Renal 2 Pharmacology Flashcards
(56 cards)
1
Q
Male Disorder A1 adrenergic antagonist drugs
A
Doxazosin Terazosin Alfuzosin-BPH only Tamsulosin-BPH only Silodosin-BPH only
2
Q
Male Disorder 5a-reductase inhibitor drugs
A
Finasteride
Dutasteride
3
Q
Erectile Dysfunction Drugs
A
-phosphodiesterase-5 (PDE5) inhibitors Sildenafil Vardenafil Tadalafil -can also tx ysubg PGE1
4
Q
Benign Prostatic Hyperlasia (BPH)–what is it? Treatment?
A
- enlargement obstructs bladder outlet
- Tx using alpha 1 adrenergic antogonists, steroid 5alpha reductase inhibitors, PDE5 inhibitor
5
Q
Lower Urinary Tract Symptoms (LUTS)
A
- interrupted stream
- hesitation
- frequency
- dribbling
- fullness
- urgency
- weak stream
6
Q
Drugs for symptomatic relief of LUTS
A
- antagonists of a1 receptors
- Terazosin, Doxasozin, Tamsulosin, Silodosin, Alfuzosin
- Drug class to relax muscle tone
- dynamic remedy
- rapid relief of symptoms ~days
7
Q
a1 adrenoreceptors in blood vessels
A
a1B more than a1A
8
Q
A1 receptors in prostate
A
- smooth muscle contraction
- a1A
9
Q
a1 receptors in detrusor
A
instability
a1D>a1A
10
Q
A1 receptors in spinal cord
A
- control of urinary function
- a1D
11
Q
Stimulation of genitourinary a1-receptors
A
mediate bladder outlet obstruction
12
Q
Detrusor instability caused by =
A
a1D receptors + NE
13
Q
Muscle contraction caused by=
A
a1A receptors + NE
14
Q
a1 antagonists
A
- compete with NE
- this mechanism reduces spasm, promotes muscle relaxation and improves urine flow
15
Q
Non-specific a1 antagonists
A
- Terazosin
- Doxazosin
- Alfuzosin
16
Q
a1 antagonists specific for a1A and/= A1D
A
- Tamsulosin
- Silodosin
17
Q
Terazosin and Doxazosin
A
- no uroselectivity
- adverse effects: postural hypotension, titrate 1st dose; fatigue
- Drug interaction with PDE-5 inhibitors
18
Q
Alfuzosin
A
- uroselective (functional) (doesn’t discriminate between subtypes but tends to accumulate in prostate!)
- a1 antagonist
- adverse effects: QT prolongation
- drug interaction with CYP450
- take immediately after meal every day
19
Q
Tamsulosin and Silodosin
A
- uroselective for a1A and a1D (a1 antagonist)
- adverse effects: reduced ejaculation; intraoperative floppy iris syndrome (IFIS)
- drug interaction with CYP450
20
Q
Avoid alfuzosin in
A
hepatic impairment
21
Q
Steroid 5a reductase inhibitors (SARI, 5ARI)
A
- Finasteride
- Dutasteride
- drug class that prevents enlargement and shrinks prostate
- structural remedy (slow BPH progression)
- delayed action–>shrinkage and symptoms relief ~3-6 months
22
Q
Why is the prostate enlarging?
