PHARM - Drugs Used to Treat Diabetes - Week 8 Flashcards
What cell is responsible for the exocrine function of the pancreas?
Acinar cells
What two cells are responsible for the endocrine function of the pancreas? What is the umbrella term for them and what do they secrete?
Islets of Langerhans
-Beta cells secrete insulin
-Alpha cells secrete glucagon
Describe in 4 steps the physiological response to high blood glucose levels.
Elevated blood glucose levels
Insulin is released by beta cells in the pancreas
Fat, muscle, and liver cells take in glucose from the blood
Normal blood glucose levels reached
How are glucose levels reduced in the cell (2)?
Conversion to glycogen and synthesis slowed
Describe in 4 steps the physiological response to low blood glucose levels.
Decreased blood glucose levels
Glucagon is released by alpha cells in the pancreas
Liver cells release glucose into the blood
Normal blood glucose levels reached
What two hormones are involved in increasing blood glucose levels?
Adrenaline and hydrocortisone
What occurs as a result of the insulin signalling cascade?
Recruitment of GLUT4 transporter proteins to the cell membrane
Define type 1 diabetes in terms of insulin availability.
Absolute lack of insulin
When does type 1 diabetes usually occur (2)?
Juvenile onset typically <20 years
Viral initiated autoimmune destruction of islet cells
Consider viral-initiated type 1 diabetes. What are individuals with this predisposed to and why?
Ketoacidosis due to the breakdown of protein and fats
Name 4 symptoms of type 1 diabetes.
Muscle cramps
Faintness
Cardiac arrythmia
Infection
Define type 2 diabetes in terms of insulin availability.
Relative lack of insulin
Name 2 possible mechanisms for type 2 diabetes and a cause if applicable.
Impaired secretion of insulin
Insulin resistance caused by impaired receptor function
Name 3 possible causes of type 2 diabetes in middle-aged individuals.
Overweight/obese
Physically inactive
Family history
Describe the 1st and 2nd phase of responses to high blood glucose levels for insulin in normal, type 1, and type 2 individuals.
1st phase: release of stored insulin
2nd phase: continued release of stored and newly synthesised insulin
Normal - sharp rise in blood insulin levels, followed by a steady decline, followed by a a steady increase, then steady decrease.
Type 1 - flat line
Type 2 - steady increase only after a significant amount of time, followed by a steady decrease.
The peak for blood insulin levels in type 2 diabetes is significantly lower than that of of the initial increase in normal individuals.
The increase in type 2 matches the second increase in glucose in normal individuals.
Define diabetes mellitus.
The chronic disturbance of carbohydrate and lipid metabolism resulting from absolute or relative lack of insulin.
Name 6 secondary complications associated with diabetes.
Hyperglycaemia
Polyuria
Atherosclerosis
Neuropathy
Nephropathy
Retinopathy
Name the four aims of diabetes therapy.
Glucose homeostasis (4-8mmol/L)
Restore metabolism
Relieve symptoms
Reduce long-term complications
Name 11 symptoms of diabetes.
Polyphagia
Polydipsia
Polyuria
Blurred vision
Weight loss
Weakness
Dry itchy skin
Impaired wound healing
Dry mouth
Recurrent infections
Impotence
What is mandatory in the treatment of diabetes? Describe three components to this.
Dietary and lifestyle modifications
-carbohydrate intake
-exercise
-stop smoking
Name two treatment options for type 1 diabetes.
Insulin injection
Islet cell transplantation
Name a treatment option for type 2 diabetes.
Hypoglycaemic agents
How is insulin administered?
Subcutaneously
Name three sources for insulin.
Porcine, bovine, and human
Human using recombinant DNA
What is the standard for dosage on insulin for the treatment of type 1 diabetes (4)?
No standard
-depends on weight, diet, and exercise
What is the aim of appropriate dosage for treating type 1 diabetes?
Avoiding hyperglycaemia
How is blood glucose monitored (what molecule is measured)?
Levels of glycated haemoglobin
Name three adverse effects of treating type 1 diabetes and what this condition is called.
Hypoglycaemia
-faintness
-sweating
-tremors
Name four possible drug interactions when treating type 1 diabetes.
