PHARMACOLOGY FINAL EXAM

Name: LABAYOG, GLEN NORWEL M.

Section: Med-2B

Discuss briefly the Pharmacodynamics and Pharmacokinetics and Clinical Uses of the following drugs:
IV. ENDOCRINE DRUS:
1. Octreotide 14. Tamoxifen 26. Chlorpropamide
2. Bromocriptine 15. Clomiphene 27. Colesevelan HCl
3. Quinagolide 16. Anastrazole 28. Pramlintide
4. Ganirelix 17. Medroxyprogesterone 29. Saxagliptin
5. Propylthiouracil 18. Mifiprestone (same as 9, 30. Etioronate
6. Methimazole disregard) 31. Cinacalcent
7. Beclomethazone 19. Norgestrel 32. Glyburide
8. Budesonide 20. Megestrol acetate 33. Glipizide
9. Mifepristone 21. Fulvestrant 34. Nateglinide
10. Fludrocortisone 22. Dutasteride 35. Metformin
11. Estradiol 23. Bicalutamide 36. Miglitol
12. Quinestrol 24. NPN Insulin 37. Troglitazone
13. Mestranol 25. Crystalline Zinc Insulin 38. Diazoxide

V.Chelator
1. Dimercaprol
2. Succimer (DMSA)
3. EDTA
4. Unithiol (DMPS)
5. Penicillamine
6. Deferoxamine
7. Deferasirox
8. Ferric Hexacyoferrate
IV. ENDOCRINE DRUGS

OCTREOTIDE
Pharmacodynamics
Somatostatin analog, supresses the release of growth hormones, glucagon, insulin, gastrin, IGF-1, serotonin
and gastrointestinal peptides. These receptors are coupled via pertussis toxin sensitive G proteins which lead to
inhibition of adenylyl cyclase. Octreotide binding to these receptors also stimulates phosphotyrosine
phosphatase and activation of the Na(+)/H(+) exchanger via pertussis toxin insensitive G proteins.

Pharmacokinetics
Volume of distribution: 13.6 L [healthy volunteers], 21.6 ± 8.5 L [patients with acromegaly]
Route of elimination: About 32% of the dose is excreted unchanged into the urine.

Clinical Uses
For treatment of acromegaly and reduction of side effects from cancer chemotherapy, also use for pituitary
adenoma, carcinoid, gastrinoma, glucagonoma and variceal bleeding.

BROMOCRIPTINE
Pharmacodynamics
Dopamine agonist, partial agonist at dopamine D2 receptors in brain, inhibits the Growth Hormone release.
It also inhibits the release of glutamate, by reversing the glutamate GLT1 transporter.

Pharmacokinetics
Absorption: Approximately 28% of the oral dose is absorbed; however due to a substantial first pass effect,
only 6% of the oral dose reaches the systemic circulation unchanged.
Metabolism: Completely metabolized by the liver, primarily by hydrolysis of the amide bond to produce
lysergic acid and a peptide fragment, both inactive and non-toxic
Route of elimination: Parent drug and metabolites are almost completely excreted via the liver, and only 6%
eliminated via the kidney.

Clinical Uses
For the treatment of galactorrhea due to hyperprolactinemia, prolactin-dependent menstrual disorders and
infertility, prolactin-secreting adenomas, prolactin-dependent male hypogonadism, as adjunct therapy to
surgery or radiotherapy for acromegaly or as monotherapy is special cases, as monotherapy in early
Parksinsonian Syndrome or as an adjunct with levodopa in advanced cases with motor complications.
Bromocriptine has also been used off-label to treat restless legs syndrome and neuroleptic malignant syndrome.

QUINAGOLIDE
Pharmacodynamics
Quinagolide achieves long-lasting reduction in prolactin levels in a dose-proportional effect via selectively
targeting D2 receptors as an agonist. It potently suppresses both basal and stimulated serum prolactin levels by
exerting a strong inhibitory effect on the secretion of the anterior pituitary hormone prolactin.

Pharmacokinetics
Absorption: The absorption of quinagolide is rapid and extensive with 95% of the dose absorbed after oral
ingestion, however the absolute bioavailability is low (4 %) due to pre-systemic metabolism
Volume of distribution: Approximate volume of distribution is 100L following a single oral admininstration
Metabolism: Quinagolide undergoes extensive first pass metabolism with sulfate and glucuronide
conjugates being the major circulating metabolites
Route of elimination: More than 95% of total dose is excreted as metabolites and the excretion via urine and
feces is approximately equal.

Clinical Uses
Indicated for the treatment of hyperprolactinemia (idiopathic or originating from a prolactin-secreting pituitary
microadenoma or macroadenoma).
GANIREFLIX
Pharmacodynamics
GnRH antagonist, blocks GnRH receptors, reduces endogenous production of LH and FSH. Ganirelix acts by
competitively blocking the GnRH receptors on the pituitary gonadotroph and subsequent transduction
pathway. It induces a rapid, reversible suppression of gonadotropin secretion. The suppression of pituitary LH
secretion by ganirelix is more pronounced than that of FSH. An initial release of endogenous gonadotropins has
not been detected with ganirelix, which is consistent with an antagonist effect. Upon discontinuation of
ganirelix, pituitary LH and FSH levels are fully recovered within 48 hours.

Pharmacokinetics
Absorption: Ganirelix is rapidly absorbed following subcutaneous injection with maximum serum
concentrations reached approximately one hour after dosing.
Volume of Distribution: The mean (SD) volume of distribution of Ganirelix in healthy females following
intravenous administration of a single 250 mg dose is 43.7 (11.4) L.
Metabolism: Following single-dose intravenous administration of radiolabeled ganirelix acetate to healthy
female volunteers, ganirelix Acetate is the major compound present in the plasma (50–70% of total radioactivity
in the plasma) up to 4 hours and urine (17.1–18.4% of administered dose) up to 24 hours. Ganirelix Acetate is not
found in the feces. The 1–4 peptide and 1–6 peptide of Ganirelix Acetate are the primary metabolites observed
in the feces.
Route of Elimination: On average, 97.2% of the total radiolabeled ganirelix dose is recovered in the feces
and urine (75.1% and 22.1%, respectively) over 288 h following intravenous single dose administration of 1 mg
[14 75 C]-ganirelix acetate. Urinary excretion is virtually complete in 24 h, whereas fecal excretion starts to
plateau 192 h after dosing.

Clinical Uses
For the inhibition of premature LH surges in women undergoing controlled ovarian hyperstimulation (prevents
premature surge of Luteinizing Hormone), and for advanced prostate Cancer.
PROPYLTHIOURACIL
Pharmacodynamics
Inhibits thyroid peroxidase reactions, blocks iodine organification, inhibits peripheral conversion of T4 into T3.
Propylthiouracil is a thiourea antithyroid agent. The two thyroid hormones manufactured by the thyroid gland,
thyroxine (T4) and triiodothyronine (T3), are formed by combining iodine and a protein called thyroglobulin with
the assistance of an enzyme called peroxidase. PTU inhibits iodine and peroxidase from their normal
interactions with thyroglobulin to form T4 and T3. This action decreases thyroid hormone production. PTU also
interferes with the conversion of T4 to T3, and, since T3 is more potent than T4, this also reduces the activity of
thyroid hormones. The actions and use of propylthiouracil are similar to those of methimazole.

