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12- REPRO > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What are the 3 naturally occurring oestrogen’s?

A
  1. 17-beta estradiol (most important)
    a. Most abundant and potent oestrogen
    b. Produced by ovarian granulosa cells
  2. Estrone
    a. Produced by ovaries and adrenals
    b. Levels increase slightly after menopause
  3. Estriol
    a. Placental – only in pregnancy
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2
Q

What is common to all endogenous oestrogen’s?

A
  • 18 carbon steroids
  • transported by SHBG
  • Bind estrogen receptors (ER-alpha and ER-beta) in target cells (OH)
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3
Q

What are the oestrogen receptors and where are they expressed?

A

ER alpha beta are expressed in reproductive system and breast tissue
ALSO - in CVS, skeleton, CNS, immune system

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4
Q

What proportion of breast cancers express ER alpha?

A

70%

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5
Q

Action of oestrogen’s

A

Development
• Pubertal breast and genital development
Menstrual cycle regulation
• Modulation of FSH and LH release
• Cyclical changes in uterus and breasts
• Induction of progesterone receptors (PR)
Metabolic
• Increase in bone mass – blocks bone resorption
• Improved TG profile – increases HDL:LDL ratio
• BUT increases coagulability – DVT/PE and stroke risk

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6
Q

5 facts about natural progestogens

A
  • 21 carbon steroid
  • secreted mainly by corpus luteam and placenta
  • secreted in the 2nd half of the cycle
  • levels decrease before menstruation (unless pregnant)
  • transported by albumin and corticosteroid binding globulin (CBG)
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7
Q

Where are progestogen receptors located?

A

Female reproductive tract, breast and CNS

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8
Q

Actions of progestogen on the endometrium, cervix and myometrium

A

o Endometrium – decrease proliferation and increase secretory changes
o Cervix – thickens and reduced secretions – reduced sperm penetration
o Myometrium – reduced uterine excitability

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9
Q

Other effects of progestogens

A
  • Breasts – glandular development
  • Hypothalamus – reduced LH surge and GnRH release – block ovulation
  • CNS – increase in body temperature (0.5’C)
  • AR – binds weakly very low pro/anti-androgenic effects
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10
Q

What synthetic oestrogen’s are in COCs

A

Ethinylestradiol (EE)
• derivative of estradiol
• addition of ethinyl group has reduced hepatic metabolism
• potent oral activity
• most commonly used
Mestranol
• pro-drug of EE – undergoes demethylation

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11
Q

1ST 2ND + 3RD generation progestogens

A 
1st generation – ethisterone
•	significant androgenic effects 
o	Acne 
o	Hirsutism 
o	Weight gain 
•	No longer used

2nd generation – levonorgestrel, norethisterone
• Some androgenic effects

3rd generation – desogestrel, gestodene
• Reduced androgenic and lipid effects
• Increased thromboembolic effects

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12
Q

COC mechanism of action

A

Inhibit ovulation prevent release of (estrogen) FSH for follicle development and (progestogen) LF (ovulation)
Also
• Thickened cervical mucous – form barrier to sperm
• Progestogen effect
• Thin endometrial lining reduce endometrial receptivity to inhibit implantation
• Estrogen and progestogen effect

**Decrease the likelihood of pregnancy by inhibiting ovulation, fertilization and implantation

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13
Q

What reduces COC effectiveness?

A
  • Poor compliance
  • Delayed start of next pack - reduced HPO suppression
  • Missed pills (47% miss 1 or more per month)
  • Vomiting or diarhoea
  • Broad spectrum A/B

P450 induction – griseofulvin, anti-epileptics (phenytoin and carbamazepine), TB drugs (rifampicin), St John’s Wort

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14
Q

Common side effects of COC

A
  • breakthrough bleeding – increase estrogen or progesterone
  • nausea – decrease estrogen dose, take at night with food
  • fluid retention, breast tenderness – reduce estrogen
  • chloasma avoid sun/stop estrogen
  • although transient, these are common reasons for stopping COCs
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15
Q

