role of enzymes and enzyme modulators in the treatment of ... · role of enzymes and enzyme...

African Journal of Basic & Applied Sciences 5 (5): 205-213, 2013ISSN 2079-2034© IDOSI Publications, 2013DOI: 10.5829/idosi.ajbas.2013.5.5.7574

Corresponding Author: Kamal Kishore, Department of Pharmacy, (Pharmacology division), M.J.P. RohilkhandUniversity,Bareilly-243006, (U.P), India.

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Role of Enzymes and Enzyme Modulators in the Treatment of Diseases

Kamal Kishore

Department of Pharmacy, Pharmacology Division, M.J.P. Rohilkhand University, Bareilly-243006, (U.P), India

Abstract: The enzymes are mostly proteins and are natural biocatalysts; they catalyze many anabolic andcatabolic specific chemical reactions without itself undergoing any change in overall reaction. The temperature,pH, concentration of substrates and enzymes can affect their actions. The enzymes are useful in digestion,coagulation, tissue repair and numerous other life essential processes. The enzyme modulators are groups intwo i.e. enzyme inhibitors and enzyme activators, bounds to enzymes either reversibly or irreversibly. Theenzyme inhibitors are the molecules that correct a metabolic imbalance by reducing enzymatic activity, likeselegiline inhibit MAO enzyme, decreases the metabolism of dopamine in brain and useful in the treatment ofB

depression and other panic disorders. However, the enzyme activators enhance enzymatic activity, such astissue plasminogens activators activate the conversion of plasminogen to plasmin that digests fibrin, fibrinogenand other proteins and equally important to treat complicated diseases of heart.

Key words: Biocatalysts Biological Polymers Enzyme Inhibitors Enzyme Enhancers.

INTRODUCTION the enzymes or enzymatic systems. Dr. Edward Howell’s

Enzymes are the vital body substances they catalyze enzymes from foods help to pre-digest the food in thethe specific chemical reactions that make life [1]. More stomach. The plant enzymes such as protease,than 3000 enzymes catalyzing a wide array of reactions are amylase, lipase and cellulase are obtained from pineappleknown to exist. They are colloidal-proteins and can be and papaya; animal enzymes such as pepsin obtainedextracted from living tissues, purified and even from organs of cows and pigs are used as enzymecrystallized. The enzymes are also known as biological supplement for the treatment of non-digestive ailments.polymers or biocatalysts. They are the catalysts for many This article provides information on vital role of enzymesanabolic and catabolic reactions. A catalyst means a and their modulators in the management of diseasesubstance that enhances the velocity or rate of a free life.chemical reaction without itself undergoing any changein overall process [2]. Human intracellular enzymes A. Classification of Various Enzymes Necessary forwork best at 37 C and pH 7. They get denatured by high Various Vital Functions of the Daily Life:o

temperature, pH, chemicals, X-rays and gamma-rays.They are basically classified into six classes based on the 1. Enzymes useful in digestion: Bromelain,type of reaction catalyzed such as oxidoreductases, Chymopapain, Diastase, Pancreatin, Papain, Pepsin.transferases, hydrolases, lyases, isomerases and ligases.Recombinant technology was only possible after the 2. Enzymes useful in coagulation: Fibrinolysin,discovery of restriction endonucleases, the enzymes Streptokinase, Thromboplastin, Urokinase. used as cutters for a desired segment [3] of genes known 3. Enzymes useful in tissue damage: Chymotrypsin,as recognition sequences. There are various other Collagenase, Serratiopeptidase, Trypsin.enzymes that have great value in recombinant 4. Thrombolytic enzymes: Alteplase, Anistreplase,technology such as DNA polymerases, ligases, kinases, Duteplase, Reteplase, Saruplase, Streptase oralkaline phosphatases and nucleases [4]. They acts as streptokinase, Tenecteplase, Tissue plasminogendrug or many drugs produces their actions by modulating activator, Urokinase.

