Principles Of Chemotherapy PDF

**PRINCIPLES OF CHEMOTHERAPY** 1\) The chemotherapeutic agent should be capable of Killing the Causative Organism or parasite while sparing the host organism life. (2) The distinction between disinfectant, antiseptic and antimicrobial is that the former permit systemic use while the latter is for i...

**PRINCIPLES OF CHEMOTHERAPY** 1\) The chemotherapeutic agent should be capable of Killing the Causative Organism or parasite while sparing the host organism life. (2) The distinction between disinfectant, antiseptic and antimicrobial is that the former permit systemic use while the latter is for invitro use ANTIBACTERIAL: these are agents used to treat bacterial infection. CLASSIFICATION OF ANTIMICROBIAL AGENTS. \(1) Based on reaction of the bacterial. (i)Bacteriostatic: These group of antibacterial agent inhibit the bacteria i.e it does not kill the bacterial but allows the natural body defend mechanism to act e.g include; macrolides, lincosamides. (ii) Bacteriocidal: These group of antibacterial agents kills the organism entirely e.g Quinolones \(2) Based on the Spectrum of activity: By spectrum we means the range of organism the drug can kill or inhibit. (i) Broad spectrum antibacterial: These group of antibacterial agent kill both Gram position and gram negative organisms, e.g Tetracyclines. (ii) Narrow Spectrum: These group of antibacterial agent kills either grand positive or grand negative organisms e.g Benzypenicilin, isoniazide. \(3) Based on mechanism of action: Based on mechanism it means that the way the anti-bacterial acts on the organism e.g Sulphanamides act by inhibiting the bacterial metabolic pathway, penicillin acts by inhibiting bacterial protein synthesis. ANTIBACTERIAL RESISTANCE. 1 enzymatic inactivation.-2 permeability barrier.- 3 efflux transporters.-4 Mutation.-5 Intrinsic resistance. -6 alternate metabolic partway **ENZYMATIC INACTIVATION**: Enzymes such as estherase, acetyltransferase inactivates antibacterial agents. The beta lactamase enzyme inactivate the beta lactam molecules rendering them inactive. e.g i) enzymatic inactivation in gram negative organisms; The beta lactamase molecule gets inactivated by beta lactam enzyme in a choline channels of the gram negative organism. They do so by preventing the binding of penicillin to its protein (penicillin binding protein). (ii) inactivation of gram positive organism; the beta lactamase enzyme also inactivate the Gram positive organism but they do so extracellularly. **PERMEABILITY BARRIERS:** Some bacterial resist the antibacterial agent By developing barriers. **EFFLUX TRANSPORTERS:** The bacterial resist antibacterial agent by exporting the drug as fast as they enter the cell. **MUTATION:** These are changes that occurs within the cells leading to resistance. **INTRINSIC RESISTANCE:** Some bacterial naturally resist antibacterial agent e.g E.coli naturally resistant to vancomycin because they are too large for it to pass through. **ALTERNATE METABOLIC PARTWAY:** Bacterial develops another metabolic pathway which the drug isn\'t used to thereby leading to antibacterial resistance. **Antibacterial agent. PENICILLIN** This is a drug of choice in treatment of streptococci, meningococcus, enterococci, trepomema pallidium and chlostridium specie. **CLASSIFICATION OF PENICILLIN**.1 Penicillin G and it\'s conveger V. Penicillin V is the oral form while G is the parentheral form. **2** penicillinase resistant penicillin e.g methicillin, nafcillin, isoxazole penicillin (cloxacillin, oxacillin,dicloxacillin). 3 Semi synthetic penicillin or extended spectrum penicillin: i) Amino penicillin (ampicillin, amoxicillin,becampicillin.