Androgenic side effects of COC

A
  • Acne
  • Weight gain
  • Depression
  • Irritability, fatigue
  • Reduced libido
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16
Q

Serious side effects of COC

A 
Enhanced coagulation (estrogens)
Breast cancer (1.24x)
Small increased risk of cervical cancer
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17
Q

Contraindications for COC

A 
•	Pregnancy 
•	History of 
  o	DVT, PE stroke 
  o	Major elective surgary 
  o	Estrogen dependent tumours 
  o	Migraine with aura – stroke rsk 
  o	Hepatic disease 
•	Breast feeding 
•	> 35 yrs old, smoker, HT and DM
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18
Q

Minipill mechanism of action

A
  • inhibition of ovulation due to inhibition of LF surge
  • thickening and reduction in amount of cervical mucous impedes sperm penetration
  • Endmetrium thins reduced implantation rates
  • BUT 30-40% of women on progestogen only OCs still ovulate less effective than combined OC
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19
Q

Define menopause, peri-menopause and post-menopause

A

Menopause - The final menstrual period (median age 50‐52 years)

Peri‐menopause - The transition to the end of a woman’s reproductive life
menstrual cycle begins to change in length and symptoms may begin to occur (takes about a decade; hormonal swings and heightened symptoms)

Post‐menopause - 12 months after the final menstrual period

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20
Q

Symptoms of menopause

A

¥ Central: Hot flushes & night sweats; insomnia; mood and memory changes

¥ Joint aches & muscle pains

¥ Urogenital: Dry vagina/dyspareunia; urinary
frequency, UTI, incontinence

¥ Skin: Dryness, thinning, loss elasticity, crawling under the skin, acne

¥ Hair: increased facial hair, thinning scalp & pubic hair

¥ Loss of libido

¥ Long term consequences: metabolic, cardiovascular, bone & brain

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21
Q

Role of oestrogen and progestogen in HRT

A

Oestrogen provides
¥ Relief of menopausal symptoms– flushes, tiredness, moods
¥ Preserves bone density, lowers cardiovascular risk (ifstarted early)

Progestogen
¥ Protects the endometrium from the stimulatory effects of oestrogen
¥ NB for a woman who has no uterus–no progestogen

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22
Q

Cyclical and continuous HRT

A 
Cyclical HRT 
¥	More appropriate for younger women
¥	Produces periods
Continuous HRT
¥	NO vaginal bleeding 
¥	Popular with older women 
¥	Note recent concerns about this
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23
Q

Oral oestrogens and the ‘first pass effect’

A

¥ Beneficial effect on HDL – inhibits hepatic lipase activity

¥ Beneficial effect on LDL – induces LDL receptors

¥ Raises TGs

¥ Increases thrombosis risk by effects on coagulation cascade and thrombophilic factors

NOTE: transdermal oestrogen does not increase VTE risk

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24
Q

Oral progestogens and the ‘first pass effect’

A

¥ Deleterious effect on HDL – induces hepatic lipase activity

¥ Deleterious to neutral effect on LDL

¥ Neutral effect on TGs

¥ Additive effect on thrombosis risk (MPA)

¥ Dose and androgenicity to be taken into account

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25
Q

Which time frame is the embryo most susceptible to damage by medications?

A

17-70 days

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26
Q

Do not prescribe a X class drug to a reproductive age woman unless ______

A

A pregnancy test is negative and effective contraception is being used

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27
Q

NSAIDS category and associated risks

A

NSAIDs inc. COX-2s (cat. C) – BUT BE CAREFUL!
¬ First trimester use & early pregnancy loss

¬ Small risk of fetal harm from 27-32 weeks until delivery
¥ premature closure of the ductus arteriosis & pulmonary hypertension

¥ necrotising enterocolitis

¥ renal failure

¥ neonatal intracranial haemorrhage

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28
Q

Opioids category, risks and recommendations

A

Opioids (cat C) – BUT BE CAREFUL
¬ Probably safe in early pregnancy but possible potential for long-term behavioural effects
¬ Neonatal respiratory depression at birth

