3. Pharmacology I Flashcards
Why do people get diabetes?
An absolute deficiency in the pancreatic hormone insulin because of abnormal beta cell function – thought to be autoimmune with both genetic and environmental triggers. ____
A defective response to insulin (insulin resistance and/or an increased demand for insulin as in the obese). ____
type 1 diabetes
type 2 diabetes
Type 1 diabetes Other names: \_\_\_\_, ketosis prone, brittle, unstable Severity: \_\_\_\_ Functioning beta cells: \_\_\_\_ Endogenous insulin production: \_\_\_\_ Exogenous insulin requirement: \_\_\_\_ Oral agent usefulness: \_\_\_\_
juvenile onset most few or none little or none required to sustain life not effective
Type 2 Diabetes Other names: \_\_\_\_ onset, ketosis resistant, stable Severity: \_\_\_\_ Functioning beta cells: \_\_\_\_ Endogenous insulin production: \_\_\_\_ Exogenous insulin requirement: \_\_\_\_ Oral agent usefulness: \_\_\_\_
adult least some or normal some, normal or elevated often not required often effective
Type 1 diabetes
Dietary control: ____ but still needs insulin
Onset age: ____, usually < than 35 years
Nutritional status at diagnosis: ____, undernourished
Ketosis prone: ____ (acetone, beta hydroxy butyrate)
Common symptoms: ____, polydypsia, ____, glucosuria, dehydration,
polyphagia
mandatory anytime thin yes hyperglycemnia polyuria
Type 2 Diabetes
Dietary control: ____ – but sometimes all that is needed to control disease
Onset age: ____, usually > 40 years. However more young people being diagnosed
Nutritional status at diagnosis: ____% obese
Ketosis prone: ____
Common symptoms: May be ____ Sometimes part of metabolic syndrome
mandatory anytime 60-90 no asymptomatic
METABOLIC SYNDROME – NEED TO HAVE 3 of THESE
A large ____. This also is called abdominal obesity or “having an apple shape.” Excess fat in the ____ area is a greater risk factor for heart disease than excess fat in other parts of the body, such as on the hips.
A high ____ level (or you’re on medicine to treat high triglycerides). Triglycerides are a type of fat found in the blood.
A low ____ cholesterol level (or you’re on medicine to treat low HDL cholesterol). HDL sometimes is called “good” cholesterol. This is because it helps remove cholesterol from your arteries. A low HDL cholesterol level raises your risk for heart disease.
High ____ (or you’re on medicine to treat high blood pressure). Blood pressure is the force of blood pushing against the walls of your arteries as your heart pumps blood. If this pressure rises and stays high over time, it can damage your heart and lead to plaque buildup.
High ____(or you’re on medicine to treat high blood sugar). Mildly high blood sugar may be an early sign of diabetes.
wasitline
stomach
triglyceride
HDL
BP
fasting blood sugar
Complications of Diabetes
- ____ disease
- Kidney failure
- ____
- Infections leading to amputations
- ____
- Untreated or poorly controlled decreases life expectancy
• Neuropathies– probably from the ____ bodies (3x mentioning this– probably IMPORTANT ;) ;).
cardiovascular
neuropathies
blindness
ketone
Small blood vessels rupturing in eye
Diabetic retinopathy
- Example of a diabetic patient. There are some BV that have burst (circled in blue) and the blood can damage the retinolàcalled ____.
- Might have something to do with diabetes, but his dad has macular degeneration in one eye- central vision loss.
diabetic retinopathy
Oral Signs of Uncontrolled Diabetes
Very \_\_\_\_ mucosa \_\_\_\_ response to local irritants Increased oral \_\_\_\_ Poor \_\_\_\_ healing Severe and rapidly progressing \_\_\_\_ disease
dry exaggerated infections wound periodontal
Metabolic Actions of Insulin
Insulin:
• Increases ____ transport into muscle and fat tissues
• Increase ____ synthesis in liver and skeletal muscle
• Decrease ____ synthesis in liver
• Increase glucose ____ in fat.
