PHCP-2_PRELIM-29-36.pdf

CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 LECTURE TOPIC 5: DISEASES OF THE THYROID PRELIMS Part 1 na natin sya with the use of thiocyanate, Thy...

CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 LECTURE TOPIC 5: DISEASES OF THE THYROID PRELIMS Part 1 na natin sya with the use of thiocyanate, Thyroid perchlorate, and pertechnetate (TcO4) Used for normalized Growth Once na Iodine na sya, it would be converted to Development thyroglobulins (kaya magpoproduce tayo ng ○ To regulate brain development MIT-DIT). Then via the action of iodide ○ Body and energy levels including organification, MIT and DIT will combine (MIT + metabolism. DIT = T3 and DIT + DIT = T4) Produces Hormones Once they are already produced in the thyroid ○ T3: triiodothyronine via proteolysis, it will deliver into the blood. Then ○ T4: tetraiodothyronine/thyroxine the T3 is readily used for body consumption T4:T3 ratio is 13:1 (utilized by the body). ○ Calcitonin However in order to use the T4, we need to For bone regulations (calcium) convert T4 into T3. ○ In peripheral tissues, T4 will be Iodine (element use to produce the thyroid converted into T3 via the enzymes hormone) 5-deiodinase in the process of ○ Main component of Thyroid hormone deiodination. Then it can be utilized by ○ RDI (recommended daily intake): the body (T3). 150mcg/day: ○ Commonly acquired from sea foods and For the medications: Iodized salt Iodides (Lugol’s solution and KI) will inhibit the FDA requirement of the Phil Iodide organification, kaya nagsstop tayo ○ Pregnant women: 200mcg/day RDI magproduce ng T3 and T4. Same lang din kapag nagbibigay ng thioamides (PTU and methimazole) Pathophysiology In peripheral tissues, Radiocontrast media (¹³¹I), ꞵ - blockers (w/o intrinsic sympathomimetic activity (e.g., propranolol)), corticosteroids, amiodarone, these examples will inhibit the conversion of T4 to T3 kapag nasa tissues sila. Sa part ng blood (T4,T3), nagkakaroon ng production ng dalawang T3: ○ 353 T3 – found in outer ring (active form) ○ 335 T3 – found in inner ring (inactive form) Iodide will enter the thyroid gland via sodium iodide symporter Once it enters the thyroid gland, it would be converted to iodine via the enzymes thyroidal peroxidase ○ Note: if the px has hyperthyroidism, all the steps above would inhibit. ○ E.g., sa NaI symporter palang, ini-inhibit A. Jacinto | M. Mendero 1  CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 LECTURE TOPIC 5: DISEASES OF THE THYROID PRELIMS ○ Destruction of thyroid cells, thyroglobulin, and thyroid peroxidase ○ No production of T3 and T4 ○ Hypothyroidism Grave’s disease ○ An autoimmune disorder ○ Produce lymphocyte (antibodies) against the TSH (gumagawa ng TSH antibodies) TSH antibodies will bind to receptor to release thyroid hormone Prolonged action, prolonged production of T4 and T3 Increased production of T4 and T3 ○ Hyperthyroidism ○ Note: TSH in the eyes = Ophthalmopathy If we experience cold, acute psychosis, or SKIN AND APPENDAGES maintain the circadian and pulsatile rhythm, or severe stress, our body releases thyroid THYROTOXICOSIS HYPOTHYROIDISM hormones. In order to do that, we need to (hyperthyroidism) inactivate the hypothalamus. ○ Hypothalamus will release thyroid Warm, moist skin; Pale, cool, puffy releasing hormone (TRH). Sweating; skin; ○ TRH will activate the Apical pituitary heat intolerance; dry and brittle gland (AP) fine, thin hair; hair; ○ If the AP is activated, it will release Plummer’s nails brittle nails thyroid stimulating hormone (TSH). Then (characterized by it will stimulate the thyroid to produce T4 Koilonychias and has and T3 