¬ neonatal withdrawal (abstinence syndrome) - 30-90% post-methadone & 50% post-buprenorphine

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29
Q

Categories of tramadol, gabapentin, pregabalin and clonidine

A

Tramadol (cat C) - No good trials or epidemiology so safety not established, but widely used & appears OK

Gabapentin (cat B1)

Pregabalin (cat B3)
• safety not established but used

Clonidine (cat B3) • safe

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30
Q

Cardiovascular drugs which are ok to use in pregnant women

A

¥ methyldopa (cat A)
¥ beta-blockers (labetolol safe; possibly avoid atenolol etc.) (cat C)
¥ calcium channel blockers (cat C)
¥ hydralazine (cat C)

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31
Q

Cardiovascular drugs which should be avoided in pregnant women

A

¥ ACE inhibitors & ARBs (cat D due renal failure/fetal death)
¥ amiodorone (cat C but causes hypothroidism & bradycardia)
¥ thiazide diuretics (cat C but cause neonatal electrolyte derangements)
¥ spironolactone (cat B3 due to feminisation of the male fetus)

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32
Q

Diabetes drugs in pregnant women

A

¥ Sulphonylureas (glibenclamide/gliclazide) cat C but not recommended
¥ Rosiglitazone not recommended
¥ Metformin cat C but probably safe and widely used
Insulin recommended

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33
Q

Antidepressants in pregnant women

A

TCA - cat C - appear safe
Venlafazine, mianserin,

MAOIs - cat B2 - unclear but no increased risk

SSRI - Cat C - appear safe, use in 3rd trimester can lead to neonatal withdrawal syndrome so reduce if possible

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34
Q

Prednisolone recommendations in pregnant women

A

cat C

o AVOID if possible, esp. first trimester high-dose (cleft palate) or later, pre-term delivery
o CONTINUE if needed in lowest effective dose (prefer < 15 mg/day)

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35
Q

Hydroxychloroquine reccomendations in pregnant women

A

cat D

  • avoid if possible (neurological disturbance)
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36
Q

Azathioprine and cyclosporine recommendations in pregnant women

A 
Azathioprine = cat D
Cyclosporine = cat C

Usually continue for organ transplant

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37
Q

Specific drugs to avoid using in pregnant women

A
  • Cytotoxics
  • Retinoids and interferon
  • Mycophenolate, danazol
  • Statins
  • Tetracyclines – after 18 weeks but typically throughout
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38
Q

Symptoms of menopause

A

¥ Central: Hot flushes & night sweats; insomnia; mood and memory changes

¥ Joint aches & muscle pains

¥ Urogenital: Dry vagina/dyspareunia; urinary
frequency, UTI, incontinence

¥ Skin: Dryness, thinning, loss elasticity, crawling under the skin, acne

¥ Hair: increased facial hair, thinning scalp & pubic hair

¥ Loss of libido

¥ Long term consequences: metabolic, cardiovascular, bone & brain

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39
Q

Indications for HRT

A

¥ Relief of menopausal symptoms

¥ Maintenance of bone density and prevention of osteoporotic fracture

40
Q

Preparations of HRT

A

Oestrogen = basis
- relief of menopausal symptoms, preserves bone density and lowers cardiovascular risk

Progestogen: protects endometrium from stimulatory effects of E, NOT for a woman without a uterus

41
Q

What type of HRT is more appropriate for younger women?

