2 - Endocrine Pharmacology Flashcards
What does a lack in iodine in the diet lead to?
Excessive secretion of TSH, resulting in thyroid hypertrophy which leads to a goiter
What is considered primary vs secondary hypo/hyperthyroidism?
- Primary - disease of thyroid gland
- Secondary - disease of pituitary or hypothalamus gland
What are the 2 synthetic thyroid preparations made by industry?
- Sodium levothroxine (T4 = Synthroid, Levoxyl)
- Sodium liothyronine (T3 = Cytomel) - oral absorption
What is the preferred drug for most cases of hypothyroidism?
Sodium levothyroxine (T4 = Synthroid, Levoxyl)
What is the use for sodium levothyroxine (T4 = Synthroid)? And how does it work?
- Replacement or supplement therapy in hypothyroidism
- Increases basal metabolic rate
What are the important adverse effects of sodium levothyroxine (T4 = Synthroid)?
- Indicates overdose = hyperthyroidism
- Palpitations, tachycardia
- Nervousness, sweating
- Increased appetite
- Weight loss
What is propylthiouracil?
“PTU” - a palliative treatment of hyperthyroidism in preparation for surgery or radioactive iodine therapy, management of thyrotoxic crisis
What drug blocks iodination reaction (blocks oxidation of iodine) in thyroid gland, and blocks synthesis of T4 and T3?
PTU - propylthiouracil
What are the side effects of PTU?
- Skin rash
- Nausea
- Agranulocytosis
What does methimazole (Tapazole) do?
- Palliative treatment of hyperthyroidism, returns patient to a normal metabolic state prior to thyroidectomy, control thyrotoxic crisis that may accompany thyroidectomy
- It blocks iodination reaction in thryoid gland, blocks iodine’s ability to combine with tyrosine to form T3 and T4
Why is methimazole (Tapazole) an undesirable drug?
- Expensive
- Inconvenient
- Adverse effects (fever, rash, hematologic disorders)
What is the process of taking Radioactive Iodine I 131?
- Patient swallows iodine “tagged” with radioactive nucleotide
- Drug binds to iodine receptors and slowly irradiates and destroys thyroid gland (< 3 months)
What are some dental considerations of patients with hypothyroidism?
- Easier from management perspective (than hyper)
- Cold, tired/fatigued
- More sensitive to CNS depressents, need to lower dose = sedatives, opiods
What is absolutly contraindicated in patients with active disease of hyperthyroidism?
Epinephrine
What are the dental considerations of patients with hyperthyroidism?
- Nervous, increased BP
- Palpitations and tachycardia
- May percieve more pain
- Less sensitive to CNS depressants, may require higher dose of pain meds and sedatives
- May be mis-labeled as having “drug-seeking” behaviors
What disease results from autoimmune destruction of pancreatic beta cells? And what is the only effective drug in treating this disease?
- Type 1 Diabetes
- Insulin
How was insulin previously prepared and how is it available today?
- Previously - bovine (cows) and porcine (pigs)
- Now - human-type insulin (recombinant technology)
How is insulin classified?
3 ways:
- Onset
- Peak
- Duration of action
Name the short-acting insulin preparations.
insulin Regular (Humulin R)
Name the rapid-acting insulin preparations.
- insulin Aspart (NovoLOG)
- insulin Glulisine (Apidra, Apidra Solostar)
- insulin Lispro (HumaLOG)
Name the intermediate acting insulin preparations.
- insulin NPH (HumuLIN, NovoLIN N)
Name the intermediate to long-acting insulin preparations.
- insulin Detemir (Levemir)
Name the long-acting insulin preparations.
- insulin Glargine (Lantus, Lantus Solostar)
What is the big risk for oral drug therapy for management of Type 2 Diabetes?
Hypoglycemia
What are the primary drug classes for oral drugs used in treatment of type 2 diabetes?
“BATSI”
- Biguanides (metformin)
- Alpha-glucosidase inhibitors
- Thiazolidinediones (TZDs)
- Sulfonylureas (“traditional” oral hypoglycemics)
- Incretins - GLP-1 agonists, DDP-4 inhibitors
What type of primary oral drugs for type 2 diabetes are newer (2nd generation) that are more potent but not more effective?
Sulfonylureas
What are the 1st generation sulfonylureas?
All end in “amide”
- tolbutamide (Orinase) ** oldest in class
- tolazamide (Tolinase)
- acetoheamide (Dymelor)
- chlorpropramide (Diabinese)
What are the 2nd generation sulfonylureas?
all end in “ide”
- glypizide (Glucotrol) **
- glyburide (Diabeta, Glynase, PresTab, Micronase)
10 to 100 times more potent than 1st generation
What is the major distinction between 1st gen and 2nd gen sulfonylureas?
Potency - 2nd is way more potent that 1st
What are the warnings with sulfonylureas?
