Lecture 15 Flashcards
Drugs to Treat Diabetes (58 cards)
1
Q
What is diabetes?
A
- elevated blood levels of glucose
- untreated, blood glucose rises so high that the transporters that reabsorb it are saturated and significant amounts of glucose are found in the urine
2
Q
What are the two things that cause high blood sugar?
A
- not enough insulin produced (type I)
- bodys cells do not respond to the insulin that is produced (Type II)
3
Q
What are the classic symptoms of diabetes?
A
- polyuria (increased urination)
- polydipsia ( increased thirst)
- polyphagia (increased hunger)
- weight loss
4
Q
What is insulin?
A
- peptide hormone synthesized by the beta cells of the islets of Langerhans of the pancreas
- is rapidly released from the pancreas into the blood in response to increased in blood glucose
- causes glucose uptake into muscle, liver, and fat cells
5
Q
What happens in liver cells during glucose uptake?
A
- glycogen synthesis: a storage form a glucose
6
Q
What happens in muscle cells during glucose uptake?
A
- used as energy and promotes protein synthesis
7
Q
What happens in fat cells during glucose uptake?
A
- increased synthesis of fatty acids = increased triglyceride synthesis
8
Q
What is the role of extracellular potassium in relation to insulin?
A
- helps insulin to drive glucose into the cell
9
Q
What are the 3 types of diabetes?
A
- type I: insulin dependent diabetes mellitus
- type II: non-insulin dependent diabete mellitus
- gestational diabetes: diabetes that occurs in pregnancy
10
Q
How does type I diabetes occur?
A
- less common
- diagnosed early
- caused by an autoimmune reaction where the bodys own immune cells attack and destroy the insulin secreting beta cells
= too little or no insulin produced - requires insulin replacement
- not preventable and not caused by bad diet
11
Q
How does type II diabetes occur?
A
- way more common
- pancreas makes sufficient insulin but the insulin produced is resistant to use
- insulin synthesis may also decrease over time
- most patients obese or overweight
- typically diagnosed later in life
12
Q
What are the risk factors in developing type II diabetes?
A
- age
- family history
- obesity
- ethnicity (african and native descent higher risk)
13
Q
How does gestational diabetes occur?
A
- first starts during pregnancy, should have oral glucose test
- diet and exercise are sufficient to keep blood glucose levels within normal ranges
- tend to have larger babies and babies with hypoglycemia in first few days of life
- blood sugar of mother usually returns to normal a few days after birth but may develop some years later
14
Q
What are the complications of diabetes mellitus?
A
- cognitive impairment
- depression
- cerebrovascular disease
- visual impairment (retinopathy)
- cardiovascular disease
- nephropathy (kidney disease)
- urinary continence
- peripheral vascular disease
- peripheral neuropathy
- foot ulcers
15
Q
What is diabetic retinopathy?
A
- most common cause of blindness
- hyperglycemia (elevated blood sugar) causes damage to retinal capillaries
- tightly controlling blood sugar minimizing risk
16
Q
What is diabetic nephropathy?
A
- characterized by proteinuria (protein in the urine), decreased glomerular filtration and increased blood pressure
- leading cause of morbidity and mortality in patients with type I
- blood glucose control delays and reduces severity; ACE inhibitors and ARBs also good (inhibits progression of kidney disease)
17
Q
Cardiovascular disease and diabetes?
A
- CVD (heart attack and stroke included) leading cause of morbidity and mortality in type II
- atherosclerosis develops earlier in type II bc of hyperglycemia + altered lipid metabolism
- Statins help (regardless of LDL levels)
18
Q
Foot ulcers and diabetes
A
- most common cause of hospitalization for diabetic patients
- lots of lower limb amputations
- infection + low blood flow = problems
19
Q
What are the 3 tests used to diagnose diabetes?
A
- fasting plasma glucose test
- casual plasma glucose test
- orla glucose tolerance test
20
Q
what is the Fasting Plasma Glucose Test?
A
- fast for at least 8 hrs then have blood sample drawn
- is the preferred test for diagnosing diabetes
21
Q
what is the casual plasma glucose test?
A
- blood drawn at any time
- symptoms have to include polyuria, polydipsia, and weight loss
- often followed up by FPGT
22
Q
What is the oral glucose tolerance test?
A
- used when other tests unable to definitively diagnose
- patients given glucose dose orally and plasma glucose measured 2 hrs later
23
Q
What is glycosylated hemoglobin?
A
- prolonged exposure of glucose in blood = glucose interacts with hemoglobin to form glycosylated derivatives (HbA1c)
- can be a poor diagnostic test but useful in providing an index of avg blood glucose levels ( and how well patients are responding to therapy)
24
Q
Treatment goals and lifestyle modifications for patients with type I diabetes
A
- tight control of blood glucose levels
- decreasing cardiovascular risk
- maintaining good kidney function
- maintain weight through diet
- exercise regularly (increased cellular response to insulin and increased glucose tolerance)
- monitor insulin levels
25
Treatment goals and lifestyle modifications for patients with type II diabetes
- dietary modifications (losing weight if obese)
| - exercise (stimulates glucose uptake)
26
Who were the effects of insulin discovered by?
- sir frederick banting
27
What are the metabolic actions of insulin?
- is anabolic (i.e. promote energy storage and conservation)
28
What are insulins anabolic actions?
- 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
29
What happens to the body when there is an insulin deficiency?
- puts the body into catabolic ("breaking down") state
| - body favours the breakdown fo complex molecules into simpler substances
30
What are the catabolic effects seen in insulin deficiency?
