The document discusses the drawbacks of developing new drugs and advantages of reusing older drugs for new purposes. It notes that developing a new drug costs around $1 billion and can take 15 years for approval, with a high failure rate. In contrast, older drugs already have known safety profiles and lower costs. The document provides many examples of drugs rediscovered to treat different diseases than their original uses, such as sildenafil for erectile dysfunction. It concludes that advancing medical knowledge allows using older, proven drugs in new areas to benefit patients, as long as off-label use follows ethical guidelines.

1. NEW USES OF OLD
DRUGS
Dr.Biswajit Kalita
Tutor
Department of Pharmacology

2. DRAWBACKS IN BRINGING A NEW DRUG
 THE COST OF BRINGING A NEW DRUG TO THE MARKET IS AROUND ONE
BILLION WHICH INCLUDE PRECLINICAL AND CLINICAL COSTS .
 THE PROCESS OF APPROVAL MAY TAKE UPTO 15 YEARS.
 IT MAY PRODUCE UNACCEPTABLE ADVERSE REACTIONS OR TOXICITY IN
EARLY YEARS OF MARKETING LEADING TO LOSS.
 APPROXIMATELY 90% OF EXPERIMENTAL DRUGS IN THE INDUSTRY FAIL.

3. USING OLD DRUGS USED
NEW INDICATIONS
• The adverse effect of the old is already known
 The cost of such drug is 20 to 30% less than that of a newly
discovered drug
 These drugs are often used off-label(unapproved).
 In USA 40% to 50% of all prescriptions are written for
unapproved/unlabelled purpose.
 Serendipity plays an important role in identification of such
new uses of old drugs.

4. Drug repositioning
 Also known as Drug repurposing, Drug reprofiling,
Therapeutic switching and Drug retasking
 It is the application of known drugs and
compounds to new indications (new diseases).
• Using drug repositioning, pharmaceutical companies have achiev
ed of number successes, for example
– Pfizer's Viagra in erectile dysfunction and
– Celgene's thalidomide in severe erythema nodosum leprosum
• Advantage of drug repositioning over traditional drug developme
nt
– Repositioned drug has already passed a significant number of toxicity and
other tests,
– Its safety is known
– The risk of failure for reasons of adverse toxicology are reduced.

5. ADDITIONAL USE OF FEW DRUGS
DISCOVERED DURING CLINICAL USAGE
DRUG INITIAL USE ADDITIONAL OR NEW
PRIMARY USE
ALLOPURINOL ANTINEOPLASTIC GOUT
AMANTIDINE ANTIVIRAL ANTIPARKINSONISM
AMPHETAMINE STIMULANT HYPERKINESIS IN CHILDREN
ATOMOXETINE ANTIDEPRESSANT ADHD
CHLORDIAZEPOXIDE MUSCLE RELAXANT TRANQUILIZER
METRONIDAZOLE ANTITRICHOMONAL ANTIBACTERIAL
PEMETREXED MESOTHELIOMA LUNG CANCER
RALOXIFENE CONTRACEPTIVE OSTEOPOROSIS
SILDENAFIL ANGINA ERECTILE DYSFUNCTION

6. NEW USES OF OLDER DRUGS
DRUG MECHANISM OF ACTION NEW USES
ANGIOTENSIN
CONVERTING ENZYME
INHIBITOR &
ANGIOTENSIN RECEPTOR
BLOCKER
DECREASES ANGIOTENSIN
II→ALTERED CEREBRAL
VASOREACTIVITY
ACT ON AT1 RECEPTOR
ON BRAIN
COMPONENTS OF RENIN
ANGIOTENSIN SYSTEM
PRESENT ON EYE:PLAY A
ROLE IN AQUEOUS HUMOR
PRODUCTION,RETINAL
BLOOD FLOW
DECREASES IOP BY
PROMOTING FORMATION
OF PROSTAGLANDINS AND
ENHANCING UVEOSCLERAL
OUTFLOW
MIGRAINE
•GLAUCOMA