onycholysis); Positive feedback (nagsusupply ng pretibial dermopathy kakulangan) (Graves’ disease) Negative feedback (sobra-sobra na yung DOC: corticosteroids pagproduce tapos magsisignaal na para maagstop sa paaggawa) Eyes, face Excess iodine: THYROTOXICOSIS HYPOTHYROIDISM Wolff chaikoff block (WCB) ○ There is large doses of iodide Retraction of upper lid Drooping of ○ It will inhibit the iodide organification (no with wide stare; eyelids (ptosis); production of T3 and T4) periorbital edema; periorbital edema Dysregulation of WCB Exophthalmos; loss of temporal ○ No inhibition of iodide organification, so diplopia (AKA double aspects of the iodide will become T3 and T4 vision) (Graves’ eyebrows; ○ Prone to hyperthyroidism disease puffy, nonpitting Hashimotos’s Thyroiditis facies; ○ An auto-immune disorder large tongue A. Jacinto | M. Mendero 2  CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 LECTURE TOPIC 5: DISEASES OF THE THYROID PRELIMS (macroglossa) bowel movements; decreased hypoproteinemia (low frequency of Cardiovascular system levels of protein) bowel ○ Warfarin is movements; THYROTOXICOSIS HYPOTHYROIDISM very protein ascites bound Decreased peripheral Increased (inactive) vascular resistance; peripheral ○ Prone to increased heart rate, vascular bleeding stroke volume (amount resistance; of blood being pump to decreased heart Central nervous system the aorta), cardiac rate, stroke output, pulse pressure; volume, cardiac THYROTOXICOSIS HYPOTHYROIDISM high output heart output, pulse failure; increased pressure; low Nervousness; Lethargy; general inotropic and output heart hyperkinesia; slowing of mental chronotropic effects; failure; emotional lability processes; Prone to arrhythmias ECG: neuropathies and angina bradycardia, DOC: propranolol – prolonged PR Musculoskeletal system decreased the oxygen interval, flat T requirement of the wave, low THYROTOXICOSIS HYPOTHYROIDISM heart, slow the heart voltage; Weakness and muscle Stiffness and rate; however, it is pericardial fatigue; increased muscle fatigue; contraindicated w/ px deep tendon reflexes; decreased deep having asthma so that hypercalcemia; tendon reflexes; give diltiazem osteoporosis increased alkaline (nondihydropyridine Prone to bone phosphatase (test CCB) to address the resorption – for bones), LDH, cardiotoxic effect of osteoporosis AST hyperthyroidism T4 - trigger bone Respiratory system eroding capacity of osteoclast THYROTOXICOSIS HYPOTHYROIDISM ○ Destruction of bones Dyspnea; decreased Pleural effusions ○ Inc of Calcium vital capacity (fluid in the lungs); Renal system hypoventilation and CO2 THYROTOXICOSIS HYPOTHYROIDISM retention Mild polyuria; Impaired water hypercapnia increased renal blood excretion; Gastrointestinal system flow; increased decreased renal glomerular filtration blood flow; THYROTOXICOSIS HYPOTHYROIDISM rate Decreased glomerular Increased appetite; Decreased filtration rate increased frequency of appetite; A. 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Mendero 3  CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 LECTURE TOPIC 5: DISEASES OF THE THYROID PRELIMS Hematopoietic system increased free fatty degradation of acids; insulin with THYROTOXICOSIS HYPOTHYROIDISM decreased cholesterol increased and triglycerides; sensitivity; Increased Decreased increased hormone increased erythropoiesis; erythropoiesis; degradation; cholesterol and The anemia of anemia increased triglycerides; hyperthyroidism is The anemia of requirements for fat- decreased usually normochromic hypothyroidism and water-soluble hormone and caused by may be vitamins; degradation; increased red blood normochromic, increased drug