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2060B: Pharmacology > Module 15: Drugs to Treat Diabetes > Flashcards

Module 15: Drugs to Treat Diabetes Flashcards

1
Q

Diabetes is a chronic disease characterized by:

A
  • Elevated blood levels of glucose (i.e. sugar)
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2
Q

T/F

- Normally glucose is efficiently reabsorbed in the proximal tubule of the kidney so it is not found in the urine.

A

True

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3
Q

What happens to blood glucose in untreated diabetes?

- Where can it be found?

A

In untreated diabetes, blood glucose rises so high that the transporters that reabsorb it are saturated
- Significant amounts of glucose are found in the urine.

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4
Q

T/F

- Many years ago diabetes was diagnosed by the sweet smell AND TASTE of the urine!

A

True

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5
Q

Why does high blood sugar result? (2)

A

High blood sugar in diabetes results from either:

  • not enough insulin produced in the body; or
  • because the body’s cells do not respond to the insulin that is produced
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6
Q

What are the classic symptoms of diabetes? (4)

A

The classic symptoms of diabetes are polyuria (increased urination), polydipsia (increased thirst), polyphagia (increased hunger) and weight loss

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7
Q

What hormone is involved with regulating blood glucose?

A

Insulin is a hormone produced by the pancreas that is involved in tightly regulating blood glucose.

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8
Q

When does diabetes occur?

A

Diabetes occurs when insulin levels are too low or when the body’s cells are resistant to the effects of insulin

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9
Q

What type of a hormone is insulin?

- Where is it released from?

A

Insulin is a peptide hormone synthesized by the β (beta) cells of the islets of Langerhans of the pancreas
- Insulin is rapidly released from the pancreas into the blood in response to increases in blood glucose

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10
Q

Where does glucose uptake occur?

- Explain each (3)

A

When insulin is secreted, it causes glucose uptake into muscle, liver, and fat cells.

  • In liver cells, glucose uptake results in glycogen synthesis (a storage form of glucose).
  • In muscle cells, glucose is used as energy and promotes protein synthesis.
  • In fat cells, insulin causes increased synthesis of fatty acids, which results in increased triglyceride synthesis.
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11
Q

T/F

Extracellular potassium is not important in the action of insulin

A

False
Extracellular potassium IS important in the action of insulin
- As it helps insulin to drive glucose into the cell.

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12
Q

Describe the process of a healthy pancreas (5):

A
  1. Stomach converts food to glucose
  2. Glucose enters blood stream
  3. Pancreas produces insulin
  4. Glucose enters body effectively
  5. Glucose levels in balance
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13
Q

What are the 3 types of diabetes?

A
  1. Type I diabetes – Also called insulin dependent diabetes mellitus.
  2. Type II diabetes – Also called non-insulin dependent diabetes mellitus.
  3. Gestational diabetes – Diabetes that occurs in pregnancy.
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14
Q

Type I:

  • %?
  • When does it appear?
  • Cause?
  • Result?
  • Preventable?
A
  • Approximately 10% of diabetics have type I diabetes.
  • Type I diabetes is usually diagnosed in children or adolescents but symptoms may not appear until early adulthood.
  • Type I diabetes is caused by an autoimmune reaction where the body’s own immune cells attack and destroy the insulin secreting β cells.
  • As a result, the body makes too little or no insulin at all and requires insulin replacement.
  • Type I diabetes is not preventable and it is not caused by eating too much sugar.
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15
Q

Describe the process of type 1 diabetes (5):

A
  1. Stomach converts food to glucose
  2. Glucose enters blood stream
  3. Pancreas produces little to no insulin
  4. Glucose unable to enters body effectively
  5. Glucose levels increase
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16
Q

Type II Diabetes:

  • %?
  • How does it effect the pancreas?
  • What may decrease?
  • Risk factors?
  • Diagnosis?
A
  • Approximately 90% of all diabetics have type II diabetes.
  • In type II diabetes the pancreas makes sufficient insulin, however, the insulin produced is resistant to use.
  • Over the course of the disease, insulin synthesis may also decrease.
  • There are many risk factors for developing type II diabetes including age, having a family member with diabetes, previous gestational diabetes, lack of exercise, heart disease, obesity, ethnicity (African and Native descent are at higher risk). It is important to note that in Canada, ~ 80% of all patients with type II diabetes are obese or overweight.
  • Type II diabetes was typically diagnosed later in life but there is a trend towards younger people getting the disease.
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17
Q