7. ANTI TNFα
eg etanercept,infliximab
TNFα ACT ON TNF
RECEPTOR PRESENT ON
NEUTOPHIL,FIBROBLAST,E
NDOTHELIAL
CELL:AMPLIFIES TISSUE
CYTOKINES,ENZYMES LIKE
COLLAGENASES AND
METALLOPROTEINASES
CICATRICAL PEMPHIGOID
SUBCORNEAL PUSTULAR
DERMATOSIS
TEN
SWEET SYNDROME
HYDRAADENITIES
SUPPURATIVA
BETA-BLOCKERS G-PROTEIN IN RBC IS
USED BY PARASITE TO
ENTER IT
TWO MAJOR Gs
ASSOCIATED RECEPTORS
ARE-BETA ADRENERGIC
AND ADENOSINE
RECEPTOR.SO BLOCKING
OF BETA RECEPTOR
PREVENTED INFECTION
MALARIA

8. BUDESONIDE GLUCOCORTICOID
HIGH TOPICAL:SYSTEMIC
ACTIVITY
UNDERGOES RAPID
BIOTRANSFORMATION IN
LIVER RESULTING IN LOW
POTENCY METABOLITE
GVHD
OTHER ORAL MUCOSAL
DISORDER
CALCIUM
CHANNEL
BLOCKERS
INHIBIT PLATELET
ACTIVATION PROBABLY BY
REDUCTION IN CALCIUM
INFLUX
IN PREVENTION OF PLATELET
ACTIVATION AFTER CORONARY
INTERVENTIONAL PROCEDURE

9. CIMETIDINE H2 ANTAGONIST WITH
IMMUNOMODULATORY
PROPERTY
INCREASES MITOGEN
INDUCED LYMPHOCYTE
PROLIFERATION AND
INHIBIT SUPRESSOR T-
CELL ACTIVITY
HUMAN PAPILLOMA
VIRUS INFECTION
EPIDERMODYSPLASIA
VERRRUCIFORMIS
CYCLOSPORIN A CALCINEURIN
INHIBITOR:REDUCES IL-2
DECREASES HISTAMINE
AND PGD2 BY MAST CELL
BLOCK ACTIVATION OF T-
CELL:ABILITY OF HIV TO
INVADE TE CELL IS
REDUCED.ALSO PREVENT
PROPER HIV VIRION
MATURATION
KERATCOJUNTIVITIS
SICCA
ASTHMAIMPROVEMENT
IN LUNG FUNCTION WITH
FEWER EXACERBATIONS
INVESTIGATED FOR USE
IN HIV-RESULT IS
CONFLICTING

10. COX-2 INHIBITOR COX-2 CAUSES PRE-RETINAL
NEOVASCULARISATION MEDIATED BY
PGE2 WHICH ACT ON EP3
RECEPTOR(PROSTAGLANDIN
ERECEPTOR 3)
ACIVATE PEROXISOME
PROLIFERATIOR NUCLEAR
TRANSCRIPTION FACTOR-g:
NEGATIVE REGULATOR OF
MACROPHAGE ACTIVATION
PROTECT NEURON BY DECREASING
RESPONSE TO GLUTAMATE BY
ACTING ON CALCIUM DEPENDENT
GLUMATE SIGNALLING PATHWAY
THERE IS INCREASED COX-2
EXPRESSION ON MALIGNANT
MELANOMA CELL
RETINOPATHY
ALZHEIMER’S DISEASE
CANCER
CHEMOPROPHYLAXIS IN
MELANOMA

11. FILGRASTIM(G-
CSF
RECOMBINANT)
STIMULATE PROLIFERATION AND
DIFFERENTIATION OFNEUTOPHIL
PROGENITOR CELL AND ALSO
PROLONGS ITS CIRCULATION
SEVERAL CYTOKINES AND GROWTH
FACTORS INCLUDING G-CSF HAVE A
KEY ROLE IN HOST’S ATTEMPT TO
RESTORE HOMEOSTASIS IN SEVERE
SEPSIS.
INHIBIT PRODUCTION OF
INFLAMMATORY CYTOKINES AS WELL
AS EXPAND T-HELPER CELL
LYMPHOCYTE RESPONSE THAT MIGHT
INCREASE PRODUCTION OF SPECIFIC
ANTIBODIES TO NEUTRALIZE
MICROBIAL PATHOGEN
PNEUMONIA
SEPSIS

