new uses for older drugs: aspirin, gabapentin and thalidomide

7/30/2019 NEW USES FOR OLDER DRUGS: ASPIRIN, GABAPENTIN AND THALIDOMIDE

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OMOTOSO KAYODE SUNDAY

010702027

11TH MAY, 2011


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INTRODUCTION

ASPIRIN

GABAPENTIN

THALIDOMIDE

CONCLUSION.


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The description of novel uses for establisheddrugs represent a growing trend in medicine, e.g. Gabapentin, an antiseizure now used in chronic

pains Thalidomide, a sedative now used in treating

neoplastic diseases

Aspirin, an analgesic currently used to treat ahost of ills. (Sirven, 2010)


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Most of these novel uses are based on the off-label

use of the drugs. (Muriel and Gillick, 2009)

Off-label use entails the use of drugs:

For unapproved clinical indications (e.g.,quetiapine [antipsychotic] for depression).

(Bennet, 2004)

In unapproved subpopulations (e.g., paroxetine

for depression in children). (American Academy ofPaediatrics, 2002)


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Off-label use is widespread and it is legal in the USaccounting for 21% of outpatient prescription.

(Muriel & Gillick, 2009)


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Aspirin is the most widely used drug in the world.(Vane &Botting, 2003; Bayer, 2010)

In 400BC, the Greek physician Hippocrates

described the use of the bark and leaves of thewillow tree to relieve pain and fever. (Sirven, 2010)

In 1832, salicylic acid was created from salicin.(Gerhardt, 1853)


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In 1897, acetylsalicylic acid (aspirin) wassynthesized and used to relieve rheumatism. (Vane &

Botting, 2003)

It was introduced into the market and became no.1drug for pain, fever and inflammation. (Sirven, 2010)

Vane (1971) described its mechanism of action asthe inhibition of the prostaglandin synthesis.


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10 pharmacological action of aspirin are analgesic,antiinflammatory and antipyretic. (Beaver, 1965)

Also inhibit platelet aggregation.

In 1988, the role of aspirin expanded beyond that ofpain relieving US Food and Drug Administration(FDA) proposed using aspirin to reduce the risk ofrecurrent myocardial infarction and to preventrecurrent transient ministrokes in men. (U.S. Preventive

Services Task Force, 2009; Wolffet al, 2009)


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Aspirin has been shown to be effective in reducing

cardiovascular morbidity and mortality in high-risk patients with myocardial infarction (MI) orstroke (secondary prevention). (Baigent et al, 2009)

Also recommended for prevention of CVD indiabetics at high risk. (Buse et al, 2007; Pignone et al, 2010)

Other uses explored for aspirin include theprevention of colon cancer, esophageal cancer, andother diseases. (Sirven, 2010)


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1-(aminomethyl)cyclohexane acetic acid, is astructural analogue of GABA. (Kong & Irwin, 2007)

It is effective as an adjunct to other anticonvulsants

in partial seizures and generalised tonic-clonicseizures. (Andrew & Fischer, 1994; Rose & Kam, 2002)

Was also effective as a monotherapy in partial

seizures. (Beydoun, 1999)


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Gabapentin has no direct GABAergic action anddoes not block GABA uptake or metabolism. (Roseand Kam, 2002)

In 2002, an indication was added for the treatment

of neuropathic pains.

Although the mechanism of action is not clearly

understood, it is thought to exert its clinical effectby selective binding of the 2 subunit of voltage-dependent calcium channels. (Gee et al, 1996)


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Gabapentin is one of drugs used in the treatmentprotocol for methamphetamine, cocaine, andalcohol addiction. (Bonnet et al, 1999; Weinstein et al, 2010)

It also helps those addicted to prescribed painmedications and reduces withdrawal syndromes.

(Weinstein et al, 2010)


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Off-label uses of gabapentin reported include: Bipolar disorder. (Letterman & Markowitz, 1999; Macdonald

& Young, 2002)

Attention deficit disorder. (Cabra et al, 1999)

Essential tremor. (Gironell et al, 1999) Hot flashes. (Loprinzi et al, 2002)

Drug and alcohol withdrawal seizures

Restless legs syndrome. (Bogan et al, 2010)

Opsoclonus-myoclonus syndrome associatedwith locked-in syndrome. (Pistola et al, 2010)


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Thalidomide (-N-[phthalimido] glutarimide) was firstsynthesized in 1953 by Ciba. (Rajkumar, 2004)

Was introduced into the market in 1957 as a non-

addictive, relatively risk-free sedative and for treatingmorning sickness . (James, 1993; Sirven, 2010)

Was taken off market in 1961 because of its potent

teratogenicity. (Lenz, 1988; 1992)


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Has R- and S- enantiomers

R- enantiomer ----- sedative activities S- enantiomer ----- teratogenic and antitumor

properties. (Stirling, 2000; Eriksson et al, 2001)

It was later re-introduced as treatment for: Erythema nodosum leprosum [ENL]. (Iyer et al,

1971)

Oral ulcer and wasting associated with HIV.(Youle et al, 1989; Reyes-Teran, 1996)


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A few decades later, the teratogenic effect ofthalidomide was exploited for its antineoplasticproperties. (Rajkumar, 2004)

Several major trials led to its approval for thetreatment of multiple myeloma and several relatedplasma cell disorders. (Rajkumar, 2004)


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Other promising uses still under investigationinclude: Karposi sarcoma (Little et al, 2000)

Renal cell carcinoma (Minor et al, 2002; Motzer et al, 2002)

Reflex sympathetic dystrophy syndrome(Rajkumar, 2004)

Inflammatory bowel disease. (Sirven, 2010)


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Mechanism of action is still unclear Inhibition of TNF-. (Sampaio et al, 1991; Moreira et al, 1993)

Promotion of the activity of T cells and natural killercells.

Inhibition of the release of cytokines. (Hideshima et al,2001; Mitsiades et al, 2002)

Toxicity peripheral neuropathy, constipation,sedation, deep venous thrombosis,hypothyroidism. (Rajkumar et al, 2000; Osman et al, 2001;

Zangari et al, 2002; Ghobrial & Rajkuymar, 2003)


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Many newer uses for old are been discovered forwhich the manufacturers never anticipated.

However, more and better detailed studies need to

be conducted to elucidate the efficacy of thesedrugs for their off-label indications.

Meanwhile, the tales of aspirin, thalidomide and

gabapentin are humbling reminders that thefuture uses of any therapeutic agent areunpredictable.


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new uses for older drugs: aspirin, gabapentin and thalidomide

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