Endocrine Pharmacology Flashcards by Izzie Setford

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

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

How well did you know this?

Not at all

Perfectly

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

It stimulates lactation

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

How well did you know this?

Not at all

Perfectly

What can hyperprolactinaemia lead to?

Hypergonadotropic hypogonadism

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

What is the most common tumour of the pituitary gland?

Prolactinoma

How well did you know this?

Not at all

Perfectly

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

> 1cm

How well did you know this?

Not at all

Perfectly

What medications will you give someone with a prolactinoma?

Dopamine (D2) Agonists

cabergoline - long half life
quinagolide
bromocriptine - short half life

How well did you know this?

Not at all

Perfectly

Where and why is ADH released?

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

How well did you know this?

Not at all

Perfectly

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

Diabetes insipidus.

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

How well did you know this?

Not at all

Perfectly

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

V1 - vascular smooth muscle - allows vasoconstriction

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

How well did you know this?

Not at all

Perfectly

What is desmopressin?

A synthetic analogue of ADH

How well did you know this?

Not at all

Perfectly

What is the difference between ddAVP and ADH action?

ADH has a shorter half life and includes vasoconstrictor effects

How well did you know this?

Not at all

Perfectly

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

For maintenance - oral, sublingual or intranasal

For acute therapy - subcutaneous, intramuscular or intravenous

How well did you know this?

Not at all

Perfectly

Name and briefly describe two thionamide drugs.

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

How well did you know this?

Not at all

Perfectly

What is the mechanism of action of thionamides?

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

How well did you know this?

Not at all

Perfectly

What is different about the action of propythiouracil?

It also reduces T4 to T3 conversion in the periphery

How well did you know this?

Not at all

Perfectly

Name four treatments other than medicine for hyperthyroidism.

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

Briefly describe T2DM pathology.

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

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

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

Mechanism of action of Metformin (a biguanide)

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

Pharmacokinetics of Sulphonylureas (Glicazide, gilpizide, glubenclamide)

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

Pharmacodynamics of Sulphonylureas (Glicazide, gilpizide, glubenclamide

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

Pharmacokinetics of thiazolidinedione. (Pioglitazone, rosiglitazone)

Rapidly absorbed
Extensive hepatic metabolism
Pioglitazone is excreted in bile

Pharmacodynamics of thiazolidinedione. (Pioglitazone, rosiglitazone)

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

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

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

What are the names of GLP-1 agonists?

Exenatide | Liraglutide

What is the mechanism of action of SGLT2 inhibitors?

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

All of the hypoglycaemic drugs are administered orally expect which?

GLP-1 agonist - subcutaneous

What are the four delivery methods of insulin injection?

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

Name five effects of glucocorticoids

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

Name common preparations of glucocorticoid.

Hydrocortisone Prednisolone Dexamethasone Betamethasone

List mechanisms of glucocorticoid administration.

``` Topical Nasal Inhaled Oral Subcutaneous Intramuscular Intravascular ```

Why can't aldosterone by given orally?

It's metabolised by the liver

Name and describe some mineralocorticoid receptor antagonists.

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

When would a MR antagonist be used?

Primary aldosteronism Heart failure Hypertension

Name some bisphosphonates

Alendronate Pamidronate Zolendronate Risedronate

Describe the pharmacokinetics of bisphosphonates

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

Describe the pharmacodynamics of bisphosphonates

Binds to bone and inhibits osteoclasts activity

List other osteoporosis treatments

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

Describe the mechanism of action of denosumab.

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

Describe the mechanism of action of teriparatide

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