1

ANTI-THYROID DRUGS Dra. Reyes Autoregulation of the Thyroid Gland

thyroid gland can regulate itself independent from
Evaluation of Thyroid Function Test hypothalamus and ant. pituitary
Wollf-Chaikoff block
1. Thyroid-pituitary relationships - Large doses of iodine inhibit iodide
2. Autoregulation of thyroid gland organification
3. Abnormal thyroid stimulators - Iodine control the thyroid
- Low iodide increase uptake
Hypothalamus- Pituitary-Thyroid Relationship - High iodide uptake stops; iodide
trapping saturation
Hypothalamus release releasing
Abnormal Thyroid Stimulators
hormones(TRH) (+) anterior pituitary to release
TSH-R Ab [stim] or TSI (Graves Disease)
TSH(+) peripheral gland (thyroid) AB work against the TSH receptors stimulates
Increase T4 (thyroid feedback mechanism the thyroid receptors hyperthyroidism not
Long loop negative feedback from thyroid to regulated by increase iodine
hypothalamus
Short loop negative feedback from ant.pit. to
hypothalamus Hyperthyroidism (Thyrotoxicosis)
- Graves Disease (cause by TSH like
Hypothalamus-Pituitary-Thyroid Relationships receptor)
Uptake of iodide by the follicles - Toxic uninodular goiter and toxic
Synthesis and secretion of thyroglobulin multinodular goiter
Generation of hydrogen peroxide and iodination - Subacute thyroiditis cause by
of tyrosine - Thyrotoxicosis factitia virus
Endocytosis and proteolysis of thyroglobulin - Thyroid storm facilitates drug induced
Secretion of serum T3 and T4 hyperthyroidism
Blood flow through the gland Hypothyroidism
Transcription of thyroperoxidase and - Myxedema
thyroglobulin genes - Cretinism
- Hashimotos thyroiditis
Thyroid Physiology Simple, Non-toxic Goiter
Thyroid follicle - Iodine deficiency
- Iodide trapping
- Iodination of tyrosine residues Test Hypothyroidism Hyperthyroidism
- Proteolysis of thyroglobulin release of T3 T4 Low High
and t4 T3 Normal or Low High
TBG FT4 Low High
- CHON transports T4 to target organs FT3 Low High
- T4 detached from TBG and enter the cell TSH High Low
deiodination acted upon by iodinase 123I uptake at

enzyme iodine prodn 24 hrs Low High

Tg-ab Often present Usually absent
Peripheral Metabolism of Thyroxine TPA Often present Usually absent
Deiodination of T4 inhibited by:
- Iodate BASIC PHARMACOLOGY OF THYROID DRUGS
- beta blockers Thyroid Hormones
- corticosteroids Antithyroids
- severe illness
- starvation Thyroid Hormone Kinetics

T3 biologically active Variable T4 T3

rT3 inactive form Volume of 10L 40L
distribution
Extrathyroidal 800mcg 54mcg
pool
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Daily 75mcg 25mcg TH Receptors