(ii) Ureidopenicillin e.g mezlocillin, piperacillin and azlocillin Class: Beta lactam molecule M.O.A: it acts on the last step of the bacterial cell wall synthesis the transpeptidation reaction, they inhibit cell wall synthesis by binding protein which catalyzy transpepdoglycan synthesis leading to the death of the organism Indications: Anthrax, diptheria, tonsillitis, bacteial endocarditis, acute nephritis, sinusitis, gas gangrene, osteomyelitis Doses: 25000-60000 I.u. Route of Administration: I.m, i.v, oral, topical Side Effect: Hypersensitivity reaction, Angioedema, nephrotoxicity, bone marrow depression, neurotoxicity which would precipitate seizures. Contraindication: Hypersensitivity reaction, endolumbar (inthrathecal), epileptic patient NURSING RESPONSIBILITIES; 1 the drug should not be administered by entrathecal route to prevent seizures. - check patient history for Hypersensitivity reaction SEMI-SYNTHETICPENICILLIN: **Cloxacillin.** Class: penicillin resistant penicillin MOA: same as penicllin Indications: osteomyelitis, respiratory tract infection, ear,nose and soft tissue infections, meningitis, septicemia, urinary tract infection and GIT infection Route: oral. Dose: Adult-250-500mg t.d.s, Children of 2yrs half teaspoon full, 3-6yrs one teaspoon full q.d.s **SideEffect:** Rashes, diarrhea **Contraindication:** HSR and ocular admin. NURSING RESPONSIBILITIES; Do not mix with blood product, lipid emulsion **Amoxicillin/ Clavulanic acid. Class: B-lactamase inhibitor** B-lactamase inhibitor are agents that prevents B- lactam enzyme from destroying the beta lactam molecules e.g clavulanic acid and amoxicillin. MOA: it acts by blocking the B-lactamase enzyme thus rendering the organism susceptibility to amoxicillin, Rapid bacterial effect at concentration obtainable to the body. Indications: same with penicillin Side Effect: same with penicillin, diarrhea Contraindication: HSR, contraceptive Route: oral, I.v. Dose: oral adult= tab 375mg t.d.s 625 bd daily. Children 2-6yrs 5ml 225/5mls **CEPHALOSPORINES:** There are 5 generations. 1st: Cephalexin, Ceohalothin, Cephadrine,. 2nd: Cefaclor, Cefuroxime, Cefdroxil. 3rd:Ceftriaxone, Cefixime, Cefpodoxime. 4th: Cefepime, Cefpirome. 5th: Ceftaroline  CEFTRIAXONE. Class: Cephalosporines MOA: same as penicillin Indication: Klepsiella, enterobacter, H-influenza, proteus Ceftraixone is a drug of choice in treatment of gonorrhea, also meningitis in adults and children under 3 months. Side effects: Abdominal pain, nephrotoxicity, rashes Contraindications: Hsr Route : Iv, Im, Dose: 1-2 gram daily Nursing responsibilities: 1. Instruct client not to take alcoholic beverages or any medication containing alcohol.This is to prevent tachycardia, abdominal paiin and hypotension.-2. Check for history of HSR.  CEPHALEXIN Class: Cephalosporines Does: 250-500mg 6hrly CEFIXIME: Dose: Adults and children over 10 years, should receive 200-400mg daily. Children 6months- 8mg/kg in divided doses.  For gonorrhea -100mg in divided doses. 5-10years- 20mg daily **CARBAPENEMS** Eg: Doripenem, imipenem, ertapenem, meropenem. imipenem are susceptible to degradation by the enzyme called dehydro-peptidase 1 which is found in the border of the renal tubules. This enzyme forms inactive metabolite that is potentially nephrotoxic subsequently with an inhibitor of renal dehydro-peptidase enzyme. Cilastin blocks the metabolism of imipenem in the kidney Thus, blocking it\'s toxicity. Cilastin has no antimicrobial activity/action. Side effects: Nausea, vomiting, diarrhea, skin rashes, seizures, liver and renal failure Dose; 0.25-0.5g in divided does. Doripenem: 0.5g every 4hours. Meropenem: 0.5g-1g 8 hourly Indication: same with cephalosporines Contraindication: HSR MOA: same with cephalosporinnes Nr: same with cephalosporines Side effects; Nausea, Vomiting, diarrhea, small rashes and seizures along with renal failure. Route: Iv, I\'m. Imipenem; Dose: 0-25 - 0.5g in divided doses. doripenems: 0-5g every 4hrs meropenem: 0.5- 1 gram every 8 hrly Contralindication: Hypersensitivity reaction INDICATION: Same with cephalosporin AMINOGLYCOSIDE: These are bacterocidal though most protein synthesis inhibitors are bacteriostatic. Examples are kenamycin, tobramycin, amikacin, Paromycin, Neomycin, Netilmycin and Gentamicin. GENTAMICIN. Class: Aminoglycosides MOA: Aminoglycoside are irreversible inhibitor of protein synthesis, they enter through the porin channels of gram negative Organism binding to Specific 30s ribosomal sub-unit Leading to the production of nonfunctional proteins. Binding to a Specific