Theme 8 - Endocrine Pharmacology Flashcards
Name the 3 hormones of the pancreas
insulin
glucagon
somatostatin
What are the metabolic effects of glucagon?
Stimulates gluconeogenesis and glycogenolysis
What effect does glucagon have on blood glucose?
increases blood glucose levels
Which 5 processes does insulin inhibit?
gluconeogenesis glycogenolysis lipolysis ketogenesis proteolysis
Which 5 processes does insulin stimulate?
- glucose uptake in muscles and tissues
- glycolysis
- glycogen synthesis
- protein synthesis
- uptake of ions
What effect does insulin have on blood glucose?
decreases blood glucose levels
Describe the mechanism of action by which insulin is released by the b-cells of the pancreas.
- K+ channels in beta-cells are regulated by intracellular ATP
- When blood glucose increases, more glucose enters beta-cells and intracellular ATP increases and closes K+ channels
- Depolarisation of beta-cells initiates influx of Ca2+ ions through voltage- sensitive Ca2+ channels
- This process triggers insulin release
Describe the structure of an insulin receptor
Membrane spanning glycoprotein with 2 alpha subunits
and 2x beta subunits covalently bonded by disulphide bonds
What is the action of an insulin receptor?
Insulin binds to a subunit, the insulin-receptor complex enters the cell and produces metabolic effects.
Name 3 rapid acting insulins
insulin lispro, insulin aspart, insulin glulisine
Name a short acting insulin
regular insulin
Name an intermediate acting insulin
NPH insulin (isophane insulin)
Name 2 long-acting insulins
insulin glargine and insulin detemir
What is premixed biphasic insulins a combination of?
Combination of prandial & basal insulin, premixed in defined ratios: 30% rapid/short-acting and 70% intermediate-acting
What is the onset and duration of action of premixed biphasic insulins?
Rapid onset (due to rapid/short acting insulin) Prolonged duration of action (due to intermediate-acting insulin)
Which insulin types are prandial?
rapid and short acting
Which insulin types are basal?
intermediate and long-acting
Discuss the chain of reactions that is initiated after binding of insulin to its receptor.
- Insulin-receptor complex enters the cell, where the insulin is destroyed by lysosomal enzymes.
- The internalisation of the insulin-receptor complex underlies the down regulation of receptors that is
produced by high levels of insulin. - The binding of insulin to the receptors
activates the tyrosine kinase activity of the β-subunit and initiates a complex chain of reactions that lead to the effects of insulin.
What is the main form of treatment for type 1 diabetes?(and why?)
insulin therapy: Insulin is administered because there is no beta-cell function
What are the treatment options for type 2 diabetes? (and why)
Diet, exercise and oral antidiabetics or Insulin injections (if no response to above): There is some beta-cell function or Insulin resistance, so the main aim is to increase insulin secretion and sensitivity and increase glucose loss.
List the 7 oral antidiabetics
- Biguanides
- Sulfonylureas
- Thiazolidinediones
- Dipeptidyl peptidase 4 (DPP-4) inhibitors
- Glucagon like peptide 1 (GLP-1) receptor agonists
- Sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Alpha-glucosidase inhibitors
Name a Biguanide
Metformin
Which 3 organs/tissues do Biguanides effect?
intestine, liver, skeletal muscle
What effect do Biguanides have on the intestines?
decreases glucose absorption
What effect do Biguanides have on the liver?
Decreases gluconeogenesis
Increases fatty acid oxidation
Increases lactate production
What effect do Biguanides have on skeletal muscle?
Decreases glucose uptake and utilisation
What is the main adverse effect of Biguanides?