Pharmacokinetics
Absorption: Well absorbed following oral administration.
Route of Elimination: Propylthiouracil is readily absorbed and is extensively metabolized. Approximately 35%
of the drug is excreted in the urine, in intact and conjugated forms, within 24 hours.
Half-life: 2 Hours

Clinical Uses
Used to manage hyperthyroidism which is due to an overactive thyroid gland (Grave's disease). Indicated for
Hyperthyroidism and thyroid storm.

METHIMAZOLE
Pharmacodynamics
Methimazole inhibits thyroid peroxidase reactions, blocks iodine organification. Methimazole appears to be
interference in an early step in thyroid hormone synthesis involving thyroid peroxidase (TPO), however the exact
method through which methimazole inhibits this step is unclear.

Pharmacokinetics
Absorption: Absorption of methimazole after oral administration is rapid and extensive, with an absolute
bioavailability of approximately 0.931 and a Tmax ranging from 0.25 to 4.0 hours. Cmax is slightly, but not
significantly, higher in hyperthyroid patients, and both Cmax and AUC are significantly affected by the oral
dose administered.
 Volume of Distribution: The apparent volume of distribution of methimazole has been reported as roughly 20
L. Following oral administration, methimazole is highly concentrated in the thyroid gland - intrathyroidal
methimazole levels are approximately 2 to 5 times higher than peak plasma levels, and remain high for 20 hours
after ingestion.
Metabolism: Methimazole is rapidly and extensively metabolized by the liver, mainly via the CYP450 and FMO
enzyme systems. Several metabolites have been identified, though the specific enzyme isoforms responsible for
their formation are not entirely clear. One of the first methimazole metabolites identified, 3-methyl-2-
thiohydantoin, may contribute to antithyroid activity - its antithyroid activity has been demonstrated in rats and
may explain the prolonged duration of iodination inhibition following administration despite methimazole's
relatively short half-life
Route of Elimination: Urinary excretion of unchanged methimazole has been reported to be between 7% and
12%. Elimination via feces appears to be limited, with a cumulative fecal excretion of 3% after administration of
methimazole. Enterohepatic circulation also appears to play a role in the elimination of methimazole and its
metabolites, as significant amounts of these substances are found in the bile post-administration

Clinical Uses
Methimazole is indicated for the treatment of hyperthyroidism in patients with Graves' disease or toxic
multinodular goiter for whom thyroidectomy or radioactive iodine therapy are not appropriate treatment
options. Methimazole is also indicated for the amelioration of hyperthyroid symptoms in preparation for
thyroidectomy or radioactive iodine therapy.

BECLOMETHAZONE
Pharmacodynamics
Inhibits synthesis of arachidonic acid by inhibiting Phospholipase A2, Reduces expression of Cyclooxygenase
and Leukotriene, increase responsiveness of Beta receptors and activate Glucocorticoid response elements in
the nucleus leading to synthesis of substance that prevent full expression of inflammation and allergy.

Pharmacokinetics
Absorption: Following oral inhalation of 320 mcg of beclomethasone dipropionate (BDP), the Cmax was 88
pg/mL and it was reached after 0.5 at post-administration. The mean Cmax of the major and most active
metabolite, beclomethasone-17-monopropionate (17-BMP), was 1419 pg/mL at 0.7 hour post-dosing.
Volume of Distribution: Following intravenous administration, the steady-state volume of distribution was 20 L
for beclomethasone dipropionate and 424 L for the active metabolite, beclomethasone-17-monopropionate.
Metabolism: During absorption, beclomethasone dipropionate is undergoes rapid and extensive hydrolysis
mediated by esterases CYP3A to form beclomethasone-17-monopropionate (17-BMP), beclomethasone-21-
monopropionate (21-BMP), and beclomethasone (BOH). 17-BMP is the major active metabolite with the most
potent anti-inflammatory activity. About 95% of the total beclomethasone dipropionate administered via oral
inhalation undergoes presystemic conversion to form 17-BMP in the lung.
Route of Elimination: Regardless of the route of administration, beclomethasone dipropionate and its
metabolites are predominantly excreted in the feces, with less than 10% of the drug and its metabolites being
excreted in the urine.

Clinical Uses
It is the drug of choice for Asthma prophylaxis. First line treatment for moderate to severe BA, COPD, Allergic
rhinitis, also used as anti-inflammatory for other conditions such as auto-immune diseases and cancer, also for
immune suppression.

BUDESONIDE
Pharmacodynamics
Inhibits synthesis of arachidonic acid by inhibiting Phospholipase A2, Reduces expression of
Cyclooxygenase and Leukotriene, increase responsiveness of Beta receptors and activate Glucocorticoid
response elements in the nucleus leading to synthesis of substance that prevent full expression of inflammation
and allergy. Budesonide is a glucocorticoid used to treat respiratory and digestive conditions by reducing
inflammation. It has a wide therapeutic index, as dosing varies highly from patient to patient. Patients should be
counselled regarding the risk of hypercorticism and adrenal axis suppression.

Pharmacokinetics
Absorption: Completely absorbed after oral administration.
 Volume of Distribution: Drug is 85% to 90% plasma protein-bound.
Metabolism: Drug has extensive first-pass metabolism and is rapidly and extensively biotransformed by
CYP3A4 to two major metabolites that have very little glucocorticoid activity.
Route of Elimination: Approximately 60% of a budesonide dose is recovered in the urine as the major
metabolites 6beta-hydroxybudesonide, 16alpha-hydroxyprednisolone, and their conjugates. No unchanged
budesonide is recovered in urine

Clinical Uses
Budesonide extended release capsules are indicated for the treatment and maintenance of mild to
moderate Crohn’s disease. Various inhaled budesonide products are indicated for prophylactic therapy in
asthma and reducing exacerbations of COPD. A budesonide nasal spray is available over the counter for
symptoms of hay fever and upper respiratory allergies. Extended release capsules are indicated to induce
remission of mild to moderate ulcerative colitis and a rectal foam is used for mild to moderate distal ulcerative
colitis.

MIFEPRISTONE
Pharmacodynamics
Competitive inhibitor at the GC receptor as well as the progesterone receptor.
Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of
intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been
shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy,
the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Mifepristone
also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid
dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or
greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and
cortisol.

Pharmacokinetics
Absorption: The absolute bioavailability of a 20 mg oral dose is 69%
Metabolism: Hepatic. Hepatic, by Cytochrome P450 3A4 isoenzyme to the N-monodemethylated metabolite
(RU 42 633); RU 42 698, which results from the loss of two methyl groups from position 11 beta; and RU 42 698,
which results from terminal hydroxylation of the 17–propynyl chain.
Route of Elimination: Fecal: 83%; Renal: 9%.