A

Cyclical - because it produces periods

- oestrogen always given, cycle in and out of progestogen

42
Q

Continuous HRT

A

Oestrogen and progestogen continuously given - popular with older women, no vaginal bleeding

43
Q

Oral oestrogen and the first pass effect

A

¥ Beneficial effect on HDL – inhibits hepatic lipase activity

¥ Beneficial effect on LDL – induces LDL receptors

¥ Raises TGs

¥ Increases thrombosis risk by effects on coagulation cascade and thrombophilic factors

NOTE: transdermal oestrogen does not increase VTE risk

44
Q

Oral progestogen and the first pass effect

A

¥ Deleterious effect on HDL – induces hepatic lipase activity

¥ Deleterious to neutral effect on LDL

¥ Neutral effect on TGs

¥ Additive effect on thrombosis risk (MPA)

¥ Dose and androgenicity to be taken into account

45
Q

Cardiovascular risk in HRT

A

Proposed mechanisms for protective oestrogen effect on cardiovascular disease
¥ lipoprotein effects (raised HDL, lowered LDL)
¥ vascular mechanisms

o	endothelium dependent 
o	endothelium independent  ¥	antioxidant effects

¥ lowering of insulin resistance
¥ coagulation and fibrinolysis

46
Q

Analgesic recommendations in pregnant women

A

Use paracetamol (cat A)

Low-dose aspirin OK (avoid high-dose) 
Codeine OK (cat C)

NSAIDs inc. COX-2s (cat. C) – BUT BE CAREFUL!

Opioids (cat C) – BUT BE CAREFUL

Tramadol (cat C) - No good trials or epidemiology so safety not established, but widely used & appears OK

Gabapentin (cat B1)

Pregabalin (cat B3)
• safety not established but used

Clonidine (cat B3) • safe

47
Q

Anti-emetics in pregnant women

A

• metoclopramide (cat A)

  • 5-HT3 antagonists (most cat B1)
  • droperidol (cat C)
  • promethazine (cat C)
  • prochlorperazine (cat C)
48
Q

Antibiotics which are safe to use in pregnant women and which might have possible risk?

A

Safe
• all penicillins (cat A & some B)

  • early generation cephalosporins (cat A or B)
  • erythromycin (cat A & other macrolides cat B)
  • clindamycin
  • metronidazole

Possible risk

¥ sulphonamides (cat C) & nitrofurantoins

¥ aminoglycosides (cat D)

¥ anti-retrovirals (mainly cat B but some D)

49
Q

Cardiovascular drugs which are ok to use in pregnant women

A

¥ methyldopa (cat A)
¥ beta-blockers (labetolol safe; possibly avoid atenolol etc.) (cat C)
¥ calcium channel blockers (cat C)
¥ hydralazine (cat C)

50
Q

Cardiovascular drugs which should be avoided in pregnant women

A

¥ ACE inhibitors & ARBs (cat D due renal failure/fetal death)
¥ amiodorone (cat C but causes hypothroidism & bradycardia)
¥ thiazide diuretics (cat C but cause neonatal electrolyte derangements)
¥ spironolactone (cat B3 due to feminisation of the male fetus)

51
Q

Diabetic drugs which carry a risk of macrosomnia, neonatal hypoglycaemia and congenital abnormalities

A

¥ Sulphonylureas (glibenclamide/gliclazide) cat C but not recommended
¥ Rosiglitazone not recommended
¥ Metformin cat C but probably safe and widely used
–> insulin recommended

52
Q

Endogenous estrogens

A

Location of production: follicle cells in oocyte

Target tissues: breast, endometrium, bone, liver

Primary effect: proliferation

53
Q

Estrogens and breast cancer

A
  • Oestrogen does not directly induce DNA mutations to cause BC
  • It stimulates proliferation of a normal ductal epithelial cells that can then develop mutations
  • It stimulates proliferation of ER+ BC cells (2/3 of BC cases)
54
Q

Estrogen and bone health

A

• ERα & ERβ are expressed in bone and B/M cells
• E2 rise ↑ at puberty triggers long bone growth → growth spurt
• E2 then maintains bone mineral density
• protective effects of E2 are multiple:
o inhibit osteoclasts
o promote osteoblast & osteocyte survival

55
Q

Synthetic oestrogen’s action

A

Agonist ligands (E2) induce LBD conformations that allow the ER to stably interact with co-activator proteins, e.g. SRC-1 or HATs → gene transcription