receptor of bacterial 30s ribosomal Sub unit to produce misinterpretation of genetic instruction from messenger RNA (MRNA) resulting in improper insertion of amino acid protein. INDICATIONS: Aerobic gram negative bacilli, Urinary tract infection, lower respiratory tract infection, Gastro intestinal infection, bone and soft tissue infections, meningitis Eye infections, Infections due to burns, surgical wound ROUTE: IM, IV,Topically and subconjuntiva by Instillations. DOSE: 60 - 80mg 8hrly 7-10 days or 2ml as a single dose for premature/neonate 6mg/kg in 2 doses, infants and children up to 2yrs 6mg/kg in 3 doses. SIDE EFFECTS: Reversible and irreversible autotoxicity which could be Vestibular or ocular, hypersensitivity reaction, neuromuscular blockage and respiratory depression. Contra indication: First trimester of pregnancy and respiratory depression N/R: The drug should not be administered to a patient who are pregnant in their 1st trimester. -Gentamycin should be administered with caution to infants and neonates with poor renal development. NB: 7 - 10 days 3 Suffice to treat the disease. -The dropper of the clients eye-drop shouldn\'t touch the patients eyelid.- should not be concurrently administered to patient receiving diuretics so as to avoid aminoglycoside toxicity **TETRACYCLINES;** they are broad spectrum antibacterial which are bacteriostatic. They also inhibit protein synthesis: They kill both gram positive and negative organism**.** Examples are Oxy-tetracycline**,** Tetracycline**,** Clo-tetracyclines**.** Tetracycline are also classified into old and new tetracyclines. Old tetracyclines: tetracycline, methacycline, oxytetracycline, lymecycline, rolitetracycline. New tetracycline: Ninocycline, dioxycycline, aminocycline. \"They are also classified in to short acting, intermediate active long acting tetracyclines, TETRACYCLINE. CLASS: Tetracyclines MOA; It Inhibits protein synthesis by binding to 30s ribosomal sub-unit thereby blocking the banding of amino acylTRNA to acceptors site of messenger MRNA ribosomal complex. This prevents addition of new amino acid to the growing peptide chain thus, inhibiting protein synthesis INDICATIONS: Bronchitis, amoebic dysentry, cholera, Pneumonia, urethritis, Prostatitis, Syphilis, clamydia infections. Route; Oral, IM, IV, Topical. Dose; 500mg start 6hrly for 5days, for Urinary tract infection 250-500mg, Orally 4x dly for 10 days SIDE EFECTS; GIT irritation, Nausea, Vomiting, Photosensitivity can also be induced especially in fair patient, Hepatic toxicity, renal insufficiency, discoloration of the teeth due to chelation of calcium orthophosphate complex Contra- indication; Pregnaney, HSR, children less than 8yrs due to teeth discoloration. Nursing Responsibility; -fluid should be Used so as to wash down the tablets so as to reduce the risk of esophageal ulcer, -The drugs shouldn't be given 2 children less 8 yrs. -Antacid containing aluminum and calcium shouldn't be administered with tetracycline. -It shouldn\'t be administered without meal or 1-2 hrs after meal. MACROLIDE; Examples are Erythromycin, Roxitromycin, Dinthromycin, Clarithromycin, Azithtromycin (CREAD) ERYTHROMICIN. CLASS: Maclolides M.O.A; It Inhibit protein synthesis by binding irreversibly to 50s ribosomal Sub-unit which blocking the amino acyl translocation leading to the death of the organism. NOTE: Erythromycin base Inactivated by gastric acid and as such must be administered as enteric coated tablet Indication; Legionella disease, clamydia, pneumonia, diphtheria, staphylococci, Syphilis. Side effects: Jaundice, GIT disturbances, Hepatitis, auto toxicity Route; Oral IV. Dose; Adult dose 250-500 mg 6 hourly or 500mg bd. children 125 mg Qds Contra indication; HSR, Impaired liver and kidney disease, pregnancy, Concomitant use of astemizole (Anti histamine), corticosteriods, ergotamine, vaproic acid Nursing Responsibility.