production Spleen
Fractional Testis
turnover per 10% 60%
day - core processes gene expression
Metabolic - hormone binds disruption of dimer
clearance per 1.1L 24L activation of receptor RNA polymerase
day transcription mRNA
Half-life 7 days 1 day Effects of Thyroid Hormones
(biologic)
Serum levels Metabolism
Total 4.8-10.4 79-149 ng/dL Important for growth and maturation of the CNS
mcg/dL (1.2-2.3 Modulates the action of catecholamines, cortisol,
(62-134 nmol/L) estrogen, testosterone, insulin, and glucagon
nmol/L) Important in skeletal and reproductive system
Free 0.7-1.86 ng/dL 145-348 Hyperthyroid (CNS effect) hyperkinesias
(9-24 pmol/L) pg/dL - Up regulation of catecholamine receptors
(2.2-5.4 effect is greater hyperthyroidism
pmol/L) saturated sympathetic effects
Amount bound 99.96% 99.6% - Hyperthyroidism insulin resistance
Biologic 1 4 - Hypothyroidism decrease resistance to
potency insulin
Oral 80% 95% Increase in the metabolism of carbohydrates, fats,
absorption and proteins
Increase metabolism of cholesterol to bile acid
*volume distribution amount of drug going to the tissue Hypothyroid
Increase T3 in tissue because T4 is converted to o Hypercholesterolemia, decreased
T3 absorption of glucose from the GUT,
decreased insulin secretion
T3 easily metabolized
T4 is synthesize more increase serum T4 Thyrotoxicosis
Best absorb in duodenum and ileum o Insulin resistant state
Shelf life (expiry) 2-3 years
Growth and Development
Mechanism of Action Potentiation, secretion and action of growth
hormone
T4 Essential for normal response to parathormone
(5-deiodinase) and calcitonin, and skeletal development
T3
Cardiovascular Effects
T3 bind to receptors associated with DNA in the nucleus Increase HR, increase SV, increase pulse pressure,
decrease vascular resistance
activate transcription Increase oxygen consumption and heat
production
generate mRNA and protein synthesis
Renal Effects
Increase growth ( increase GH transcription and Increase renal blood flow, increase GFR, increase
induction of anabolic enzymes) urine output
T3 more potent; the one acting on the receptor **(+) Na+ K+ ATPase Pump increase temperature

TH receptors
Pituitary THYROID PREPARATIONS
Liver
Kidney Adverse Effect: Hyperthyroidism
Heart
Intestine In children:
Restlessness

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Insomnia Induction of thyroid hormone Iodides

Accelerated bone maturation and growth synthesis or release with (Amiodarone)
In adults: induction of hypothyroidism or Lithium
Increased nervousness occasionally hyperthyroidism Aminogluthemide
Heat intolerance Thioamides
Episodes of palpitations Ethionamide
Tachycardia
Unexplained weight loss
In older patients:
Increases the risk for atrial fibrillation
Osteoporosis Drug Effect Drugs
Alteration of Thyroid Hormone Transport and
Synthetic Preparations Serum Total T3 and T4 Levels, No Modification
Levothyroxine (T4) of FT4 or TSH
Liothyronine (T3) Increased TBG Estrogen
Liotrix (T4:T3) Tamoxifen
Heroin
Animal Origin Methadone
Desiccated Thyroid Mitotane
Fluorouracil
Comparison Between Thyroid Preparations Decreased TBG Androgens
Glucocorticoids
Parameters Synthetic 1Liotrix, Displacement of T3 and T4 from Salicylates
(Levothyroxine) Liothyronine, TBG with transient Fenclofenac
2Dessicated hyperthyroxinemia Mefenamic
Thyroid *** displace T3/T4 acid
Potency Lesser Greater (3-4x) exacerbates hyperthyroidism Furosemide
1
Stable Yes No Induction of increase hepatic enzyme activity
Cost Low Low 2 Nicardipine
Hormone Imatinib
content or Uniform Variable 2 Protease inhibitors
concentration
Allergenic Drug Effect Drugs
foreign protein Absent Present 2 Other Interactions
Laboratory Interference with T4 Cholestyramine
measurement Easy Difficult 1/2 absorption Colestipol
of serum levels Chromium
Half-life Longer (7days) Shorter picolinate
(24hrs) 1 Ciprofloxacin
Adverse Lesser Greater risk PPI
effects for Sucralfate
cardiotoxicity AlOH
2 Sodium
polystyrene
Drug Interactions sulfonate
Raloxifene
Drug Effect Drugs SevelamerHCl
Change in Thyroid Hormone Synthesis Ferrous sulfate
Inhibition of TRH or TSH Dopamine Calcium
secretion Levodopa carbonate
Hypothyroidism or Corticosteroids Bran, soy, coffee
Hyperthyroidism Somatostatin Drug Effect Drugs
Metformin Effect of Thyroid Function on Drug Effects
Bexarotene Anticoagulation Warfarin
- lower doses in
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hyperthyroidism Dose Adjustment in Women who:

