Pharmacology Flashcards
What are exocrine glands?
Have ducts
What do the ducts of endocrine glands secrete?
Hormones
Which endocrine glands creates ACTH?
Anterior pituitary
What does ACTH stand for?
Adrenocorticotropic hormone
Where synthesises cortisol from ACTH?
Adrenal cortex
Where are the adrenal glands?
Superior to the kidneys
What 3 endocrine glands are in the brain?
Pineal
Hypothalamus
Pituitary
What is the differences in endocrine glands in males and females?
Testes in males
Ovaries (& placenta) in females.
What is autocrine signalling?
When a cell secretes a hormone which is taken up and acted upon by the same cell
What is paracine signalling?
When a cell secretes a hormone which is taken up by neighbouring cells
What is endocrine signalling?
When a cell secretes a hormone which is taken into the blood supply and distributed to many cells around the body
What are the 3 classes of hormones?
Proteins and peptides
Steroids
Tyrosine and tryptophan
Give an example of a peptide hormone
Insulin
Oxytocin
Give an example of a steroid type hormone
Cortisol
Testosterone
Give an example of a tyrosine type hormone
Adrenaline
thyroid hormone
Melatonin
Describe the storage of amino acids
Pre-synthesised stored in vesicles
When are amino acids released?
released in response to stimuli by Ca2+ exocytosis
Where are amines released into?
Free plasma
Where are precursors for peptides synthesised?
Ribosomes on RER
How are peptide precursors coverted to mature hormones?
Convertase enzymes using proteolytic steps
What influx needs to happen for the release of peptides into the plasma?
Ca++ influx
Where are steroids stored?
They aren’t!
Synthesised and secreted upon demand.
What converts cholesterol to steroids?
pregnenolones
Are steroids hydrophobic or hydrophillic?
Hydrophobic
Are steroids in free or bound plasma?
Mostly bound to plasma proteins.
Remember only FREE steroids are biologically active
What do carrier proteins do?
Increase amound of steroids and thyroxine transported in blood and prevent excretion by stopping filtration at the kidney
Which carrier protein binds cortisol?
Cortisol binding globulin (CBG)
What does thyroxine binding globulin bind?
T4 thyroxine.
some T3
Name two general carrier proteins
Albumin
Transthyretin
Why do proteins and peptides not need carrier proteins?
Soluble in plasma so don’t need carrier proteins for transport
What is the feedback system re hormones?
Negative feedback
Which part of the is at the top of the feedback loop ?
Hypothalamus
What does the hypothalamus do?
Secretes corticotropin releasing hormone
What does the release of corticotropin hormone do?
Stimulates the anterior pituitary to secrete ACTH
What does the release of ACTH stimulates?
Adrenal cortex secretes cortisol
What is the half life of steroids and thyroid hormones?
Hours to days
What kind of receptors are the cell surface receptors?
G protein coupled.
Specifically Gs, Gi or Gq.
Intracellularly, what are the different kinds of nuclear receptors?
Class 1, 2 and hybrid
What interacts with the hybrid nuclear receptors?
thyroid hormone
Where are class 1 receptors found?
Cytoplasm, bound to inhibitory heat shock proteins.
What activates class 1 nuclear receptors?
Steroid hormones
What activates class 2 nuclear receptors?
Lipids
Where are class 2 nuclear receptors found?
In the nucleus
Which protein activates protein kinase A?
cAMP
What does protein kinase A do?
Phosphorylates target proteins and therefore gives effects
What is needed for cAMP to be synthesised?
ATP and adenylyl cyclase
What can stop cAMP from being formed?
Gi receptors, encouraged by melatonin
What encourages formation of cAMP?
Gs, encouraged by adrenaline, glucagon
What does prolactin do?
Produces breastmilk
Which hormone can be described as a chronic stress hormone?
Cortisol
Which is the acute stress hormone?
Adrenaline
When should cortisol levels be tested?
9AM due to diurnal variation this is when they are highest
What condition develops if cortisol levels are too high?
Cushing’s syndrome
Which hormone uses receptor kinases?
Insulin
What needs to occur for cellular effects to take place when insulin is being signalled?
Needs to be phosphorylated
Which hormone is signalled via a nuclear receptor class 1?
Steroid hormones
Where is the class 1 receptor in steroid signalling?
Either cytoplasm or nucleus
When steroids combine with an intercellular receptor what do they produce?
Heat shock producing proteins
What does the receptor steroid complex do?
Moves to the nucleus and forms a dimer.
Give an example of a biguanide
Metformin.
Only one!
What is the risk in using metformin in a patient with existing renal dysfunction?
Metformin is renally excreted so may not be excreted well if kidneys damaged and may build up and cause further damage.
Give two examples of sulphonylureas
Glicazide
Glimeparide
What effect can sulphonylureas have on weight
Can cause weight gain
What class of drug does pioglitazone belong to?
Thiazolidinediones (also called PPAR gamma agonists)
What affect does pioglitazone have on weight?
Gain weight.
When should pioglitazone not be prescribed?
heart failure
bladder cancer
What is the max dose of metformin possible?
1g BD
What affect does metformin have on weight?
Neutral.
Possible reduction
When can metformin cause hypoglycaemia?
Does not cause hypos when used as monotherapy
Can metformin be used in pregnancy and lactation?
Yes
What other conditions can benefit from metformin?
Gestational DM
PCOS
NAFLD
What are common side effects of metformin?
Anorexia, nausea, v&d, abdo pain
What vitamins does metformin interfere with?
B12 and folic acid
When should metformin be discontinued?
If eGFR
What is the mechanism of action of sulphonylureas?
Binds to K+ channel and speeds up its release of K, ultimately releasing insulin
What are the adverse effects with sulphonylureas?
Hypoglycaemia
weight gain
Avoid in renal/liver failure
Give two examples of sulphonylureas
Gliclazide
Glipazide
Is gliclazide safe to use in pregnancy?
No. Causes hypoglycaemia
What is the mechanism of action of pioglitazone?
Lipophilic so binds to PPARgamma in adipose easily and changed DNA to make glucose more readily absorbed
What are the side effects of pioglitazone?
weight gain
Fluid retention
How do DPP4 and incretin analogues inhibitors work?
Decrease the total blood glucose by decreasing glucagon from pancreatic alpha cells.
What is extenatide an example of?
Incretin analogue
How do incretin analogues work?
Binds to GLP1 receptor that increases [cAMP]. Increases insulin secretion and suppresses glucagon secretion.
How is extenatide administered?
Subcutaneously BD
Where does GLP-1 come from?
L cells
Where does GIP come from?
K cells
What are the benefits of using a GLP1 antagonists (incretins)?
No hypoglycaemia
Reduces appetite
What is an example of a DPP4 inhibitor?
Vildagliptin, Linagliptin
What are the benefits of using a DPP4 inhibitor?
No hypoglycaemia
weight neutral
How do SGLT2 inhibitors work?
Block the reabsorption of glucose into the prox. tubule of kidney so more excretion of glucose
What are the benefits of SGLT” inihibs?
weight loss
Little risk of hypoglycaemia
What is an example of SGLT2?
Dapagliflozin
What is the disadvantage of SGLT2 inhibs?
Thrush
Increase in urine infection
What is a possible dangerous side effect of Exenatide?
?pancreatitis/ pancreatic cancer