BP.16 Drugs and hormones

Question 1

What is a hormone

2) how is this different to a neurotransmitter

Answer 1

chemical secreted from a tissue into blood stream whereby it is carried to non-adjacent sites in the body and exerts effect
2) it is secreted by a neuron directly onto adjacent neurones or tissue

Question 2

Describe the HPA axis:

include tissue/organs involved then what drug they secrete (when final is cortisol)

Answer 2

1. hypothalamic nuclei
(releases CRH)
2. anterior pituitary
(releases ACTH)
3. adrenal cortex
(releases cortisol

Question 3

What does cortisol inhibit?

2) What does this set-up?

Answer 3

1)Secretion by hypothalamic nuclei of CRH
and
Secretion by anterior pituitary of ACTH

Question 4

What stimulates the hypothalamic nuclei in the HPA axis

2) the pancreas to secrete insulin

Answer 4

stress (physical or mental)

2) high blood glucose

Question 5

Effects of cortisol (5)

Answer 5

Increase and maintain normal glucose levels in blood
Increase gluconeogenesis
decrease in protein synth (amino acid free for gluconeogenesis)
Role in regulating brain function
Immune response/inflammation

Question 6

Syndrome + disease caused by:

1) cortisol hypersecretion
2) cortisol hyposecretion

Answer 6

1) Cushing’s syndrome, cushing’s disease

2) Adrenal Insufficiency, addison’s disease

Question 7

Symptoms of cushing’s disease:

Answer 7

buffalo lump, fat redistributed (muscle wasting of arms and legs, increased abdominal fat), poor wound healing, easy bruising

Question 8

Causes of cushing’s disease:

2) Treatment:

Answer 8

Adrenal or pituitary tumour (Cushing’s Disease)
Side effect of chronic glucocorticoid therapy
2) Removal of tumour

Inhibition of cortisol synthesis by metyrapone

Question 9

What is the aldosterone formed from?

Answer 9

cortiosterone

Question 10

how does metyrapone work?

Answer 10

11ß-hydroxylating enzyme can be blocked by metyrapone so decreasing the amount of cortisol available for secretion

Used to treat Cushing’s Syndrome

Question 11

At high levels cortisol can inhibit A and B

Answer 11

At high levels cortisol can inhibit inflammation and the immune response

Question 12

What effect does insulin have:

2) what synthesises it?
3) what causes the cells to secrete it

Answer 12

Uptake/storage of glucose (as glycogen)
Inhibits fat breakdown
2) beta-cell of the islets of Langerhans in the pancreas
3) glucose enters beta-cell, glycolysis= ATP, ATP production leads to closure of the ATP sensitive K+ channel (KATP) channel on the cell surface; the subsequent membrane depolarization leads to opening of voltage-gated L-type calcium channels, influx of calcium and the release of insulin

Question 13

3 disorders of insulin :

Answer 13

1. Diabetes mellitus
2. insulin hyposecretion
3. insulin receptor hyposensitivity

Question 14

main cause of type 1 DM (insulin dependent diabetes
)
2) Treatment:

Answer 14

Insulin hyposecretion due to a loss of beta-cell
2) Substitute with insulin . one background intermediate acting (e.g isophane insulin) AND one before a meal, short term fast acting (soluble insulin)

Question 15

what are the different “acting” insulin preparations, describe structure of drug

Answer 15

1) short (soluble)
2) intermediate (in complex with zinc salts as particles)
3) long (in complex with zinc salts as large particles)

Question 16

How is short acting insulin administered

Answer 16

subcutanous (routine) & iv administration (emergency)

Question 17

cause of type 1 DM (non-insulin dependent):

2) drug used to treat…

Answer 17

Metabolic demands of obesity, Desensitization of insulin receptors
Pancreatic insufficiencey
2) sulphonylureas

Question 18

When treating type 1 DM with sulphonylureas, how do they work?

Answer 18

Sulphonylureas (e.g. glibenclamide) block the KATP channels so cause depolarisation and increase insulin secretion independently of glucose levels (need partially functioning beta cells).

Question 19

Describe the HPA axis:
include tissue/organs involved then what drug they secrete (when final is estrogen and progesterone)
B) describe -ve feedback loop:

Answer 19

1. hypothalamus
(releases GRH)
2. pituitary
(releases FDH and LH)
3. adrenal cortex
b) 
 estrogen and progesterone, inhibit hypothalamus and pituatry

Question 20

What does estrogen and progerstrone cause?

Answer 20

ovulation

Question 21

What does 1) GRH, 2) FSH and 3) LH stand for?

Answer 21

1) gonadotrophin releasing H
2) Follicle stimulating H
3) lutenising H

Question 22

Physiological effects of 1)estrogen and 2)progestrone on endometrium

Answer 22

Estrogen-
sensitises LH releasing cells in pituitary
proliferation of endometrium
Inhibits FSH so regulates cycle

Progestrone-
renders the endometrium suitable for implanting of a fertilized ovum
Inhibits further release of GRH, FSH, and LH so regulates cycle and ovulation

Question 23

1) If fertilised ovum is implanted how is progesterone secretion maintained?
2) what 2 things does progesterone do?

Answer 23

1) ovum secretes human chorionic gonadotrophin, this stimulates corpus luteum to continue secreting progestrone
2) maintains endometrium and pregnancy
Inhibits further secretion of GRH, FSH, and LH, this prevents further follicles developing (-ve feesback)

Question 24

What are the 2 main types of oral contraceptives:

Answer 24

Combined oestrogen and progestrone (combined pill)

Progestrone alone (progestrone only pill/minipill)

Question 25

Oral contraceptives target the ___A__ feedback system clamping secretion of ______B______

Answer 25

A) negative

B) GRH FH and LH

Question 26

Oral contraceptives target the ___A__ feedback system clamping secretion of ______B______

Answer 26

A) negative

B) GRH FH and LH

Question 27

How does the combined pill work?

Answer 27

Estrogen inhibits secretion of FSH via –ve feedback, this prevent development of ovarian follicle

Progestrone inhibits secretion of LH, (-ve feedback) prevents ovulation and also makes the cervical mucus less suitable for passage of sperm

Question 28

How is the combined pill taken?

Answer 28

Taken for 21 days then a 7 pill free period causes withdrawal bleeding (false period)

Question 29

How does the progesterone only pill work?

2) how is it taken?
3) is it as reliable as the combined pill?

Answer 29

1) Mainly effective due to effect on cervical mucus.

Does not actually blocked ovulation

2) Taken continuously, can cause irregular periods
2) Less reliable than combined pill

Question 30

What drugs can interact with contraceptives and why?

Answer 30

Broad spectrum antibiotic (e.g. amoxicillin)

Enzyme inducers (e.g Barbiturates, phenytoin, rifampicin) (interact with GABA, enduce cytochrome P450)

Question 31

How are contraceptives metabolised (3)?

Answer 31

Fraction (variable) of exogenous hormone is conjugated in the liver (glucuronidation), and excreted in bile into duodenum
Gut flora with glucuronidase activity cleave the conjugate allowing reabsorption of active hormone. (may represent significant reservoir)
Broad spectrum antibiotic (e.g. amoxicillin), kill gut flora and so remove this reservoir