- higher doses in 1. Became pregnant
hypothyroidism 2. Begin estrogen therapy
Glucose control Increased hepatic 3. Take oral contraceptives
production and glucose
intolerance -increase protein binding of T4 to TBG
- hyperthyroidism
Increased insulin action and Antithyroids Drug Action
glucose disposal Iodide uptake
- hypothyroidism Iodination iodides, thioamides

Drug Effect Drugs

Effect of Thyroid Function on Drug Effects THIOAMIDES
Cardiac Drugs Digoxin
- higher doses in Carbimazole
hyperthyroidism Methimazole
- lower doses in Propylthiouracil (PTU)
hypothyroidism
Sedative; Increased sedative and -Thiocarbamide group (S-C-N) essential for antithyroid
Analgesics e.g. respiratory depressant activity
opioids effects SCN part thiocarbamides promote
- hypothyroidism mechanism of action inhibit peroxidase
Converse catalase reaction (-) thyroid hormone synthesis
- hyperthyroidism
SCN iodide transport (-) organification
Special Instructions: thioamide coupling
***food causes delay absorption of drugs
1. Dose MOA
Infants (1-6 months) PTU >Methimazole
o 10 to 15 mcg/kg/d Inhibit thyroid peroxidase-catalyzed reactions
Adult Block iodine organification
o 1.7 mcg/kg/d Block coupling of iodotyrosines by inhibiting
Adult with Cardiac Disease iodination of tyrosine residues in thyroglobulin
o 12.5-25 mcg/d for 2wks then increase Inhibit peripheral deiodination of T4 and T3 (PTU
daily dose to 25 mcg every 2wks >Methimazole)
2. Administered 30mins before to 1hr after meals
3. Monitor TSH 6-8 wks from initiation of treatment Pharmacokinetics
4. Stop treatment if angina pectoris or cardiac arrhythmia PTU
occurs Absorption: rapid and incomplete
Undergoes large first-pass effect in the liver
Special Problems Bioavailability: 50-80 %
Myxedema and Coronary Artery Disease Peak plasma concentration achieved after 1hr
Myxedema Coma Vd: total body water = thyroid gland
o IV Levothyroxine 300-400 mcg loading Half-life: 1.5hrs
dose; 50-100 mcg daily dose Excretion: kidneys (24hrs)
o IV Hydrocortisone if with adrenal or
pituitary insufficiency Methimazole
Hypothyroidism and Pregnancy Absorption: complete but rate is variable
- Levothyroxine Vd: total body water = thyroid gland
- Dose should be lower Half-life: 6-15 hrs
Subclinical Hypothyroidism Excretion: kidneys slower (65-70 % recovered
o No symptoms of hypothyroidism in the urine in 48hrs)
o TSH > 10ml U/L develop symptoms
Drug-induced Hyporthyroidism -half-life has little influence on duration of action or dosing
- Discontinue the drug interval more concentrated in thyroid hormone

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More Common with PTU

Clinical Uses and Dosing Hepatitis
Methimazole
Graves Disease; Toxic Goiter (maintenance agent) IODIDES
o 20-40 mg single AM dose for 4-8 wks
o Euthyroid = 5-15 mg OD MOA
Thyroid Storm PTU is recommended Involves inhibition of the following:
o 60 mg daily per rectum o Organification
PTU o Hormone release (>6 mg/d)
Graves Disease; Toxic Goiter Others:
o 100-150 mg every 6-8 hrs o Decrease size and vascularity of the gland
o Euthyroid = 50-150 mg OD Expected effect:
Neonatal Graves Disease o Thyrotoxic symptoms improve in 2-7
o 5-10 mg/kg/d in 3 divided doses days
Thyroid Storm Induce Hyperthyroidism (Jod-Basedow
o 250 mg PO every 6hrs phenomenon)
o 400mg as retention enema every 6hrs Precipitate Hypothyroidism

