Renal Test 3

Front 1

Stress urinary incontinence is caused by

Back 1

Urethral underactivity

Front 2

Urge urinary incontinence is caused by

Back 2

Bladder overactivity

Front 3

For bladder overactivity, which drug class constitutes the treatment of choice in the majority of cases

Back 3

Anticholinergics

Front 4

Overflow incontinence is caused by

Back 4

Urethral overactivity
Bladder underactivity

Front 5

Which one of the following is the preferred agent for the treatment of urethral underactivity

Back 5

Duloxetine

Front 6

Which one of the following is considered the cornerstone of management of urethral underactivity

Back 6

Behavioral interventions

Front 7

What are the 3 types of tissues in Prostate?

Back 7

1. epithelial
-Under androgen control. DHT stimulates the growth of this tissue
-prostatic secretions in ejaculate (have antibacterial properties)
-glandular tissue
2. Stromal
-More stromal tissue than epithelial
-(alpha1 smooth muscle)
-Respond to Norepinephrine

3. Capsule
(alpha1 smooth muscle)
-fibrous tissue

Front 8

What 2 active metabolites does Testosterone turn into and through what enzymes?

Back 8

1.(DHT) Dihydrotestosterone via 5α-reductase

2.Estradiol
via CYP19/Aromatase

Front 9

What are the effects of DHT in prostate?

Back 9

1.DHT 10x more potent 2.androgen than Testosterone
3.normal prostate growth
4. growth that causes BPH
5.

Front 10

What are the effects of estrogen in prostate?

Back 10

1. Stimulates stromal tissues of prostate
2. may induce androgen receptors
3. testosterone to estrogen ratio decreases due to increase in estrogen level due to adipose (fat tissue)

Front 11

What is a static factor in BPH?

Back 11

Prostate enlargement
-due to epithelial tissue increase by DHT
-blocks bladder neck preventing urine flow

Front 12

What is a dynamic factor in BPH?

Back 12

Contraction of prostate a round urethra
- Affects tone of stromal tissue (deceased urethra size)
- Improves urinary flow
Treatment: (α1-antagonists)
-Relax smooth muscle in (urethral sphincter and prostate)
-Do NOT reduce PSA levels
-Do NOT reduce prostate size
-Onset 1-6 weeks (much faster than 5α-reductace inhib)
-improves symptoms and quality of life
-start low and go slow
1. Prazosin
2. Terazosin
3. Tamsulosin

Front 13

What medications may exacerbate BPH symptoms?

Back 13

1. α-agonists
(decongestants)

2. anticholinergics
ex: antihistamines, antispasmodics, anti-parkinsons meds, tricyclic antidepressants

3. diuretics

4. testosterone replacement

Front 14

Which drugs are non selective α1 antagonists for BPH?

Back 14

Prazosin (bid to tid)
Doxasosin (qd)
Terazosin (qd)
Alfuzosin (qd)
AE: all can cause first-dose orthostatic hypotension. Do not add these drugs with other hypertension meds

Front 15

Which drug is prostatic selective α1A- antagonist for BPH?

Back 15

Tamsulosin
affect receptors in prostate

Front 16

(Smith notes)
Which Drugs target Overactive bladder?

Back 16

1. Anti-cholinergics
2. Tricyclic antidepressants
3. Topical estrogen

Front 17

Which drugs target Urethral Underactivity/Stress

Back 17

1. Dual Serotonin,Norepi reuptake inhibitor (Duloxetine)
2. α agonists (Pseudophedrine)
3. Estrogen
4. Tricyclic antidepressants (Impramine)

Front 18

What do anticholinergics do?

Back 18

1. Suppress premature detrusor contractions, enhancing bladder storage, relieve UI symptoms and complications

Front 19

Which anticholinergics are used for overactive bladder?

Back 19

-Nonspecific muscarinic receptor antagonists
1. Oxybutanin
(many side effects, CYP3A4 DDIs)
2. Tolterodine
In CYP2D6 poor metabolizers, do NOT use with CYP3A4 inhibitors
3. Trospium Cl
Antimuscarinic effects in bladder and GI
Increased AE in elderly due to increased sensitivity NOT change in PK.

-Selective M3 anticholinergics
1. Solifenacin
less AEs, no other advantage over others
2. Darifenacin
less AEs, no other advantage
3. Propantheline
High incidence of AEs

Front 20

What are the symptoms of BPH?

Back 20

1. frequency
2. incomplete bladder emptying
3. weak urine stream
4. urgency to urinate
5. straining on urination
6. nocturia
7. UTI
8. urospesis
9. bladder stones
10. hematuria

Front 21

What is Mild, Moderate, Severe BPH in the LUTS severity assesment test?

What scores are bad in Quality of Life Assesment?