Describe the process of type II diabetes (5):

A
  1. Stomach converts food to glucose
  2. Glucose enters blood stream
  3. Pancreas produces sufficient insulin but it is resistant to effective use
  4. Glucose unable to enter body effectively
  5. Glucose levels increase
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18
Q

Gestatonal Diabetes:

  • When does it occur?
  • Prevention?
  • Treatment
  • Effect on baby?
  • After birth?
A
  • Usually begins ~ halfway through pregnancy.
  • All women should have an oral glucose tolerance test between weeks 24-28 of pregnancy to test for gestational diabetes.
  • Usually diet and exercise are sufficient to keep blood glucose levels within normal ranges.
  • Pregnant women with gestational diabetes tend to have larger babies and babies with hypoglycemia in the first few days of life.
  • After birth, the blood sugar of the mother usually returns to normal however; blood glucose should be continually monitored as many patients develop diabetes 5 – 10 years later.
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19
Q

List the complications of diabetes (10):

A
  1. Cognitive impairment
  2. Depression
  3. Cerebrovascular disease
  4. Visual impairment
  5. Nephropathy
  6. Weight loss
  7. Urinary incontinence
  8. Peripheral vascular disease
  9. Peripheral neuropathy
  10. Foot ulcers
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20
Q

Diabetic retinopathy:

  • Under the age of 65?
  • Damages what?
  • What minimizes risk?
  • Prevention?
A
  • Diabetic retinopathy is the most common cause of blindness in people under the age of 65.
  • Hyperglycemia causes damage to retinal capillaries.
  • Tightly controlling blood sugar minimizes the risk of retinopathy.
  • Patients with type I or type II diabetes should have an eye exam once a year.
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21
Q

Diabetic Neuropathy:

  • Characterized by (3)?
  • Earliest sign?
  • Leading cause of?
  • Reduce risk by?
  • Prevention?
A
  • Diabetic nephropathy is characterized by proteinuria (protein in the urine), decreased glomerular filtration and increased blood pressure.
  • Proteinuria is the earliest sign of diabetic nephropathy.
  • Diabetic nephropathy is the leading cause of morbidity and mortality in patients with type I diabetes.
  • Tight control of blood glucose both delays and reduces the severity of diabetic nephropathy.
  • ACE inhibitors and ARBs are useful in preventing diabetic nephropathy. Experts suggest patients with type I diabetes take an ACE inhibitor or ARB regardless of their blood pressure.
22
Q

Cardiovascular disease:

  • Leading cause in?
  • What develops easier?
  • Results from? (2)
  • Reduce risk?
A

0 CVD including heart attack and stroke are the leading causes of morbidity and mortality in type II diabetics.

  • Atherosclerosis develops much earlier in diabetic patients than in non-diabetics.
  • CVD in diabetes results from a combination of hyperglycemia and altered lipid metabolism.
  • Statins reduce cardiovascular events in diabetic patients, regardless of their LDL cholesterol levels.
23
Q

Diabetic foot ulcers:

  • Common?
  • Affects what part?
  • Prevention?
A
  • Are the most common cause of hospitalization for diabetic patients.
  • Diabetes accounts for approximately half of all lower limb amputations every year due to infection.
  • All diabetic patients should have regular foot exams.
24
Q

How is diabetes diagnosed?

A
  1. Fasting Plasma Glucose Test
  2. Casual Plasma Glucose Test
  3. Oral Glucose Tolerance Test (OGTT)
  4. Glycosylated Hemoglobin
25
Q

Describe the fasting plasma glucose test:

A

Patients fast for at least 8 hours and then have a blood sample drawn to measure blood glucose.
- If the fasting plasma glucose is > 7.0 mmol/L then diabetes is diagnosed.

The fasting plasma glucose test is the preferred test for diagnosing diabetes.

26
Q

Describe the oral glucose tolerance test:

A

This test is used when the other tests are unable to definitively diagnose diabetes.

  • Patients are given an oral 75 gram dose of glucose and plasma glucose is measured 2 hours later.
  • If plasma glucose is > 11.1 mmol/L then the patients will be diagnosed with diabetes.
27
Q

Describe using 4. Glycosylated Hemoglobin to diagnosis diabetes:

A

Upon prolonged exposure in the blood, glucose interacts with hemoglobin to form glycosylated derivatives, mostly HbA1C.