- Monitor patient vital signs because the said drug increase QT interval. - The drug should be administered with caution to patients with hepatitis because its the liver metabolized the drug. **CHLORAMPHENICOL;** this do not belong to any class, it is a drug and also a class of drug MOA; It acts by inhibiting Protein synthesis by binding to 50s ribosomal sub-Unit, this inhibitions is due to inhibition of peptidyl transferase step of protein synthesis thereby preventing the insertion of amino acid in a chain Indication; typhoid fever, meningio cocci bacteria, anaerobic infections, ricketisia infection such as rocky mountain fever and brucellosis Side effects; Haematalogic toxicity\", bone marrow depression which is dose related and reversible, suppression of red blood cell presenting as Anaemia, Thrombocytopenia, aplastic anemia which is non- dose related, In neonate the drug causes a condition called Gray baby syndrome Route; Oral, Iv, Topical, instillation. Dose;1- 2 caplet 6 hrly, in children 1/2 tea spoon every 6 hours Contra-indication; Neonates or premature infants, tolbutamide, Warfarin, Penitonlyn, penicillin and aminoglycoside NR- Watch out for hyper-sensitively reaction rwaction, don\'t touch the dropper of the eye drop, must not exceed 21 day after opening. -Avoid prolonged high dose so as prevent aplastic anaemia. -Anaemic patient should not receive the drug and if they should, get a hematinic class of drug (folic acid) to treat the anaemia. **QUINOLONE:** Earliest generations; Nalidizic acid**,** Cinoxacin**.** 2nd Generation**;** norfloxacin**,** Enoxacin**,** Lomefloxacin**, O**floxacin**,** Ciproflaxocin**.** 3rd Generation; Levofloxacin**,** Gartifloxacin**,** Gemifloxacin**,** sparfloxacin**.** 4th Generation**;** Tranfluxaxin CIPROFLOXACIN. Class: Quinolones MOA: Quinolones blocks bacteria DNA Synthesis by inhibiting Topo-isomerase II and IV (DNA gyrase mediated super coiling of DNA) required for transcriptions and replication. Topo-isomerase are enzyme that change the configuration and topology of the DNA **indication**; Urinary tract-infection, respiratory tract infection, Bone, joint, soft tissue Infections, GIT infection, Myco bacteria Infections, It is also use in multi-drug resistant tuberculosis **Side effects;** Nausea, abdominal discomfort, Headache, Dizziness, seizures, rashes, damage to growing cartilage arthropathy. **Contraindications:** Pregnancy, sparfioxcin and gemifloxacins can prolong QT interval and such must not be used from arrythmic patient **Rout;** Iv, oral, Instillation. **Dose**; UTI and, GIT infection 500 mg bd. NOTE: Ciprofloxacin is supposed to treat a disease after 7 - 10 days Nursing responsibility: 1.The drug should be taken without food so as to accelerate absorption.-Caution should be taken in epileptic patient or cerebral arteriosclerotic patient.- The drug should not be taken with antacid so as not to reduce its absorption.- The drug should be administered with anti convulsant for patients suffering from seizure. - The drug should be taken with copious fluid so as to prevent formation of crystal urea. NB: The drug can be used as a second line treatment in tuberculosis management as well as peptic ulcer. **URINARY TRACT ANTISEPTICS/ANTI MICROBIALS** UTI in women of Childbearing age and in the elderly are one and the most Common Problems Seen by primary Care physicans. Escherichia Coli is the cause, the most Common pathogen; Staphylococeus Saprophyticus is the Second most Common bacteria pathogen Causing UTI. Others, Klebsiella pneumonia and proteus mirabilis **DRUG TREATMENT** Methenamine, Nitrofurantoin and Quinolones, Nalidixic acid. Drug Inhibits bacterial growth in Urine because they are Concentrated in renal tubules. **METHENAMINE (HEXAMENYLENE TETRAMINE)** Group: -Hexamethylene tetramine. M.O.A: It hydrolysis the drug to formaldehyde (which is toxic to most bacteria). It has activity in an acidic environment with (PH ≤ 6). It acts by denaturing proteins and nucleic acids of bacteria. NH4(CH2)6 + 6H2O + 4H→ 4NH4 + 6HCHO \*Indications:- Urinary tract Infection (prophylaxis) It has no bacteria activity in tissue or blood. \* Route: Oral: DOSE: - 6-12-years = 1 5-1g every 12hours, 12years and Adults - 1g twice to 4x Various agents are used to acidify urine e.g ascorbic acid (Vitamin. C), and Low pH alone is Bacteriostatic: Acidification