Pharm 38 Objectives Flashcards
What are the 3 main steroid products of the adrenals.
- Glucocorticoid
- Mineralocorticoid
- Androgens
What is the primary physiologic glucocorticoid?
Cortisol
What is the primary pharmacologic congener of glucocorticoid?
Hydrocortisone
What is the primary physiologic mineralocorticoid?
Aldosterone
What is the primary pharmacologic congener of mineralocorticoid?
Fludrocortisone
What is the primary drug therapy option for Addison’ and its typical dosing regimen?
- Hydrocortisone
- Dose: 2/3 in am and 1/3 in afternoon
What medication is used as an adjunct drug therapy to support blood pressure, if needed?
Fludrocortisone (potent mineralocorticoid)
When is the most appropriate time(s) of day to dose the glucocorticoid (and mineralocorticoid if necessary)?
Give most of the dose in the AM and smaller doses throughout the day
- 2/3 in AM and 1/3 in afternoon
When should you dose adjustment glucocorticoid (and mineralocorticoid if necessary)?
- Dosage is increase in times of stress —> double the dose
- If surgery dose may need to be greatly increased for 48-72 hrs
What is T3?
Active thyroid hormone
What is the Physiologic Abundance of T3?
- 20% secreted by thyroid gland
- Most produced from T4 in the liver
What is the Biologic activity of T3?
Activates gene transcription leading to increase syntheses of proteins necessary for growth development, and calorigenesis (heat production)
What is the onset of T3?
Within a few hours
What is the duration/half life of T3?
Approx. 1 day
What is T4?
- Inactive thyroid hormone
- Precursor for T3
What is the Physiologic Abundance of T4?
- 80% secreted by thyroid gland.
- Produced in thyroid gland and stored in thyroid follicles
What is the Biologic activity of T4?
Some of T4 is converted to T3 in liver and muscles and this conversion is the final step of thyroid activity
- T4 can also be converted into reverse T3 (rT3) which is the inactive and stored form of the hormone—> this is seen in pts taking too much T4
What is the onset of T4?
3-5 days
What is the duration/half life of T4?
Approx. 7 days
What pharmacologic product contains T4? and “who is best pt” for this drug?
Levothyroxine (T4)
- Can be used on its own
- Preferred thyroid supplement for most pts
What pharmacologic product contains T3? and “who is best pt” for this drug?
Liothyronine (T3)
- Used in pts who doesn’t get adequate convert T4 to T3.
What are CI with Liothyronine (T3)?
- Should not be used on it own for thyroid supplement
- Do not use in pts with cardiac issues
What pharmacologic product contains T4 and T3? and what can it cause?
“Thyroid USP” or Desiccated Porcine Thyroid Extract (T4 and T3)
- Animal based: ground up pig thyroid “natural product”
- Can cause over stimulation of the heart and thyroid
What are the 2 Thyroid synthesis inhibitors used in Hyperthyroidism?
- Propylthiouracil (PTU)
- Methimazole
What is the duration/half life and how long does it take to reach Euthyroid state with Propylthiouracil (PTU)?
- Short half-life, required TID
- 6-12 mos for euthyroid state
What are the ASEs of Propylthiouracil (PTU)?
- Agranulocytosis
- Not always able to establish a euthyroid state: may lead to hypothyroidism
- Concerns w/ pregnancy and lactation
- Severe liver damage
What is the duration/half life and how long does it take to reach Euthyroid state with Methimazole?
- Longer half live, once-daily dosing
- May take 3-12 wks for euthyroid state
Methimazole is an adjunct therapy to what?
Thyroid irradiation
What are the ASEs of Methimazole
- Agranulocytosis
- MORE dangerous than PTU during lactation and during the 1st trimester of pregnancy
What is the role of Beta Blockers for pts with hyperthyroidism?
- Use for occasional or short time only for symptomatic tx not tx hyperthyroidism
- Longer term use can cause problems during pregnancy
What Beta Blocker is most commonly used in pts with hyperthyroidism?
Non selective: Propranolol
- Suppress: tachy, tremors, anxiety, and others
Why is it important to screen for and closely monitor hypothyroidism during pregnancy?
- During 1st trimester insufficient thyroid hormones can result in permanent neuropsychologic deficits in child.
How is thyroid dosing adjusted during pregnancy?
Frequently increasing during pregnancy
Why is Hypothyroidism in infants a concern?
- May be permanent or transient
- Can cause mental retardation and derangement of growth
What are the concerns with use of thyroid synthesis inhibitors for Hyperthyroidism during pregnancy?
- Only use or moderate to severe hyperthyroidism
- PTU and Methimazole readily cross the placenta and both are FDA cat. D
What are the BBW for Methimazole and PTU?
- D/t fetal abnormalities associated with Methimazole, PTU may be the tx of choice when antithyroid an drug is indicated during or just prior during the 1st trimester
- Liver tox is higher with PTU the use of Methimazole may be preferred during the 2nd or 3rd trimester
How often should maternal thyroid fxn be monitored?