[5] worked on enzyme therapy and proposed that

African J. Basic & Appl. Sci., 5 (5): 205-213, 2013

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5. Therapeutic enzymes: Aeromonas aminopeptidase, 5. HMG-CoA-reductase inhibitors or fungalAgalsidase beta, Alpha-glactosidase-A, Dornase metabolites or statins: Atorvastatin, Cerivastatins,alpha, Galsulfase or N-acetylgalactosamine-4- Fluvastatin, Lovastatin, Mevastatin, Pravastatin,sulfatase, Imiglucerase or glucocerebrosidase or Rosuvastatin, Simvastatin.alglucerase, Laronidase or alpha-L-iduronidase. 6. -lactamase inhibitors: Clavulanic acid, Tazobactam,

6. Enzymes for miscellaneous use: Adenylyl cyclase, Sulbactam.Aldehyde dehaydrogenase, Alpha chymotrypsin, 7. Na K+ATPase inhibitors: Acetyl digoxin, AcetylAminopeptidase, Amylase, Angiotensinogenase, strophanthidin, Amrinone, Bufotoxin, Convallotoxin,Aromatase, Asparaginase, Synthase, Carbonic Deslanoside, Digitoxin, Digoxin, Gitalin, Gitoxin,anhydase, Cephalosporinase, Cholesterase, Co- Milrinone, Proscillaridin-A, Strophanthin-Genzyme Q10, Cyclo-oxygenase, Cytochrome-P, (Ouabain), Strophanthin-K, Theventin, -methylDecarboxylase, Dihydrofolate, Eductase, DNA digoxin.Polymerase, Dnase or Streptodornase, Esterases, 8. Na H ATPase inhibitors: Esomeprazole,Flavin enzymes, Folate synthetase, Gluco-6- Lanzoprazole, Omeprazole, Pantoprazole,phosphate dehydrogenase, Guanyl cyclase, HMG- Rabeprazole.CoA reductase, Hyaluronidase, Kininase-II-ACEIs, L- 9. Penicillinase inhibitors: Cloxacillin, Dicloxacillin,asparaginase, Lipase, Monoamino-oxidase-A andB, Methicillin, Nafcillin, Oxacillin.Na K ATPase, Na H /K+ATPase, Penicillinase, 10. Phosphodiesterase-inhibitors: Amrinone,+ + + +

Peptidase, Peroxidase, Phosphodiesterase, Benzimidazoline, Caffeine, Ibopamine, Inamrinone,Phospholipase-A andC, Protein kinase, Milrinone, Pimobendan, Theophylline, Vesnarinone.Streptokinase, Transcriptase, Tyrosine kinase, 11. Miscellaneous drugs that inhibit drug metabolizingUrokinase, Xanthine oxidase, Zymase, -lactamase. enzymes: Allopurinol, Amiodarone, Chloramphenicol,

B.classification of Various Agents That Inhibiting Erythromycin, Isoniazid, Ketokonazole,Enzymes: Metronidazole, Omeprazole, Phenylbutazone,

1. Aldehyde dehydrogenase inhibitors: Acamprosate,Citrated calcium carbimide, Disulfiram, Few C. Classification of Various Agents That Activatescephalosporins, Griseofulbin, Metronidazole, Various Enzymes: These are the agents which activateNaltrexone, Topiramate, Certain oral hypoglycemic plasminogen and convert insoluble clot to soluble. Theyagents. are effectively useful in the treatment of myocardial

2. Mono amino oxidase inhibitors: like-Streptokinase, Urokinase, i. Non selectivea. Hydrazines: Iproniazide, Isocarboxazide, Phenelzine. Tissue Plasminogen Activators: Alteplase, Anistreplase,b. Non-hydrazines: Tranylcypromine. Duteplase, Reteplase, Retiplase, Saruplase, Tenecteplase.ii. Isoenzyme selective Miscellaneous agents: ASVIN (an enzyme from snakea. MAO : Brofaromine, Clorgiline, Moclobemide, venom).A

Nialamide, Toxoxatone.b. MAO : Selegiline. Therapeutic Impact of Selected EnzymesB

3. Angiotensin converting enzyme inhibitors:Benazepril, Captopril, Cilazopril, Enalapril, Enalaprilat,Fosinopril, Imidapril, Lisinopril, Moexipril,Perindopril, Quinapril, Ramipril, Spirapril,Trandolapril, Zofenopril.

4. Renin-angiotensin antagonists: Candesartan,Eprosartan, Irbesartan, Losartan, Olmesartan,Saralasin, Telmisartan, Valsartan, Zolasartan.

