Pharmacology - Women's and Men's Health

Question 1

What is tamsulosin indicated for?

Answer 1

Moderate-severe symptomatic BPH
(regardless of prostate size)

Question 2

What is the MOA of tamsulosin?

Answer 2

MOA: reduces vasoconstriction induced by endogenous catecholamines by blocking the α-adrenoreceptors on the smooth muscle
- Decreases muscle tone
- Reduces bladder obstruction – relaxes prostate smooth muscle to improve urinary flow rate

Question 3

How is tamsulosin selective for the prostate?

Answer 3

selective for α1A receptors (prostate) over α1B receptors (cardiac), so it favors selectivity for the prostate

Question 4

How is tamsulosin administered?

Answer 4

PO

Question 5

Does tamsulosin bind to plasma proteins?

Answer 5

> 90%

Question 6

What is the Vd of tamsulosin?

Answer 6

0.2L/kg

Question 7

How is tamsulosin metabolised?

Answer 7

by CYP enzymes in the liver

Question 8

What is the half life of tamsulosin?

Answer 8

10-15h

Question 9

How is tamsulosin eliminated?

Answer 9

10% excreted unchanged in urine

Question 10

How long does it take for the onset of tamsulosin’s effects?

Answer 10

Fast, takes days to weeks

Question 11

What are the adverse effects associated with tamsulosin?

Answer 11

Abnormal ejaculation, back pain, muscle weakness, fatigue

Question 12

What are the contraindications for tqmsulosin?

Answer 12

Concurrent use of another α1-adrenoreceptor antagonist

Question 13

What is the MOA of finasteride?

Answer 13

Competitively inhibits 5α reductase (Type II), which decreases conversion of testosterone to DHT, resulting in ↓prostate size

Question 14

What is finasteride indicated for?

Answer 14

Moderate or severe LUTS w large prostate (>40g)

Question 15

How long does it take for the onset of finasteride’s effects?

Answer 15

Slow, may take up to 6-12 months to decrease prostate size

Question 16

How is finasteride administered?

Answer 16

PO

Question 17

What is the bioavailability of finasteride?

Answer 17

65%

Question 18

Does finasteride need dose adjustments?

Answer 18

No - renal, liver, old age

Question 19

Is finasteride highly protein bound?

Answer 19

Yes (~90%)

Question 20

How is finasteride metabolised?

Answer 20

By liver CYP enzymes

Question 21

What is the half life of finasteride?

Answer 21

~6h

Question 22

How is finasteride excreted?

Answer 22

50% excreted unchanged in faeces
Metabolites are excreted in urine and faeces

Question 23

What are the adverse effects of finasteride?

Answer 23

• Ejaculatory disorders (reduced semen or delayed) – more common than α1 antagonists
• Decreased libido (3-8%)
• Erectile dysfunction (3-16%)
• Gynecomastia and breast tenderness (1.0%)
• Lesser risk of hypotension
• More hair growth – reducing conversion of testosterone to DHT means testosterone levels are higher, resulting in increased hair growth

Question 24

What are the contraindications for finasteride?

Answer 24

Women and children, pregnancy

Question 25

What is the MOA of sildenafil?

Answer 25

Inhibit PDE5 enzyme (breaks down cGMP), resulting in increased cGMP activity, inducing smooth muscle relaxation to cause an erection

Question 26

Why is sildenafil v selective for the penis?

Answer 26

PDE5 is highly expressed in the corpora cavernosa of the penis and its vasculature, but poorly in the myocardium, which provides tissue specificity for the penis

Question 27

How is sildenafil administered?

Answer 27

PO

Question 28

What is the bioavailability of sildenafil?

Answer 28

~40%

Question 29

How long does it take for the onset of sildenafil?

Answer 29

30-60min

Question 30

How long can the effects of sildenafil last?

Answer 30

maximum of 12h

Question 31

Does sildenafil need dose adjustments?

Answer 31

No - renal, liver, old age

Question 32

Is sildenafil distributed by the body well?

Answer 32

Yes

Question 33

How is sildenafil metabolised by the body?

Answer 33

Liver - mainly CYP3A4 (and a bit of CYP2C9)

Question 34

How long is the half-life of sildenafil?

Answer 34

~4h

Question 35

How is sildenafil excreted?

Answer 35

Metabolites largely excreted in faeces (~80%), minorly in urine (13%) Unchanged drug excreted in urine

Question 36

What are the adverse effects associated with sildenafil?

Answer 36

- Headache - Flushing - Dyspepsia - Dizziness - Back pain - Blur vision/Blue green tinting of vision - Priapism

Question 37

What are the contraindications for sildenafil?

Answer 37

Any patient on GTN should not be taking any PDE-5i - potentiates vasodilation effect of GTN via inc cGMP due to concomitant blockade of cGMP degradation by sildenafil - results in potentially life-threatening hypotension

Question 38

What is the MOA of ethinyl estradiol?

Answer 38

Synthetic estrogen - reduces FSH release from anterior pituitary to suppress the development of the ovarian follicle (endometrium unsuitable for ovum implantation)

Question 39

How is ethinyl estradiol administered?

Answer 39

PO, parenterally, transdermal or topically

Question 40

What is the bioavailability of ethinyl estradiol?

Answer 40

45%

Question 41

How long does it take for the onset of ethinyl estradiol?

Answer 41

30-60min

Question 42

Does ethinyl estradiol exhibit high plasma protein binding?

Answer 42

Very high plasma potein binding (~98%)

Question 43

How is ethinyl estradiol metabolised>

Answer 43

Metabolised by liver via Phase I – hydroxylation by CYP3A4 Phase II – conjugation w glucuronide and sulfation into hormonally inert Ethinylestradiol glucuronides and Ethinylestradiol sulfate Ethinylestradiol sulfate undergoes enterohepatic recirculation

Question 44

What is the half-life of ethinyl estradiol?

Answer 44

13-27h

Question 45

How is ethinyl estradiol excreted?

Answer 45

Metabolites excreted in faeces and urine

Question 46

What are the adverse effects associated with ethinyl estradiol?

Answer 46

- breast tenderness - headache - fluid retention (bloating) - nausea - dizziness - weight gain rare: - venous thromboembolism - MI - liver damage

Question 47

What is ethinyl estradiol contraindicated for?

Answer 47

- Patients w known Hx or at high risk for VTE - Advanced diabetes w vascular disease - Hypertension (>160/100mmHg) - Avoid in breastfeeding (<21 days postpartum) and breast cancer

Question 48

What is the MOA of norethindrone

Answer 48

Synthetic progesterone - reduces LH release to prevent ovulation (makes endometrium unsuitable for ovum implantation) - progesterone receptor agonist

Question 49

How is norethindrone administered?

Answer 49

PO

Question 50

What is the bioavailability of norethindrone?

Answer 50

64%

Question 51

Is norethindrone highly plasma protein bound?

Answer 51

Yes

Question 52

How is norethindrone metabolised?

Answer 52

Metabolised in liver by reduction, followed by glucuronidation and sulfation

Question 53

What is the half-life of norethindrone?

Answer 53

8h

Question 54

How is norethindrone excreted?

Answer 54

Metabolites excreted in urine (~50%) and faeces (~40%)