Clinical Uses
Mifepristone is used for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Also
indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's
syndrome who have type 2 diabetes mellitus or glucose intolerance and are not candidates for surgery or have
had unsuccessful surgery.

FLUDROCORTISONE
Pharmacodynamics
Fludrocortisone is a strong agonist of mineralocorticoid receptors and moderate activation of glucocorticoid
receptors. Increases Na reabsorption, K and H excretion. • Fludrocortisone binding to mineralocorticoid
receptors causes alterations to DNA transcription and translation of proteins that result in an increased density
of sodium channels on the apical side of renal tubule cells and an increased density of Na+-K+-ATPase on the
basolateral side.

Pharmacokinetics
Administration: Oral administration is rapid and complete
Volume of Distribution: The apparent volume of distribution is 80-85L. Distribution into CSF appears minimal.
CSF-to-plasma drug concentration ratio is 1:6
Route of Elimination: Approximately 80% of is excreted in urine with the other 20% is likely eliminated via fecal
or biliary route
Half-life: Is in between 1-3.5 hours though prescribing information gives an approximate half-life of 18-36
hours
Clinical Uses
Use for Chronic adrenal insufficiency (Addison’s disease), Congenital Adrenal Hyperplasia and Adrenal
replacement therapy post-adelectomy. It is Indicated for treatment of salt-losing androgenital syndrome.

ESTRADIOL
Pharmacodynamics
Estradiol activates estrogen receptors. Also, it leads to changes in rates of transcription of estrogen regulated
genes. Overdose may present with withdrawal bleeding, nausea, vomiting, breast tenderness, abdominal pain,
drowsiness, and fatigue.

Pharmacokinetics
Absorption: Present with 30ug oral dose and 1.2mg topical dose delivered via a patch. Estradiol is bound to
albumin in serum but also exhibits binding to sex hormone binding globulin.
Route of Elimination: 59% is eliminated in the urine and bile, while 2-3% is eliminated in the feces. Over 90% is
eliminated unchanged
Metabolism: Estradiol is metabolized in the liver.
Half-life: 30ug oral dose has a half-life of 8.4 hrs and the 1.2mg topical dose has a half-life of 30hrs

Clinical Uses
Estradiol is use for Primary hypogonadism, Postmenopausal Hormonal replacement therapy, Osteoporosis and
for Contraception Intractable dysmenorrhea.

QUINESTROL
Pharmacodynamics
Quinestrol is the 3-cyclopentyl ether of ethinyl estradiol (the active metabolite). After gastrointestinal
absorption, it is stored in adipose tissue where it is slowly released and metabolized principally to the parent
compound, ethinyl estradiol. Ethinyl estradiol is a synthetic derivative of the natural estrogen estradiol.

Pharmacokinetics
Absorption: Absorbed following oral administration
Metabolism: Metabolized principally to the parent compound, ethinyl estradiol. Ethinyl estradiol is
metabolized in the liver. Quantitatively, the major metabolic pathway for ethinyl estradiol, both in rats and in
humans, is aromatic hydroxylation, as it is for the natural estrogens.
Route of Elimination: Elimination half-life is >120 hours

Clinical Uses
Used in hormone replacement therapy, treating symptoms of menopause such as hot flashes. Also used to
treat breast and prostate cancer.

MESTRANOL
Pharmacodynamics
Mestranol is the 3-methyl ether of ethinylestradiol. Not initially biologically active as a contraceptive
hormone but it is rapidly demethylated in the liver to its biologically active form.

Pharmacokinetics
Mestranol undergoes rapid hepatic demethylation to ethylene estradiol which is the active form of the drug
metabolized with a first-pass effect and are enterohepatically recirculated.

Clinical Uses
Mestranol was used as one of the first oral contraceptives.

TAMOXIFEN
Pharmacodynamics
Estrogen antagonist actions in breast tissue and CNS, Estrogen agonist effects in uterus, liver and bone.
Tamoxifen is competitive partial agonist inhibitor of estradiol at the estrogen receptor. It has a long duration of
action as the active metabolite N-desmethyltamoxifen. It has a narrow therapeutic index as higher doses can
lead to breathing difficulty or convulsion.
Pharmacokinetics
Absorption: Tamoxifen is non-steroidal; given orally. dose: 10-20 mg BID
Half-life: 7-14 hours
Route of Elimintation: predominantly excreted by the liver

Clinical Uses
Tamoxifen is indicated to treat estrogen receptor positive metastatic breast cancer in adults, as an adjuvant
in the treatment of early stage estrogen receptor positive breast cancer in adults, to reduce the risk of invasive
breast cancer after surgery and radiation in adult women with ductal carcinoma in situ.

CLOMIPHENE
Pharmacodynamics
Partial agonist in pituitary, reduces negative feedback by estradiol, increases FSH and LH output. It
effectively inhibits the action of stronger estrogens, leads to an increase in the secretion of gonadotropins and
estrogens by inhibiting estradiol’s negative feedback effect on the gonadotropin and stimulates ovulation in
women with oligomenorrhea or amenorrhea and those with ovulatory dysfunction.

Pharmacokinetics
Absorption: Readily absorbed orally in humans.
Metabolism: Hepatic
Route of Elimination: Excreted principally in the feces. Mean urinary excretion was approximately 8% with
fecal excretion of about 42%
Half-life: 5 to 7 days

Clinical Uses
Used mainly in female infertility due to anovulation (e.g. due to polycystic ovary syndrome) to induce
ovulation.

ANASTROZOLE
Pharmacodynamics
Reduces estrogen synthesis by inhibiting aromatase. It reversibly binds to aromatase enzyme, and through
competitive inhibition blocks the conversion of androgens to estrogens in peripheral tissue.

Pharmacokinetics
Absorption: Bioavailability in humans is unknown. Anastrozole is rapidly absorbed and Tmax is typically
reached within 2 hours of dosing under fasted conditions.
Volume of Distribution: The volume of distribution of anastrozole into brain tissue in mice is 3.19 mL/g.
Distribution into the CNS is limited due to the activity of P-gp efflux pumps at the blood brain barrier, of which
anastrozole is a substrate.
Metabolism: Anastrozole is primarily metabolized in the liver via oxidation and glucuronidation to a number of
inactive metabolites, including hydroxyanastrozole (both free and glucuronidated) and anastrozole
glucuronide. Oxidation to hydroxyanastrozole is catalyzed predominantly by CYP3A4 (as well as CYP3A5 and
CYP2C8, to a lesser extent) and the direct glucuronidation of anastrozole appears to be catalyzed mainly by
UGT1A4
Route of Elimination: Hepatic metabolism accounts for approximately 85% of anastrozole elimination.
Approximately 10% of the administered dosage is eliminated unchanged in the urine

Clinical Uses
Anastrozole is indicated as adjunct therapy in the treatment of hormone receptor-positive early breast
cancer in postmenopausal women, and as a first-line treatment for hormone receptor-positive (or hormone
receptor-unknown) locally advanced or metastatic breast cancer in postmenopausal women. It may also be
used in the treatment of advanced breast cancer in postmenopausal women who experience disease
progression despite treatment with tamoxifen.