+

+ +

Cimetidine, Ciprofloxacin, Diltiazem, Disulfiram,

Propoxyphene, Quinidine, Sulfonamides, Verapamil.

complications, thrombosis and angina pectoris

Co-enzyme Q10: It is a solid waxy, fat soluble vitamin likeco-factor required for the mitochondrial electron-transportchain. It is found in foods and synthesized in almost allbody tissues. It is also obtained from tobacco leafextracts, fermented sugar cane and beets. Its leveldecreases due to excessive exertion, hypermetabolism andacute shock. It is used in cardiovascular complications.Pharmacological actions: it protects cells of skin fromoxidative damage by UVR. It involved in electron


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transport and energy production in mitochondria. hypertension. Adverse effects: streptokinase may causeMechanism of action: it acts as co-factor and enhance anaphylaxis, bronchospasm, hypersensitivity, fever,ATP production, antioxidant prevent against peroxidation hypotension and arrhythmias. Uses: it is preferred in casesof lipid membranes and also inhibiting the oxidation of of acute arterial thromboembolism, acute myocardialLDL-cholesterol. ADME: well absorbed from small infarction, acute thrombotic stroke, deep venousintestine after oral administration, when taken with high thrombosis, local thrombolysis in the anterior chamber oflipid food, excreted in bile and faces. Interactions: the eye, myocardial infarction and unstable angina [9].HMG-CoA reductase inhibitors suppressed thebiosynthesis of Q10. Dose: 150-300mg/orally/day. Uses: it Urokinase: It is a proteolytic but not antigenic,is preferred in congestive heart failure, angina pectoris, fibrin-selective, thrombolytic, or fibrinolytic agent. It isischemia and reperfusion injury [6], atherosclerosis, developed by recombinant technology as pro-urokinaseamyotrophic lateral sclerosis, Parkinson disease, and is also derived from the human kidney (present inHuntington’s chorea, mitochondrial disorders, periodontal urine). It is converted to urokinase from pro-urokinasediseases, muscular dystrophy, immune dysfunctions, upon its binding to fibrin. Mechanism of action: it directlyobesity, aging disorders, cancer, to enhance athletic converts plasminogen into plasmin. Contraindicated in:performance and as cellular antioxidant [7]. bleeding risks, vascular aneurysm, endocardial thrombi

Alteplase: It is an enzyme that catalyzes tissue 12 hours/i.v. Adverse effects: urokinase may cause fever,plasminogen to plasmin and is commonly used to prevent bleeding, GIT bleeding and hemolytic stroke. Uses: it isclot-related myocardial disorders. Mechanism of action: preferred in cases like central deep vein thrombosis suchit dissolves blood clots by converting plasminogen into as superior vena cava syndrome and ascendingplasmin that digests fibrin, fibrinogen and other proteins. thrombophlebitis. It is also effective in acute coronaryInteractions: its action accelerates in combination with thrombosis, myocardial infarction and multiple pulmonaryheparin. Contraindicated in: bleeding, defective emboli [10].homeostasis, trauma, surgical procedures, stroke, acutepericarditis, hypoglycemia and hyperglycemia. Dose: 100 Anistreplase: Anistreplse or anisoylated plasminomg/i.v. infusion. Adverse effects: Alteplase may cause gen-streptokinase activator complex is a humannausea, vomiting, fever, arrhythmias, allergy, plasminogen and streptokinase. The anisoyl group ishypotension, intracranial hemorrhage and GIT bleeding. removed in blood by a hydrolytic deacylation process.Uses: it is preferred in cases of angina pectoris, as an Dose: 30 units/i.v. infusion over 2-5 minutes. Adverseanticoagulant, intravascular thrombosis, ischemic effects: anistreplase may cause hypotension and allergydiseases, myocardial infarction, pulmonary embolism and [11].to dissolve thrombi [8].