12. GABAPENTINE INCREASES GABA IN CNS
DECREASES GLUTAMATE
BLOCK Na AND Ca CHANNEL
DECREASES PAIN THROUGH
DECENDING INHIBITORY
MECHANISM AND CHANGES IN
SYMPATHETIC SYSTEM
NEUROPATHIC PAIN
SACRAL PERINEURAL
CYST INDUCED PAIN
INHALED
FUROSEMIDE
IT MAY ACT AS
BRONCHODILATOR.THE EXACT
MECHANISM IS NOT KNOWN
ASTHMA

13. GLUCOCORTICOID LOW DOSE HYDROCORTISONE ACT AS
ANTIINFLAMMATORY AND IMMUNE
BALANCING ROLE IN ACUTE
SEPSIS→DECREASES PROINFLAMMATORY
CYTOKINES(IL-6,IL-8) AND TNFα
ACT SYNERGISTICALLY WITH INTERFERONS
TO PRODUCE Fc RECEPTORS ON HUMAN
MONOCYTE AND PERITONEAL
MACROPHAGES WHICH CORRELATED WITH
INCREASED PHAGOCYTOSIS
SEPTIC SHOCK

14. LEVAMISOLE ANTIHELMINTHIC DRUG
NICOINIC RECEPTOR
ANTAGONIST
ACT AS T-CELL
STMULATOR→SO IT ACTS
AS IMMUNOSTIMULANT
PEDICULOSIS
SLOW SPEADING
VITILGO
LIDOCAINE STEROID DEPENDENT
BRONCHIAL ASTHMA AS
NEBULIZED LIDOCAINE

15. MAGNESIUM SULPHATE BLOCK CALCIUM
MEDIATED SMOOTH
MUSCLE
CONTRACTION:RESULT IN
BRONCHODILATATION
COMPETE WITH
CALCIUM ENTRY IN
MUSCLE CELL
ASTHMA
TOCOLYTICS
MENATETRENONE(VIT K2) ACTIVATE OSTEOBLAST
AND PROMOTE BONE
FORMATION
ALSO INHIBIT BONE
RESORPTION THROUGH
INCREASED OSTEOCLAST
APOPTOSIS AND
DECREASED OSTEOCLAST
FORMATION
PREVENT PREDNISOLONE
INDUCED BONE LOSS

16. METHOTREXATE(MTX) PROMOTE
EXTRACELLULAR
ADENOSINE
RELEASE→BIND TO
ADENOSINE RECEPTOR ON
TARGET CELL→INHIBIT
PROINFLAMMATORY
AGENTS LIKE LTB4,TNFα
IN MACROPHAGE IT
INHIBIT EXPRESSION OF
TNFα,IL-6,IL-8
CROHNS DISEASE
PALMOPLANTAR
POMPOLYX
MYCOSIS FUNGOIDES
ASTHMA
METRONIDAZOLE DECREASES OXIDATIVE
STRESS BY INHIBITING
NEUTROPHIL GENERATED
INFLAMMATORY
MEDIATORS
SUPRESSES T-CELL
MEDIATED IMMUNITY
IMMUNOMODULATORY
EFFECT ON LEUCKOCYTE
CHEMOTAXIS
SEBORRHEIC DERMATITIS

17. NITOGEN
MUSTARD(MECHLORETHA
MINE)
IMMUNOMODULATOR
EFFECT ON T-
CELL→SPECIFIC
CYTOTOXIC EFFECT ON
PATHOGENIC
INFILTRATING T-CELL
MAY ACT AS TOPICAL
IMMUNOGEN LIKE
DIPHENCYPRONE
ALOPECIA AREATA
OCTREOTIDE ANALOGUE OF
SOMATOSTATIN
IT SLOWS GASTRIC
EMPTYING,INHIBIT
INSULIN RELEASE
DECREASES PEPTIC
SECRETION
INCREASES GUT TRANSIT
TIME
DUMPING SYNDROME

18. PACLITAXEL ANTIPROLIFERATIVE
AGENT
PROMOTE
POLYMERISATION OF α and
ß SUBUNIT OF
TUBULIN→STABILIZE
MICROTUBULE
PREVENT RESTENOSIS
AFTER CORONARY
ANGIOPLASTY
RETINOID IT HAS
ANTIPROLIFERATIVE,
DIFFERENTIATING, APOPTIC
WITH MODERATE
ANTITUMOUR ACTIVITY
AIDS-RELATED KAPOSI
SARCOMA

