Ketorolac
Systematic (IUPAC) name
(±)-5-benzoyl-2,3-dihydro- 1H-pyrrolizine-1-carboxylic acid, 2-amino-2-(hydroxymethyl)-1,3-propanediol
Identifiers
CAS number	74103-06-3
ATC code	M01AB15
PubChem	3826
DrugBank	DB00465
Chemical data
Formula	C15H13NO3
Mol. mass	376. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 4 g/mol
Pharmacokinetic data
Bioavailability	100% (All routes)
Metabolism	Hepatic
Half life	3. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The liver is a vital organ in the human body and is present in Vertebrates and some other animals The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity 5-9. 2 hrs, young adults; 4. The hour (symbol h) is a unit of Time. It is not an SI unit but is accepted for use with the SI 7-8. 6 hrs, elderly (mean age 72)
Excretion	Renal:91. Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The kidneys are complicated organs that have numerous biological roles 4% (mean) Biliary:6. Bile or gall is a bitter yellow or green Alkaline fluid secreted by Hepatocytes from the Liver of most Vertebrates In many species 1% (mean)
Therapeutic considerations
Pregnancy cat.	C(AU) C(US)
Legal status	℞ Prescription only
Routes	oral, I.M., I.V.

Ketorolac or ketorolac tromethamine (marketed as Toradol - generics have been approved) is a non-steroidal anti-inflammatory drug (NSAID) in the family of heterocyclic acetic acid derivatives, often used as an analgesic, antipyretic (fever reducer), and anti-inflammatory. The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during For a topic outline on this subject see List of basic Australia topics. The United States of America —commonly referred to as the The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction In Pharmacology and Toxicology, a route Intramuscular injection is the injection of a substance directly into a Muscle. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAID s or NAID s, are drugs with Analgesic, Antipyretic and in higher Antipyretics are Drugs that reduce body temperature in situations such as Fever. Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens Ketorolac acts by inhibiting bodily synthesis of prostaglandins. A prostaglandin is any member of a group of Lipid compounds that are derived enzymatically from Fatty acids and have important functions in the Animal body Ketorolac in its oral and intramuscular preparations is a racemic mixture of (S)-(−)-ketorolac, the active isomer, and (R)-(+)-ketorolac. In Chemistry, a racemic mixture, or racemate, is one that has equal amounts of left- and right-handed enantiomers of a chiral An ophthalmic solution of ketorolac is available under the name Acular, and is used to treat eye pain and to relieve the itchiness and burning of seasonal allergies.

The brand name Toradol is a trademark of the Syntex company of the United States. Laboratorios Syntex SA was a pharmaceutical company formed in Mexico City in 1944 by Russell Marker to manufacture therapeutic steroids from the Mexican yam The United States of America —commonly referred to as the

Contents 1 Chemistry 2 Mechanism of action 3 Indications 4 Contraindications 5 Adverse effects 6 Warnings and precautions 7 Cautions 8 Dosage, availability and price 9 External links 10 References

Chemistry

Ketorolac, like other 2-arylpropionate derivatives (including ketoprofen, flurbiprofen, naproxen, ibuprofen etc. Ketoprofen, (RS2-(3-benzoylphenyl-propionic acid (chemical formula C16H14O3is one of the propionic acid class of non-steroidal anti-inflammatory Flurbiprofen is a member of the Phenylalkanoic acid derivative family of Non-steroidal anti-inflammatory drugs (NSAIDs used to treat the inflammation and pain Naproxen ( INN) (nəˈprɒksən is a Non-steroidal anti-inflammatory drug (NSAID commonly used for the reduction of moderate to severe Pain, Fever Ibuprofen ( INN) (ˌaɪbjuːˈpɹəʊfɛn (from the now outdated nomenclature i so- bu tyl- pro panoic- phen olic acid is a Non-steroidal ) contains a chiral carbon in the α-position of the propionate moiety. The term chiral (pronounced /ˈkaɪɹ(əl̩/ is used to describe an object that is non- superimposable on its mirror image As such there are two possible enantiomers of ketorolac with the potential for different biological effects and metabolism for each enantiomer. In Chemistry, an enantiomer ( from the Greek ἐνάντιος opposite and μέρος part or portion is one of two Stereoisomers that are nonsuperimposable