Streptase or Streptokinase: It is obtained from - technique and is a mutant of alteplase containing 527hemolytic streptococci group-C. It combines with amino acids. It is more fibrin-selective and more resistantcirculating plasminogen to form an activation complex, to plasminogen activator inhibitor-1. It is given as a singlewhich then causes limited proteolysis of other bolus injection of 30-50 mg. It has a longer t and greaterplasminogen molecules to plasmin. Antistreptococcal efficacy [12].antibodies present due to the initial dose of streptokinasemake a loading dose necessary in the beginning. Saruplase: It is a full-length, human, unglycosylated,Mechanism of action: streptokinase activates the single-chain polypeptide containing 411 amino acids,conversion of plasminogen (profibrinolysin) into plasmin urokinase type plasminogen activator and also known as(fibrinolysin), which stimulates the conversion of fibrin prourokinase. It is obtained by recombinant technology(insoluble) into fibrin fragments (soluble). Dose: 250,000 from E. coli. It is a fibrin-specific fibrinolytic agent and isunits followed by 100,000 units/hour for 1-3 days/i.v. effectively used for the treatment of thrombotic disordersContraindicated in: active internal bleeding, bleeding such as acute myocardial infarction. Dose: 20 mg/i.v.diathesis, cerebral tumor. If hemostasis is important, bolus followed by a 60 mg infusion for 60 minutes. Uses:pregnancy, previous cerebrovascular accident, recent it is preferred in thrombotic disorders and myocardialcranial trauma, surgery within ten days and uncontrolled infarction [13].

and allergy to streptokinase. Dose: 3,00,000 units/hour for

Tenecteplase: It is developed by the recombinant

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Imiglucerase: It is administered as enzyme replacement Pharmacological actions: it reduces mucous viscosity intherapy in Gaucher’s disease, a familial disorder affecting cystic fibrotic patients. Mechanism of action: cleavesmainly the liver, spleen, bone marrow and lymph nodes extracellular DNA and reduces sputum viscosity.due to the deficiency of beta-glucocerebrosidase activity, Precautions: breast feeding mothers. Dose: 2.5 mg/OD orleading to the accumulation of glucocerebrosidase in BD/inhaled by nebulizer. Adverse effects: dornase alphamany body tissues. It improves hematological may cause chest pain, conjunctivitis, laryngitis,abnormalities, hepatosplenomegalia and quality of life in pharyngitis, rashes, urticaria and changes in voice. Uses:patients of Gaucher’s disease. Mechanism of action: it it is preferred in the treatment of cystic fibrosis [17].catalyzes the hydrolysis of glucocerebrosidase to glucoseand ceramide. Dose: 60 units/kg/i.v. infusion/two weeks. Serratiopeptidase: It is a natural protein breaking enzyme.Adverse effects: imiglucerase may cause abdominal Pharmacological actions: It exerts anti-inflammatory,cramps, angioedema, diarrhea, dizziness, fatigue, fever, proteolytic, fibrinolytic and mucoprotease actions byflushing, headache, hypotension, nausea, vomiting, hydrolyzing bradykinin, histamine and 5HT. It controlstachycardia and urticaria. Uses: it is preferred in the permeability and reduces dilatation of blood capillaries.treatment of Gaucher’s disease [14]. Enhances fibrinolytic activity of plasmin by inhibition of

Agalsidase Beta: It is an enzyme used for the treatment of microcirculation by preventing clogging ofFabry’s disease; a lysosomal storage disorder caused by microcapillaries due to fibrin. Improving clearance anda deficiency of alpha-galactosidase, leading to drainage by reducing viscosity and elasticity of mucus.progressive accumulation of glycosphingolipids, Mechanism of action: it exerts anti-inflammatory,particularly GL-3 in many body tissues. Mechanism of proteolytic, fibrinolytic and mucoprotease actions byaction: it provides an exogenous alpha-galactosidase-A hydrolyzing bradykinin, histamine and 5HT. It alsoand catalyzes the hydrolysis of glycosphingolipids masking of antigenicity of -macroglobulin. Dose:including GL-3. Dose: 1 mg/kg/i.v. infusion/two weeks for 2.5-20mg/TDS. Uses: it is preferred in case of inflammatory20 weeks. Adverse effects: agalsidase beta may cause conditions like arthritis, atherosclerosis, fibrocystic breastnausea, vomiting, abdominal pain, abnormal tear cancer and carpal tunnel symdrome. It dissolves ovariansecretion, anemia, bradycardia, dizziness, drowsiness, breast cysts, no living tissues, blood cysts and arterialedema, fatigue, fever, headache, hypersensitivity plaques. It speed the healing of torn ligaments, sportsreactions, hypertension, injection site pain, myalgia, injures and post operative healing [18].palpitation, paraesthesia, proteinuria, tachycardia, tremorsand visual disturbances. Uses: it is preferred in the Trypsin: It is obtained from ox pancreas, destroystreatment of Fabry’s disease [15]. proteins and removes dead tissues and promoting