• So every one of these things above is going to lower blood glucose.
- Fat
- ____: (typically wasting away) b/c they can’t get sugar into their fatty tissues so the body just starts breaking down the ____ for energy so the body starts withering away.. Insulin will decrease the breakdown of lipids and increase lipogenesis (synthesis of lipids) and it occurs in liver and fatty tissues.
• Protein
• All ____. Decreases protein breakdown in the liver. Increases synthesis
and increases ____ uptake in the skeletal muscle. They test for this drug now in athletes. Talks about how a guy will be giving a shot of insulin in the butt to another guy at the gym. These ppl are running the risk of becoming severely hypoglycemic.
glucose
glycogen
glucose
breakdown
type 1
fat
anabolic
amino acid
• Precursor of insulin called ____ in the pancreas.
• There is an ____ and ____ of insulin that are tethered together in the
precursor proinsulin by this connecting peptide (____) which is later
cleaved off by the insulin.
• But still, there are still ____ bonds that hold the A-chain and B-chain
together even tho the C peptide or connecting peptide is gone.
pro-insulin A chain B chain c-peptide disulfide
This is a Hersh original of an islet cell of the pancreas:
1. Certain tissues like skeletal muscles and fatty tissue have a____
that pumps glucose into the tissues.
2. Via several metabolic steps ,____ is generated
3. ATP causes ____ channels to close (remember that potassium flows out) so now
you have more positive on the inside (b/c positive K+ are kept in).
4. Lets ____ in.
5. Insulin granules fuse with the ____ and insulin gets spit out.
- We have one class of oral drugs that are used in Type 2 diabetes called à ____.
- Have sulfonyl linkages in them.
- Their MOA (mechanism of action): Directly close ____ channels and cause insulin ____. These are the oral drugs that you will most likely see ____ b/d they’re ____-releasers. Not as high as shooting insulin itself into your body subcutaneously or inhaling insulin into you.
glucose transporter ATP K+ calcium membrane
sulfonylureas K+ secretion hypoglycemia insulin
Pharmacological Goals of Insulin Therapy
• To \_\_\_\_ (in the case of Type 1) or \_\_\_\_ (in the case of Type 2) endogenous insulin – Decrease in blood \_\_\_\_ – Promotion of \_\_\_\_ synthesis – Decrease \_\_\_\_ and protein breakdown – Promote \_\_\_\_ and protein synthesis
replace supplement glucose glycogen fat fat
Types of Insulin
- Beef – ____ amino acids different than human
- Pork – ____ amino acid different than human
- Human insulin (Humulin®) – a product of ____ engineering. Placing the gene for insulin in ____or yeast and the microbe then secretes insulin.
• Insulin analogs
– Insulin lispro – reverse ____ at B28 and ____ at B29 to ____ up absorption (within 5 minutes)
– Insulin glargine – add two extra ____ so it forms precipitates in subcutaneous tissue ____ absorption but lengthening ____ of action (up to 36 hours)
3
1
genetic
e coli
proline
lysine
speed
AA
slowing
duration
Routes of Administration of Insulin
• Usually \_\_\_\_ • Occasionally \_\_\_\_ • Clear (non-suspension) ultra short and short acting preparations can be administered \_\_\_\_ • Novel delivery systems – \_\_\_\_ – Subcutaneous abdominal pumps – \_\_\_\_ insulin
subcutaneously
intramuscularly
intravenously
pens
inhaled
Subcutaneous Insulin Pump
• This is what the abdominal pump looks like (looks like a pager).
• There is a catheter that is leading to this disc (w/ needle), needs to be
changed every ____ days.
• There’s a ____ on this: translating carbohydrates > insulin
units.
• Easy to ____ and give too much.
