Pharm 38 - Adrenal, Thyroid, Pancreas Flashcards
Identify the three main steroid products of the adrenals
- Cortisol - aka hydrocortisone
- Aldosterone - Primary mineralocorticoid
- Androgens (DHEA, DHEA-S, androsterone)
- primary physiologic glucocorticoid
- primary mineralocorticoid hormones
(name the primary pharmacologic congener of each)
- Primary physiologic glucocorticoid: Cortisol (pharmacologic congener: hydrocortisone)
- Mineralocorticoid hormone: aldosterone (pharmacologic congener: aldosterone)
Primary drug to treat Addison’s disease
hydrocortisone
Drug to treat Addison’s disease related HTN
Fludrocortisone
Dosing regiment to treat Addison’s
a. Dosing regimen involves trying to mimic the body’s normal physiologic levels and patterns of glucocorticoid secretion
i. Need low levels at bedtime
ii. Highest levels 1-2 hours before waking
iii. Fluctuates up and down throughout the day
iv. Stressful events: Require doubling of the dosages
Thus: give 2/3 of dose in AM and 1/3 at HS
Addison’s disease dosing adjustments need to occur…
- During:
- stressful events
- sickness
- emotional stressors
Of the thyroid hormones, which is physiologically active?
Physiologically inactive?
Active: T3
Inactive: T4
Of the thyroid hormones, which is more abundant?
Less abundant?
More abundant: T3
Less abundant: T4
1/2 life of T3
one day
1/2 life of T4
seven days
drug used in combo with levothyroxine for individuals that do not convert T4 to T3 very well
liothyronine
also never used alone for thyroid supplementation
PREFERRED thyroid supplement in patients
Levothyroxine
Thyroid drug that is not as active as liothyronine
Levothyroxine
thyroid drug converted to T3 in peripheral circulation
Levothyroxine
Levothyroxine 1/2 life
5 to 7 days
Two goals of HYPERthyroidism treatment
- Goal one: suppress thyroid hormone synthesis
2. Goal two: suppress the beta adrenergic symptoms seen in hyperthyroidism
How is goal 1 of HYPERthyroidism treatment handled?
Thyroid hormone suppression is achieved through the pharmacologic agent propylthiouracil (PTU).
Propylthiouracil (PTU) is what kind of a drug
thyroid synthesis inhibitor
Propylthiouracil (PTU):
1/2 life / dosing
short 1/2 life that requires TID dosing
Propylthiouracil (PTU): full benefits are acheived…
in 6 to 12 months
How is goal 2 of HYPERthyroidism treatment handled?
Beta blockers! They stop the beta adrenergic symptoms that are seen with hyperthyroidism.
Describe the role of beta-blockers for symptomatic treatment of HYPERthyroidism.
They prevent the beta adrenergic symptoms that are seen with hyperthyroidism.
Symptoms controlled include: tachycardia, tremor, anxiety, other symptoms.
Drug of choice for symptomatic treatment of HYPERthyroidism
propanolol
labetalol
metoprolol
Role of beta-blockers for symptomatic treatment of HYPERthyroidism and PREGNANCY:
- duration of dose
- drugs of choice
a. Short term or occasional use is okay during pregnancy
i. Do not want to use in long term pregnancy HTN control
b. Long term use is associated with growth retardation
c. drugs: labetalol, metoprolol
Describe the particular importance and reason to screen for and closely monitor HYPOthyroidism during pregnancy.
a. In first trimester
i. Can result in permanent neuropsychologic deficits in the child
ii. Thyroid hormone production generally increases during pregnancy in response to hcg
Describe potential concerns with thyroid synthesis inhibitors during pregnancy.
Category D for pregnancy: readily cross the placenta.
thyroid synthesis inhibitors
methimazole
propylthiouracil (PTU)
methimazole and pregnancy
- what’s it cause?
- when to use?
- What’s it cause: Fetal abnormalities
2. drug of choice for hyperthyroidism during second and third trimesters
PTU and pregnancy
- what’s it cause?
- when to use?
- Liver toxicity
- Drug of choice for hyperthyroidism during or just prior to first trimester of pregnancy. Also used to treat thyroid storm in pregnant women.