Laronidase: It is an enzyme used for the treatment of non- Contra-indicated in Asthma, Allergic conditions, hepaticneurological manifestations of mucopolysaccharidosis-I, disorders and renal failure. Adverse effects: burninga lysosomal storage disorder caused by the deficiency of sensation and pain at injection site. Uses: it is preferred inalpha-L-iduronidase. Dose: 0.58 mg/kg/i.v. infusion/once chronic wound treatment [19]. a week. Adverse effects: laronidase may cause flushing,musculoskeletal pain, rashes, headache and abdominal Chymotrypsin: It is a proteolytic enzyme, obtained frompain. Uses: it is preferred in non-neurological pancreas of bovine, speed up healing of damaged tissuesmanifestations of mucopolysaccharidosis-I and to and other complication. ADME: applied locally orimprove pulmonary functions [16]. administered orally. Uses: it is preferred in inflammatory

Dornase Alpha: It is an enzyme prepared from Chinesehamster ovary cells. It is a 260 amino acid, Alpha Chymotrypsin: It is used during surgery forphosphorylated, glycosylated, recombinant human extraction of dislocated lens of eye. It dissolveddeoxyribonuclease-1 (rhDNase) or is a genetically suspensory ligament of the lens. Adverse effects: raiseengineered product of a naturally occurring human intraocular tension, vitreous loss and retinal damage.enzyme that breaks extracellular deoxyribonucleic acid or Uses: it is preferred in to dissolve suspensory ligamentsDNA. It is useful in the treatment of cystic fibrosis. of dislocated lens of eye [21].

plasmin inhibitors. It reduces swelling and improves

2

wound healing. ADME: administered intravenously.

conditions [20].


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Hyaluronidase: It depolymerizes hyaluronate which - Antitrypsin: It is a proteolytic enzyme that hydrolyseforms a protective barrier in the tissues. Hyaluronidase and destroy proteins. It has a very vital function in lungs.prepared from mammalian testis can be used In normal lung the alveoli are chronically exposed to lowtherapeutically to enhance dispersion of drugs like local level of neutrophil elastase released from activated andanaesthetics in various parts of the body [22]. It enhances degenerating neutrophils. This proteolytic activity canspreading of drug fluids in intracellular spaces, destroy the elastin in the alveolar walls if unopposed byadministered through the subcutaneously or the inhibitory action of -antitrypsin. Deficiency of

antitrypsin results in emphysema. The deficiency ofantitrypsin can be reversed by intravenous administration

absorption of drugs by breaking ground substances. of -antitrypsin [29]. Dose: 150 units. Adverse effects: allergic reactions,anaphylaxis, enhances infections and spreading of Papain: It is dried and purified latex of the fruit of caricamalignant cells. Uses: it is preferred to enhances the fluid papaya belonging to the caricaceae family. It containsdiffusion of subcutaneously or intramuscular injection several proteolytic enzymes such as peptidase, renin,and to reducing ganglion cyst [23]. amylolytic, clotting and an enzyme with mild activity on

Collagenase: It is an exotoxin (a virulence factor) and cuts, acts as ant-inflammatory agent and along withhelps to facilitate the spread of gas gangrene. It normally antibiotics to treat skin diseases. It is an importanttargets the connective tissue in muscle cells and other ingredient of solutions used in cleaning contact lenses. Itbody organs [24]. Collagen, a key component of the is used in tenderizing meat, clarifying beverages, makinganimal extracellular matrix, is made through cleavage of cheese, softening textiles and tanning leather. It is alsopro-collagen by collagenase once it has been secreted used to raise platelet count in dengue fever [30], effectivefrom the cell. This stops large structures from forming in chikungunya, alcohol induced acute gastric damageinside the cell itself. Collagenase production can be and blood oxidative stress [31].induced during an immune response, by cytokines thatstimulate cells such as fibroblasts and osteoblasts and Chymopapain: It is protein, chemically related to papain,cause indirect tissue damage. Mechanism of action: it comparing 218 amino acids. Adverse effects: risk ofbreaks the peptide bonds in collagen and assist in anaphylactic shock. Uses: it is injected into thedestroying extracellular structures in pathogenesis of intervertebral disc for the treatment of sciatica due tobacteria such as Clostridium. Adverse effects: erythema herniated lumbar disc [32].and hypersensitivity reactions. Uses: it is preferred inremoval of dead tissues and promotes wounds and burns Bromelain: It is a protein digesting and milk clottinghealing [25]. enzyme. It consists of a mixture of proteolytic enzymes