*methimazole duration of action 24 hrs May be hypothyroidism or hyperthyroidism

*PTU shorter duration of action; for neonatal, graves depending on the state of patients iodine
disease and pregnant
Clinical Uses and Dosing of Saturated Potassium Iodide
Methimazole and PTU Treatment Guide Solution
Normalization of FT4 and FT3, decrease in TSH Thyroid Storm
Reduction in the size of goiter o 10 drops PO daily
For toxic goiter once euthyroid medical treatment Prior to radiation emergencies
followed by subtotal thyroidectomy Pre-operative preparation prior to thyroid
surgery
Effect on Pregnancy (Category D) o 5 drops 2x daily 10-14 days prior
Cross the placental barrier fetal
thyroid Clinical Effects
Low concentration on breast milk Discernable effect in 24 hrs
PTU >Methimazole Maximal effect Is attained after 10-15 days of
o Reasons: continuous therapy
Strongly protein bound
Crosses placenta less readily Precautions
Methimazole associated with Initiated after onset of thioamide therapy
congenital malformation (fetal Avoided with radioactive iodine treatment
scalp defects) Should not be used alone rebound
Aplasia cutis (teratogenic) thyrotoxicosis increase thyroid hormone
release
Adverse Effects Chronic use should be avoided in pregnancy
Maculopapular rash (4-6%) increase iodide uptake in fetal thyroid
Fever
Gastrointestinal distress nausea Adverse effects
Hypothyroidism Acneiform rash
Swollen salivary gland
More Common with Methimazole Mucous membrane ulcerations
Altered sense of taste Conjunctivitis
Cholestatic jaundice Rhinorrhea
Agranulocytosis (0.1-0.5 %) Drug fever
o Granulocyte <500 cells/mm3 Metallic taste
o Observed with >40 mg/dl Bleeding disorders
o Manifestations: sore throat or high fever Anaphylactic reactions

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Iodism (Iodine Toxicity)

** reversible discontinue drug Advantages
Dose related Easily administered
Brassy taste Effective
Salivation Less expensive
Flu-like manifestations Pain-free
Acneiform lesions
Enlarged parotid, submaxillary gland Disadvantages
Slow onset of effect
RADIOACTIVE IODINE Hypothyroidism
131I administered orally as Sodium
Adverse Effects
MOA Hypothyroidism (80%)
Sodium 131I o Levothyroxine 150 mcg daily
Sore throat
Absorbed and concentrated by thyroid gland Sialitis

Incorporated in storage follicles Precautions and Contraindications

Elderly
and rays emitted Underlying heart disease or severe thyrotoxicosis
Avoid iodides
Cytotoxicity limited to thyroid follicles Monitor serum FT4 and TSH regularly
Pregnant and lactating women
rays promote the following:
epithelial swelling and necrosis ANION INHIBITORS
follicular disruption Perchlorate (ClO4-)
edema Pertechnetate (TcO4-)
leukocyte infiltration Thiocyanate (SCN-)

thyroid parenchyma destruction MOA

Block uptake of the iodide by the thyroid through
Phamacokinetics competitive inhibition of the iodide transport
Absorption: rapid mechanism
Distribution: thyroid gland and incorporated into
storage follicles Clinical Use
Penetration range: 400-2000 m Iodide-induced hyperthyroidism (e.g.
Half-life: 5 days amiodarone-iunduced hyperthyroidism)
o Potassium perchlorate
Clinical Uses and Dosing (Unwanted effect: aplastic anemia)
** do not respond to conventional tx like thioamide
Graves Disease = 80-120 Ci/g ADJUNCTS TO THYROID THERAPY
For those with underlying heart disease or severe
thyrotoxicosis, and elderly patients Adrenoceptor-Blocking Agents
Treatment of relapse of hyperthyroidism after - Propranolol
thioreylene therapy or surgery - Metoprolol
Test thyroid function - Atenolol
- Esmolol
Clinical Effects
Given 5-7 days after stopping methimazole Action: control tachycardia, hypertension and
Shrinkage in the size of the gland after 6-12 weeks atrial fibrillation
from administration Clinical uses:
o Graves Disease, toxic goiter, subacute
Course After Treatment thyroiditis
Progressive improvement over 2-3 months 20-40 mg PO q6 hrs
Inadequate therapy repeat after 6-12 months o Neonatal Graves disease
Transient hypothyroidism lasting for 6 months 2 mg/kg/d in divided doses
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o Thyroid storm
1-2 mg slow IV Thyrotoxicosis
40-50 mg PO q6 hrs In 3-6 weeks improvement with thioamides
2-4 months after initiation of therapy FT4 and
Calcium Channel Blocker (asthma) total T3 normalizes
- diltiazem Once euthyroid: follow-up every 4-6 months