19. STATIN INCREASES BONE
VOLUME
INCREASES RATE OF BONE
FORMATION
OSTEOPOROSIS
TETRACYCLIN INHIBIT PHOSPHOLIPASE
A2→DECREASES
PRODUCTION OF
LIPOOXYGENASE,CYCLOXYG
ENASE
DECREASE
PROINFLAMMATORY
MEDIATORS
INCREASE INHIBITOR OF
MATRIX
METALLOPROTEINASES
OSTEOARTHRITIS
AS A DMARD

20. THALIDOMIDE IMMUNOMODULATOR AGENT
WITH
ANTIANGIOGENIC,ANTIINFLAMMAT
ORY PROPERTIES
IT CAN INDUCE G1 GROWTH
ARREST AND APOPTOSIS
DOWNREGULATE TNFα
MAY DECREASE
EXPRESSION OF ADHESION
MOLECULE ON MYELOMA AND
MARROW STROMAL CELLS
ANTIRETROVIRAL EFFECT AS
ARESULT OF INHIBITORY EFFECT ON
PRODUCTION OF TNFα
SARCOIDOSIS
APTHOUS ULCER IN HIV
BECHET DISEASE
CHRONIC GVHD
PLASMA CELL DISORDER
LIKE MYELOMA
OROFACIAL
GRANULOMATOSIS AND
ORAL MANIFESTATION OF
CROHN’S DISEASE
DISCOID LUPUS
ERYTHROMATOSUS
COMPLEX REGIONAL
PAIN SYNDROME
KAPOSI’S SARCOMA

21. ZILEUTON INHIBIT PRODUCTION OF LTB4→IT IS
NATURAL LIGAND FOR PEROXISOME
PROLIFERATOR ACTIVATED RECEPTOR-
gamma WHICH REGULATE
LIPOPROTEIN
METABOLISM,INFLAMMATORY
RESPONSE,CELL
PROLIFERATION,DIFFERENTIATION
AND APOPTOSIS IN CELLS INCLUDING
SEBACEOUS GLAND CELL
IT REVERSES AIRWAY CONSTRICTION
AND NUMBER OF INFLAMMATORY
CELLS IN LUNG
ACNE
RSV INFECTION

22. SIROLIMUS(RAPAMYCIN,R
APAMUNE)
IT INHIBIT ACTIVATION OF
mammalian TARGET OF
RAPAMYCIN(mTOR)→BLOC
K THE PROGRESSION OF
CELL CYCLE FROM G1→S
PHASE SO T-CELL ARE
ARRESTED IN G1 PHASE
ANTITUMOUR AGENT
Autoimmune
Lymphoproliferative
Syndrome
lymphangioleiomyo
matosis, a rare lung
disease
COLESEVALAM BILE ACID BINDING RESIN INITIALLY USED FOR
FAMILIAL
HYPERCHOLESTEROLAEMIA
IT HAS GAINED APPROVAL
TO IMPROVE GLYCEMIC
CONTROL IN TYPE 2
DIABETES

23. CONCLUSION
 WITH THE ADVANCEMENT IN OUR KNOWLEDGE IN VARIOUS FIELDS
OF MEDICAL SCIENCES,WE CAN MAKE USE OF TIME TESTED DRUGS
IN DIVERSE AREAS OF CLINICAL PRACTICE FOR THE BENEFIT OF THE
PATIENT.
 PHARMACEUTICAL MARKETING PRACTICES AND PHYSICIAN
DISSATISFACTION WITH CURRENTLY AVAILABLE TREATMENTS MAY
BE KEY FACTORS IN PRESCRIBING THE DRUG FOR OFF-
LABEL(UNAPPROVED) INDICATIONS.
 HOWEVER UNETHICAL PROMOTIONAL OF IRRATIONAL USE OF
DRUGS FOR BENEFIT OF PHARMACEUTICAL COMPANIES NEED TO
BE CURBED.
 IT IS IMPORTANT THAT OFF-LABEL USE OF COMPOUNDS BE
BROUGHT UP-TO-DATE WITH CURRENT FDA POLICIES AND TO
EMPHASIZE THE RESPONSIBILITY OF PRESCRIBING PHYSICIAN IN
USE OF THESE COMPOUNDS.