L-asparaginase: L-asparaginase is required for the protein plant and ananas comsus, belonging to the bromeliaceaesynthesis. While most normal tissues are able to family. Uses: it is use as anti-inflammatory agent for softsynthesize L-asparaginase in amounts sufficient for the tissues and in case of oedema caused by surgery orprotein synthesis, some types of lymphoid malignancies injury, because it blocks pro-inflammatory agents and alsoderive the required amino acid from plasma. Asparaginase reduces migration of neutrophils to sites of acuteis an enzyme that catalyzes the hydrolysis of asparagine inflammation. It is investigated for the treatment ofto aspartic acid, deprives malignant cells of the asparagine traveler’s diarrhea, bruising, gout, arthritis, haemorrhoids,and leading to cell death [26]. Uses: it is preferred in acute menstrual pain, autoimmune disorders and AIDS. It is alsolymphoblastic leukemia, chronic lymphocytic leukemia, used for the commercial production of proteinHodgkin’s lymphoma, multiple myeloma, non-Hodgkin’s hydrolyzates, as a meat tenderizer and in leather industrylymphoma, plasma cell leukemia and to reduced [33].immunogenicity [27].

Dnase or Streptodornase: It is produced by hemolytic Disulfiram: Their active metabolite irreversibly inhibitsstreptococci that are used medically, often in combinationwith streptokinase to dissolve purulent or fibrinoussecretions from infections [28].

1

1 1-

intramuscularly and known as spreading factor. 1-

Mechanism of action: enhances spreading and1

fats. Uses: it digest proteins, helps in wound and minor

obtained from the stem and ripened fruits of the pineapple

Therapeutic Impact of Selected Enzymes Modulators

aldehyde dehydrogenase and ultimately increases theconcentration of acetaldehyde in tissue and blood thatcauses aldehyde syndrome. Symptoms: Flushing, burning


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sensation, throbbing headache, perspiration, Pharmacological actions: relaxes vascular smoothuneasiness, tightness in chest, dizziness, vomiting, visual muscles, reduces peripheral vascular resistance, blocksdisturbances, mental confusion, postural fainting and vasoconstrictor and secretary effects of angiotensin-IIcirculatory collapse and thirst. Dose pattern: Treatment is and enhances excretion of water, salts and uric acid.start after abstaining the patient or person or drinker from Mechanism of action: binds and antagonized the actionsalcohol overnight. Then disulfiram given 1gm on 1 day, of angiotensin-II mediated through AT receptors. ADME:st

0.75gm on 2 day, 0.5gm on 3 day, 0.25or 0.5gm daily for well absorbed after oral administration, bounds to plasmand rd

1-2 weeks followed by 0.125-0.25gm/day. Sensitization to proteins metabolized in liver into a more active carboxylicalcohol develops after 2-3 hours of first dose and lasts for acid metabolite and excreted in urine. Contraindicated in:7-14 days after stopping it. Contra-indicated in: pregnancy and breast feeding. Dose: 50mg/OD. Adversephysically dependent, cardiovascular disorders, epilepsy effects: anaemia, angioedema, asthenia, cough, dizziness,and cirrhosis. Adverse effects: rashes, metallic taste, fatigue, hepatitis, hyperkalaemia, hypotension, lightnervousness, malaise and abdominal pain. Uses: it is headedness, migraine, myalgia, pruritis, rashes, tastepreferred in the following cases to reduce cravings for disturbance, urticaria, vasculitis and vertigo. Uses: it isalcohol, to prevent alcohol drinking and in the treatment preferred in essential hypertension and hyperuricaemiaof chronic alcoholism [34]. [37].