NSAIDs are not recommended for use with other NSAIDs because of the potential for additive side effects. Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAID s or NAID s, are drugs with Analgesic, Antipyretic and in higher

The protein-binding effect of most non-aspirin NSAIDs is inhibited by the presence of aspirin in the blood. Aspirin, or acetylsalicylic acid (ASA (əˌsɛtɨlsælɨˌsɪlɨk ˈæsɨd is a Salicylate drug, often used as an Analgesic to relieve

Mechanism of action

The primary mechanism of action responsible for Ketorolac's anti-inflammatory/antipyretic/analgesic effects is the inhibition of prostaglandin synthesis by competitive blocking of the the enzyme cyclooxygenase (COX). In Pharmacology, the term mechanism of action (MOA refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect Anti-inflammatory refers to the property of a substance or treatment that reduces Inflammation. Antipyretics are Drugs that reduce body temperature in situations such as Fever. Like most NSAIDs, Ketorolac is a non-selective cyclooxygenase inhibitor. Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAID s or NAID s, are drugs with Analgesic, Antipyretic and in higher

As with other NSAIDs, the mechanism of the drug is associated with the chiral S form. Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAID s or NAID s, are drugs with Analgesic, Antipyretic and in higher Conversion of the R enantiomer into the S enantiomer has been shown to occur in the metabolism of ibuprofen; it is unknown whether it occurs in the metabolism of ketorolac. Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life.

Indications

Ketorolac is indicated for short-term management of pain (up to five days maximum).

Contraindications

Ketorolac is contraindicated in patients with a previously demonstrated hypersensitivity to ketorolac, and in patients with the complete or partial syndrome of nasal polyps, angioedema, bronchospastic reactivity or other allergic manifestations to aspirin or other non-steroidal anti-inflammatory drugs (due to possibility of severe anaphylaxis). Nasal polyps are polypoidal masses arising mainly from the Mucous membranes of the Nose and Paranasal sinuses They are overgrowths of the Angioedema ( BE: angiooedema) also known by its Eponym Quincke's edema, is the rapid swelling ( Edema) of the Dermis Bronchospasm is a sudden constriction of the muscles in the walls of the Bronchioles It is caused by the release ( Degranulation) of substances from Mast cells Allergy is a disorder of the Immune system often also referred to as Atopy. Anaphylaxis is an acute systemic (multi-system and severe Type I Hypersensitivity allergic reaction in humans and other Mammals As with all NSAIDs, ketorolac should be avoided in patients with renal dysfunction. (Prostaglandins are needed to dilate the afferent arteriole; NSAIDs effectively reverse this. ) The patients at highest risk, especially in the elderly, are those with fluid imbalances or with compromised renal function (e. g. , heart failure, diuretic use, cirrhosis, dehydration, and renal insufficiency).

Adverse effects

Similar to other NSAIDs. See inset "Ketorolac adverse effects. "