MEDROXYPROGESTERONE ACETATE
Pharmacodynamics
Inhibits gonadotropin production, reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of
the endometrium, and induces p53 dependent apoptosis in cancer cell lines.
Pharmacokinetics
Absorption: Rapidly absorbed in the GI tract to the blood circulation through oral administration. Absorption
half-life of 15-30 mins, biological half-life is 3-5 days
Metabolism: Metabolized primarily by the liver
Route of Elimination: Excreted primarily in the urine

Clinical Uses
Medroxyprogesterone acetate (MPA) oral tablets are indicated to treat secondary amenorrhea, reduce the
incidence of endometrial hyperplasia in postmenopausal women, and to treat abnormal uterine bleeding due
to hormonal imbalance, not organic pathology. Oral tablets containing MPA and conjugated estrogens are
indicated to prevent postmenopausal osteoporosis and to treat moderate to severe menopausal symptoms
such as vasomotor symptoms, vulvar atrophy, and vaginal atrophy. Subcutaneous MPA is indicated to prevent
pregnancy and manage pain associated with endometriosis. Intramuscular MPA is indicated to prevent
pregnancy, and at higher concentrations for palliative treatment of endometrial or renal carcinoma.

MIFEPRESTONE
Pharmacodynamics
Competitive inhibitor at the GC receptor as well as the progesterone receptor.
Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of
intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been
shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy,
the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Mifepristone
also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid
dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or
greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and
cortisol.

Pharmacokinetics
Absorption: The absolute bioavailability of a 20 mg oral dose is 69%
Metabolism: Hepatic. Hepatic, by Cytochrome P450 3A4 isoenzyme to the N-monodemethylated metabolite
(RU 42 633); RU 42 698, which results from the loss of two methyl groups from position 11 beta; and RU 42 698,
which results from terminal hydroxylation of the 17–propynyl chain.
Route of Elimination: Fecal: 83%; Renal: 9%.

Clinical Uses
Mifepristone is used for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Also
indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's
syndrome who have type 2 diabetes mellitus or glucose intolerance and are not candidates for surgery or have
had unsuccessful surgery.

NORGESTREL
Pharmacodynamics
Activates progesterone receptors, change rates of transcription of progesterone-regulated genes.
Norgestrel (and more specifically the active stereoisomer levonorgestrel) binds to the progesterone and
estrogen receptors within the female reproductive tract, the mammary gland, the hypothalamus, and the
pituitary. Once bound to the receptor, progestins like levonorgestrel will slow the frequency of release of
gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing
hormone) surge. Loss of the LH surge inhibits ovulation and thereby prevents pregnancy.

Pharmacokinetics
Absorption: Well absorbed after oral administration.
Volume of Distribution: Unknown.
Metabolism: Metabolized in the liver.
Route of Elimination: Excreted in the urine and feces as glucoronide and sulphate conjugates.

Clinical Uses
Norgestrel in combination with ethinyl estradiol is indicated for the prevention of pregnancy in women who
elect to use this product as a method of contraception.
MEGESTROL ACETATE
Pharmacodynamics
Megestrol is a synthetic progestin and has the same physiologic effects as natural progesterone. These
effects include induction of secretory changes in the endometrium, increase in basal body temperature,
pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. Mestrogel has slight
glucocorticoid activity and very slight mineralocorticoid activity. This drug has no estrogenic, androgenic, or
anabolic activity.

Pharmacokinetics
Absorption: Variable, but well absorbed orally.
Volume of Distribution:
Metabolism: Primarily hepatic. Megestrol metabolites which were identified in urine constituted 5% to 8% of
the dose administered. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted
for at least part of the radioactivity not found in urine and feces. No active metabolites have been identified.
Route of Elimination: The major route of drug elimination in humans is urine. Respiratory excretion as labeled
carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine
and feces.

Clinical Uses
For the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a
diagnosis of acquired immunodeficiency syndrome (AIDS). Also used for the palliative management of
recurrent, inoperable, or metastatic breast cancer, endometrial cancer, and prostate cancer in Canada and
some other countries.

FULVESTRANT
Pharmacodynamics
Fulvestrant for intramuscular administration is an estrogen receptor antagonist without known agonist
effects. Fulvestrant competitively and reversibly binds to estrogen receptors present in cancer cells and
achieves its anti-estrogen effects through two separate mechanisms. First, fulvestrant binds to the receptors and
downregulates them so that estrogen is no longer able to bind to these receptors. Second, fulvestrant
degrades the estrogen receptors to which it is bound. Both of these mechanisms inhibit the growth of
tamoxifen-resistant as well as estrogen-sensitive human breast cancer cell lines.

Pharmacokinetics
Absorption: Slowly absorbed and maximum plasma concentrations (Cmax) are reached after about 5 day
Metabolism: Metabolism of fulvestrant appears to involve combinations of a number of possible
biotransformation pathways analogous to those of endogenous steroids, including oxidation, aromatic
hydroxylation, conjugation with glucuronic acid and/or sulphate at the 2, 3 and 17 positions of the steroid
nucleus, and oxidation of the side chain sulphoxide. Identified metabolites are either less active or exhibit similar
activity to fulvestrant in antiestrogen models. Studies using human liver preparations and recombinant human
enzymes indicate that cytochrome P-450 3A4 (CYP 3A4) is the only P-450 isoenzyme involved in the oxidation of
fulvestrant; however, the relative contribution of P-450 and non-P-450 routes in vivo is unknown.
Route of Elimination: Fulvestrant was rapidly cleared by the hepatobiliary route with excretion primarily via
the feces (approximately 90%). Renal elimination was negligible (less than 1%).

Clinical Uses
For the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with
disease progression following anti-estrogen therapy, as monotherapy or in combination with other
antineoplastic agents.

DUTASTERIDE
Pharmacodynamics
Androgen synthesis inhibitor, inhibits 5a reductase enzyme that converts testosterone to dihydrotestosterone.
Dutasteride is a synthetic 4-azasteroid compound that selectively inhibits both the type I and type II isoforms of
steroid 5α-reductase, an intracellular enzyme that converts testosterone to 5α-dihydrotestosterone (DHT).
Dutasteride works by reducing the levels of circulating DHT. It was also shown to reduce the size of the prostate
gland, improve urinary flow, and symptoms of benign prostatic hyperplasia alone or in combination with
tamsulosin. The effect of the reduction of DHT by dutasteride is dose-dependent, with the maximum effect
observed within 1-2 weeks following initial administration. Dutasteride are also neurosteroidogenesis inhibitors,
preventing the 5α-reductase-mediated biosynthesis of various neurosteroids including allopregnanolone (from
progesterone), THDOC (from deoxycorticosterone), and 3α-androstanediol (from testosterone). These
neurosteroids are potent positive allosteric modulators of the GABAA receptor and have been found to possess
antidepressant, anxiolytic, and pro-sexual effects in animal research.