4-5
learning curve
overshoot
Pharmacokinetics Characteristics of Some Insulin Preparations
• But you can see that the differences between all of the solutions other than being Humulin or non-Humulin is all pharmacokinetics: ____, ____, and ____.
- Ultra short (Insulin Lispro): IV that’s reserved when somebody’s blood sugar is sky ____. Gives example of someone who’s not wearing a diabetes identifying band and with their breath could get mistaken for being drunk and thrown to jail, and with their blood sugar being dangerously high and potentially causing organ failure, they would be given IV Insulin Lispro.
- Typically, you see people being on ____- or intermediate-acting insulin in combination with a ____-acting one. There are formulations where two of them are together to take adv. of ones that act quicker with ones that last longer.
onset
peak
duration
high
short
long
Factors that may require adjustment in insulin dose
- Exercise – ____
- Stress – ____
- Acute infection – ____
- Pregnancy – ____
- Thyroid hormone, glucocorticoids, oral contraceptives – ____
- Thiazide and loop diuretics - ____
decrease increase increase increase increase increase
When to treat most insulin dependent diabetics
• ____ appointments are recommended
– Avoid peak insulin levels – ____
• Make sure your patient has eaten ____ and taken their insulin
AM
hypoglycemia
breakfast
Complications in Insulin Dependent Diabetic Patients
- Hyperglycemia–no one ____ in dental chair because their sugar is too high. May see classic signs of dry mouth, ____ (exaggerated deep breathing), acetone breath. Get them to ____ and delay dental care
- Hypoglycemia–can happen quickly and be ____. Tremors, drooling, ____, rapid pulse, cold clammy feeling. Get oral ____ into them before they become unconscious. If unconscious ____ 1 mg intramuscularly and basic ____. Get medical help
dies
kussmaul
physician
deadly confusion carbohydrates glucagon life support
Sulfonylureas
• Only effective in patients with functioning ____ cells
• Stimulate the release of insulin by blocking ____ Channels in pancreatic islet cells.
• 2nd generation drugs appear to also increase insulin ____ of tissues
beta
ATP dependent K+ channels
sensitivity
• 1st gens are used as much anymore, but if it were to come up, you might see chlorpropamide or tolbutamide
• Diabinase sounds like diabetes.
• The reason for the switch to 2nd gen over the last ten years is that there’s alittle less ____ going on. Instead of being a 3% incidence, it more like 1.5% incidence of
hypoglycemia occurring. Also these drugs may sensitize the tissues to insulin.
• 1st gen does not address insulin ____ problem.
• glyburide is in the top 100-150 selling drugs in the US. Glymepride is the 2nd most common.
◦ typically 2 pills a day (based on the half-life)
• The biggest limitation on sulfonylureas is that they cause the release of insulin whenever and not when you’ve just eaten a meal.
◦ The reason why they have a high incidence of hypoglycemia.
• Brand names
◦ Glucotrol = control glucose ◦ Diabeta = diabetes
hypoglycemia
resistance
Adverse Effects of Sulfonylureas
• Only seen in about 4% of individuals
• Hypoglycemia – more with ____ generation
• ____ effect
• ____ with drugs containing sulfonamide linkages
• ____
• Drug interactions
– Highly ____ bound drugs (NSAIDs)
– ____ inhibitors (Azoles antifungals, metronidazole, H2 receptor blockers)
first disulfiram cross allergenicity teratogenic protein CYP 2C9
Repagliuide (Prandin®)
- Like sulfonylureas a ____ channel blocker in the islets leading to increased insulin release
- It has a non-sulfonamide structure so it can be employed in patients allergic to ____
- ____ can occur especially in patient who has delayed intake of a meal
- Highly ____ bound so NSAIDS can increase blood levels and risk of hypoglycemia
- A cytochrome P450 substrate so CYP inhibitors like ____, clarithromycin and ____ antifungals can increase blood levels.
potassium sulfonylureas hypoglycemia protein erythromycin azole