Back 21

Mild: 0-7
Moderate: 8-19
Severe: 19-35

Quality Test:
Bad = 4, 5, 6
Give med for 5 and 6 regardless of other test

Front 22

What is the treatment for BPH symptoms:
1. no/little symptoms
2. small prostate
3. AUA index score less than 7

Back 22

Watchful waiting

Front 23

What is the treatment for BPH symptoms:
1. AUA score less than 7
2. little or no symptoms
3. large prostate

Back 23

5α-reductase inhibitors

Front 24

What is the treatment for BPH symptoms:
1. AUA score greater than 7
2. moderate symptoms
3. small prostate

Back 24

α1-blocker

Front 25

What is the treatment for BPH symptoms:
1. AUA score greater than 7
2.moderate symptoms
3.large prostate
3.

Back 25

Combination therapy
5α-reductase inhibitors and
α1-blocker

Front 26

What is watchful waiting?

Back 26

1. Annual visits for BPH symptoms
2. Lifestyle modification
-decrease late-night fluid intake
-moderate caffeine and alcohol
-limit salt intake
-urination schedules

Front 27

What are 5α-reductace inhibitors?

Back 27

-Reduce DHT and thus reduce prostate growth and decreases size
-halts disease progression
-inhibits male pattern baldness
-Reduce PSA levels
- Slow onset 3-6 months to see effect
-Sexual dysfunction is a side effect
-Teratogenic
-Dose once daily
-No cardiovascular side effects

1. Finasteride (type 2)

2. Duasteride (type 1, 2)

Front 28

What are the Risk Factors for Stress Urinary Incontinence?

Back 28

1. mainly in women
2. pregnancy
3. childbirth
4. menopause
5. cognitive impairment
6. obesity
7. age

Front 29

True/False:
UIncontinence only occurs during exertion not when inactive?

Back 29

True

Front 30

What are the treatments for Urinary Incontinence?

Back 30

1. Behavioral modification
2. estrogen (topical only)
3. α agonists (except in HTN)
4. Duloxetine (cymbalta)

Front 31

What are the treatments for OAB over active bladder disorder?

Back 31

1. Behavior modification
-bladder diary
-scheduled voiding
-alter fluid intake
-pelvic excersises

2. Medications
(anticholinergics)
Immediate release- improved adherence

Front 32

(Gupta)
Hows does 5α-reductase convert Testosterone to DHT?

Back 32

saturates 4,5 double bond on Testosterone and turns into single bonds with 2 hydrogens (DHT)
-The DHT is more active than Testosterone.
-Metabolism happens in the PROSTATE, NOT the liver (in the liver 5-AR responsible for cholesterol metabolism

Front 33

(Gupta)
How does Finasteride work?
5α-reductase inhibitor (Type II selective 5-AR)

Back 33

-Forms covalent bond with 5-AR/NADPH complex at Carbon 2 (double bond) on Finasteride

-Irreversible inhibition: takes 30 days for complex to regenerate active enzyme

-Orally absorbed

-Primarily metabolized by CYP3A4 (but NO active metabolites, just for elimination purposes)

-excreted in urine and feces

-long elimination half life

Front 34

(Gupta)
How does Duasteride work?

Back 34

1) Inhibits both type I and type II isozymes of 5-AR (non-selective)

2) Long plasma half life (5 weeks) due to high volume of distribution and plasma protein binding
(99% protein bound, binds proteins in semen)

3) Has equal active metabolite
(6'-Hydroxydutasteride)

4) Longer plasma and biological half life of active metabolite (irreversible inhibitor)

Front 35

What are the 2 types of α1 antagonists for BPH?

Back 35

1) Quinazolines
-Prazosin
-Terazosin
-Doxazosin
-Alfuzosin

2) Catecholamine Sulfonamides
-Tamsulosin

Front 36

Which drug has a longer duration of action: Terazosin or Prazosin?
Which has better bioavailability?
Where are they metabolized?

Back 36

1) Terazosin
2) Terazosin
3) metabolized by hepatic enzymes

Front 37

Which drug has a longer duration of action: Doxazosin or Alfuzosin?
Which drug is more selective for α1A receptors?

Back 37

1) Doxazosin
2) Alfuzosin is more selective for α1A which are present in the prostate and urethra (less blood pressure side effects)

Front 38

(Gupta)
Tamsulosin
(Catecholamine-Sulfonamide)
α1-Antag

Back 38

1) Selective for α1A and α1D

2) R-isomer is active (NOT S-isomer)

3) NO active metabolites

4) Metabolized by CYP3A4 and CYP2D6

5) Sulfonamide type allergy

6) Excreted in Urine

Front 39

(Gupta)
Oxybutynin metabolism
(anticholinergic)

Back 39

1) M1, M2, M3 antagonist

2) Poor oral bioavailability due to extensive first pass metabolism (Deliver locally to avoid first pass metabolism)

3) Metabolized into equally active metabolite (therapeutic effects come from this metabolite, but metabolite has worse anticholinergic side effects)

4) Extended Release version slows down the active metabolite N-DEO (with the worse side effects
5) R-isomer is active

Front 40

(Gupta)
Tolterodine tartrate (Detrol LA)
metabolism

Back 40

1) Metabolized by CYP2D6 to equally active metabolite (5-HM)

2) Undergoes first pass metabolism

3) Undergoes metabolism by CYP3A4 (inactive metabolite formed)

4) If someone is a poor metabolizer of CYP2D6, will this affect therapeutic effect?
-No because you still have active parent drug (tolterodine) going to the slow route of CYP3A4 instead.