Pharmacokinetics
Absorption: Following oral administration of a single dose of 0.5 mg dutasteride, the peak serum
concentrations were reached within 2 to 3 hours. Following daily oral administration of 0.5 mg dutasteride, the
steady-state concentration of 40 ng/mL is expected to be achieved at 6 months following initial administration.
Volume of Distribution: Dutasteride displays a large volume of distribution ranging from 300 to 500 L. Following
daily oral administration of 0.5 mg dutasteride healthy subjects for 12 months, the semen dutasteride
concentrations averaged 3.4 ng/mL (range: 0.4 to 14 ng/mL) with 11.5% of serum dutasteride concentrations
being partitioned into semen.
Metabolism: The drug is extensively metabolized in the liver by CYP3A4. it has three major metabolites,
including 6'-hydroxydutasteride, 4'-hydroxydutasteride, and 1,2-dihydrodutasteride; the former two are formed
by CYP3A4, while the latter is not. All three metabolites are active; 6'-hydroxydutasteride has similar potency as
a 5α-reductase inhibitor to dutasteride, while the other two are less potent.
Route of Elimination: Dutasteride has an extremely long terminal or elimination half-life of about 4 or 5 weeks.
The elimination half-life is increased in the elderly (170 hours for men age 20–49 years, 300 hours for men age
>70 years. Dutasteride is eliminated mainly in the feces (40%) as metabolites. A small portion (5%) is eliminated
unchanged in the urine

Clinical Uses
Indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged
prostate gland to improve symptoms, and reduce the risk of acute urinary retention and the need for BPH-
related surgery alone or in combination with tamsulosin.

BICALUTAMIDE
Pharmacodynamics
Competitive antagonist at androgen receptor. Bicalutamide is an antineoplastic hormonal agent primarily
used in the treatment of prostate cancer. Bicalutamide is a pure, nonsteroidal anti-androgen with affinity for
androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). Consequently,
Bicalutamide blocks the action of androgens of adrenal and testicular origin which stimulate the growth of
normal and malignant prostatic tissue. Prostate cancer is mostly androgen-dependent and can be treated
with surgical or chemical castration.

Pharmacokinetics
Absorption: Bicalutamide is well-absorbed following oral administration, although the absolute bioavailability
is unknown.
Volume of Distribution:
Metabolism: Bicalutamide undergoes stereo specific metabolism. The S (inactive) isomer is metabolized
primarily by glucuronidation. The R (active) isomer also undergoes glucuronidation but is predominantly
oxidized to an inactive metabolite followed by glucuronidation. Metabolized in the Liver.
Route of Elimination: Urine (36%), feces (42%)
Half-Life: 5.8 d Peak plasma time: 31 hr Peak plasma concentration: 0.77 mcg/mL

Clinical Uses
Used in patients with metastatic carcinoma of the prostate.

NPN INSULIN
Pharmacodynamics
Regulates glucose metabolism. Insulin and its analogues lower blood glucose by stimulating peripheral
glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production; insulin
inhibits lipolysis and proteolysis and enhances protein synthesis; targets include skeletal muscle, liver, and
adipose tissue. Insulin NPH and insulin regular is a combination insulin product with intermediate action that has
more rapid onset than that of insulin NPH alone.
Pharmacokinetics
Absorption: Administered intramuscularly, subcutaneously and intra-peritoneal. Bioavailability is well
absorbed. Onset is at 1-1.5 hr (a combination insulin product, insulin NPH and insulin regular, also has
intermediate action, but it has a more rapid onset than does insulin NPH alone); 4-12 hr peak effect. Duration of
14-24 hr.
Distribution: Distributed widely throughout the body.
Metabolism: Some insulin is bound and inactivated by peripheral tissues, but the majority appears to be
degraded in the liver and kidneys.
Route of Elimination: Filtered by the renal glomeruli and undergoes some tubular reabsorption. Plasma half-
life is about 9 minutes after I.V. administration. Excreted in the urine.

Clinical Uses
Used with a proper diet and exercise program to control high blood sugar in people with diabetes.
Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual
function problems. Use for proper control of diabetes may also lessen your risk of a heart attack or stroke.
Intended for Diabetes Mellitus Type I and Diabetes mellitus type II.

CRYSTALLINE ZINC INSULIN

Pharmacodynamics
Regulates of glucose metabolism. It promotes glucose and amino acid uptake into muscle and adipose
tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid,
and protein synthesis. It inhibits gluconeogenesis in the liver.

Pharmacokinetics
When administered Subcutaneously; effect begins approximately 30 minutes post-dose.
Peak insulin concentrations occurred between 1.5 to 2.5 hours post-dose
When administered by Inhalation; time to maximum serum insulin concentration ranges from 10-20 minutes
after oral inhalation of 4 to 48 units of human insulin.
The metabolism and elimination are comparable to regular human insulin
The swallowed fraction was not absorbed from the GI tract and was eliminated unchanged in the feces.

Clinical Uses
Indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.

CHLORPROPAMIDE
Pharmacodynamics
Chlorpropamide, a second-generation sulfonylurea antidiabetic agent, is used with diet to lower blood
glucose levels in patients with diabetes mellitus type II. Chlorpropamide is twice as potent as the related
second-generation agent glipizide.

Pharmacokinetics
Absorption: Readily absorbed from the GI tract. Peak plasma concentrations occur within 2-4 hours and the
onset of action occurs within one hour. The maximal effect of chlorpropamide is seen 3-6 hours following oral
administration.
Metabolism: Up to 80% of dose is metabolized likely through the liver to to 2-hydroxylchlorpropamide (2-OH
CPA), p-chlorobenzenesulfonylurea (CBSU), 3-hydroxylchlorpropamide (3-OH CPA), and p-
chlorobenzenesulfonamide (CBSA); CBSA may be produced by decomposition in urine. It is unknown whether
chlorpropamide metabolites exert hypoglycemic effects.
Route of Elimination: 80-90% of a single oral dose is excreted in the urine as unchaged drug and metabolites
within 96 hours.

Clinical Uses
Used as Antidiabetic agent. Used with diet to lower blood glucose levels in patients with diabetes mellitus
type II. For treatment of Non-insulin-dependent diabetes mellitus (NIDDM) in conjunction with diet and exercise.
COLESEVELAM HCL
Pharmacodynamics
Non-absorbable polymers that bind bile acids and similar steroids in the intestines preventing their
reabsorption, increases cholesterol utilization for replacement, and modestly lowers LDL levels by increasing
hepatic LDL receptors.