A
-aging puls dihydrotestosterone
23
Q
Enable prostate epithelium survival and growth
A
- androgenic steroids, testosterone and dihydrotestosterone (DHT)
- DUT potency ~10x >testosterone
- T converted to DHT via SAR (steroid alpha reductase) types I and II
- hypertrophic prostate has ecess SARII
24
Q
Steroid 5a-reductase (SAR) types I and II convert
A
serum testosterone to DHT in cells
25
Hypertrophic prostate has excess
SAR-II
26
DHT 'starvation' may cause
epithelial atrophy, shrinkage, gradual relief of LUTS
27
DHT starvation can be caused by
inhibiting SAR II
28
Direct Effects of SAR II Inhibition (Finasteride or Dutasteride)
- testosterone accumulation
| - DHT depletion
29
Indirect Effects of SAR II Inhibition
- AR receptor less occupied
| - no gene transcription
30
Finasteride Selectivity
-specific inhibitor of SAR II
31
Dutasteride selectivity
-dual inhibitor of SAR I and II
32
Both finasteride and dutasteride
take about 3 months for a measurable effect
- have similar efficacy
- improved LUTS, reduced prostate volume and serum PSA
- reduced need for surgery
- no dosage adjustment needed for age or renal insufficiency
- no established clinically significant drug interaction (CYP3A metabolism)
- caution with liver abnormalities
33
Adverse Effects of Finasteride and Dutasteride
-Erectile dysfunction, gynecomastia, depressed libido, ejaculation disturbances
34
Tadalafil
- phosphodiesterase-5 inhibitor
| - approved for use BPH
35
Erectile (endothelial) Dysfunction associated conditions
-Hypertension, CAD, depression, alcohol abuse, drug abuse, endocrine disorders, diabetes, hypogonadism, trauma to pelvis or spine, hperlipidemia, LUTS, PVD, vascular surgery, smoking, anemia
36
Corporus cavernosum
- relaxed smooth muscle-->blood in sinusoids-->rigid organ
| - neuronal input (NANC) and endothelial lining modulate smooth muscle tone
37
Corpus spongiosum
-NOT prominent in erectile dysfunction
38
Nitric Oxide and cGMP
-No interacts directly with guanylate cyclase which activates cGMP which causes smooth muscle relaxation (vasodilation) and erection
39
Phosphodiesterase-5
-metabolizes cGMP back into GMP
40
PDE-5 inhibitors
-enhance cGMP signaling by blocking metabolism of cGMP -Sildenafil, Vardenafil, Tadalafil
41
PDE-5 Inhibitor onset
~15 minutes (take 1 hour before)
42
PDE-5 Inhibitor span of efficacy
- sildenafil: 3-4 hours; t1/2 4 hrs
- vardenafil: 4-5 hours; t1/2 4 hours
- tadalafil: ~36 hours ; t1/2 18 hours
43
PDE-5 inhibitors clearance by
hepatic CYP3A4
44
PDE5 expressed in
corpus cavernosum
45
PDE6 expressed in
retina
- Sildenafil, vardenafil)
- adverse effect is blue vision disturbance
- take about 10fold to cause this affect
46
PDE1 expressed in
vasculature, heart, brain
- would take about 80 fold to cause affect
- little clinical significance
47
PDE11
- heart pituitary testes
| - 800 fold to cause affect
48
PDE3
heart
| -negligible effect
49
PDE-5 related inhibitor side effects
- headache
- dyspepsia
- nasal congestion
- sidlenafil, vardenafil, tadalafil
50
Tadalafil other side effects
-back pain, myalgia, limb pain
51
PDE-5 inhibitors contraindications
- do not use with organic nitrates!
- use of PDE-5 inhibitors concurrently with nitrates (e.g. glyceryl trinitrate) may induce extreme hypotension
- drops of 25 mm Hg have been reported, with syncope
52
Vardenafil and nonspecific a-receptor antagonists
- patients should be hemodynamically stable prior to initiating therapy
- initiate vardenafil at the lowest recommended dose
53
Tadalafil and nonspecific a-receptor antagonists
-when tadalafil is used for treatment of BPH, concurrent alpha1-blockers are not recommended.
54
Sildenafil and nonspecific a-receptor antagonists
-alpha-blockers should be initiated at the lowest recommended dose in patients currently receiving sildenafil
55
Intracavernosal injection of vasoactive drugs
- effective for treating eternal dysfunction
- papaverine, phentolamine, prostaglandin E1
- relaxed smooth muscle-->blood in sinusoids-->rigid organ
56
PGE1
-interacts with GPCR which activates Adenylate cyclase and activates cAMP--> smooth muscle relaxation