Prednisone, Hydrocortisone Signs of Remission

To control inflammation Decreased size of thyroid gland
Absence of S/S of hyperthyroidism
Indications Decreased thyroid stimulating Ab
o Thyroid storm decrease TH Normal serum TSH response to TRH
Hydrocortisone 50mg IV q6hrs
o Subacute thyroiditis
o Ophthalmopathy BONE STRUCTURE AND METABOLISM
60-100 mg PO/day for 1 week
then every other day to be Component of the human skeleton
tapered in 6-12 weeks Cortical bone (80%)
o Dermopathy Trabecular bone (20%)
Topical application covered with
an occlusive dressing Component of osteoid
o Neonatal Graves disease Collagen
For very ill infants 2 mg/kg/d in Osteocalcin
divided doses Phosphoproteins (osteonectin)
Hydroxyapatite
Lithium
Inhibit thyroid hormone release Major mineral constituents of the bone
Inhibit TH synthesis Calcium (98%)
Can cause hypothyroidism Phosphates (85%)
o Absorption: duodenum and upper
Amiodarone jejunum
Anti-arrhythmic agent o Secretion: ileum
Iodine rich drug o Excretion: kidneys
Iodine sufficiency: hypothyroidism
Iodine deficiency: induces thyrotoxicosis Bone Homeostasis
Metabolite 3 hormones principally controlling serum Calcium
o Desethylamiodarone and Phorphorus
Potent inhibitor of T4-T3 o 1,25 (OH) 2D3 - Calcitriol
conversion o FGF 23 more on kidney (+) PO4
secreteion, no effect on Ca++ (-) renal
SPECIAL PROBLEM WITH HYPERTHYROIDISM prodn of vitamin
o PTH
Thyroid storm PTU (better)
- -methimazole Calcitriol increase serum Ca++ Ca++ goes to
- Iodides the bone
- Propranolo PTH increase dose resorption
- hydrocortisone Decrease dose bone formn (indirect effect)
Ophthalmopathy (rare) Vitamin D (-) PO4 and Ca++ excretion
- Difficult to treat when present
- (+) sterod, REI exposed post orbit to PARATHYROID HORMONE
high energy pump Control influx of Ca++ in the blood
Dermopathy For prodn of Vit. D in the kidney
Thyrotoxicosis during pregnancy -- PTU *vit. D block formn of PTH
Amiodarone-induced thyrotoxicosis Kidney increase reabsorption of Ca++ and Mg
- Thioamide
- corticosteroid
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Action of PTH (calcipotriol)

Increase no. of activity of osteoclast (indirect) Doxercalciferol (1 - 1(OH) D2
To promote osteocastic activity osteoblast hydroxyvitamin D2)
should stimulate RANK ligand (+) osteoclast Paricalcitriol (19-nor-
increase bone turnover 1,25-dihydroxyvitamin 19-nor-1,25(OH)D2
bone resorption at excess level D2)
Low intermittent bone formation
Pharmacodynamics (Calcitriol)
Vit. D tightly CHON bound
Teriparatide (Recombinant PTH) MOA: under investigation
MOA o On the intestine:
o Acts on receptors coupled to G-0protein Induction of new protein
signalling pathways synthesis (calcium binding
Action: stimulates bonde turnover protein and TRPV6 intestinal
Dosage: 20mcg SC daily calcium channel)
Clinical use: osteoporosis Modulation of calcium flux across
Side effect the brush border and basolateral
o Hypercalcemia membranes
o Hypercalciuria o On the bone:
Induce RANK ligand in
VITAMIN D osteoblasts and osteocalcin
Food Action
Skin (+) sunlight o Stimulate intestinal calcium and
phosphate transport/absorption
Sources: o Promote bone resorption
Sunlight o Regulate PTH, insulin and cytokine
Fortified products secretion
Cod liver oil o Proliferation and differentiation of a large
Sardines, tuna, mackerel number of cells
Egg yolk
Vitamin D Functions
*skin synthesize 7 dehydrocholesterol acted upon by UV Bone mineralization
cholecalciferol Healthy immune system, cell growth regulation
and differentiation
Prohormone Deficiency thin, brittle and misshapen bone
- Converted in liver to 25 (OH)D3 (ricketts, osteomalacia)
- In kidney 24,25 (OH) 2D3
- Calcitriol w/ clinical used Recommended intake
- Cholecalciferol food dairy Age Group Requirement
- Ergocalciferol plant Birth 50 200 IU
- Paricalcitriol chronic parathyroidism 51-70 400 IU
71 and above 600 IU