Beta blockers
Corticosteroids
Diuretics
Alcohol
Consider type 2 diabetes caused by a relative lack of insulin. What kind of drug action is desirable to treat it? Give an example.
Drugs that stimulate the pancreas to release insulin
Sulphonylureas
Consider type 2 diabetes caused by insulin resistance. What kind of drug action is desirable to treat it? Give two examples.
Drugs that sensitise the body to insulin and/or control hepatic glucose production
Biguanides
Thiazolidinediones
What kind of drug action is desirable to treat type 2 diabetes by targeting glucose absorption? Give an example.
Drugs that slow the absorption of carbohydrates
Alpha-glucosidase inhibitors
What kind of drug action is desirable to treat type 2 diabetes by targeting glucose reabsorption? give an example.
Drugs that increase excretion of glucose
Sodium glucose cotransporter 2 inhibitors
What kind of drug action is desirable to treat type 2 diabetes by targeting incretins? give an example.
Drugs that regulate insulin and glucagon
Incretin mimetics and enhancers
What drug class is the first-line treatment for diabetes type 2? Name an example.
Biguanides - metformin
Name four mechanisms of action for metformin.
Increased insulin-mediated glucose uptake
Reduced hepatic glucose production
Decreased carbohydrate absorption
Reduced LDL cholesterol and triglyceride levels
How is metformin administered?
Orally
How often is metformin administered typically?
Once a day
Name four advarse effects of metformin.
Diarrhoea
Nausea
Abdominal discomfort
No weight gain with possible modest weight loss
What can occur if metformin is improperly prescribed.
Lactic acidosis
In patients with what 2 diseases is metformin contraindicated?
Renal and hepatic diseases
What line of treatment are sulphonyureas?
First or second.
Describe the mechanism of action for sulphonyureas (5).
Acts on B cells to stimulate insulin secretion
Binds Katp channel reducing K+ permeability and causing Ca2+ entry and insulin release.
How are sulphonyireas administered? How often?
Orally once daily
Do sulphonyureas cross the placenta and/or enter breast milk?
Yes to both
How are sulphonyureas removed from the body?
Excreted via the kidney
Name two adverse effects of sulphonyureas.
Hypoglycaemia
Weight gain
Where in the kidney are sodium glucose cotransporter 2 proteins found? What percentage of glucose do they reabsorb?
Along the tubules following bowmans capsule. Reabsorb up to 90%, with the remaining taken care of by cotransporter 1.
How are SGLT2 inhibitors administered, how often, and how are they removed?
Orally once daily
Excreted via kidney
If something is administered once daily, what does that suggest about its half life?
Long half life
Name 6 adverse effects of using SGLT2 inhibitors.
Genital infections
Polyuria
Dysuria
Modest weight loss
Urinary tract infections
Thirst
Why should SGLT2 inhibitors be used with precaution in the elderly (3)?
It can cause volume depletion, hypotension, and fainting
What effect do SGLT2 inhibitors have on loop diuretics and thiazides? What should be done as a result of this?
It can increase their effects. Precaution should be taken when co-administering these drugs.
What effect do incretins have on the pancreas (3) and what receptor do they target?
Increases insulin secretion
Decreases glucagon secretion
Increases insulin biosynthesis
What effect do incretins have on the liver?
Decreased glucose production
What effect do incretins have on adipose and muscle tissue?
Increases glucose uptake/storage
What effect do incretins have on the stomach?
Decreases gastric emptying
What effect do incretins have on the brain (2)?
Increases neuroprotection
Decreases apetite
How are glucagon-like peptide 1 receptor agonists administered?
Subcutaeneous injection
Name four mechanisms of action for GLP-1 receptor agonists.
Potentiates glucose mediated insulin secretion
Suppresses glucagon secretion
Slows gastric emptying
Loss of appetite
What is the central action of GLP-1 receptor agonists?
Loss of appetite
Name 7 adverse effects of GLP-1 receptor agonists.
Nausea
Vomiting
Diarrhoea
Weight loss
Antibody formation
Immune reactions
Pancreatitis