Selegiline: It is a MAO enzyme inhibitor, decreases the Cardiac Glycosides: They are the drugs having cardiacB

metabolism of dopamine in brain. Mechanism of action: it inotropic property, increase myocardial contractility andacts by inhibiting the breakdown of dopamine in brain and output of a hypodynamic heart without increasing O

consumption. Mechanism of action: Inhibition ofDose: 5mg/BD/orally. Adverse effects: nausea and Na K ATPase enzyme and produce positive inotropicconfusion. Uses: it is preferred in depression, panic effect. Pharmacological actions: increased the force ofdisorders, chronic pain, Parkinsonism and Alzheimer’s contraction of myocardium. Decreased the heart rate bydisease [35]. increasing circulation (positive inotropic effect),

Captopril: It is a dipeptide, sulphyhydral containing activity, Direct action on SA and AV nodes, digitalisproline surrogate, angiotensin converting enzyme decreased the conduction (so increase the P-R interval ininhibitors hypotensive agent. Mechanism of action: ECG). In CHF patient it decreases vasoconstriction andinhibition of vasoendothelial kininase-II enzyme and peripheral resistance. In CHF patients it increases diuresisprevent the conversion of angiotensin-I to angiotensin-II but ineffective in other renal problems like edema state.or decreasing peripheral resistance. ADME: well absorbed Higher doses may cause nausea and vomiting,orally, converted into active forms in liver and excreted hyperapnoea, mental confusion, psychosis, visualthrough kidney. Interactions: NSAIDs inhibits disturbances and central sympathetic stimulation. Adversehypotensive action, hyperkalemia with potassium sparing effects: Abdominal, pain, anorexia, arrhythmias, diarrhea,diuretics, Antacids reduce bioavailability and lithium disorientation psychosis, fatigue, gynaecomastia,clearance inhibited. Contraindicated in: pregnancy due headache, hyperapnoea, malaise, mental confusion,to teratogenic effect. Dose: 25-50mg/BD/TDS/1 hour nausea, restlessness, skin rashes, visual disturbances andbefore or 2 hours after a meal. Adverse effects: acidosis, vomiting. Uses: they are preferred in congestive heartangioedema, bronchospasm, dizziness, dysguesia, fetal failure and cardiac arrhythmias [38].damage, flushing, GIT upsets, granulocytopenia,headache, hyperkalemia, hypotension, maculopapular Caffeine: It is a purine derivative alkaloid methylxanthine,rash, nausea, non-productive cough, photosensitivity,proteinurea, renal failure, skin rashes, stomatitis,tachycardia, vertigo, vomiting and weight loss. Uses: it ispreferred in hypertension, cardiac failure, myocardialinfarction, diabetic neuropathy and progressive renalinsufficiency [36].

Losartan: It is a vasoconstrictor, AT angiotensin-II1

antagonist and also have some ACE inhibiting properties.It is useful in the treatment of hypertension.

1

2

also interferes with reuptake of dopamine at synapses.+ +

increasing vagal tone, decreasing sympathetic over

stimulate CNS. Pharmacological actions: it stimulates thehigher centers of CNS and produces insomnia. Itstimulates respiration by acting on medullary centre andproduces wakefulness. It removes fatigue anddrowsiness. It improves performance and motor activities.It produces feeling of wellbeing, alertness and reducesfatigue. It enhances the contractile capacity of skeletalmuscles and it enhancing the secretion of HCl and pepsinin stomach. Mechanism of action: facilitateneurotransmission by increasing the release of


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acetylcholine. ADME: well absorbed after oral Tissue Plasminogen Activator: It is fibrin-selective butadministration from the GIT, widely distributed, t is 3-6 does not activate systemic plasminogen. It is synthesized1/2

hours, rapidly metabolized by demethylation and by recombinant technology and is also obtained fromoxidation in liver and excreted by kidneys. Interactions: cultured human melanoma cells. Mechanism of action: itenhancing the absorption of ergotamine and induces fibrinolysis of the formed thrombus byNeurotoxicity with antihistaminics and amantadine. preferentially activating plasminogen bound to fibrin.Contraindicated in: peptic ulceration. Dose: 200- Dose: 100 mg/i.v./3 hours. Uses: it is preferred in the500mg/day. Adverse effects: nausea, vomiting, gastric treatment of deep vein thrombosis [42].irritation, agitation, convulsions, delirium, excitement,insomnia, muscular twitching, nervousness, panic, CONCLUSIONpalpitation, restlessness, rigidity, rise in bodytemperature, tolerance and tremors. Uses: it is preferred in The enzymes are the biocatalysts; they catalyzenarcolepsy, algesia, tiredness, migraine and apnoea in many anabolic and catabolic specific chemical reactionsneonates [39]. without itself undergoing any change in overall reaction.