Chemical and Generic Abbreviation Dose of Calcitriol

Names 0.25 to 1 mcg daily
Cholecalciferol Vitamin D3 Raise serum calcium between 24-48 hrs
Ergocalciferol Vitamin D2
Calcifediol (25- 25(OH) D3 Approved Analogs
hydroxyvitamin D3) Doxercalciferol
Calcitriol (1,25- Paricalcitriol
dihydroxyvitamin D3) 1,25(OH) 2D3
Secalcifediol (24,25 For the treatment of the following:
dihydroxyvitamin D3) 24,25(OH) 2D3 Hypocalcemia
Dihydrotachysterol DHT Secondary hyperparathyroidism secondary to
Calcipotriene None CKD

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o One cup calcium-fortified juice

Vitamin D for: o 4 oz tin of canned sardines or salmon
o A cup of cooked spinach
Hypoparathyroidism o 1 cup of ice cream
o 25,000 to 10,000 units 3x a week o One cup yogurt
Intestinal Osteodystrophy
o 25,000 to 50,000 units 3x a week Calcium Supplements
Vitamin D Deficiency / Nutritional Ricketts IV preparation for massive blood transfusion
o Dose: o Calcium gluceptate (0.9 meq calcium/ml)
4000 units/day o 50,000 units/week o Calcium gluconate (0.45 meq calcium/ml)
o Prevention: o Calcium chloride (0.68 1.36 meq
800-1200 units/day calcium/ml)
X-linked Hypophosphatemia Oral preparation
o Calcitriol 0.25 5 g daily (with oral o Calcium carbonate (40% calcium)
phosphate) o Calcium lactate (13% calcium)
o Calcium phosphate (25% calcium)
Adverse Effects o Calcium citrate (17% calcium)
Hypercalcemia renal failure and kidney
stones Preparat Advanta Administra Disadvant
Polyuria and polydipsia ion ges tion ages
Calcium Most Take orally Constipatio
Precaution carbonate elemental with meals n
calcium or citrus
Desired: Calcium x Phosphate = <55 mg/dl
=40% juice
Calcium and Phosphate dietary restrictions Least Absorption
Monitor the following: expensive reduced with
o Serum calcium and phosphate levels fasting or
o Serum PTH and alkaline phosphatase achlorydia
o Serum levels of vitamin D metabolites Calcium No Take on Expensive
citrate constipati empty
CALCIUM on stomach
Better Indications:
absorptio Constipation
Most abundant mineral in the body n than or gas on
99% of total body calcium: teeth an bones CaCO3 by CaCO3
1%: blood, muscles, extracellular fluids >20% Ca++ -based
Elemental kidney
Roles: Ca++ stones
- Bone mineralization =21%
- Muscle cell contraction Calcium No Oral Expensive
- BP regulation phosphate constipati
on
- Normal heart rhythm
Better
- Blood cholesterol control absorptio
- Neural transmission n 39%
- Enzyme activity Elemental
- Salivary gland secretion calciulm
- Cellular proliferation =25%
- Blood coagulation Calcium Inexpensi Oral Elemental
- Cell membrane integrity lactate ve Ca++
(13%)
Dietary Sources Calcium Less IV (0.45 meq Elemental
o Milk and other dairy products (primary gluconate irritation calcium/ml) Ca++ (9%)
source) to veins 5-20 ml 10%
o Green vegetables solution slow
infusion
o Calcium fortified cereals, juices, tofu Oral