Monitored after 2wks of TSI has been initiated and then every 2 to 4 wks.
PTU is a treatment for what thyroid emergency in pregnant women?
Thyroid Storm
What medication is the most notorious for causing thyroid disorders? and why?
Amiodarone
- Increases risk for thyroid disease in 1 year by 10x
- Can cause both Hyperthyroidism and Hypothyroidism
What are some other medications the can cause thyroid disorders?
- Tyrosine Kinase inhibitors (chemo drugs)
- Lithium
- Interleukin-2
- Interferon-alfa
What is the secretory product of Pancreatic a-cells?
Glucagon
What is the secretory product of Pancreatic b-cells?
Insulin and amylin
What is the secretory product of Pancreatic δ-cells?
Somatostatin
What is the secretory product of Pancreatic g-cells?
Gastrin
What is the secretory product of Pancreatic f-cells?
Pancreatic polypeptide
What is the role of intestinal L-cells?
Synthesize proglucagon which is converted to glucagon-like peptide “GLP”
What is the pharmacological product of Pancreatic a-cells?
Glucagon for injection
What is the pharmacological product of Pancreatic b-cells?
Many insulin products (ie amylin —> pramlintide)
What is the pharmacological product of Pancreatic δ-cells?
Octreotide
What does Somatostatin inhibit?
Somatostatin causes widespread inhibition of endocrine and exocrine fx of pancreas, gall bladder, and gut
What does Somatostatin regulate?
Secretion of alpha and beta pancreatic cells
What are the indications of Octreotide?
- Acromegaly
- Metastatic, carcinoid tumors
- Vasoactive intestinal peptide-secreting tumor
What is the 1st step of the 7 steps in insulin secretion and how the beta-cell acts as a glucose sensor?
- Increased blood glucose -GLUT2-> increased intracellular glucose
What is the 2nd step of the 7 steps in insulin secretion and how the beta-cell acts as a glucose sensor?
- The metabolism of glucose causes a rise in the ATP:ADP ratio
What is the 3rd step of the 7 steps in insulin secretion and how the beta-cell acts as a glucose sensor?
- Increase ATP/ADP inactivated K+ channel
What is the 4th step of the 7 steps in insulin secretion and how the beta-cell acts as a glucose sensor?
- Depolarization of the membrane
What is the 5th step of the 7 steps in insulin secretion and how the beta-cell acts as a glucose sensor?
- Ca2+ channel opens
What is the 6th step of the 7 steps in insulin secretion and how the beta-cell acts as a glucose sensor?
- Intracellular Ca2+ levels increase
What is the 7th step of the 7 steps in insulin secretion and how the beta-cell acts as a glucose sensor?
- Exocytotic release of insulin from storage granules
What cells produce Glucagon?
Alpha cells of the pancreases in response to decreased blood glucose concentration
How does glucagon act as a counter-regulatory concentration?
- When blood sugar levels are high, glucose enters the alpha cells and is converted to ATP
- When ATP levels are high, ATP- gated potassium channels remain open
- When BG falls, ATP levels in the cell fall, with low ATP the ATP gated potassium channels close.
When fasting is insulin still be secreted?
Even when fasting, insulin is secreted around the clock but at low rate which results in low plasma insulin concentration.
How does basal and prandial vary based on physiologic serum insulin levels?
- If BG suddenly rises insulin is quickly secreted and rises to 10x the basal level within 3-5 minutes
- Insulin levels decrease after about 10 minutes but if glucose levels cont. to be elevated for much longer then insulin concentrations increase even higher than initial rise
How does b-cell secretagogue drugs stimulate the release of insulin?
Increase the release of insulin from pancreatic beta cells by:
- Inhibiting ATP sensitive potassium channels in the plasma membrane
- Decrease glucagon secretion
What are the physiologic effect of insulin?
Anabolic hormone:
- cell growth, differentiation, gene expression
- “storage hormone”, increases synthesis of glycogen, lipids, carbs and protein while inhibiting their breakdown
- Insulin reduces glucose output by the liver
Insulin activates what transporter? and what does the activation result in?
- GLUT4
- Promotes uptake of glucose by skeletal muscles and adipose tissue
What is Insulin used for in a medical setting? and what do we measure?
- Treat DM
- Measure the effects of insulin to increase cellular uptake of glucose
An increased expression of glucose transport proteins allows for what?
Cellular use of glucose for energy
What is seen when a DM pt is treated with insulin?
Decrease in blood/plasma glucose concentration
What are the 2 indications for the laboratory assessment of hemoglobin glycosylation A1c?
- Diagnosis of DM
- Glycemic goals for DM pts
What are glycemic goals for DM pt decided?
- Clinicians + patients determine a specific A1c goal for each pt.
- Want a realistic goal: don’t want pt to drop to hypoglycemia
What does the A1c measure and how often should it be rechecked?
- Approximated average of glycemia over the previous 3 mos
- Should be re-checked every 3 mos
