Drug Profile

Pharmacology-2 (P0 802)

Clinical Programme

Pharmacology & Toxicology

 Triamcinolone
Glucocorticoid replacement
therapy

IDs from 2014110 to 2014123

 Triamcinolone
Background:
It is an intermediate-acting (lasts from 12 to 36 hours) synthetic glucocorticoid given orally or by injection or by
inhalation or as a topical ointment or cream.

History :
Triamcinolone acetonide has a history of use for almost 50 years history in the United States

Invention:
Publishing date: Apr 25, 1967
Marketed by: Bristol-Myers, Squibb, Princeton, New Jersey
Innovators: Chemists of the Schering Corporation in Broomfield New Jersey
Generic Name: Kenalog
IUPAC name: 1-dehydro-9-fluoro-16-hydroxyhydrocortisone
 Main Use
Glucocorticoid replacement therapy for
glucocorticoid effects such as:
Anti-inflammatory
Immunosuppressant agent
**However, triamcinolone is insufficient alone
for adrenocortical insufficiency (Addison's
disease) because essentially devoid of
mineralocorticoid activity.
Diseases and disorders:
Glucocorticoids are involved in treatment of many
diseases.
If there is a decline in the natural body production of
glucocorticoids then a replacement therapy must be
started.
External Glucocorticoids may be taken to speed up the
treatment of a certain disease.
Triamicinolone has a special function over other synthetic
glucocorticoids which is that it has zero salt/water
retention (no mineralocorticoid activity)
Cont.: Main Use
Triamicinolone may be used in the following cases:

Diseases Disorder

1. Asthma 1. Adrenocortical insufficiency

2. Dermatological diseases 2. Hypercalcemia
3. Allergic conditions 3. Rheumatic disorders
4. Neoplastic diseases 4. Ocular disorders
5. Thyroiditis 5. Hematological disorders
6. Pericarditis 6. Multiple sclerosis
Cont.: Main Use
Course regimen and treatment timeline
Course regimen:
Adult dose for adrenocortical insufficiency: 4 to 12 mg/day
orally + mineralocorticoid therapy.
Adult dose for anti-inflammatory: 2 to 3 injections of 40 mg at 1
to 2 weeks interval
Treatment timeline:
Differs according to different cases and situations
 Mechanism of action
They mainly act through intracellular receptors (steroid
receptors) which are bound to heat shock protein
(stabilizing protein that prevents receptor from
interacting with DNA unless GC binds to it).
GC enters the cell and binds to the specific receptor
forming a complex enters nucleus through a nuclear
pore bind to specific DNA sequence regions known as
Glucocorticoid response elements (GRE) which acts as an
enhancer to initiate transcription of specific gene
sequence.
Cont.: Mechanism of action
Triamcinolone is a synthetic analog for glucocorticoid with anti-inflammatory and
immune-modulating properties. Triamcinolone acts as an agonist.
Upon cell entry, it binds to and activates the glucocorticoid receptor (GR).
GR are widely distributed all over the body and also found in the brain.
The steroid-GR complex, moves into the nucleus where it binds to specific sequences on
the upstream regulation elements of the target genes, resulting in the increased
transcription of the gene with increased synthesis of gene products, which is the
increased production of glucocorticoids.
 Cont.: Mechanism of action
Glucocorticoids then decrease the production and
release of pro-inflammatory cytokines inhibit
phospholipase A2 block the release of arachidonic
acid (precursor of prostaglandins and leukotrienes)
from membrane bound protein phospholipid
decrease in PG and LK is a central anti-inflammatory
action influencing the inflammatory response by
stabilizing mast cells and basophil membrane
decreased release of histamine.
Off label use: Thyroid eye disease
A subconjunctival injection of triamcinolone was given to patients with grave's disease (Thyroid-associated
Ophthalmopathy) and showed promising results.
TAO is an autoimmune process that can cause periorbital inflammation leading to swelling, fatty infiltration,
and scarring of the eyelid muscles resulting in eyelid retraction and upper scleral exposure is the most
common clinical features of TAO.
A study suggests that an injection of 20 mg triamcinolone into the subconjunctival region of the lid, between
the conjunctiva and Muller's muscle, improves upper eyelid retraction within 1 month in three of the four
patients.
Even though this report is still a class 4 clinical trial, it has shown significant results.
Mechanism of action in Treatment of TAO:
Same mechanism of action is followed only the injection is completely absorbed in eyelid which makes it
locally acting and thus avoids all systemic side effects.
 Adverse effects
Common: Less common:
Anxiety Cough Rare:

Oliguria Insomnia Polyphagia

Dizziness and headaches Hirsutism Large, flat, blue or purplish

Irregular heartbeat
Mood changes
Shortness of breath
Swelling of the peripheries
Weight gain
patches in the skin
Muscle weakness
Pimples
Rashes and sweating
Redness, swelling, tenderness, or
Anorexia pain at the injection site
Nausea and vomiting Thinning of the scalp hair
Troubled healing
 Contraindications
Triamcinolone should not be used in the following cases:
Acute renal insufficiency Seizures
Pregnancy and lactation. Osteoporosis
Cushing syndrome Water Retention
Glaucoma and Cataracts Hypothyroidism
Chronic Heart Failure Diabetes

Ulcers Allergies towards corticosteroid

Recent article about the drug
Alternative receptor incorporated in
the treatment of the same disease

Unknown receptors or not yet discovered

 References
https://www.accessdata.fda.gov/drugsatfda_docs/summary_review/2008/022220s000_
SUMR.pdf
https://docs.google.com/viewer?url=patentimages.storage.googleapis.com/pdfs/US3316
152.pdf
https://www.drugs.com/monograph/triamcinolone.html
https://books.google.com.eg/books?id=jglFsz5EJR8C&pg=PA209&lpg=PA209&dq=triamci
nolone+discovery&source=bl&ots=DF4e3taV2a&sig=WcbFNryeQAlSLGZW1X0PU85VWb8
&hl=en&sa=X&ved=0ahUKEwid45KW_qTTAhVHJlAKHfppAtIQ6AEIPjAG#v=onepage&q=tri
amcinolone%20discovery&f=false
http://www.authorstream.com/Presentation/sambakolati-1614157-sar-corticosteroids/
https://www.youtube.com/watch?v=XTKxecofK64
https://www.ucalgary.ca/airwayinflammation/Newtonmc
Lippincott pharmacology 6th edition
http://www.uninet.edu/cin2001/html/conf/bala/bala.html
Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12th Edition
https://clinicaltrials.gov/ct2/show/NCT01599273?term=kenalog+thyroid&rank=2
http://www.nature.com/eye/journal/v22/n2/abs/6702933a.html
https://www.drugbank.ca/drugs/DB00620
https://pubchem.ncbi.nlm.nih.gov/compound/6436#section=GHS-Classification
https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020468s024lbl.pdf
http://www.webmd.com/drugs/2/drug-9/triamcinolone-acetonide-
injection/details/list-contraindications
https://www.drugs.com/drug-interactions/acarbose-with-triamcinolone-9-0-2232-
0.html?professional=1
https://www.drugs.com/drug-interactions/cipro-with-triamcinolone-672-332-
2232-0.html?professional=1
https://www.drugs.com/drug-interactions/isoniazid-with-triamcinolone-1393-0-
2232-0.html?professional=1
http://packageinserts.bms.com/pi/pi_kenalog-40.pdf
https://link.springer.com/article/10.1007/s00417-012-2153-y