Endocrine Pharmacology

Question 1

What are the mechanisms by which drugs can work on the individual?

Answer 1

Receptor binding - agonist, antagonist, partial agonist 
Action on ion channels
Action on enzyme
Transporters 
Cytotoxic agents

Question 2

What is the function of prolactin and how is secretion controlled?

Answer 2

It stimulates lactation

Secreted by the lactotrophs in the anterior pituitary, and is under negative feedback by dopamine

Question 3

What can hyperprolactinaemia lead to?

Answer 3

Hypergonadotropic hypogonadism

Question 4

List the drugs that can interfere with prolactin secretion, and why.

Answer 4

Antipsychotics - typical & atypical 
Antiemetics - domperidone 
Antidepressants - SSRIs
Opiates
H2 receptor antagonists 
- these affect prolactin because they all interfere with the action of dopamine

Question 5

What is the most common tumour of the pituitary gland?

Answer 5

Prolactinoma

Question 6

What size constitutes a macroadenoma (rather than a microadenoma)?

Answer 6

> 1cm

Question 7

What medications will you give someone with a prolactinoma?

Answer 7

Dopamine (D2) Agonists

• cabergoline - long half life
• quinagolide
• bromocriptine - short half life

Question 8

Where and why is ADH released?

Answer 8

Released from the anterior pituitary (peptide hormone) in response to low plasma volume or increased serum osmolality

Question 9

What condition can occur when ADH isn’t produced or doesn’t have an effect on the kidney?

Answer 9

Diabetes insipidus.

• cranial (lack of ADH production)
• nephrogenic (ADH resistance in kidneys)

Question 10

Where are V1 and V2 receptors for ADH located, and what are their functions?

Answer 10

V1 - vascular smooth muscle - allows vasoconstriction

V2 - receptors in distal tubule/collecting duct - adds AQ1 channels to reabsorb more water

Question 11

What is desmopressin?

Answer 11

A synthetic analogue of ADH

Question 12

What is the difference between ddAVP and ADH action?

Answer 12

ADH has a shorter half life and includes vasoconstrictor effects

Question 13

What is the difference in the ways ddAVP can be administered?

Answer 13

For maintenance - oral, sublingual or intranasal

For acute therapy - subcutaneous, intramuscular or intravenous

Question 14

Name and briefly describe two thionamide drugs.

Answer 14

Carbimazole- more common
- converted to methimazole via first pass metabolism
Propylthiouriacil
- less active with shorter half life

Question 15

What is the mechanism of action of thionamides?

Answer 15

Inhibits thyroid peroxidase 
- Inhibits iodide oxidation
- Inhibits iodination of tyrosine residues 
- Inhibits iodotyrosine coupling 
Takes weeks for effects to occur

Question 16

What is different about the action of propythiouracil?

Answer 16

It also reduces T4 to T3 conversion in the periphery

Question 17

Name four treatments other than medicine for hyperthyroidism.

Answer 17

Beta-blockers - just reduces sympathetic symptoms
Potassium iodide - acute reduction of thyroid hormone
Radioactive iodine
Surgery

Question 18

Briefly describe T2DM pathology.

Answer 18

Insulin resistance
- usually develops due to a combination of lifestyle and genetic factors
- insulin signalling impaired at cellular level
Impaired insulin secretion
- initial hyperinsulinaemia can no longer cope with resistance, bet-cell failure occurs

Question 19

What are the first, second and third line treatments for T2DM?

Answer 19

Lifestyle changes
1st - Metformin (Sulphonylureas)
2nd - ADD ONE OF: sulphonylureas (thiazolidinedione, DDP-IV inhibitor)
3rd - ADD OR SUBSTITUTE ONE OF: Thiazolidinedione, DDP-IV inhibitors, injected insulin or injected GLP-1 agonists

Question 20

Mechanism of action of Metformin (a biguanide)

Answer 20

Inhibits mitochondrial glycerophosphate dehydrogenase in the liver and activates AMPK
- decreases gluconeogensis
- inhibits action of PEPCK and G6Pase
An insulin sensitiser

Question 21

Pharmacokinetics of Sulphonylureas (Glicazide, gilpizide, glubenclamide)