decreased cell turnover hyperchromic, or metabolism; decreased requirements for hypochromic and warfarin requirement fat- and may be due to water-soluble decreased vitamins; production rate, decreased drug decreased iron metabolism; absorption, increased decreased folic warfarin acid absorption, requirement or to autoimmune pernicious anemia Part 2 Reproductive system Thyroid preparations (Medications/Therapies) THYROTOXICOSIS HYPOTHYROIDISM Synthetic Menstrual Hypermenorrhea Levothyroxine, Liothyronine, Liotrix irregularities; (laging may Bad for the tx of obesity decreased fertility; menstruation); Levothyroxine (T4) increased gonadal infertility; ○ DOC for thyroid replacement and steroid metabolism decreased libido; suppression Therapy Impotence; ○ Half life: long (1½) that is usually 7 Oligospermia (low days production of ○ Given once daily sperm); Liothyronine (T3) decreased ○ Half life: 24h T½ (shorter) gonadal steroid ○ Not recommended for routine therapy metabolism ○ greater risk for cardiotoxicity. ○ Best for short-term suppression of Metabolic system TSH (Thyroid Stimulating Hormone) Liotrix (combination of T4 & T3) THYROTOXICOSIS HYPOTHYROIDISM ○ Ratio of 4:1 (4 yung T4, 1 yung T3) Increased basal Decreased basal Shelf life of this medication is 2 years metabolic rate; metabolic rate; Store in dark bottles to decrease negative nitrogen slight positive deionization balance; nitrogen balance; Hyperglycemia; delayed A. Jacinto | M. Mendero 4  CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 LECTURE TOPIC 5: DISEASES OF THE THYROID PRELIMS Thioamides hyperthyroidism MOA: inhibits thyroid peroxidase and blocks ○ Eg., amiodarone-induced organification hyperthyroidism Methimazole and Propylthiouracil (PTU) ○ ADR: Aplastic anemia ○ This medication is for Thyrotoxicosis ○ Carbimazole (drug that converts into methimazole): in vivo it becomes Iodides methimazole Inhibit organification and hormone release of T4 Fatal ADR of Thioamides: Agranulocytosis & T3. Reduce the size and vascularity of the glands Methimazole Use: for preparation in surgical ○ 10x more potent than PTU thyroidectomy (removal of thyroid gland) ○ DOC for adults & children Ex.: Lugol's solution & Potassium Iodide. ○ ADR: Cholestatic Jaundice. Propylthiouracil (PTU) Radioactive lodine (¹³¹I) ○ Has blackbox warning, which is only isotope for thyrotoxicosis severe hepatitis Oral in a form of Na ¹³¹I ○ Reserved for 1st trimester pregnancy, MOA: emit ꞵ rays thyroid storm, and px w/ ADR from Half life: W/ 5 days T½ methimazole Penetration range: 400-2000μm ○ Can be used as rectal enema Note: Should not be administered to pregnant or nursing mothers Anion inhibitors ○ It may cross the placenta or in breast monovalent anions milk) Perchlorate (C104), Pertechnetate (TcO4), ○ It destroys the infant's thyroid gland. thiocyanate (SCN) MOA: block uptake of Iodide through Beta blockers competitive inhibition of iodide transport Propranolol (usually given) Problem: unpredictable effectiveness or erratic ○ Does not have intrinsic ○ Hindi madalas ginagamit sympathomimetic activity ○ Adjunct effect: Thyroid storm; HTN, Potassium perchlorate tachycardia, AFib (Atrial Fibrillation) ○ Blocks the thyroidal uptake of iodine, especially in px w/ Iodine induced Types of hypothyroidism Cause Pathogenesis Goiter Degree of hypothyroidism Hashimoto’s thyroiditis Autoimmune destruction of Present early, absent later Mild to severe thyroid Drug-induced Blocked hormone formation Present Mild to moderate Dyshormonogenesis Impaired synthesis of T4 Present Mild to severe due to enzyme deficiency (peroxidase or proteolysis) Radiation, ¹³¹I, x-ray, Destruction or removal of Absent Severe (forever taking thyroidectomy gland levothyroxine or any thyroid A. 