Pharmacokinetics
Absorption: Hydrophilic, water-insoluble polymer that is not hydrolyzed by digestive enzymes and is not
absorbed.
Volume of Distribution: Its distribution is limited to the gastrointestinal tract.
Metabolism: Not metabolized systemically and does not interfere with systemic drug-metabolizing enzymes
such as cytochrome P-450.
Route of Elimination: Excreted in urine or feces as a complex bound to bile acids

Clinical Uses
Approved for treatment of hypercholesterolemia and may be used for treatment of type 2 diabetes as an
adjunct to diet and exercise. Used for treating bile salt–induced diarrhea.

PRAMLINTIDE
Pharmacodynamics
Analog of amylin, binds to amylin receptors, reduce post-meal glucose excursions, lowers glucagon levels
and slows gastric emptying leading to decrease appetite. Suppresses glucagon release, delays gastric
emptying and has CNS-mediated anorectic effects.

Pharmacokinetics
Absorption: Injectable anti-hyperglycemic agent. It is rapidly absorbed after SQ injections (after eating).
Most reliable absorption from abdomen and thigh.
Metabolism and Elimination: Metabolized and excreted in the kidney.

Clinical Uses
Used for postprandial blood glucose levels Approved for pre-prandial use in person with types 1 & 2 DM.
Modulates postprandial glucose level. It is approved for use in insulin-treated type 1 and type 2 patients who
are unable to achieve their target.

SAXAGLIPTIN
Pharmacodynamics
Post-administration of saxagliptin, GLP-1 and GIP levels rise up to 2- to 3- fold. Because it is very selective of
DPP-4 inhibition, there are fewer systemic side effects. Saxagliptin inhibits DPP-4 enzyme activity for a 24-hour
period. It also decreased glucagon concentrations and increased glucose-dependent insulin secretion from
pancreatic beta cells. The half maximal inhibitory concentration (IC50) is 0.5 nmol/L. Saxagliptin did not prolong
the QTc interval to a clinically significant degree.

Pharmacokinetics
Absorption: Following a 5 mg single oral dose of saxagliptin to healthy subjects, the mean plasma AUC values
for saxagliptin and its active metabolite were 78 ng•h/mL and 214 ng•h/mL, respectively. The corresponding
plasma Cmax values were 24 ng/mL and 47 ng/mL, respectively. Saxagliptin did not accumulate following
repeated doses. The median time to maximum concentration (Tmax) following the 5 mg once daily dose was 2
hours for saxagliptin and 4 hours for its active metabolite. Bioavailability, 2.5 - 50 mg dose = 67%.
Metabolism: The metabolism of saxagliptin is primarily mediated by cytochrome P450 3A4/5 (CYP3A4/5). 50%
of the absorbed dose will undergo hepatic metabolism. The major metabolite of saxagliptin, 5-hydroxy
saxagliptin, is also a DPP4 inhibitor, which is one-half as potent as saxagliptin.
Route of Elimination: Saxagliptin is eliminated by both renal and hepatic pathways. Following a single 50 mg
dose of 14C-saxagliptin, 24%, 36%, and 75% of the dose was excreted in the urine as saxagliptin, its active
metabolite, and total radioactivity, respectively. A total of 22% of the administered radioactivity was recovered
in feces representing the fraction of the saxagliptin dose excreted in bile and/or unabsorbed drug from the
gastrointestinal tract.
Clinical Uses
Used as treatment of type 2 diabetes mellitus to improve glycemic control in combination with other agents
or as monotherapy.

ETIDRONATE
Pharmacodynamics
Supress the activity of osteoclasts in part via inhibition of farnesyl pyrophosphate synthesis, inhibit resorption
and formation of bone by acting on the basic hydroxyapatite crystal structure. Short-chain organic
polyphosphate compounds that reduce both the resorption and the formation of bone by an action on the
basic hydroxyapatite crystal structure. Primary toxicity of the low oral bisphosphonate doses used for
osteoporosis is gastric and esophageal irritation.

Pharmacokinetics
Available as oral medications. Oral bioavailability is low (<10%), and food impairs their absorption.

Clinical Uses
Used to manage the hypercalcemia associated with some malignancies. Used to treat Paget’s disease.
Chronic bisphosphonate therapy is used commonly to prevent and treat all forms of osteoporosis been shown
to increase bone density and reduce fractures.

CINACALCET
Pharmacodynamics
Activates the calcium sensing receptors in the parathyroid gland, inhibits PTH secretion. Cinacalcet is a drug
that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues). Secondary hyperparathyroidism
(HPT) in patients with chronic kidney disease (CKD) is a progressive disease, associated with increases in
parathyroid hormone (PTH) levels and derangements in calcium and phosphorus metabolism.

Pharmacokinetics
Absorption: Rapidly absorbed following oral administration.
Metabolism: Metabolism is hepatic by multiple enzymes, primarily CYP3A4, CYP2D6, and CYP1A2. After
administration of a 75 mg radiolabeled dose to healthy volunteers, cinacalcet was rapidly and extensively
metabolized via: 1) oxidative N-dealkylation to hydrocinnamic acid and hydroxy-hydrocinnamic acid, which
are further metabolized via ß-oxidation and glycine conjugation; the oxidative N-dealkylation process also
generates metabolites that contain the naphthalene ring; and 2) oxidation of the naphthalene ring on the
parent drug to form dihydrodiols, which are further conjugated with glucuronic acid.
Route of Elimination: Cinacalcet is metabolized by multiple enzymes, primarily CYP3A4, CYP2D6 and CYP1A2.
Renal excretion of metabolites was the primary route of elimination of radioactivity.

Clinical Uses
It is used for the treatment of secondary hyperparathyroidism in patients with Chronic Kidney Disease who
are on hemodialysis or peritoneal dialysis. Also for the treatment of hypercalcemia in patients with parathyroid
carcinoma.
GLYBURIDE
Pharmacodynamics
It is a 2nd generation sulfonylurea, acts as an insulin secretagogue; Increases insulin secretion from pancreatic
beta cells by losing ATP sensitive K+ channels.

Pharmacokinetics
Absorption: Almost completely absorbed from GI tract. A micronized tablet results in significant absorption; a
3-mg micronized tablet provides blood levels similar to a 5-mg conventional tablet.
Distribution: 99% protein-bound. Distribution isn’t fully understood.
Metabolism: Metabolized completely by the liver to inactive metabolites.
Excretion: Excreted as metabolites in urine and feces in equal proportions. Duration of action is 24 hours, and
half-life is 10 hours.

Clinical Uses
Glyburide is indicated alone or as part of combination product with metformin, as an adjunct to diet and
exercise, to improve glycemic control in adults with type 2 diabetes mellitus.
GLIPIZIDE
Pharmacodynamics
It is a 2nd generation sulfonylurea, acts as an insulin secretagogue; Increases insulin secretion from
pancreatic beta cells by losing ATP sensitive K+ channels. Glipizide is a blood glucose-lowering agent. The initial
onset of blood glucose-lowering effect occurs around 30 minutes post-administration with the duration of
action lasting for about 12 to 24 hours.