  • Glycosylated hemoglobin is useful in providing an index of the average blood glucose levels over the previous 2-3 months.
  • Measuring glycosylated hemoglobin is a good determinant of how well a patient is responding to therapy.
  • The target for management of diabetes is to maintain HbA1C < 7% of total hemoglobin.
28
Q

T/F
The complications of diabetes arise from prolonged elevations of plasma glucose. Therefore, the primary goal of diabetes therapy is to maintain tight control of plasma glucose levels.

A

True

29
Q

What does “tight control” mean?

- What is the target?

A

“Tight control” means keeping plasma glucose levels in the normal range for the entire day.

The targets for plasma glucose are:

  • Pre-meal plasma glucose 4.0 - 7.0 mmol/L
  • Peak post-meal glucose 5.0 - 10 mmol/L
  • HbA1C < 7%
30
Q

As diabetes is closely associated with cardiovascular disease and nephropathy, it is also crucial to decrease these risk factors:

A
  1. Cardiovascular risk
    - Blood pressure – systolic < 130, diastolic < 80
    - Lipids – LDL < 2.6 mmol/L, triglycerides < 1.7 mmol/L, HDL (men) > 1.0 mmol/L, HDL (women) > 1.3 mmol/L.
  2. Kidney Function
    - Urine albumin to creatinine ratio < 30 mg/g (albumin/creatinine).
31
Q

As diabetes is closely associated with cardiovascular disease and nephropathy, it is also crucial to decrease these risk factors:
- Type I

A

Diet

  • Most patients with type I diabetes are thin, therefore the goal is to maintain weight, not lose it.
  • Total caloric intake should be split throughout the day with meals 4-5 hours apart.

Exercise

  • Exercise increases the cellular response to insulin and increases glucose tolerance so patients should be encouraged to exercise.
  • Strenuous exercise may cause hypoglycemia so close patient oversight is required.

Insulin

  • Survival requires insulin.
  • Blood glucose levels must be monitored 3 or more times per day.
32
Q

As diabetes is closely associated with cardiovascular disease and nephropathy, it is also crucial to decrease these risk factors:
- Type II

A

Diet

  • Diet is a crucial component of treatment in type II diabetes.
  • Dietary modifications alone (i.e. caloric restriction) often normalize insulin release and decrease insulin resistance.
  • Patients with type II diabetes are often obese so losing weight is a treatment goal.

Exercise
- Exercise stimulates glucose uptake and should be encouraged in patients with type II diabetes.

33
Q

Who discovered insulin?

- Why is this important?

A

The effects of insulin were discovered by Sir Frederick Banting, a Canadian!
- Before the discovery of insulin, patients diagnosed with diabetes would die within 2-3 years of diagnosis.

34
Q

What is the metabolic action of insulin?

A

Insulin can be thought of as anabolic (i.e. “building up” or conservative).
- This means that the actions of insulin promote energy storage and conservation

35
Q

What is the anabolic action of insulin?

A
  • Cellular uptake of glucose into liver, muscle, and fat.
  • Glucose uptake results in the formation of glycogen (liver and muscle) and triglycerides (adipose tissue).
  • Decreased hepatic gluconeogenesis (i.e. glucose synthesis).
  • Cellular uptake of amino acids (mostly into muscle).
  • Amino acid uptake results in increased protein synthesis.
36
Q

What does insulin deficiency do to the body?

A

Insulin deficiency puts the body into a catabolic (“breaking down”) state.
- This means the body favours the breakdown of complex molecules into simpler substances.

37
Q

The catabolic effects seen in insulin deficiency include (3) :

A
  1. Glycogenolysis – conversion of glycogen to glucose.
  2. Gluconeogenesis – new glucose synthesis.
  3. Decreased glucose utilization.

All of these effects contribute to the signs and symptoms of diabetes.
- Notice that these catabolic effects all act to raise blood glucose

38
Q

How many types of insulin are there?

  • How do they differ?
  • How are they classified (4)?
A

There are 7 main types of insulin available to treat diabetes.
- The different types of insulin differ in their appearance, time course of action, and route of administration.

