Download Historical background. Actions & therapeutic uses. Side effects

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The Contents
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Historical background.
Actions & therapeutic uses.
Side effects.
Contraindication & precautions.
Routes & Doses.
Pharmacokinetics.
Historical Background
• In early 1979, a chemist called Dr.Wilfried Bauer
synthesized a compound with the research number
SMS 201-995. The molecule was given the generic
name octreotide, reflecting its structure with eight
amino acids .
• Subcutaneous Somatostatin was launched in 1988,
and in 1991 it received the Prix Gallen.
• The long-acting formulation, was launched in 1997.
This provides patients with a more convenient
treatment option via a single injection every 4 weeks.
Actions
GH
• Anterior pituitary
TSH
• Gastrointestinal system
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Somatostatin suppresses the release of
gastrointestinal hormones:
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Gastrin
Cholecystokinin (CCK)
Secretin
Motilin
Vasoactive intestinal peptide (VIP)
Gastric inhibitory polypeptide (GIP)
• Lowers the rate of gastric emptying, and reduces smooth
muscle contractions and blood flow within the intestine.
• Suppresses the release of pancreatic hormones
• Inhibits the release of insulin
• Inhibits the release of glucagon
• Suppresses the exocrine secretory action of pancreas.
Therapeutic Uses
• Acromegaly.
• Tumors causing diarrhea like metastatic carcinoid &
VIPomas.
• Other causes of secretory diarrhea.
• Decrease the GI secretions.
• Insulinoma & correction of hypoglycemic drugs
overdosage.
• Varices associated with liver cirrhosis.
Side Effects
• >16%:
• Endocrine & metabolic: Hyperglycemia .
• Gastrointestinal: Diarrhea (36% to 58%),
abdominal discomfort (5% to 61%),
flatulence (<10% to 38%), constipation (9%
to 21%), nausea (5% to 61%), cholelithiasis
(27%; length of therapy dependent), biliary
duct dilatation (12%),loose stools (5% to
61%), vomiting (4% to 21%)
• nervous system: Fatigue (1% to 20%), malaise (16% to
20%), dizziness (5% to 20%), headache (6% to 20%), fever
(16% to 20%)
• Cardiovascular: Sinus bradycardia (19% to 25%), chest pain
(16% to 20%)
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Hematologic: Antibodies to octreotide (up to 25%)
• Local: Injection pain (2% to 50%; dose and formulation
related)
• Neuromuscular & skeletal: Backache (1% to 20%),
arthropathy (16% to 20%)
• Respiratory: Dyspnea (16% to 20%), upper respiratory
infection (16% to 20%)
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Miscellaneous: Flu symptoms (1% to 20%)
• 5% to 15%:
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Endocrine & metabolic: Hypothyroidism (2% to 12%),
goiter (2% to 8%)
• Gastrointestinal: Abdominal pain, anorexia, cramping,
dehydration, hemorrhoids, tenesmus (4% to 6%), dyspepsia
(4% to 15%), steatorrhea (4% to 6%), feces discoloration
(4% to 6%), weight loss
• Cardiovascular: Conduction abnormalities (9% to 10%),
arrhythmia (3% to 9%), hypertension, palpitation, peripheral
edema
• Central nervous system: Anxiety, confusion, depression,
hypoesthesia, insomnia
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Dermatologic: Pruritus, rash
• Genitourinary: UTI, renal calculus
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• Hematologic: Anemia
• Hepatic: Hepatitis
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Neuromuscular & skeletal: Arthralgia, leg cramps, myalgia,
paresthesia, rigors, weakness
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Otic: Earache, otitis media
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Respiratory: Coughing, pharyngitis, rhinitis, sinusitis
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Miscellaneous: Allergy, diaphoresis
• 1% to 4%:
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Endocrine & metabolic: Hypoglycemia (2% to 4%), hypokalemia,
hypoproteinemia, gout, cachexia, menstrual irregularities, breast
pain, impotence
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Gastrointestinal: Colitis, diverticulitis, dysphagia, gastritis,
gastroenteritis, gingivitis, glossitis, melena, stomatitis, taste
perversion.
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Cardiovascular: Angina, cardiac failure, cerebral vascular
disorder, edema, flushing, hematoma, phlebitis, tachycardia
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Central nervous system: Abnormal gait, amnesia, dysphonia,
hallucinations, nervousness, neuralgia, neuropathy, somnolence,
tremor, vertigo
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Dermatologic: Acne, alopecia, bruising, cellulitis.
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Genitourinary: Incontinence
• Hematologic: Epistaxis
• Hepatic: Ascites, jaundice
• Local: Injection hematoma
• Skeletal: Hyperkinesia, hypertonia
• Ocular: Blurred vision, visual disturbance
• Otic: Tinnitus
• Renal: Albuminuria, renal abscess
• Respiratory: Bronchitis, pleural effusion,
pneumonia, pulmonary embolism
Contraindication & Precautions
• CONTRAINDICATION: Hypersensitivity to
octreotide or any component.
• PRECAUTIONS — Patients must be monitored
closely for biliary tract abnormalities,
hypothyroidism, and glucose tolerance.
• use with caution in patients with renal impairment
and consider dosage modification in patients with
severe renal failure requiring dialysis.
• Chronic usage is associated with depressed
vitamin B12 levels so we monitor it’s levels in
patients receiving long-term therapy.
• Monitor growth hormone in long-term therapy.
• Pregnancy: class B
Doses
• Dosage should be individualized
according to the patient's response
• Secretory diarrhea : I.V., SubQ: Doses of 110 mcg/kg every 12 hours have been used
in children beginning at the low end of the
range and increasing by 0.3 mcg/kg/dose
at 3-day intervals. Suppression of growth
hormone is of concern when used as
long-term therapy.
• Congenital hyperinsulinism: SubQ: Doses
of 3-40 mcg/kg/day have been used.
• Acromegaly:
SubQ, I.V.: Initial: 50 mcg 3 times/day; titrate to
achieve growth hormone levels <5 ng/mL or IGF-I
(somatomedin C) levels <1.9 units/mL in males
and <2.2 units/mL in females. Usual effective
dose 100 mcg 3 times/day. Range 300-1500
mcg/day.
• Note: Should be withdrawn yearly for a 4 week
interval (8 weeks for depot injection) in patients
who have received irradiation. Resume if levels
increase and signs/symptoms recur.
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Continuous I.V. infusion rates have ranged from
25-50 mcg/hour for the treatment of esophageal
variceal bleeding.
Pharmacokinetics
• After subcutaneous injection, octreotide is absorbed
rapidly and completely from the injection site. Peak
concentrations of 5.2 ng/mL (100 mcg dose) were reached
0.4 hours after dosing.
• Using a specific radioimmunoassay, intravenous and
subcutaneous doses were found to be bioequivalent.
• The elimination of octreotide from plasma had an apparent
half-life of 1.7 to 1.9 hours compared with 1-3 minutes with
the natural hormone.
• Metabolism: Extensive by the liver
• Elimination: 32% excreted unchanged in urine