Pharmacokinetics
Absorption: Absorbed rapidly and completely from the GI tract.
Distribution: Probably distributed in the extracellular fluid. Drug is about 92% to 99% protein-bound.
Metabolism: Metabolized almost completely by the liver to inactive metabolites.
Excretion: Excreted primarily in urine; small amounts are excreted in feces. Renal clearance of unchanged
glipizide increases with increasing urinary pH. Duration of action is 10 to 24 hours; half-life is 2 to 4 hours.

Clinical Uses
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
mellitus.

NATEGLINIDE
Pharmacodynamics
Insulin secretagogue, similar to sulfonylureas with some overlap in binding sites, reduces circulating glucose,
increases glycogen, fat and protein formation and gene regulation.

Pharmacokinetics
Absorption: Rapidly absorbed when given 0-30 minutes prior to meal ingestion than if given during the meal
Distribution: Extensively bound to serum proteins
Metabolism: Extensively metabolized by cytochrome P450 2C9
Elimination: Eliminated in the kidney

Clinical Uses
For the treatment of non-insulin dependent-diabetes mellitus in conjunction with diet and exercise. • Used in
diabetics with sulfa allergies.

METFORMIN
Pharmacodynamics
Reduced hepatic and renal gluconeogenesis with decreased endogenous glucose production activates
AMP-stimulated protein kinase leading to inhibition of gluconeogenesis. Slowing of glucose absorption from GIT,
Increases glucose to lactate conversion by enterocytes. Direct stimulation of glycolysis in tissues. Increased
glucose removal from blood and Reduction of plasma glucagon levels.

Pharmacokinetics
Absorption: Oral administration; bioavailability is ~50% and is absporbed through the upper small intestine.
Distribution: Not bound to plasma proteins.
Metabolism: Not metabolized.
Elimination: Excreted by the kidneys as active compound.

Clinical Uses
Used as first line therapy for type 2 DM, insulin sparing (does not increase weight or provoke hypoglycemia).
Also, for prevention of type 2 DM and also used for fatty liver.

MIGLITOL
Pharmacodynamics
Competitive inhibitors of intestinal a-glucosidases: Sucrase, maltase, glucoamylase and dextranase. It
reduces post meal glucose excursions by delaying the digestion and absorption of starch and disaccharides,
six times more potent in inhibiting sucrase and has effects on isomaltase and β-glucosidases.

Pharmacokinetics
Absorption: After oral administration, it is rapidly and at low doses also completely absorbed
 Distribution: Virtually not bound to plasma proteins
Metabolism: Unknown
Elimination: It is rapidly eliminated from plasma with apparent elimination half-life of 0.4-1.8 hours

Clinical Uses
It is a FDA-approved for use in type 2 DM as monotherapy or in combination with sulfonylureas. It reduces
cardiovascular events in Diabetes.

TROGLITAZONE
Pharmacodynamics
Troglitazone is an oral antihyperglycemic agent which acts primarily by decreasing insulin resistance.
Troglitazone is used in the management of type II diabetes (noninsulin-dependent diabetes mellitus (NIDDM)
also known as adult-onset diabetes). It improves sensitivity to insulin in muscle and adipose tissue and inhibits
hepatic gluconeogenesis. Troglitazone is not chemically or functionally related to either the sulfonylureas, the
biguanides, or the g-glucosidase inhibitors. Troglitazone may be used concomitantly with a sulfonylurea or
insulin to improve glycemic control.

Pharmacokinetics
Absorption: Absorbed rapidly. Food increases the extent of absorption by 30% to 85%
Metabolism: A sulfate conjugate metabolite (Metabolite 1) and a quinone metabolite (Metabolite 3) have
been detected in the plasma of healthy males. A glucuronide conjugate (Metabolite 2) has been detected in
the urine and also in negligible amounts in the plasma. In healthy volunteers and in patients with type 2
diabetes, the steady-state concentration of Metabolite 1 is six to seven times that of troglitazone and
Metabolite 3. In in vivo drug interaction studies, troglitazone has been shown to induce cytochrome P450
CYP3A4 at clinically relevant doses.
Route of Elimination: Not Available

Clinical Uses
Troglitazone is use for the treatment of Type II diabetes mellitus. It is used alone or in combination with a
sulfonylurea, metformin, or insulin as an adjunct to diet and exercise.

DIAZOXIDE
Pharmacodynamics
Diazoxide is a potassium channel activator. Its mechanism of action revolves around enhancing cell
membrane permeability to potassium ions. This action consequently elicits the relaxation of local smooth
muscles. This switches off voltage-gated calcium ion channels which inhibits the generation of an action
potential.

Pharmacokinetics
Absorption: Readily absorbed following oral administration
Protein binding: Very high (more than 90%) to serum proteins.
Metabolism: Hepatic.
Route of elimination: Proglycem is extensively bound (more than 90%) to serum proteins, and is excreted in
the kidneys.
Half-life: 28 ±8.3 hours in normal adults.

Clinical Uses
Diazoxide is used parentally to treat hypertensive emergencies. Also used to treat hypoglycemia secondary
to insulinoma.
V. CHELATORS

DIMERCAPROL
Pharmacodynamics
The sulfhydryl groups of dimercaprol form heterocyclic ring complexes with heavy metals, particularly
arsenic, mercury, and gold, preventing or reversing their binding to body ligands. Due to its oily nature,
dimercaprol is not absorbed orally and its administration requires a deep intra-muscular injection that is
extremely painful and allergenic. It was found to mobilize and relocate lead to the brain, increasing its
neurotoxic effects. Despite that fact that dimercaprol increases cadmium excretion, there is an associated
increase in kidney cadmium concentration. Because of this, dimercaprol must be avoided in patients with
cadmium toxicity.

Pharmacokinetics
Absorption: Absorbed slowly through the skin. It is given by deep intramuscular injection as a 100-mg/mL
solution in peanut oil (should not be used in patients who are allergic to peanuts.)
Distribution: Distributed to all tissues, mainly the intracellular space, with the highest levels of dimercaprol
occurring in the liver and kidneys.
Metabolism: Uncomplexed dimercaprol is metabolized rapidly to inactive products.
Excretion: Most dimercaprol-metal complexes and inactive metabolites are excreted in urine and feces.

Clinical Uses
For the treatment of arsenic, gold and mercury poisoning. Indicated in acute lead poisoning when used
concomitantly with edetate calcium disodium. Most beneficial when given very soon after exposure to the
metal because it is more effective in preventing inhibition of sulfhydryl enzymes than in reactivating them. It
limits toxicity from arsenic, gold, and mercury, which form mercaptides with essential cellular sulfhydryl groups. It
is used in combination with CaNa2 EDTA to treat lead poisoning. Dimercaprol should not be used in iron,
cadmium, or selenium poisoning because the resulting metal complexes are more toxic than the metal alone,
especially to the kidneys. It is contraindicated for use following chronic exposures to heavy metals because it
does not prevent neurotoxic effects.

SUCCIMER (DMSA)
Pharmacodynamics
It is orally active, heavy metal chelating agent, chemically similar to dimercaprol but contains two carboxylic
acids that modify the spectrum of absorption, distribution, and chelation of the drug. It has an improved toxicity
profile over dimercaprol.