Ketorolac adverse effects
Body system	Effects
General	Edema. Oedema (or Edema in American English formerly known as dropsy or hydropsy, is the increase of Interstitial fluid in any organ &mdash swelling Less frequently, hypersensitivity reactions (such as anaphylaxis, bronchospasm, laryngeal edema, tongue edema, hypotension), flushing, weight gain, or fever. The larynx (plural larynges) colloquially known as the voicebox, is an organ in the Neck of Mammals involved in protection of the The tongue is the large bundle of Skeletal muscles on the floor of the Mouth that manipulates Food for chewing and swallowing (deglutition In Physiology and Medicine, hypotension refers to an abnormally low Blood pressure. For a person to flush is to become markedly Red in the Face and often other areas of the skin from various physiological conditions Weight gain is an increase in Body weight. This can be either an increase in Muscle mass, fat deposits or excess fluids such as Water. Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris Very infrequently, asthenia. Asthenia ( Greek: ασθένεια, lit lack of strength but also disease) is a medical term denoting symptoms of physical weakness
Cardiovascular	Hypertension. Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Less frequently, palpitation, pallor, or fainting (syncope). A palpitation (medical term ectopic heart beat) is an abnormal awareness of the beating of the Heart, whether it is too slow too fast irregular Pallor (also called pastiness or wanness) is a reduced amount of oxy Hemoglobin in Skin or Mucous membrane, a pale color which can
Dermatologic	Rash or pruritus. A rash is a change of the Skin which affects its color appearance or Texture. Itch ( Latin: pruritus) is an unpleasant Sensation that evokes the desire or Reflex to scratch Less frequently, Lyell's syndrome, Stevens-Johnson syndrome, musculo-papular rash, exfoliative dermatitis, or urticaria. Toxic epidermal necrolysis (TEN also known as Lyell's syndrome, is a life-threatening dermatological condition that is frequently induced by a reaction to medications Stevens-Johnson syndrome (SJS is a life-threatening Condition affecting the Skin in which Cell death causes the epidermis to separate from the Erythroderma is defined as a generalized skin disorder characterized by reddening and scaling of 100% of the Skin.
Gastrointestinal	Nausea, dyspepsia, gastrointestinal pain, constipation, diarrhea, flatulence, gastrointestinal fullness, vomiting or stomatitis. Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort Dyspepsia (from the Greek "δυς-" (Dys- and "πέψη" (Pepse known in plain English as indigestion, meaning hard Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm Constipation, costiveness, or irregularity, is a condition of the Digestive system in which a person (or animal experiences hard Feces that In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Flatulence is the production of a mixture of gases in the digestive tract of Mammals that are byproducts of the digestion process Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the Stomatitis is an Inflammation of the Mucous lining of any of the structures in the Mouth, which may involve the Cheeks, Gums, Less frequently, peptic ulceration, gastrointestinal hemorrhage, gastrointestinal perforation, melena, rectal bleeding, gastritis, eructation, anorexia, or increased appetite. A peptic ulcer, also known as PUD or peptic ulcer disease, is an Ulcer (defined as mucosal erosions equal to or greater than 0 Bleeding, technically known as hemorrhaging / haemorrhaging (see American and British spelling differences) is the loss of Blood from In Medicine, melena or melaena refers to the black "tarry" Feces that are associated with gastrointestinal Hemorrhage. The rectum (from the Latin rectum intestinum, meaning straight intestine) is the final straight portion of the Large intestine in some Mammals Gastritis is an inflammation of the lining of the stomach There are many possible causes Anorexia (deriving from the Greek "α(ν-" ( a(n-, a prefix that denotes absence + "όρεξη (orexe = appetite is the decreased sensation Very infrequently, pancreatitis. Pancreatitis is the Inflammation of the Pancreas. See also Acute pancreatitis and Chronic pancreatitis for more details
Hemic and lymphatic	Purpura. Purpura (from the Latin purpura, meaning "purple" is the appearance of red or purple discolorations on the Skin, caused by Bleeding underneath Less frequently, postoperative wound hemorrhage, thrombocytopenia, epistaxis, or anemia. Thrombocytopenia (or -paenia, or thrombopenia in short is the presence of relatively few Platelets in Blood. Epistaxis (or a nosebleed in Plain English) is the relatively common occurrence of Hemorrhage from the Nose, usually noticed when the blood drains Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative Very infrequently, leukopenia or eosinophilia. Leukopenia (or leukocytopenia, or leucopenia, from Greek λευκό -white and πενία -deficiency is a decrease in the number of Eosinophilia is the state of having a high concentration of eosinophils ( Eosinophil granulocytes in the Blood.
Neurological	Drowsiness, dizziness, headache, sweating, injection site pain. Somnolence (or " drowsiness " is a state of near- Sleep, a strong desire for sleep or sleeping for unusually long periods (c Many different terms are often used to describe what is collectively known as dizziness. A headache ( cephalalgia in medical terminology is a condition of pain in the Head; sometimes Neck or upper back pain may also be interpreted An injection is an infusion method of putting Liquid into the Body, usually with a hollow needle and a Syringe which is pierced through Less frequently convulsions, vertigo, tremors, abnormal dreams, hallucinations, or euphoria. An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting Vertigo (from the Latin vertere, to turn and the suffix -igo, a condition i Tremor is an unintentional somewhat rhythmic muscle movement involving to-and-from movements (oscillations of one or more parts of the body Dreams are the images sounds thoughts and feelings experienced while Sleeping, particularly strongly associated with Rapid eye movement sleep. A hallucination, in the broadest sense is a Perception in the absence of a stimulus. Euphoria is a medically recognized emotional state related to Pleasure and Happiness. Very infrequently, paresthesia, depression, insomnia, inability to concentrate, nervousness, excessive thirst, dry mouth, abnormal thinking, hyperkinesis, or stupor. Paresthesia (pron /ˌpɛɹɪsˈθiʒə/ paraesthesia in British English, pron In the fields of Psychology and Psychiatry, the terms depression or depressed refer to both expected and pathologically chronic or severe Insomnia is a symptom of a sleeping disorder characterized by persistent difficulty falling asleep or staying asleep despite the opportunity Anxiety is a physiological and psychological state characterized by Cognitive, Somatic, Emotional and Behavioral components Hyperkinesis is a state of overactive restlessness in Children. Stupor is the lack of critical cognitive function and Level of consciousness wherein a sufferer is almost entirely unresponsive and only responds to base stimuli such as pain
Respiratory	Less frequently, dyspnea, asthma and pulmonary edema. Dyspnea or dyspnoea (pronounced disp-nee-ah, IPA /dɪsp'niə/ from Latin dyspnoea, from Greek dyspnoia from Asthma is a chronic Condition involving the Respiratory system in which the airways occasionally constrict become inflamed, and are lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive Very infrequently, rhinitis or cough. Rhinitis is the medical term describing irritation and inflammation of some internal areas of the Nose.
Urogenital	Less frequently, acute renal failure. Renal failure or kidney Very infrequently polyuria or increased urinary frequency. In Medicine, polyuria is a condition characterized by the passage of large volumes of urine (at least 2 The urinary system (also called Excretory system or the genitourinary system (GUS is the Organ system that produces stores and eliminates Urine.