5) But there are DDIs with CYP3A4 inhibitors that are significant in CYP2D6 Poor Metabolizers

Front 41

(Gupta)
Trospium Chloride
metabolism

Back 41

1) Poor oral absorption
2) Does NOT cross BBB
3) Less CNS side effects as a result- this is good, you want it to stay in the bladder
4)Limited Metabolism (not metabolized by CYP enzymes. Only metabolized by esterases.
5) There are less DDIs due to no CYP based metabolism

Front 42

What are the 3 mechanisms of Angiotensin II?

What is the end result?

Back 42

1) Direct effect to increase Na+ reabsorption in proximal tubule

2) Release of aldosterone from adrenal cortex

3) Altered renal hemodynamics (direct renal vasoconstriction, enhanced noradrenergic neurotransmission in kidney, increased renal SNS tone)
End Result:
SLow pressor response

Front 43

Where is Renin produced?

Back 43

Juxtaglomerular cells in the juxtaglomerular apparatus

Front 44

What are the 3 pathways for regulating RENIN release?

Back 44

1) Macula Densa Receptor
(increased Na in DCT inhibits renin release, vise versa)

2) Intrarenal Baroreceptor
(Decreased stretch(low BP) leads to Increased renin release and vice versa

3) B-Adrenergic receptor
(catecholamines (norepi/epi) stimulate renin release via B1 receptors on Juxtaglomerular cells)

Front 45

ACE inhibitors
Mechanism of Action

Back 45

1) Inhibit the conversion of Ang I to Ang II

2) Increase levels of Bradykinin (potent vasodilator)

3) Interfere with short negative feedback loop of renin release

4) ACE inhibitors up-regulate COX-2 and NOS and may increase renin release

Front 46

What are the 2 ACE inhibitors examples and their properties?

Back 46

1) Captopril
- short half life

2) Enalapril (Vasotec)
- Prodrug (Enalaprilat is active metabolite)
-Highly potent
-active met half life = 11 hrs

Front 47

What are the Adverse Effects of ACE inhibitors?

Back 47

1) First-Dose HYPOtension
2) Dry cough (due to accumulation of bradykinin)
3) Acute Renal Failure (bilateral renal stenosis)

4) Fetopathic Potential (never give in pregnancy)

5) Skin Rash (captopril)

6) Proteinuria

7) Angiodema (swelling of the throat)

8) Dysgeusia (loss of taste, captopril)

9) Neutropenia

10) Glycosuria

11) Hepatotoxicity

Front 48

What are the DDIs of ACE inhibitors?

Back 48

1) Antacids (reduce bioavailability)

2) Casaicin (increase cough)

3) NSAIDs (inhibit prostaglandin synthesis and may reduce antihypertensive effect)

4) K+ sparing diuretic and K+ supplements

5) Digoxin and Lithium (increase plasma levels)

Front 49

ARB (Angiotensin II receptor blockers)
Mechanism of Action

Back 49

1. Inhibit the Angiotensin II receptors
2. Type 1 and Type 2 Angiotensin receptors (Ex: AT1 and AT2) AT1 is primarily in the vasculature

3) Ang II interaction with AT1 causes vasoconstriction

4) ARBs target AT1

5) Prolongued use of ARBs will STOP Ang II inhibition of RENIN release = ↑ Renin = ↑ Ang II (these meds will eventually lose their effectiveness over time)

Front 50

ARB example and characteristics

Back 50

1) Can combine ARBs with hydrochlorothiazide

2) Irbesartand and Losartan can treat diabetic nephropathy

3) ARBs are just as good as ACE, but considered 2nd line for people intolerant to ACE side effects.

Front 51

What are the DDIs of ARBs?

Back 51

1) Teratogenic
2) careful in hypotenive patients, or acute renal failure
3) HYPERkalemia when given with K+ sparing drugs
4) Affect CYP2C9 and CYP3A4 Drugs
a) fluoxetine (inducer 2C9)
b) carbamazepine (2C9 inhibitor)
c) Macrolide antibiotic (3A4 inhibitor)
d) rifamycins (3A4 inducer)

Front 52

Renin Inhibitors
Mechanism of Action

Back 52

1) Aliskerin is only drug in class
2) Inhibitor of RENIN which decreases renin activity (inhibits the conversion of Ang to Ang I)

3) GREATER antihypertensive effects than ACE and ARBs.
because it does not have the problem of increasing Renin