- glycogenolysis: conversion of glycogen to glucose
- gluconeogenesis: new glucose synthesis
- decreased glucose utilization
- all these effects act to raise blood glucose
- all contribute to the signs and symptoms of diabetes
31
What groups can the 7 different insulins be separated into based on time course of actions?
- short duration-rapid acting
- short duration-slower acting
- intermediate duration
- long duration
32
What are the 3 different types of short duration rapid acting insulin?
- insulin lispro
- insulin aspart
- insulin glulisine
33
How do short duration rapid acting insulins work?
- administered in association with meals to control the postprandial (i.e after eating) rise in glucose
- subcutaneous, but may be IV
- all supplied as clear solution
34
What is the only short duration slower acting insulin?
- unmodified human insulin
35
What are short duration slower acting insulins?
- injected before melas to control postprandial rises in glucose or infused to provide basal control of blood glucose
- administration: subcutaneous or IM (rare)
- insulin molecules form small aggregates (dimers) after injection which slowly absorbs
- is a clear solution
36
what are the two intermediate duration insulins?
1. neutral protamine hormone (NPH) insulin
| 2. insulin detemir
37
How to intermediate duration insulins work?
- onset of action delayed so may not be used at mealtime
- injected once or twice daily to control blood glucose between meals
- subcutaneous injection
- NPH cloudy liquid, determir clear solution
38
Why are the actions of intermediate duration insulins delayed?
- NPH insulin: insulin conjugated to protamine ( a large protein). protamine makes the molecule less soluble and decreases the absorption
- determir: molecules bind strongly to each other with delays absorption
39
What is the only long acting insulin?
- insulin glargine
40
What are long actin insulins?
- long duration of action so administered subcutaneously
- long dur = low solubility at physiological pH
- once injected it forms micro precipitates that slowly dissolve and release in small amounts over time
- clear solution
41
When can you mix insulins and why?
- short action + long duration
- optimal to be done with single syringe
- only NPH insulin can be mixed with short action
- short acting insulin should be drawn into syringe first
- mixture stable for ~ a month
42
What are some complications of insulin therapy?
- hypoglycemia (if severe = coma, convulsions, death)
- rapid decrease in blood glucose result in activation of the SNS = tachycardia, palpitations, sweating, nervousness
- gradual decrease of blood glucose levels = CNS symptoms = headache, confusion, drowsiness, and fatigue occur
-
43
How can hypoglycemia be managed?
- rapid treatment is crucial to prevent irreversible brain damage
- if conscious = fast acting oral sugar should be used (glucose tablets, orange juice, corn syrup, honey, pop)
- if unconscious = IV glucose
- keep hormone glucagon on hand
44
What is glucagon?
- hormone produced by pancreas by alpha cells that causes the conversion of glycogen to glucose i.e raises blood sugar
- effective in treating hypoglycemia
- often used in unconscious patient
- ineffective in starving or malnourished patients bc they have no glycogen stores to begin with
45
What are oral antidiabetic drugs used for?
- treating type II diabetes
| - mostly ineffective in treating type I
46
What are the 6 classes of oral antidiabetic drugs?
1. biguanides
2. sulfonylureas
3. meglitinides
4. thiazolidinediones (glitazones)
5. alpha-glucosidase inhibitors
6. gliptins
47
What are biguanides and how do they work?
- drug of choice
- lower BG in 3 ways:
1. increases the sensitivity and number of insulin receptors
2. decreases hepatic gluconeogenesis
3. reduces intestinal glucose absorption
- dont increase insulin levels = no risk of hypoglycemia
48
What are the adverse effects of biguanides?
- nausea
- decreased appetite
- diarrhea
- decreased absorption of vit b12 and folic acid
- lactic acidosis (rare)
49
What are sulfonylureas and how do they work?
- stimulate release of insulin from the pancreas
- inhibit glycogenolysis (breakdown of glycogen to glucose)
- 1st generation and 2nd generation (2nd gen are more potent and cause fewer drug interactions)
50
What are the adverse effects of sulfonylureas?
- hypoglycemia
| - pancreatic burnout
51
What are meglitinides and how do they work?
- stimulate insulin release from the pancreas
- have a short half life (effective for postprandial rises in glucose)
- less likely to cause hypoglycemia and pancreatic burnout
52
What are glitazones and how do they work?
- increase insulin sensitivity in target tissues and decrease hepatic gluconeogensis
- activate the PPARgama receptor (intracellular receptor) = turns on genes that regulate carb metabolism = increased sensitivity to insulin by increases in the # of glucose transporters
- also increased HDL and decreases triglyceride levels via activation of PPARalpha
53
What are the adverse effects of glitazones?
- fluid retention/edema
- headache
- myalgia
54
What are alpha-glucosidase inhibitors?
- act at intestine to delay carb absorption
- alpha- glucosidase mediates carb breakdown into monosaccharides for absorption
- inhibitors block the enzyme and decrease complex carb metabolism (reduces postprandial glucose rise)
55
What are the adverse effects of AGIs?
- flatulence
- cramps
- abdominal distention
- diarrhea
- decreased iron absorption
56
What are Gliptins and how do they work?
- inhibit dipeptidyl peptidase 4 (DPP-4) which breaks fown the incretin hormones GLP-1 and GIP (released from GI-tract after a meal and cause increased release of insulin and decreased release of glucagon)
- inhibiting DPP-4 allows more GLP-1 and GIP to reach pancreas = increased insulin release and suppression of glucagon release
- no major adverse effects
57
What are incretin mimetics?
- synthetic incretin analogs that mimic the actions of incretin hormones
- cause an increase in insulin release and a decrease in glucagon release
- administered by subcutaneous injection
- adjunct with biguanides or sulfonylureas
58
What are the adverse effects of incretin mimetics?
- hypoglycemia
| - pancreatitis
