ___ ___ PDE-5 inhibitor. Approved for __ hours, but reported to last even 100 hours. It has increased occurance of ___, but little if any ___ ___. It is NOT affected by food or fatty meals.
Definition
- longest lasting
- 36 hours
- increased occurance of priapasm
- little to no visual disturbances
-
Term
Contraindications to PDE-5 Inhibitors:
Definition
- concurrent organic NITRATES (short or long acting, nitroglycerin or isosorbide)

- severe coronary disease- obtain stress test prior to prescribing
Term
why can you not give PDE-5 inhibitors to someone who is taking nitrates?
Definition
- these are both vasodilators so blood pressure drops way too low
Term
Big PDE-inhibitor side effect on vision:
Definition
- Non-arteritic Ischemic Optic Neuropathy: most common optic nerve disease in people over 50. Onset is sudden loss of vision in one eye, usually in the morning when pt wakes up.

Risk factors: ischemic heart disease, HTN, hypercholesterolemia, Diabetes, age
Term
PDE-5 inhibitors should not be given to someone with history of ___ ___ ___ ___.
Definition
- Non-arteritic Ischemic Optic Neuropathy (NAION)

the blue green vision might be a precursor to this, so if pt experiences blue green vision, stop PDE inhibitor right away and don't give them another one
Term
PDE-5 inhibitors are metabolized by ___.
Definition
3A4
Term
Drugs that inhibit 3A4 metabolism will ___ amounts of PDE-5 inhibitors.
Definition
increase
Term
drugs that induce 3a4 metabolism will __ PDE 5 inhibitors.
Definition
decrease
Term
CYP3A inhibitors that will increase PDE-5 inhibitor concentrations:
Definition
Erythromycin > clarithromycin > azithromycin
Ketaconazole
Cimetidine
SSRIs (sertraline, fluoxetine, ..)
irreversible inhibition
ethinyl-estradiol (some birth control pills)
grapefruit juice
Term
PDE 5 inhibitors also interact with alcohol
Definition
Term
Androgen replacement therapy is indicated in ____. These pts should avoid oral estrogens b/c these could increase LFTs. Testosterone can be __ __ to __ times a week, or can be given transdermally in a __ or ___.
Definition
- hypogonadism
- injected 2-3 times a week
- patch or gel
Term
sometimes androgen replacement therapy can work in men with Ed
Definition
Term
Centrally acting oral drugs like ___ can also help with erectile dysfunction by enhancing the __ __ __signals that normally occur in the brain during sexual stimulation.
Definition
- Apomorphine
- central natural erectile signals
Term
Apomorphine, a centrally acting oral drug, is a ___ ___ __ __ and acts mainly on ___ ___ receptors in the brain.
Definition
- non-selective dopamine receptor agonist
- dopamine D2-like
Term
Patients that are not responding to oral drugs for ED can be offered __ ___. The main drugs used for this are ___ and ___.
Definition
- intracavernous injections
- Papaverine
- Alprostadil
Term
Alprostadil causes blood vessels to expand, increasing blood flow throughout the body. Thus, by increasing blood flow to the penis, alprostadil helps facilitate an erection.
Alprostadil is a vasoactive prostaglandin E1.
It is more effective when used in combination with phentolamine and papaverine; this is considered a tri-mix combination therapy. This tri-mix has an extremely high rate of efficacy at 92%
However, alprostadil is normally administered by itself. Sexual activity is reported after 94% of injections, a figure that no other sexual dysfunction treatment option has reached. It also has an almost immediate onset of action.
Side Effects: penile pain, prolonged erections, priapism, and fibrosis
alprostadil is also now available in a cream, under the brand name Befar
Definition
Term
43% of American women suffer from sexual dysfunction. (50 million American women!) Highest proportion occures between the ages of 18 and 29.
Most women can reach orgasm when the clitoris is stimulated, but only about half of women regularly reach orgasm during sexual intercourse. About 1 of 10 women never reaches orgasm.
Definition
Term
Female sexual dysfunction categories:
Definition
Desire disorder: a persistent absence of desire for sexual activity.
Arousal disorder: a persistent inability to attain or maintain sufficient sexual excitement.
Orgasm disorder, a persistent difficulty, delay or absence of orgasm after sufficient stimulation.
Pain disorder, persistent genital pain associated with sexual intercourse or stimulation
Term
Female arousal and orgasmic disorders can be caused by lack of __ __ to the clitoris and general area and may be related to the following conditions:
Definition
Menopause
Vascular disease
High blood pressure
Diabetes
Pelvic trauma
Other conditions related to poor blood flow
Term
Causes of female sexual dysfunction:
Definition
Fluctuations in the levels of estrogen and testosterone hormones, which occur monthly and during pregnancy, can affect sex drive.

In postmenopausal women, sex drive may be reduced because estrogen levels decrease. Sex drive may also be reduced in women who have had both ovaries removed.

A reduction in sex drive may result from depression, anxiety, stress, or problems in a relationship. Use of certain drugs, including anticonvulsants, chemotherapy drugs, -blockers ( Antihypertensive Drugs), and oral contraceptives, can also reduce the sex drive. So can drinking excessive amounts of alcohol.

Women who have undergone treatment for breast or ovarian cancer are at high risk for sexual dysfunction.
Term
___ is the most commonly used drug for female sexual dysfunction, especially in post-menopausal women. This works to stimulate sexual desire. Creams, patches, and combinations with estrogen and progesterone are being developed.
Definition
Term
side effects of testosterone for female sexual dysfunction:
Definition
- masculinization
- toxicity in high doses
Term
Testerone for treatment of FSD, __ __doses required, 20 mg administered subcu every 3 weeks.
Definition
extremely low
Term
Estrogen is available in pill, patch or cream to help alleviate postmenopausal symptoms like __ __, __, and ___.
Definition
vaginal dryness, itching, discomfort
Term
Side effects of conjugated estrogens:
Definition
- headache
- abdominal pain
- nervousness
- nausea
- back pain
- joint pain
- vaginal bleeding

Patients may also experience vaginal spotting, loss of periods or excessively prolonged periods, breast pain, breast enlargement and an increase or decrease in sexual drive.
Term
HCTZ, alpha and beta blockers cause sexual dysfunction (side note).
Definition
Term
Due to Viagra’s PDE5 inhibition it may improve vaginal engorgement and lubrication. Viagra for women is called Avlimil and was created in 2003.
84 percent success rate of decreasing symptoms of female sexual dysfunction, but It doesn’t have FDA approval yet.
Befar, the topical alprostadil cream, may be used to treat Female Sexual Arousal Disorder.  It would cause clitoral stimulation by vasodilatation.
Definition
Term
nonpharmacologic treatment of ED for everyone:
Definition
Reduce fat and cholesterol in diet
Decrease or limit alcohol consumption
Eliminate tobacco use and substance abuse
Weight loss as appropriate
Regular exercise
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