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Mendero 5  CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 LECTURE TOPIC 5: DISEASES OF THE THYROID PRELIMS supplement) Congenital (cretinism) Athyreosis or ectopic Absent or present Severe - Has mental thyroid, iodine deficiency, retardation (baby) TSH receptor blocking antibodies Secondary (TSH deficit) Pituitary (does not release Absent Mild TSH) or hypothalamic disease Management Levothyroxine Hyperthyroidism Myxedema coma – end state of untreated Grave's disease: autoimmune disease that hypothyroidism stimulates antibodies to thyroidal antigen ○ Symptoms are: (TSH-R Ab) Weakness ○ TSH-R Ab – acts on TSH receptors Stupor which increases the production of T4 & Hyponatremia T3 Hypoventilation ○ most common form of hyperthyroidism: Hypoglycemia AKA diffuse toxic goiter Hypothermia ○ Lab Test: Water intoxication Test the T3, T4, FT3, FT4 Shock and death This is all elevated, but the TSH ○ Considered as medical emergency is suppressed ○ Medication: Presence of anti-thyroglobulin, Supplied as IV (be careful when thyroid peroxidase, TSH-R AB administering an IV to avoid ○ Management: excessive water intake) Give Methimazole & PTU or Loading dose: 300-400 mcg Thyroidectomy (DOC for Levothyroxine patients with very large gland or After Loading dose: 50-100 multinodular goiter) mcg regular dose Px will be on replacement therapy Hypothyroidism in pregnancy (give levothyroxine) An increase of 30-50% thyroxine dose is RAI (Radioactive Iodine) required to normalize the TSH level during Cause destruction of pregnancy. thyroid gland Tx for px over 21 years Subclinical hypothyroidism old elevated TSH and normal thyroid hormone level Contraindicated to Given if: Thyroid hormone therapy for TSH pregnant / nursing >10mIU/L mothers ○ Adjunct therapy: Drug induced hypothyroidism Give propranolol for Give levothyroxine if the drug cannot stop the tachycardia, HTN, AFib hypothyroidism If propranolol is contraindicated: Amiodarone Induced hypothyroidism give Diltiazem ○ Levothyroxine is continually given due to Vitamins (essential) long T1⁄2 of amiodarone A. 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Mendero 6  CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 LECTURE TOPIC 5: DISEASES OF THE THYROID PRELIMS Bile acid sequestrant (BAS) If the px cannot take it orally (e.g., colestipol, cholestyramine, give 400 mg q6h via rectal colesevelam) enema (make a solution colestipol, wherein dissolved the 50 mg tab cholestyramine – most into 90ml H₂0) common ○ If di pwede si PTU give methimazole 60 Colesevelam – has a mg OD rectally lesser affinity on T4 ○ Hydrocortisone 50 mg IV q6h Barbiturates (BARB) It blocks T4-T3 conversion and BAS & BARB can help protect against shock lower T4 Ophthalmopathy Toxic uninodular goiter (TUG) and toxic Rare and difficult to treat mononodular goiter (TMG) Tx: Often seen in women with nodular goiter. ○ Total surgical excision of the thyroid Lab: FT4 is moderately elevated or normal but gland T3 or FT3 is elevated ○ Short course prednisone can be given Management: RAI or Thyroidectomy for severe acute inflammation TMG: associated w/ large goiter ○ Give methimazole or PTU followed by Dermopathy / Pretibial myxedema Subtotal Thyroidectomy. Tx: corticosteroids on the affected area Subacute thyroiditis Thyrotoxicosis during pregnancy Caused by viral infections wherein there's a Tx: destruction of thyroid parenchyma ○ Note: don't use RAI transient release of stored thyroid hormones, it ○ Give PTU at minimum dose is called “spontaneously resolving (