The following has 300 mg of Calcium:

o 1 glass (250 ml) of milk
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Calcium Supplements o Increase calcium excretion

High dietary sodium and protein
Taking supplements in divided doses avoids side
effects Contraindications
Absorption of supplements is optimal in doses of Hypercalciuria
500mg or less; percent of calcium absorbed declines Nephrolithiasis
as the amount of calcium intake increases Sarcoidosis
Hyperparathyroidism
Clinical use:
Dietary deficiency of calcium Organ PTH Vitamin D FGF 23
Chronic hypocalcemia due to Intestine Increase Increases Decrease calcitriol
hypoparathyroidism or malabsorption calcitriol calcium and production w/c
Hypocalcemic tetany production phosphate decreases calcium
Osteoporosis w/c absorption and phosphate
increases absorption
Cardiac dysrhythmias caused by severe
calcium
hyperkalemia and
phosphate
Side effects: absorption
o Well tolerated when taken in divided doses Kidney Decreased Calcium and Increased
o Nausea, gas, constipation, indigestion, calcium phosphate phosphate
bloating and excretion may excretion
o Doses higher than required increased be decreased Inhibits calcitriol
Hypercalcemia phosphate by calcifediol production
Impaired kidney function and stone excretion and calcitriol
Increased
formation
calcitriol
Decreased absorption of other excretion
minerals (iron, magnesium, Bone High doses Increases Decrease
phosphorus) -increased calcium and mineralization due
calcium phosphate to
Calcium interactions and resorption by hypophosphatemia
o Decreased plasma concentration phosphate calcitriol
Digoxin resorption Bone
o Decreased the absorption Low doses formation
-increased increased by
Fluoroquinolones, levothyroxine,
bone calcitriol and
tetracyclines, phenytoin formation secocalcifediol
o Increase potential for hypercalcemia and Serum Increased Increased -
hypercalciuria calcium
Thiazides and similar diuretics Serum Decreased Decreased decreased
o Increase urinary calcium excretion phosphate
Aluminum and magnesium-
containing antacids Dilis 2184 mg
o Decrease dietary calcium absorption 1200 mg/dl = for menopausal; avoid high sodium
Mineral oil and stimulant laxatives intake
o Depletion of calcium stores PO4 part of osteoid, for bone mineralization
Prolonged glucocorticoid
CALCITONIN
Other factors influencing calcium absorption and excretion
o Favor absorption Secreted by parafollicular cells of the thyroid gland
Vitamin D Disulfide bond between positions 1 and 7 is essential
o Interfere with absorption for biologic activity
Increasing age Half-life = 10mins
Fibers Metabolic clearance = 8-9 ml/kg/min
Caffeine Clearance: kidney
Alcohol Principal effects:
o Decrease excretion o Decrease renal reabsorption of:
High potassium intake Calcium

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Phosphate o Increase calcitriol [1,25(OH)2 D) level

Sodium (indirect)
Potassium Due to decrease serum calcium and
Magnesium phosphate, and increase PTH
o Inhibits osteoclastic bone resorption o Inhibit the cytokines that recruit osteoclast

Other effects: Action

o Decrease gastrin secretion o Prevent accelerated bone loss and increase
o Reduce gastric acid output BMD during postmenopausal period
o Increase GIT secretion of:
Sodium Clinical use
Potassium o Treatment and prevention of postmenopausal
Chloride osteoporosis
Water Conjugated estrogen 0.625 mg/day
Ethinyl estradiol 25-50 g/day
Pentagastrin potent stimulator
Calcinar parenteral and nasal preparations Adverse effects
o Increase BP
Clinical uses: o Hypercoagulability (thrombotic stroke, VTE)
o Piagets disease o Hypertriglyceridemia
50-100 MRC units SQ or IM o Salt and water retention
200-400 units/day nasal inhalation
o Hypercalcemia SELECTIVE ESTROGEN RECEPTOR MODULATOR
o Osteoporosis (Raloxifene)