Antagonist ligands (i.e. “anti-oestrogens”) induce a LBD conformation that interacts with co-repressors, e.g. HDACs → chromatin condensation

  • some synthetic ligands are agonists in some tissues and antagonists in others (partial agonist)
56
Q

Mechanism of action of selective oestrogen receptor modulators (SERMs)

A
  • ER LBD consists of 12 α-helices → helices 1-11 form a pocket
  • and helix 12 forms the lid
  • E2 binds LBD of ER → helix 12 (pink) closes over E2
  • Exposes amino acids critical for co-activator binding and co-repressor release
  • SERMs are often bigger → prevent helix 12 from closing
  • Co-activators don’t bind → antagonism
57
Q

SERM uses

A

• prevention and treatment of BC

  • prevention and treatment of osteoporosis
  • infertility (Clomiphene)
58
Q

Action of tamoxifen in breast cancer

A

¥ In BC cells, it antagonises E2’s effects on proliferation

59
Q

Agonist and antagonist effects of tamoxifen

A 
Antagonist effects on the breast = anti-estrogen
Partial agonist (estrogenic) effects on:
•	Bone  maintains bone density = reduced hip fractures 
•	Blood lipids  reduced LDL cholesterol so cardioprotective 
•	Endometrial epithelium  increased endometrial cancer
60
Q

Differences between tamoxifen and raloxifene

A

Raloxifene not as effective as tamoxifen in preventing DCIS

61
Q

What are aromatase inhibitors used for

A

First line adjuvant therapy in BC in post menopausal women

- reduces circulating oestrogen levels

62
Q

Australian adjuvant hormone prescription guidelines

A

• BC prevention in high risk women → tamoxifen
• BC treatment in premenopausal women → tamoxifen (10y)
• BC treatment in postmenopausal women → depends on stage & risk:
High risk of recurrence: treat with A.I’s
Low risk: treat with tamoxifen

63
Q

Androgenic and estrogenic effects of testosterone

A 
Androgenic – masculinizing
•	foetal male sex organ development 
•	pubertal maturation of male sex organs 
•	maintenance of male characteristics 
•	spermatogenesis

Anabolic – growth stimulating
• increase in protein synthesis in growing tissues
• increase in muscle and bone mass (+ maintenance)

64
Q

Control of testosterone synthesis at puberty

A

• GnRH → ALP → LH and FSH
• LH → Leydig cells secrete testosterone
• FSH → Sertoli cells (nurse cells) in seminiferous tubules:
o support spermatogenesis

o secrete androgen binding protein (ABP/SHBG)
• Secreted T binds to ABP

  • Intra-testicular T levels&raquo_space; circulating levels (25-100x)
  • T binds AR in Sertoli cells to regulate spermatogenesis
  • Circulating T inhibits both GnRH and gonadotrophin production – negative feedback loop
65
Q

Causes of androgen deficiency - male hypogonadism

A

Testicular (primary hypogonadism)

Hypothalamic-pituitary (Secondary hypogonadism)

66
Q

Androgen replacement therapy

A

• Testosterone is inactivated by the liver (T1/2 = 10m)
• Testosterone esters given by IM injection
o Bioconverted into testosterone
o Lasts 2-3 weeks
o Safe, effective and easy to monitor
• Newer formulations avoid first pass metabolism
o S.c implants stable levels, long lasting
o Transdermal gels and patches increased compliance

67
Q

When to prescribe ART

A
  1. Testicular or hypothalamic-pituitary disorders with severe androgen deficiency – ART is unquestioned
  2. Other conditions may be associated with partial androgen deficiency
68
Q

Adverse effects of misused AAS

A
  1. Masculinisation
    • in women: hirsutism, ↓breast tissue & menstruation
    • female foetuses: during pregnancy
      2. Acne
  1. Testicular atrophy & ↓ spermatogenesis
    a. prolonged use of AAS, ↓ LH & FSH (reversible?)
  2. Premature epiphyseal closure (↓stature)
  3. Mood disturbance &↑aggression
  4. Dyslipidaemia & Hypertension
  5. Polycythaemia

