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Semester 4 - Clinical Pharmacology And Therapeutics > Repoductive And Post-Reporductive Health > Flashcards

Repoductive And Post-Reporductive Health Flashcards

1
Q

What drug group are important in reproductive and post-reproductive health?

A

Sex steroid hormones (oestrogen, progestogens, androgens)

Inhibitors and antagonists (RU486, finasteride)

MIxed agonists / antagonists (SERMs and SPRMs)

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2
Q

What are the sex hormones and what are they synthase from?

A

From cholestrol to
Progesterone to
Testosterone to
Oestrogen (estradiol)

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3
Q

How do steroid hormones act classically?

A

Classically, they act through nuclear receptors.

They exert effect through gene transcription

But also a membrane receptor for oestrogen

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4
Q

What are the major effects of oestrodiol?

A

Stimulates growth of the endometrium and breast; stimulates production off PR

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5
Q

What are the major effects of progesterone?

A

Stimulates growth of the endometrium and breast; maintains pregnancy; inhibits production of ER

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6
Q

What are the major effects of testosterone?

A

Stimulates male characteristics; hairy body; deep voice; anabolism; aggression

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7
Q

What are the actions of oestrogen?

A 
Mild anabolic 
Na and water retention 
Raised HDL, lower LDL 
Decreases bone respiration
Impair glucose tolerance 
Increase blood oagulabulity
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8
Q

What are the side effects of oestrogen?

A 
Breast tenderness 
Nausea, vomitting 
Water Retention 
Increased blood coagulability 
Thromboembolism
Impaired glucose tolerance
Endometrial hyperplasia and cancer
Ovarian metaplasia and cancer
Breast hyperplasia and cancer
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9
Q

What are the actions of progesterone / progestin?

A 
Secretory endometrium 
Anabolic
Increases bone mineral density 
Fluid retention 
Mood changes
Maintains pregnancy
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10
Q

What are the side effects of progesterone?

A 
Weight gain
Fluid retention
Anabolic
Acne
Nausea / vomiting
Irritability, depression, PMS
Lack of concentration
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11
Q

What are the actions and side effects of testosterone?

A 
Male secondary sexual characteristics 
Anabolic
Acne
Voice changes
Increases aggression

Metabolic - adverse effects on lipid profiles particularly the HDL-C/ LDL-C ratio hence increased risk of atherosclerotic disease in males

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12
Q

Outline the menstrual cycle

A

Ovulation occurs due to LH surge
Oestrogen and progesterone have different effects on endometrial tissue and on cervical mucus.
Oestrogen and progesterone together produces suppression of HPO axis.

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13
Q

Summarise hormonal contraception

A 
Interruption of physiological control of the menstrual cycle 
Endometrial and cervical mucus effects 
Inhibition do ovulation 
Many routes of administration:
-Oral
-Nasal
-Transdermal
-Implants
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14
Q

Describe the pharmacokinetic points regarding oestrogen

A

Natural and synthetic oestrogen are well absorbed in the GI tract

Also readily absorbed from skin and mucus membranes

Metabolism - liver

Excretion - in the urine as glucuronides and sulphates

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15
Q

Describe the pharmacokinetics of progesterone

A

Injected progesterone is bound to albumin with one stored on adipose

Metabolised in liver

Metabolites excreted in the urine conjugated to glucuronic acid.

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16
Q

What are the adverse effects of COP?

A

Risk of thromboembolism is small (15/100,000)

Smoking increases the risk substantially

Also for long term use in women over 35

Also consider obeisity and hypertension

17
Q

Describe the pharmacokinetic points of the oral contraceptive pill

A

COCP and POP contraceptives are metabolised in the liver by CYP 450 enzymes

Therefore efficacy is reduced by enzyme inducing drugs:
Anti-epileptics, some antibiotics, some natural products e.g. St Johns Wart.

Soya products enhance oestrogen absorption and reduce its storage in adipose and muscle and so cause the half life to be reduced form 15 to 7 hours.

18
Q

Summarise the menopause

A

Ovarian follicle supple depleted
Consequently ovarian sex steroid production stops
End of female reproductive capacity.

ALSO
Loss of oestrogen and progesterone leads to a range of systemic effects as symptoms of menopause

19
Q

Why prescribe HRT?

A

Symptoms: e.g. hot flushes / sweats and dyspareunia

Osteoporosis

NOT for heart disease

20
Q

What are the routes do administration of HRT?

A 
Oral
Transdermal
Implant
Transnational
Nasal
21
Q

What are the risks of HRT?

A

Unopposed oestrogen - rsk of developing endometrial and ovarian cancers

Opposed oestrogen - Increase risk of developing cancer

Increase risk of venous thromboembolism

Cardiovascular disease

Increased risk of stroke (oral not transdermal)

22
Q

What is mifepristone (RU486)?

A

Progesterone receptor antagonists

Act as anti-progesterone

Sensitising the myometium to prostaglandin-induced constructions.

Used for termination of pregnancy

23
Q

What is a SERM?

A

Selective oestrogen receptor modulator.

cf pure agonist and pure antagonist.

SERMs are distinct in having varying effects in differing tissues.

E.g. Tamoxifen, Raloxifene

24
Q

What is clomiphene?

A

Clomiphene used in the treatment of anovulation

Completes with oestrogen for ER bidding

Leads to ovulation induction though increased production of anterior pituitary hormones

25
Q

What is tamoxifen?

A

A pro-drug - little affinity for the ER.

Metabolised in the liver to a active derivative

Tamoxifen active metabolites conpete with oestrogen for binding to the ER

26
Q

How does Tamoxifen work?

A

A pro-drug -little affinity for the ER. Metabolised in the liver to an active derivatives. Tamoxifen active metabolites compete with oestrogen binding to the ER.

Acts as a SERM

Has converse effects in breast tissue and endometrial tissue

In Endometrium, acits as ER agonist

In breast, acts as ER antagonist

In breast, binding of the ER following tamoxifen treatment causes cells to arrest the cell cycle

27
Q

What is Ulipristal acetate?

A

Selective progesterone modulator

When used for emergency contraception of the primary mode of action os through to be most likely the delay or inhibition of ovulation

Also effective for the treatment of uterine fibroids

Semester 4 - Clinical Pharmacology And Therapeutics (26 decks)

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