Answer 21

Well absorbed, peak plasma concentration within 2-4 hours
Metabolised by the liver
Duration of action is up to 24 hours

Question 22

Pharmacodynamics of Sulphonylureas (Glicazide, gilpizide, glubenclamide

Answer 22

Binds to its receptor on beta-cells and inhibits the KATP channels, causing the membrane to depolarise and cause insulin release.
- increases insulin

Question 23

Pharmacokinetics of thiazolidinedione. (Pioglitazone, rosiglitazone)

Answer 23

Rapidly absorbed
Extensive hepatic metabolism
Pioglitazone is excreted in bile

Question 24

Pharmacodynamics of thiazolidinedione. (Pioglitazone, rosiglitazone)

Answer 24

Bind to PPARgamma and increase transcription of insulin sensitising genes

• PPARgamma is a nuclear receptor expression in adipose tissues, muscle and the liver
• stimulates triglyceride synthesis in adipose tissue, preventing fat deposits in inappropriate places
• increases tissue sensitivity to insulin

Question 25

What are the endogenous in retains - and what do they do?

Answer 25

GLP-1 and GIP enhance insulin secretion in response to oral glucose and are broken down by DPP-4

Question 26

What are the names of GLP-1 agonists?

Answer 26

Exenatide

Liraglutide

Question 27

What is the mechanism of action of SGLT2 inhibitors?

Answer 27

They inhibit the SGLT2 transporter on the proximal convoluted tubule - preventing glucose reabsorption

Question 28

All of the hypoglycaemic drugs are administered orally expect which?

Answer 28

GLP-1 agonist - subcutaneous

Question 29

What are the four delivery methods of insulin injection?

Answer 29

Subcutaneous injections - with pens/cartridges
Continuous subcutaneous insulin infusion - pump
IV - during acute illness
Intramuscular

Question 30

Name five effects of glucocorticoids

Answer 30

• Anti-inflammatory - inhibits transcription of pro-inflammatory cytokines
• reduced T-lymphocytes
• counter-regulatory metabolic effects - Gluconeogenesis + lipolysis
• improves alertness (circadian rhythm)
• mineralocorticoid effect

Question 31

Name common preparations of glucocorticoid.

Answer 31

Hydrocortisone
Prednisolone
Dexamethasone
Betamethasone

Question 32

List mechanisms of glucocorticoid administration.

Answer 32

Topical
Nasal
Inhaled
Oral
Subcutaneous 
Intramuscular 
Intravascular

Question 33

Why can’t aldosterone by given orally?

Answer 33

It’s metabolised by the liver

Question 34

Name and describe some mineralocorticoid receptor antagonists.

Answer 34

Spironolactone
- competitive antagonist at MR, androgen and progesterone receptors
- unwanted side effects of gynaecomastia and hyperkalaemia
Eplerenone
- selective MR antagonist

Question 35

When would a MR antagonist be used?

Answer 35

Primary aldosteronism
Heart failure
Hypertension

Question 36

Name some bisphosphonates

Answer 36

Alendronate
Pamidronate
Zolendronate
Risedronate

Question 37

Describe the pharmacokinetics of bisphosphonates

Answer 37

Oral and IV administration
- zolendronate IV once a year
- Alendronate is taken orally once a day on an empty stomach
Free excretion by the kidney

Question 38

Describe the pharmacodynamics of bisphosphonates

Answer 38

Binds to bone and inhibits osteoclasts activity

Question 39

List other osteoporosis treatments

Answer 39

Calcium and vitamin D for bone formation
Denosumab
Teriparatide
Strontium renegade stimulates osteoblasts and inhibits osteoclasts
HRT - (if menopause related)
SERMs - bind to oestrogen receptors and decrease bone resorption

Question 40

Describe the mechanism of action of denosumab.

Answer 40

Monoclonal antibody that inhibits RANK ligand which signals the osteoclasts
- reduces resorption
Subcutaneous injection every 6 months

Question 41

Describe the mechanism of action of teriparatide

Answer 41

Recombinant parathyroid hormone, binds to osteoblasts to increase bone formation
- subcutaneous injection as a peptide