Warnings and precautions

The most serious risks associated with ketorolac are, as with other NSAIDs, gastrointestinal ulcerations, bleeding and perforation; renal events ranging from interstitial nephritis to complete renal failure; hemorrhage, and hypersensitivity reactions. The kidneys are complicated organs that have numerous biological roles Nephritis is Inflammation of the Kidney. The word comes from the Greek nephro- meaning "of the kidney" and -itis meaning "inflammation" Renal failure or kidney

As with other NSAIDs, fluid and solute retention and edema have been reported with ketorolac; ketorolac elevated liver protein levels; it also inhibits platelet aggregation and may be associated with an increased risk of bleeding.

It should be noted that when administered intravenously through the same IV catheter as Morphine the two drugs have been known to sometimes combine to form a precipitate in the IV, which may block the line. Line flushing with a syringe of saline can push the blockage through.

Cautions

Ketorolac is not recommended for pre-operative analgesia or co-administration with anesthesia because it inhibits platelet aggregation. Surgery (from the χειρουργική cheirourgikē, via chirurgiae meaning "hand work" is a medical specialty that uses operative manual and instrumental Anesthesia, or anaesthesia (see spelling differences; from Greek grc αν- an-, "without" and grc αἲσθησις

Ketorolac is not recommended for obstetric analgesia because it has not been adequately tested for obstetrical administration and has demonstrable fetal toxicity in laboratory animals. Obstetrics (from the Latin obstare, "to stand by" is the surgical speciality dealing with the care of a woman and her offspring during Pregnancy

Ketorolac has been co-administered with meperidine and morphine without apparent adverse effects. Pethidine ( INN) or meperidine ( USAN) (commonly referred to as Demerol but also referred to as isonipecaine lidol pethanol piridosal Algil Alodan Medical uses Morphine can be used as an analgesic in hospital settings to relieve pain in Myocardial infarction pain in

Ketorolac is not recommended for long-term chronic pain patients.