- Increased cardiac mortality
- Sulfonamide allergy - contraindicated
- Caution with use if severe hepatic disease
What is a serious drug interaction with sulfonylureas?
Aspirin - it may enhance the hypoglycemic response to the sulfonylurea
= Hypoglycemia
What are the 2 mechanisms taking aspirin with sulfonylureas can cause hypoglycemia?
- Aspirin displaces the sulfonylurea from plasma proteins causing increased blood levels of sulfonylurea
- Salicylate inhibition PGE increases the insulin response and enhances the response to sulfonylureas
What is the most popular drug for Type 2 Diabetes? And what class of drug is it?
- metformin (Glucophage)
- Biguanide
What are the characteristics of metformin (Glucophage)?
- Inhibits absorption of glucose from the gut
- Decreases hepatic glucose production
- Increases insulin sensitivity at receptor sites
- Increases peripheral glucose uptake and utilization
What are the benefits of metformin?
- More effective for reducing glycemic level
- No weight gain
- Reduces all-cause and cardiovascular mortality
- **Reduces rates of cancer **in patients with type 2 diabetes
What are the risks of taking metformin?
- Lactic acidosis if renal impairment
- Avoid alcohol - hepatic impairment, acute CHF
- Gastrointestinal side effects
What type of drugs inhibit an enzyme responsible for degrading complex carbs in the gut? And what are the preparations of this drug?
- Alpha-glucosidase inhibitors
- acarbose (Precose)
- miglitol (Glyset)
** There is a delay in blood glucose concentrations after a meal when taking these drugs **
How do thiazolidinediones work?
- Lower blood glucose by improving target cell response to insulin without increasing pancreatic insulin secretion
- Reduces insulin resistance
- Activity depends on the presence of insulin for activity
What are the common preparations of thiazolidinediones?
end with “zone”
- pioglitazone (Actos)
- rosiglitazone (Avandia)
What is rosigltiazone (Avanida) associated with (side effects)?
- >30 deaths due to liver failure**
- Increased risk of heart failure
- Contraindicated in pts with serious heart failure
What are the 2 types of incretin mimetics “Incretins”?
- GLP-1 receptor agonist (glucagonlike peptide -1)
- DPP-4 inhibitors - these drugs end in “liptin”
What is the “new” concern for the Incretins?
- That these drugs cause inflammation and possible pre-cancerous changes of pancreas
What is the nomal and fasting blood sugar ranges?
- Normal - 70-120 mg/dL
- Fasting - 70-110 mg/dL
What is the gold standard for measuring diabetes?
Glycataed Hemoglobin (HbA1c)
- Measures glycemic control for 6-12 weeks
- Normal <6%
- Diabetes diagnosis >6.5%
- Diabetics goal: <7%
What are the American College of Physicians clinical practice guidelines for diabetes?
- Add drug therapy when lifestyle changes fail to improve hyperglycemia
- Initial monotherapy with metformin (drug of choice)
- Add 2nd drug if hyperglycemia persists
What is a steroid produced and secreted by the ovary?
estradiol - natural estrogen
What is used for Estrogen Replacement Therapy (ERT)?
ethinyl estradiol - orally active
Up to the 1990’s only 2 benefits of hormone replacement therapy have been clinically proven, what are they?
- Hormones relieve menopausal symptoms
- Hormones stave off bone loss
What are the different Estrogen Replacement drugs (HRT)?
- _Conjugated equine estrogens _
- Premarin
- _Esterified estrogens _
- Estratab, Menest
-
Estradiol preps
- Estraderm, transdermal patch, Estraderm cream, Climara transdermal patch, Estrace cream
What conjugated equine estrogens are effective in treatment of vasomotor symptoms of menopause?
Premarin
What are some common side effects of Conjugated equine estrogens (Premarin)?
- Peripheral edema
- Breast tenderness
- Bloating
- Headache
What is one serious side effect noted in women with an intact uterus that take conjugated equine estrogens (Premarin)?
- Increased risk for endometrial (uterine) cancer
Taking estrogen (such as Premarin) after menopause may also increase risk for breast cancer
What drug has the same effects as Premarin at half the dose?
Esterified estrogens (Estratab, Menest)
What are combination drugs used for?
- Estrogen with progesterone (Prempro)
- Adding progesterone to the preparation reduces risk for endometrial cancer
In the HERS study, women taking estrogen for 4 years noticed what?
- Cholesterol levels went down
- Increases in blood clots
- No reduction in heart disease
What is the HRT current thinking?
- Estrogen in combination with progestin may increase risk of stroke
- This outweighs long term use to prevent osteoporosis
What are the risks of Prempro?
Increased risks of:
- Heart disease
- Stroke
- Pulmonary embolism
- Invasive breast cancer
What is hormone replacement therapy used for today?
- Short term use only = less than 5 years
- Treat symptoms of menopause