Most notorious drug for causing thyroid disorders
amiodarone: causes:
- Hyperthyroidism: May increase synthesis and release of thyroid hormone
- Hypothyroidism: Esp. in patients with preexisting thyroid disease
amiodarone drug class
Class III anti-dysrhythmic:
- K+ channel blocker
- blocks Na+, Ca++
- blocks adrenergic alpha and beta receptors
Other drugs that cause thyroid disorders
- GI drugs: ones that alter cations/bind to things in the GI tract (acid suppressants, acid neutralizers, sucralfate)
- Lithium (painless thyroiditis)
- warfarin
Alpha cells of the pancreas (20% of islet mass) secrete (2)
glucagon*
proglucagon
Beta cells of the pancreas (70-75% of islet mass) secrete (4)
insulin*
C-peptide
proinsulin
amylin
Amylin is co-secreted with ___ from the ___ cells as well
Amylin is co-secreted with insulin from the beta cell as well
Delta cells of the pancreas (3-5% of islet mass) secrete
somatostatin
Somatostatin causes
widespread inhibition of endocrine and exocrine functions of the pancreas, gallbladder, and gut
- When somatostatin is released from the hypothalamus, it inhibits growth hormone and TSH - Inhibits LH, PTH, calcitonin, serotonin
When released by the pancreatic delta cells, somatostatin functions to…
Regulate secretion from alpha and beta pancreatic cells to stop their secretory functions.
This inhibits the release of gastrin and histamine secretion from the G cells in the stomach to slow/stop digestion when the gastric pH is < 2
G cells of the pancreas (1% of islet mass) secrete
gastrin
F cells of the pancreas (1% of islet mass) secrete
pancreatic polypeptides that are used as a tumor marker to diagnose/monitor pancreatic endocrine tumors
L cells of the intestines secrete
proglucagon (a glucagon-like peptide) that becomes a glucagon-like peptide “GLP” that is used for T2DM treatment
7 steps to insulin secretion and how the beta cell acts as a glucose sensor
1) Increased blood glucose enters the beta cell
2) The beta cell metabolizes this glucose to create ATP
a) This causes a rise in the ratio of ATP : ADP
3) The increased ratio causes inactivation of the K+ channel
4) Depolarization of the cell membrane ensues and…
5) Ca2+ channels open and the cell is flooded with Ca2+
6) Intracellular Ca2+ levels increase
7) Increased Ca2+ levels lead to an exogenous release of insulin by the beta cell
Describe the release of glucagon by the alpha-cell, and how it acts as a counter-regulatory glucose sensor.
In low glucose levels:
1) ATP levels fall in the alpha cell
2) K+ gated channels CLOSE
3) Cell membrane depolarizes
4) Ca2+ channels open and the cell is flooded with Ca2+
5) Cells exocytosis the stored glucagon granules to provide energy to the body
Basal physiologic serum insulin levels
1) Even when fasting, insulin is secreted around the clock at low levels
a) Results in a low plasma insulin concentration
Prandial physiologic serum insulin levels
ii. During a meal, there is a sudden increase in glucose that stimulates a surge of insulin 10+ times it’s basal level
1) This occurs in 3-5 minutes
2) Insulin levels start to decrease after about ten minutes
3) 15 - 20 minutes post prandial, if glucose levels continue to rise, insulin levels start to increase again parabolically
What does insulin do in the body?
Insulin functions in fatty acid synthesis, protein synthesis, glycogen synthesis, cell growth and survival, and amino acid and electrolyte transport
Insulin effects on the liver
i) Allows for storage of glucose as glycogen
ii) Excess glucose is converted into fatty acids
Insulin effects on the muscle
i) Muscles cannot use glucose without insulin
ii) Insulin is necessary for entry of glucose into muscles
Insulin effects on adipose tissue
Converts glucose to glycerol for use with triglycerides
Effects of insulin deficiency on fatty acid metabolism
1) Adipose tissue lipase is activated and increases levels of free fatty acids in the plasma
a) These are used for cellular energy
b) Also functions to increase cholesterol and triglyceride synthesis in the liver
c) Excess free fatty acid breakdown
i) Leads to ketones and ketoacidosis
Effects of insulin deficiency on protein metabolism
1) Protein synthesis stops, catabolism of proteins increases, and plasma amino acid levels increase
2) Excess AAs are burned for energy or used for gluconeogenesis
3) Urea levels increase in the urine
4) Muscle wasting, weakness, and organ dysfunction can follow
A1C indications (2)
i. Dx tool for DM
ii. Monitor DM patients glycemic goals