Hepatitis & hepatic tumours

    • 2° to 17α-alkylated androgens e.g. stanozolol
    • is not produced by other classes of AAS
69
Q

3 regions of the prostate and their significance in cancer

A

• Transition zone: surrounding the urethra
o From which benign prostatic hyperplasia and 20% of prostate cancers arise

• Peripheral zone: most of the prostate tissue
o Gives rise to 70% of cancers

• Central zone

70
Q

Androgens and the prostate

A
  • Androgen receptor is expressed in both stromal and epithelial cells
  • Development of the prostate is driven by 5alpha dihydrotestosterone (DHT)
  • DHT is a metabolite of testosterone, converted in the prostate by 5-alpha reductase (type 2)
  • DHT is more potent than testosterone (> 10X) due to higher affinity for the androgen receptor
71
Q

What is benign prostatic hyperplasia?

A
  • Nodular overgrowth of both epithelial and fibromuscular components of the periurethral and transition zone of the prostate
  • Androgen dependent

Does not predispose to prostate cancer

72
Q

Incidence of BPH

A

o Rises with age
o Over 50% of men have microscopic evidence of BPH by 60 years of age
♣ 25% of these will develop symptoms of prostatism
♣ mean age of onset = 65 years

73
Q

Obstructive and irritative symptoms of BPH

A 
Obstructive symptoms: due to pressure on urethra from enlarging prostate
•	Decreased force of urine stream 
•	Hesitancy in initiating voiding 
•	Post-voiding dribble 
•	Sensation of incomplete emptying 
Irritative symptoms: 
•	Dysuria 
•	Frequency 
•	Urgency 
•	Nocturia
74
Q

Main drugs in the treatment of BPH

A
  1. Alpha adrenergic blockers
  2. 5-alpha-reductase inhibition
    a. finasteride
    b. dutasteride
75
Q

4 examples of alpha-1-adrenergic blockers

A
  • Prazosin – oldest, shorter half life requires multiple daily dosing
  • Terazosin – longer half life than prazosin
  • Alfuzosin
  • Tamsulosin – selective alpha-1-antagonist, some selectivity for the bladder, better tolerated and less postural hypotension
76
Q

Action of alpha 1 adrenergic blockers in BPH

A
  • Rapid symptom reduction
  • Improve urinary flow rate (16-25%)
  • Do not influence prostate size or disease progression
  • 1st line therapy in BPH if prostate volume <30ml and moderate to severe symptoms
  • provide symptom relief at 48 hours with maximum effect at weeks 4-6
77
Q

5 alpha reductase inhibitors

A
  • Indicated for use in men with moderate to severe symptoms of BPH
  • Most effective in men with larger prostate
  • Reduce prostate volume
  • Improve symptoms and urine flow
  • Reduce disease progression – decrease incidence or acute urinary retention and requirement for prostate surgery
  • Evidence for improved quality of life
78
Q

Side effects of alpha 1 adrenergic blockers

A
  • fall in BP
  • Postural hypotension, dizziness, syncope
  • Tiredness
  • Headache
  • Ejaculatory dysfunction – tamsulosin
  • Interaction with phosphodiesterase-5 inhibitors to potentiate hypotension
79
Q

Dutasteride

A
  • Type 1 + 2, 5-alpha reductase inhibitor
  • More effective in combination with alpha blocker than when used alone
  • Prostate volume starts to reduce after 1 month
  • Maximum effect on symptoms and prostate volume can take up to 6-12 months
80
Q

Finasteride

A
  • Type 2, 5-alpha reductase inhibition

* Similar effectiveness and safety/side effect profile to dutasteride

81
Q

Sexual adverse effects from dutasteride/finasteride

A
  • Erectile dysfunction
  • Ejaculatory disorders
  • Reduced libido
  • Gynaecomastia
  • Sexual dysfunction more common when used in combination with tamsulosin
  • Used as a monotherapy most side effects resolve spontaneously with ongoing therapy by 2 years but SE more likely to be ongoing if used in combination with tamsulosin
82
Q