The insulins can be separated based on time course of actions:

  • Short duration-rapid acting
  • Short duration-slower acting
  • Intermediate duration
  • Long duration
39
Q

Short Duration Rapid Acting Insulin:

  • 3 classes?
  • When is it administered?
  • Route of admin?
  • Colour?
A

This class includes three different types of insulin:

  • Insulin lispro
  • Insulin aspart
  • Insulin glulisine
  • This class of insulin is administered in association with meals to control the postprandial (i.e. after eating) rise in glucose.
  • The route of administration is subcutaneous, although they may be used IV if required.
  • All three types are supplied as a clear solution.
40
Q

Short Duration Slower Acting Insulin:

  • Types?
  • When is it administer?
  • How is it admin?
  • How does it work?
  • Colour?
A
  • The only type of short duration slower acting insulin is unmodified human insulin.
  • Short duration slower acting insulins can be injected before meals to control postprandial rises in glucose or infused to provide basal control of blood glucose.
  • They can be administered subcutaneously or IM (rare).
  • Following subcutaneous injection, the insulin molecules form small aggregates (i.e. dimers), which slows absorption.
  • Supplied as a clear solution.
41
Q

Intermediate Duration Insulin:

  • Types?
  • When is it admin?
  • Delayed?
  • How is it admin?
  • Colour
A

There are two intermediate duration insulins:

  • Neutral Protamine Hormone (NPH) insulin
  • Insulin Detemir

The onset of action of both of these are delayed, so they may not be used at mealtime to control postprandial rises in blood glucose.
- Instead they are injected once or twice daily to control blood glucose between meals and in the evening.

Why are the actions delayed?

  • NPH insulin – is insulin conjugated to protamine (a large protein). The protamine makes the molecule less soluble and decreases the absorption.
  • Insulin Detemir – Insulin detemir molecules bind strongly to each other which delays absorption. (remember Module 2?)
  • Both NPH insulin and insulin detemir are administered by subcutaneous injection.
  • NPH insulin is supplied as a cloudy suspension and insulin detemir is a clear solution.
42
Q

Long Acting Insulin:

  • types?
  • advantage?
  • how it works?
  • colour?
A
  • Insulin glargine is the only type of long acting insulin.
  • The main advantage of insulin glargine is its long duration of action therefore, it is administered by subcutaneous injection once daily at bedtime.
  • The long duration of action of insulin glargine is attributed to its low solubility at physiological pH. When it’s injected, it forms microprecipitates that slowly dissolve and therefore release insulin glargine in small amounts over an extended time.
  • Insulin glargine is supplied as a clear solution.
43
Q

What are rules when injecting insulin?

A
  1. Only NPH insulin can be mixed with short acting insulins.
  2. When the mixture is prepared, the short acting insulin should be drawn into the syringe first.
  3. Mixtures are stable for 28 days.
44
Q

What are complications of insulin therapy?

A

Primary = hypoglycaemia <3mmol/L

Rapid decreases in blood glucose, such as in overdose, result in activation of the sympathetic nervous system which causes:

o Tachycardia
o Palpitations
o Sweating
o Nervousness

45
Q

When blood glucose levels decrease more gradually, CNS symptoms such as:

A

headache, confusion, drowsiness, and fatigue occur.

46
Q

T/F

If hypoglycemia is severe coma, convulsions, or even death may occur.

A

True

47
Q

How does one manage hypoglycaemia?

A

Rapid treatment of hypoglycemia is crucial to prevent irreversible brain damage.

If patients are conscious, fast acting oral sugar should be used.
- Good examples are glucose tablets, orange juice, corn syrup, honey and pop (not diet).

If the patient is unconscious, IV glucose may be required.

Diabetic patients are also recommended to keep the hormone glucagon on hand.

48
Q

What is glucagon?

  • Causes?
  • Treats?
  • Unconscious vs. conscious PT’s
A

Glucagon is another hormone produced by the pancreas.

  • Glucagon causes the conversion of glycogen to glucose (opposite action to insulin);
  • and is therefore effective in treating hypoglycemia
  • It is most often used in the community when a hypoglycemic patient is unconscious. Once the patient regains consciousness, oral sugar solutions should be used.
  • For unconscious patients, IV glucose is preferred to glucagon but is impractical outside of medical supervision.
49
Q

Glucagon is ineffective in starving or malnourished patients. Why?

A

Malnourished or starving patients often do not have any glycogen stores to begin with.

50
Q

Oral antidiabetic drugs are used to treat type II diabetes and are for the most part ineffective in type I diabetes.

There are six classes of oral antidiabetic drugs:

A
  1. Biguanides
  2. Sulfonylureas
  3. Meglitinides
  4. Thiazolidinediones (glitazones)
  5. Alpha-glucosidase inhibitors
  6. Gliptins

2060B: Pharmacology (18 decks)

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