GLUCOCORTICOID
- Onset of action: 4-6 hours
- Duration of action: 6-10 hrs
MOA on the bone
o Antagonize vitamin D excretion
o Stimulate renal calcium excretion
o Block bone formation (collagen synthesis)
o Inhibit secretion and effectiveness of cytokine
that stimulate osteoclastic bone resorption
o Increase PTH-stimulated bone resorption
Clinical uses for disorers associated with the bone
o Reverse hypercalcemia secondary to:
Multiple myoma
Lymphomas
Sarcoidosis
Vitamin D intoxication
Dose
o Prednisone 30-60 mg PO daily
Adverse effects on the bone
o Osteoporosis in adults
o Stunt skeletal development in children
ESTROGEN - protective to bone
MOA
o Block PTH action reduce
resorption
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With contribution of Elbert Mendez
MOA
Estrogen-agonist = bone
Estrogen antagonist = endometrium and
breast
Action
Increases bone mineral density
Reduction in the risk of vertebral fracture
with osteoporosis
Adverse Effects venous thromboembolis (caucasian)
Clinical use: to prevent post menopausal osteoporosis and
fracture
Biphophanates
P-O-P structure of pyrophosphate
MOA
Inhibit recruitment and apoptosis of osteoclast
Stimulate osteoclast activity (indirectly)
Apoptosis of osteoclast:
Amino biphosphanate
Alendronate, riserdronal
Other effects:
Inhibit 1,25 (OH)2 D3 prodn
Inhibit intestinal Ca++ transport
- Given orally
- Absorption is impaired by food
bone - Cause GI irritation
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Unwanted effects: Strontium renalate

GI upsets, esophageal irritation(except etidronate) Block osteoclast diffrentiation and apoptosis
Bone pain inhibit bone resorption
Increase risk of fracture osteomalacia
(etidronate) Calcimimetics: Cinacalcet
Renal deterioration (zoledronate) MOA: stimluate Ca++ sensing receptor blocks PTH
Osteoscoliosis secretion

Pagets Disease Galium Nitrate

Should not exceed for 6 mos. (-) bone resorption for hypercalcemia and
Malignant hypercalcemia malignancy; given IV
- Etidronate (least effective) AE: nephrotoxicity
- Fanidronal
- Zolendronate only if necessary no PHOSPHATE
renal impairment decrease serum Ca++
only an alternative
Alternative to estrogen for symptomatic hypercalcemia
Alendronate hypophosphatemia
Riserdronate
hypercalcemia
Plicamycin (mithamycin) tx of last resort furosemide
- Bind to DNA interrupt DNA directed buphosphanate
RNA synthesis calcitonin
galium nitrate
Unwanted effect plicamycin
Hypocalcemia PO4
Hepatonephrotoxicity Glucocorticoid

Thiazides Hypocalcemia
MOA: Ca++
Increase effectiveness of PTH in stimulating Vit D
reabsorption of Ca++ in renal tubules
Enhance Ca++ reabsorption by increasing Na Hyperphosphatemia
reabsorption Sevelamer (PO4 binding gel)

Effects: Hypophosphatemia
Decrease secretion of the ff. in urine: Emergency tx
- Calcium Treat underlying cause
- Oxalate
Inhibit excretion of: Hyperparathyroidism cinaclet
- Magnesium
- Zinc Osteoporosis
Clinical use: reduce hypercalciuria Ca++ and Vit D
Contraindication: hyperparathyroidism Biphosphanate
Calcitonin
Flouride Raloxifen
MOA: stabilize hydroxyapatite crystal of bones and teeth Teriparatide
Clinical use:
- Effective prophylaxis of dental caries Pagets Disease
- Topical preparartion *to reduce pain and prgressive deformity
- Calcitonin
Adverse effects: - Biphosphanate
Nausea and vomiting - Plicamycin
GIT blood loss Vit D chronic kidney disease
Athralgia and athritis
Note! For any mistakes, please make necessary correction. Thanks!

Jcelimpin 1c 9/10/2011
With contribution of Elbert Mendez
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Jcelimpin 1c 9/10/2011
With contribution of Elbert Mendez