Dosage, availability and price

Oral dosage is 10 mg; United States price for 20 tablets hovers around US$28. Australian pricing for 20 tablets is around AU$43. 39. ^[1]

Injected dosages are 15, 30 and 60 mg; United States price for 10 vials of 30 mg each is around US$45, making the intramuscular preparation considerably more expensive per dose. One 60-mg dose would require the administration by injection of two vials, at about $9 per dose. Australian pricing for 5 vials is around AU$57. 90^[1], or $23. 16 per dose. Ketorolac is not available on the Pharmaceutical Benefits Scheme. The Pharmaceutical Benefits Scheme or PBS is a program of the Australian Government that provides subsidised prescription drugs to residents of Australia ^[2]

In the United States^[3], United Kingdom^[4], Canada^[5] and Australia^[6] this drug cannot be sold over-the-counter and must be administered only with a prescription. A prescription (℞ is a health-care program implemented by a Physician or other medical practitioner in the form of instructions that govern the plan of care for an individual

SYNTEX (U.S.A.) L.L.C., Palo Alto, California, U. Laboratorios Syntex SA was a pharmaceutical company formed in Mexico City in 1944 by Russell Marker to manufacture therapeutic steroids from the Mexican yam Palo Alto (ˌpæloʊˈæltoʊ from Spanish: palo: "stick" and alto: "high" i S. A. developed the ophthalmic solution Acular, and holds the registered trademark on that name. The brand name Acular product is manufactured and distributed by Allergan, Inc. Allergan Inc, is a global specialty Pharmaceutical company. Their product ranges include ophthalmic pharmaceuticals Dermatology products and , under license from Syntex. ^[7]

Apotex Products Group, a Canadian manufacturer, offers generic Ketorolac tromethamine 0. Country to "Dominion of Canada" or "Canadian Federation" or anything else please read the Talk Page A generic drug (generic drugs short generics is a drug which is produced and distributed without Patent protection 5% ophthalmic solution under the name "APO-KETOROLAC"^[8] in Canada and some other countries.

Syntex and Allergan sued Apotex for patent infringement of U. Patent infringement is the act of utilizing a patented Invention without permission from the Patent holder S. Patent No. A patent is a set of Exclusive rights granted by a State to an inventor or his assignee for a fixed period of time in exchange for a disclosure of an 5,110,493 over the generic Ketorolac tomethamine product. In May, 2005, the United States court of appeals for the Federal Circuit handed Apotex a victory, ruling that a lower court upholding the Syntex patent misapplied the rules for judging whether an invention was obvious. Year 2005 ( MMV) was a Common year starting on Saturday (link displays full calendar of the Gregorian calendar. The United States courts of appeals (or circuit courts) are the intermediate appellate courts Allergan claims the patent is valid until 2009. This article is about the year For the film see 2009 Lost Memories. ^[9]

External links

• rxlist.com monograph on ACULAR (ketorolac tromethamine ophthalmic solution) 0. 5% Sterile
• allergan.com ACULAR product information
• medicinenet.com information on ketorolac tromethamine - ophthalmic (Acular)
• Druglib published studies related to Toradol (Ketorolac)

References

• Handley, D. A. , P. Carvoni, J. E. McCray, J. R. McCullough (1998). "Preclinical Enantioselective Pharmacology of (R)- and (S)- Ketorolac. ", J Clin Pharmacol 38, 25-35.
• 1993. Physicians' Desk Reference, Forty-seventh edition. Montvale, N. J. , Medical Economics Co. Inc. , 2411-2415.

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