Allopurinol: It is a purine compound, structurally tissue repair and numerous other life essentialsimilar to hypoxanthine, converted to alloxanthine processes. The enzyme modulators i.e. enzyme inhibitorsand inhibits biosynthesis of uric acid. It is used to treat like MAO inhibitors in depression, ACEIs and reninhyperuricaemia. Mechanism of action: suppressed antagonists in hypertension, statins in hyperlipidimia,oxidation of purine to uric acid by inhibiting xanthine Na K ATPase inhibitors in congestive heart failure,oxidase enzyme. ADME: well absorbed after oral Na H ATPase inhibitors in ulceration, aldehydeadministration, t is 2 hours, excreted in urine, as such dehydrogenase inhibitors in alcohol withdrawal and1/2

or as alloxanthine. Interactions: suppressed many others may help to treat life threatening disorders.metabolism of 6-mercaptopurine, azathioprine, The enzyme activators such as tissue plasminogenswarfarin, theophylline, cyclophosphamide and oral activators also equally important to treat complicatedanticoagulants, rise skin reactions with ampicillin diseases of heart. The information regarding the enzymesand interfere with mobilization of iron. Contraindicated and their modulators may have a great value in properin: kidney and liver diseases, pregnancy and disease management.lactation. Dose: 50mg/day gradually increased upto300-600mg/day. Adverse effects: nausea, vomiting, REFERENCESdiarrhea, alopecia, aplastic anaemia, arthralgia,drowsiness, eosinophilia, exfoliation, fever, haemolytic 1. Robert, K., K. Danyl and W. Victor, 2006. Harper'sanaemia, headache, hepatitis, hepatotoxicity, illustrated biochemistry. 27th edition. Boston:hypertension, leucopenia, leukocytosis, liver damage, McGraw Hill Publishers, pp: 49-59.lymphadenopathy, malaise, myalgia, neuropathy, 2. Satyanarayana, U. and U. Chakrapani, 2007.paraesthesia, rashes, renal impairment, taste alteration, Biochemistry. 8th edition, Vijayawada: Uppalathrombocytopenia, urticaria, vasculitis, vertigo and visual Publishers, pp: 84-85.disturbances. Uses: it is preferred in chronic gout, 3. Kaplan, N.P., N.P. Colowick and R. Wu, 1980.hyperuricemia, nephropathy, tophi or uric acid stones and Recombinant DNA: recombinant DNA part F:given with cytotoxic agents to excrete out uric acid methods in enzymology. Academic Press, pp: 68. produce by cytotoxic agents [40]. 4. Glick, B.R. and J.J. Pasternak, 1994. Molecular

Clavulanic Acid: Produced by streptomycin clavuligeru, recombinant DNA. Washington, DC: ASM Press,poor antimicrobial activity irreversibly inhibits pp: 16-17.

-lactamases produces by gram+ve and gram-ve 5. Howell, E., 1995. Enzyme nutrition: the food enzymebacterias. Mechanism of action: prevent breakdown of comcept. Ist edition. Avery publishing group, USA.lactam ring by irreversibly inhibiting lactamase or pp: 1-167.penicillinase enzyme. Dose: 125mg with 250mg 6. Khan, A.K., P. Chattopathyay, D. Kumar, K. Kishoreamoxicillin/TDS or QID/orally. Adverse effects: diarrhoea and A.K. Wahi, 2009. Ischemic reperfusion injuryand nausea when combined with amoxicillin. Uses: with alters the rat heart activity. Arch. Appl. Sci. Res.,penicillins against penicillin resistance organisms [41]. 1(2): 74-80.

The enzymes are useful in digestion, coagulation,

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+ +

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