Pharmacokinetics
Absorption: After absorption, succimer is biotransformed to a mixed disulfide with cysteine. It is orally
bioavailable, and because of its hydrophilic nature, it does not mobilize metals to the brain or enter cells.
Excretion: eliminated in both urine and bile. The fraction eliminated in bile can undergo enterohepatic
circulation.

Clinical Uses
It has been approved in the U.S. for treatment of children with BLL greater than 45 μg/dL. It is used off label
for the treatment of adults with lead poisoning and for the treatment for arsenic and mercury intoxication,
although no large clinical trials have been undertaken for these indications.

EDETATE CALCIUM DISODIUM

Pharmacodynamics
It is an effective chelator divalent and trivalent metals in the body, in which CaNa2EDTA is the preferred
EDTA salt for metal poisoning. Accessible metal ions with a higher affinity for CaNa2EDTA than Ca2+ (such as
lead as well as endogenous iron, zinc, and manganese) will be chelated, forming water soluble complexes.
These complexes are mobilized, and usually excreted in urine. It does not significantly penetrate cells due to its
charged nature at physiological pH. It side effects include hypocalcemia and ECG changes. It is also
nephrotoxic, capable of causing renal tubular necrosis.
Pharmacokinetics
Absorption: Less than 5% of CaNa2EDTA is absorbed from the GI tract.
Route of administration: IV (diluted in either 5% dextrose or 0.9% saline) IM has good absorption but pain
occurs in injection site. In blood, CaNa2EDTA is found only in the plasma.
Half-life: 20-60 min
Metabolism: Very little metabolic degradation
Distribution: It is distributed mainly in the ECF, little to the spinal fluid (5% of plasma concentration)
Excretion: CaNa2EDTA is excreted in the urine by glomerular filtration. Excretion rate is not affected by pH or
rate of urine flow.
It is co-administered with dimercaprol in severe lead poisoning. To prevent dangerous hypocalcemia, EDTA is
given as calcium disodium salt.

Clinical Uses
It is used for Acute lead poisoning (in combination with dimercarpol). Make note that it is not an effective
chelator of arsenic and mercury in vivo.

UNITHIOL (DMPS)
Pharmacodynamics
It is a chelator of heavy metals (such as lead, arsenic and especially, mercury), in which forms water-soluble
complexes that are excreted in urine. Its side effects include mild dermatological reactions, vasodilation, and
hypotension.

Pharmacokinetics
Route of administration: Oral
Excretion: Rapidly excreted, primarily through the kidneys.
Distribution: Negatively charged, hydrophilic nature. It does not mobilize metals to the brain or enter cells.

Clinical Uses
It is use for Acute severe arsenic poisoning, Chronic arsenic poisoning, Acute severe mercury poisoning and
for Lead poisoning.

PENICILLAMINE
Pharmacodynamics
Penicillamine is a chelating agent used in the treatment of Wilson's disease. It is also used to reduce cystine
excretion in cystinuria and to treat patients with severe, active rheumatoid arthritis unresponsive to
conventional therapy. Penicillamine is used as a form of immunosuppression to treat rheumatoid arthritis.
Penicillamine inhibits macrophages, decreases IL-1 and the number of T-lymphocytes, and prevents collagen
cross linkage. In Wilson's disease it binds copper, allowing it to be eliminated in the urine.

Pharmacokinetics
Absorption: Well absorbed after oral administration.
Distribution: Limited data available.
Metabolism: Metabolized by liver to inactive compounds.
Excretion: Only small amounts excreted unchanged; after 24 hours, about 50% of drug excreted in urine and
about 50% in feces.

Clinical Uses
Used for treatment of Wilson's disease, used to reduce cystine excretion in cystinuria and used to treat
patients with severe, active rheumatoid arthritis that is unresponsive to conventional therapy.

DEFEROXAMINE
Pharmacodynamics
Deferoxamine, is a chelating agent used to remove excess iron or aluminum from the body. It acts by
binding free iron or aluminum in the bloodstream and enhancing its elimination in the urine. By removing excess
iron or aluminum, the agent reduces the damage done to various organs and tissues, such as the liver.
Pharmacokinetics
Absorption: Deferoxamine is rapidly absorbed after intramuscular or subcutaneous administration, but only
poorly absorbed from the gastrointestinal tract in the presence of intact mucosa.
Distribution: About an hour.
Metabolism: Deferoxamine is mainly metabolised in the plasma and hepatic metabolism is minimal. A
number of metabolites have been isolated but not characterised. Some metabolites of deferoxamine, most
notably the product of oxidative deamination, also chelate iron, and thus the antidotal effect of the drug
appears unaffected by hepatic metabolism.
Route of Elimination: Deferoxamine mesylate is metabolized principally by plasma enzymes, but the
pathways have not yet been defined. Some is also excreted in the feces via the bile.

Clinical Uses
Used to treat acute iron or aluminum toxicity (an excess of aluminum in the body) in certain patients. This
agent is also frequently used to treat hemochromatosis, a disease of iron accumulation that can be either
genetic or acquired. Reduces mortality in persons with sickle cell disease or β‐thalassemia who are transfusion
dependentAlso used in certain patients with anemia who must receive many blood transfusions.

DEFERASIROX
Pharmacodynamics
Deferasirox is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron
with high affinity in a 2:1 ratio. Although deferasirox has very low affinity for zinc and copper there are variable
decreases in the serum concentration of these trace metals after the administration of deferasirox.

Pharmacokinetics
Absorption: The absolute bioavailability (AUC) of deferasirox tablets for oral suspension is 70% compared to
an intravenous dose.
Metabolism: Hepatic. CYP450-catalyzed (oxidative) metabolism of deferasirox appears to be minor in
humans (about 8%). Glucuronidation is the main metabolic pathway for deferasirox, with subsequent biliary
excretion.
Route of Elimination: Deferasirox and metabolites are primarily (84% of the dose) excreted in the feces. Renal
excretion of deferasirox and metabolites is minimal (8% of the administered dose).

Clinical Uses
Oral treatment of iron overload caused by blood transfusions, a problem in the treatment of thalassemia and
myelodysplastic syndrome. Also, for the treatment of chronic iron overload due to blood transfusions
(transfusional hemosiderosis) in patients 2 years of age and older.

FERRIC HEXACYOFERRATE
Pharmacodynamics
Primarily by ion exchange, and secondarily by mechanical trapping or adsorption, the compound has high
affinity for univalent cations, particularly cesium and thallium.

Pharmacokinetics
Used as an oral drug, insoluble, undergoes minimal gastrointestinal absorption (<1%). Because the
complexes it forms with cesium or thallium are nonabsorbable, oral administration of the chelator diminishes
intestinal absorption or interrupts enterohepatic and enteroenteric circulation of these cations, thereby
accelerating their elimination in the feces.

Clinical Uses
Treatment of contamination with radioactive cesium (137Cs) and intoxication with thallium salts.