Androgen receptor antagonists used in prostate cancer

A

flutamide, bicalutamide, nilutamide, cyproterone acetate

83
Q

Androgens and prostate cancer

A
  • Growth and development of the normal prostate is androgen dependent
  • Prostate cancer development is dependent on the presence of androgens
  • Anti-androgen therapy induces apoptosis and reduced cell proliferation
  • Androgen independent growth is inevitable in advanced disease following a period of antiandrogen therapy – tumour recurrence and progression on therapy
84
Q

Inhibitors of androgen production used in hormonal therapy for prostate cancer

A

GnRH analogues: goserelin + leuprolide

Diethyl-stilboestrol

85
Q

Flutamide action and side effects

A
  • Non-steroidal synthetic androgen receptor antagonist – blocks androgen binding
  • Used often in combination with GnRH agonist to prevent an initial flare of disease from GnRH therapy
SE:o	Gynacomastia 
o	Hot flushes 
o	Reduced libido 
o	Reduced facial hair and body hair 
o	Diarrhoea
o	Abnormal liver functions
86
Q

Cyproterone acetate

A

• A derivative of progesterone
• Dual action:
o Competes with DHT for androgen receptor – partial agonist
o Suppresses hypothalamic GnRH secretion
• May be used in combination with GnRH agonists
• Side effects – reduced libido, gynacomastia, impaired spermatogenesis, tiredness

87
Q

GnRH agonists

A
  • Endogenous GnRH secretion from hypothalamus is pulsatile
  • Continuous GnRH agonist inhibits pituitary LH and FSH secretion, thereby decreasing testosterone
  • May cause an initial flare of disease due to a transient rise in testosterone levels
  • Administered by S.C injections or IM
  • Also used for other conditions where suppression of gonadotrophins is indicated
88
Q

Erectile dysfunction prevalence

A

Prevalence: 52% in men 40-70yrs (minimal to moderate and complete erectile dysfunction)

Prevalence of complete erectile dysfunction increases from 5 15% as age increases from 40 to 70 years

89
Q

Erection development

A
  1. Sexual arousal activated in higher cortical centres which then stimulates the medial preoptic and paraventricular nuclei of the hypothalamus
  2. These signals descend to activate sacral parasympathetic nerves (S2-4)
  3. Neurovascular events result in release of the NT NO from both nerves and endothelial cells
90
Q

Drugs used for erectile dysfunction

A

Phosphodiesterase (PDE-5) inhibitors = 1st line
Sildenafil – Viagra
Vardenafil – Levitra
Tadalafil – Cialis

91
Q

Action of PDE-5 inhibitors

A
  • Breaks down cGMP, the 2nd messenger of NO
  • Increased response to NO release resulting in increased smooth muscle relaxation and vascular engorgement
  • Only acts in the presence of sexual stimulation
  • No effect on libido or in men with normal erectile function
92
Q

Side effects of PDE-5 inhibitors

A
  • Headache
  • Facial flushing
  • Nasal congestion
  • Dyspepsia
93
Q

Side effects specific to sildenafil and tadalafil

A

PDE-6: retina sildenafil = blue vision in 3% of people lasting 2-3 hours

PDE-11: Skeletal muscle tadalafil = back and muscle pain

94
Q

Contraindications for PDE-5 inhibitor

A
  • Men taking nitrate drug for heart disease – have severe risk of hypotension
  • Caution in men with severe CVD
  • Severe postural hypotension
  • Severe aortic stenosis
  • Retinitis pigmentosa
  • Introduce with caution in men using alpha blockers
95
Q

Adverse effects of intracavernosal alprostadil

A

penile pain
penile fibrotic changes
priapism = erection > hour

12- REPRO (7 decks)

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