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22 terms

Pharmacology Thyroid + Insulin 231

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Thyroid Hormone Regulation +negative feedback
Hypothalamus release-> Thyrotropin Releasing Hormone (TRH) -> anterior pituitary
Anterior pituitary release ->Thyrotropin/Thyroid Stimulating Hormone (TSH) -> thyroid
Thyroid release -> T3 & T4
Negative Feedback -> T3 and T4 on anterior pituitary
T3 & T4
T3 is more potent, but T4 is excreted more from the thyroid
Both transported in plasma by thyroxine-binding globlin (TBG)
Half-life: 6 - 7 days due to binding (extends half-life)
T4 converted to T3 in cell -> T3 enters nucleus
Effects of Thyroid Hormones (3 main)
Development and growth:
-important for brain development
Calorigenic effect:
- increase oxygen consumption (makes you skinny)
Cardiac Effects:
-increases heartrate --mimics sympathetic N.S.
Hasimoto's thyroiditis
Most common form of hypothyroidism
Leads to:
-impairment of growth
-mental retardation (in children)
-weight gain
-fatigue
-cold intolerance
Infantile Cretinism
hypothyroidism in prenatal to 3 months old
-mental retardation, deaf, mute, dwarfism, poor thermoregulation

-can be prevented if detected early
Myxedema
advanced hypothyroidism in adults characterized by sluggishness, slow pulse, puffiness in the hands and face, and dry skin (myx = mucous)
Can lead to coma
Hypothyroidism Treatment (3 drugs)
-essentially hormone replacement
Levothyroxine (L-T4) - analogue of T4
- first-line therapy, long half-life (slow onset)
-dosage and adjustment: start low and go slow
Liothyronine (L-T3) - analogue of T3
- more potent and faster onset (4-8 hours)
Liotrix (Combination of L-T4 and L-T3)
Hyperthyroidism
-Increased metabolism (weight loss)
-skin is flushed
- Increased apetite
- tachycardia, hypertension and tremor
Graves' Disease
the most common form of hyperthyroidism; caused by an autoimmune defect that creates antibodies that stimulate the overproduction of thyroid hormones; exophthalmos (bulging eyes) is a featured characteristic
Treatment:
antithyroid drug therapy (radioactive iodide) and thyroidectemy.
Thyroid Storm
Crisis Alert!!!
Hypermetabolism and increased sympathetic signaling.
essentially all the symptoms of hyperthyroidism at once
treatment with antithyroid drugs and symptomatic use of beta-blockers. These go against the sympathetic signaling
Anti-thyroid drugs
Thioamides
Methimazole and Propylthiouracil
MOA: Inhibition of thyroid peroxidase to decrease organification- stops the formation of T3 and T4
-does not effect T3 and T4 that have already been made - so onset of action may be 3-4 weeks.
Toxicity: itchy rash, fever
Anti-thyroid drugs
Anions
Perchlorate (ClO4-)
Pertechnetate (TcO4-)
Thiocyanate (SCN-)
MOA: Competitive inhibition of I- uptake into the thyroid - inhibition of organification
Fast onset (2 days)
Anti-thyroid drugs
Radioactive iodine
sodium-131-iodine
MOA: emits beta particle radiation, slowly destroying the thyroid tissue
Diabetes
Type 1
aka - insulin-dependant diabetes mellitus (IDDM)
-Juvenille onset, due to destruction of beta cells (that produce insulin)
-Absence of insulin results in catabolism
Treat by giving insulin
Diabetes
Type 2
Tissue insensitivity to insulin
-obesity
treatment: sulfonylureas (enhance insulin secretion), Glitinides (enhance insulin secretion), biguanides (sensitizes cells to insulin), thiazolidinedione (sensitizes cells to insulin)
Insulin effects
Liver: stimulates glycogen synthase activity, increases glucose uptake, inhibits glycogen phosphorylase, and inhibits gluconeogenesis
Muscle: promotes protein synthesis, and glycogen synthesis
Adipose Tissue: promotes triglyceride deposition, reduces circulating free fatty acids, and reduces intracellular lipolysis
Insulin Preparations
(regular, Neil Patrick Harris and lente)
all given parenterally
Crystallin zinc insuling (regular insulin)
-fast onset (minutes), fast duration of action (8-12 hours)
NPH insulin (neutral protamine Hagedorn)
-Onset (1-2 hrs) duration (18-24)
Combination Regular and NPH
-used to imitate regular insulin release (which has two phases: fast and slow release)
Lente: onset (2.5 hrs), duration (22 hrs)
ultralente: onset (4 hrs), duration (28 hrs)
Insulin analogues
all given parenterally
Insulin Lispro & Insulin Aspart:
Very fast onset (30-45 min) and very short duration of action (3-5 hrs). Good for taking before meals
Insulin Glargine:
for basal level of insulin - not for meals
Sulfonylureas
MOA: Enhances insulin secretion
First-Generation
Tolbutamide: Short duration of action (safest)
Chlorpropamide: Longer duration of action (not as safe)
Second-Generation
More potent
Glyburide, glipizide, glimepiride
ADR:
Nausea and vomiting, flushing/alcohol intolerance, hypoglycemia
Glitinides
Repaglinide, nateglinide

MOA: Enhance insulin secretion - just like sulfonylureas
unlike sulfonylureas, short duration of action which decreases the chance of hypoglycemia
Biguanides
Metformin, butformin, phentformin
MOA: reduces gluconeogenesis from liver, decrease glucose absorption in gut, increased sensitivity of cells to insulin
First Line therapy for Type II diabetes
Does not cause hypoglycemia because it does not effect insulin itself
Thiazolidinedione derivatives
Rosiglitazone, pioglitazone
MOA: agonist of PPAR gamma
increases sensitivity to insulin, increase glucose uptake in muscle of fat tissue, reduces hepatic glucose output
ADR: cardiotoxicity, weight gain, heart problems in general