IC16 PK of female endocrine drugs

Question 1

ethinyl estradiol: drug type

Answer 1

synthetic oestrogen

Question 2

ethinyl estradiol: MOA

Answer 2

• Oestrogen receptor agonist
• Blocks FSH release from pituitary → suppresses development of ovarian follicle
  Endometrium unstable for implantation of ovum

Question 3

ethinyl estradiol: indications

Answer 3

Menopausal symptoms
Gynaecological disorders
(some) Hormone-sensitive cancers
Birth control pill; oral contraceptive

Question 4

ethinyl estradiol: PK
absorption

route of administration, onset, F

Answer 4

Well absorbed orally; taken OD
Onset: 30-60 mins
F ~0.45

Other Administration methods: parenteral, transdermal, topical

Question 5

ethinyl estradiol: PK
distribution

protein bidning & Vd

Answer 5

Very highly plasma protein bound (~98% by albumin) ⇒ small Vd

Question 6

ethinyl estradiol: PK
metabolism

location & phases, t1/2

Answer 6

By liver

Phase I: EE undergoes hydroxylation by CYP3A4
Phase II: conjugation with glucuronide & sulfation into hormonally inert ethinylestradiol glucuronide & ethinylestradiol sulphate
* Formation of EE sulphate → enterohepatic recirculation involved

t1/2 ~13-27 hours

Question 7

ethinyl estradiol: excretion

Answer 7

Metabolites excreted in faeces & urine

Question 8

ethinyl estradiol: Adverse effects

Answer 8

Breast tenderness, headache, nausea, fluid retention, dizziness, weight gain
Serious: venous thromboembolism (VTE), MI/ stroke, liver damage

Question 9

ethinyl estradiol: c/i

Answer 9

• Patients with known hx/ susceptibility to arterial/ venous thrombosis
• Advanced diabetes with vascular disease
• Hypertension >160/100 mmHg
• Avoid in breastfeeding (<21 days postpartum) & breast cancer women

Question 10

Norethindrone: drug type

Answer 10

synthetic progesterone

Question 11

Norethindrone: MOA

Answer 11

• Progesterone receptor agonist
• Blocks release of LH → prevents ovulation
  Endometrium unstable for implantation of ovum

Question 12

Norethindrone: Indication

Answer 12

Endometriosis
Abnormal periods/ bleeding → bring on normal menstrual cycle
Birth control pill; oral contraceptive

Question 13

Norethindrone: PK
absorption

route of administration, F

Answer 13

Well absorbed orally; taken OD
F ~0.64

Question 14

Norethindrone: PK
distribution

plasma protein binding, Vd

Answer 14

Highly plasma protein bound (ie albumin) ⇒ small Vd

Question 15

Norethindrone: PK
metabolism

phases, t1/2, EE

Answer 15

• By liver: phase I (reduction) & phase II (glucuronidation & sulfation)
• t1/2 ~8 hours
• Some % may be metabolised in liver to EE
  Take note of potential CVS complications (ie VTE) → may have similar SE

Question 16

Norethindrone: PK
excretion

Answer 16

Metabolites in urine (~50%) & faeces (~40%)

Question 17

Norethindrone: AE

Answer 17

• Headache, dizziness
• Bloating, weight gain
• Episodes of unpredictable spotting & bleeding (initial); amenorrhea (miss 1-2 cycles)

Question 18

Norethindrone: c/i

Answer 18

Women planning pregnancy soon after cessation of therapy
Ovulation suppression may persist for 1.5 years