GIT disturbances (diarrhoea, nausea, anorexia)
Name 3 Sulfonylureas
Gliclazide
Glimepiride
Glibenclamide
What is the mechanism of action of Sulfonylureas? (3)
Stimulate secretion of insulin by β-cells, decrease serum glucagon levels, increase affinity of insulin to receptors for the hormone
What do Sulfonylureas need to function?
functioning β-cells
What is the main adverse effect of Sulfonylureas?
hypoglycaemia
Name a Thiazolidinedione
Pioglitazone (it is the only one available as the rest have been withdrawn due to adverse effects)
What is the mechanism of action of Thiazolidinediones? (3)
- Increase sensitivity to insulin (decrease insulin resistance)
- Selective agonist (PPAR-gamma)
- Increase transcription of insulin-sensitive genes
What do Thiazolidinediones need to function?
circulating insulin
What is the main adverse effect of Thiazolidinedione?
fluid retention
heart failure (reason why most drugs were withdrawn)
Name 3 DPP-4 inhibitors
Sitagliptin
Vildagliptin
Saxagliptin
What is the mechanism of action of DPP-4 inhibitors?
Inhibits DPP-4 enzymes (inactivates incretins) in order to prevent a decrease in incretins
What are the incretins and what do they do?
GLP-1, GIP: Promotes insulin release and inhibits glucagon secretion
What is the main adverse effect of DPP-4 inhibitors?
GIT disturbances
Name 2 GLP-1 receptor agonists
Exenatide
Liraglutide
What is the mechanism of action of GLP-1 receptor agonists?
- Increases the secretion of GLP-1 from pancreatic beta cells
- Retards gastric emptying
- Suppresses glucagon secretion
What do GLP-1 receptor agonists need to function?
Must be administered subcutaneously, and require beta-cell functioning
What is the main adverse effect of GLP-1 receptor agonists?
GIT disturbances
Name 3 SGLT2 inhibitors
Dapagliflozin
Empagliflozin
Canagliflozin
What is the mechanism of action of SGLT2-inhibitors?
suppress SGLT2 action and increase urinary glucose excretion
What is the function of SGLT2?
Responsible for reabsorption of glucose in renal distal tubules
Wha is the main adverse effect of SGLT2-inhibitors?
UTI/Fungal genital infections
Name an alpha-glucosidase inhibitor
Acarbose
What is the mechanism of action of alpha-glucosidase inhibitors?
Inhibits intestinal alpha-glucosidase, which delays the digestion of starch and sucrose and decreases absorption, which leads to a decreased post- prandial plasma glucose.
What is the main adverse effect of alpha-glucosidase inhibitors?
GIT disturbances
What are the main uses of glucagon in pharm (not as a hormone)? (5)
hypoglycaemia beta-blocker calcium channel blocker tricyclic antidepressant overdose relaxes the GIT for radiographic examinations
What is the mechanism of action of glucagon? (5 steps)
- One signal molecule binds to G-protein linked receptor and activates the G-protein
- G-protein turns on adenylyl cyclase (amplifier enzyme)
- Andenylyl cyclase turns ATP into cyclic AMP
- cAMP activates protein kinase A
- Protein kinase A phosphorylates other proteins which leads to a cellular response
What is the mechanism of action of corticosteroids?
Involved in the regulation of genes that in
turn induce specific mRNA synthesis which leads to the synthesis of specific proteins. They occupy a cytosolic receptor which after activation in the nucleus
of the cell, acts on DNA transcription.
What is the main glucocorticoid?
cortisol
Name 2 short-acting glucocorticoids
Hydrocortisone
Cortisone
Name 3 intermediate-acting glucocorticoids
Prednisolone
Prednisone
Methylprednisolone
Name 2 long-acting glucocorticoids
Dexamethasone
Betamethasone
Name a mineralocorticoid as a steroid drug
fludrocortisone
general mineralocorticoid (steriod)= aldosterone
What are the 2 groups of corticosteroids?
glucocorticoids and mineralocorticoid
What is the main clinical use of corticosteroids? (5)
- Suppression of the immune system by organ transplants.
- Anti-inflammatory properties
- Treatment of allergic symptoms and signs such as eczema and asthma.
- In anaphylactic shock.
- Replacement therapy in cases of adrenal cortex insufficiency.
Name 6 inhaled corticosteroids
Beclomethasone Budesonide Ciclesonide Fluticasone Mometasone Triamcinalone
What are inhaled corticosteroids used for?
Bronchospasm
Seasonal rhinitis
Perrenial rhinitis
(Rhinitis is a condition that typically involves nasal obstruction or congestion, runny nose or post-nasal drip, itchy nose, and/or sneezing)