of urine acid release of HCHO and lower of PH - Adverse Effect:- Gastritis, Chemical Cystitis, Hematuria, dysuria, nausea, decreased appetite, Skin rash. \* Contra-Indication:- Renal insufficiency, liver disease, severe dehydration, Combined therapy with Sulphanamide react with formaldehyde and must not be given\... **NURSING RESPONSIBIITY** 1\) Monitor Urine PH, Value of 5 1 or less is required for optimum drug action 2\) Monitor I or O ratio and pattern, drug not effective when fluid intake is maintained at 1500-1200ml 3\) Copious amount may Increase diuresis, elevate Urine PH and dilute formaldehyde concentration. 4\) Consult physician about changing to enteric coated tablet, if pt complains of gastric distress 5\) Supplemental acidification to maintain PH of 5:5 or below is required for drug action. Maybe necessary accomplished by drugs (ascorbic acid) **NITROFURANTOIN** \*Group - Urinary tract antiseptics \*M.O.A: Sensitive bacteria reduces the drug to an active agent that inhibit various enzymes and damage DNA. \*Indications: Prostaties, treatment of UTI, Prostatectomy, recurrent infections and bacteriaurial after prostatectomy. \*Route -- Oral. \*Dose= 100mg nightly for (4day with Iron meal) \*Side effect - GIT disturbance, acute pneumonitis, Neurological problems, Hypersensitivity; reactions, Chills, Fever, Leukemia, granuloctopenia, haemolytic anemia, associated with G-6pD deficiency, nausea & vomiting, diarrhea \*Contra-Indications:- Severe renal disease, neonates G-6PD deficiency, anuria, Oliguria, Children of Less than I month, pregnancy Clients. **NURSING RESPONSIBILITIES** 1\) Therapy should not exceed I4 days and repeated Course should be separated by rest period. Contra-Indicated above **ACIDIFYING AGENTS** Used to lower the PH (acidity) of Urine. Substances that can produce a urine of PH of 6.5 or Lower Usually Inhibits bacterial growth in Urine. USES: - in Chronic UTI where suppression of bacterial growth is important e. g Mandelic acid, hippuric acid, ascorbic acid, NH~4~Cl and ketogenic diet. **ANTI TUBERCULOSIS** Mycobacterium Tuberculosis is a mycobacteria species that is responsible for tuberculosis, it can lead to serious infections of the Lungs, GIT, Skeleton & meninges. Treating the disease possess great therapeutic problem. The Organism grows slowly, thus the disease may be treated for 6 months - 2yrs. **TB DRUG REGIMEN** There are first and second line drug used in the management of TB **First line:** Isoniazid**,** Rifampicin**,** Pyrazinamide, Ethionamide **Second line:** Amino salicyclic acid**,** Amikacin, Cycloserine, Capreomycin**,** Ciprofloxacin etc In the six month treatment course, in the first four month, isoniazid and rifampicin and pyrazinamide is used. In the next two month isoniazid and rifampicin combination is used. Areas where drug resistance occurs, the second line is added until sensitivity test are carried out. Addition of a second line does not reduce the anti-microbial duration instead it helps to prevent drug resistance. Patient related factor such as HIV/AIDS can also be another reason for including a second line in which case five or six drugs are used. **N/B**: Regimen means combining drug to a certain duration. Anti TB drug undergoes resistance more than any other drug. **ISONIAZID / ISONICOTINIC HYDRAZIDE (INH)** **CLASS: Anti TB** **Mechanism of Action:** It acts by inhibiting the mycobateria biosynthesis of mycotic acid. It is a pro drug that is activated by an enzyme called mycobacterium catalase peroxidase (kat-G). The active form forms acyl carrier protein (ac p-m) and keto beta acyl carrier protein which inhibit the synthesis of mycolic acid. **Indications:** It is used in the management of all forms of TB **Side effects:** Isoniazid induce hepatitis, anaemia, fever, chills, peripheral neuritis, rashes. **Contraindications:** Pregnancy, liver disease, renal disease. **Dose:** 5mg/kg/day. **Route of administration:** Oral route and intravenous route. **RIFAMPICIN** **CLASS: Anti TB** **Mechanism of Action:** It acts by inhibiting the DNA dependant, RNA polimeris of sensitive bacteria. Overall, it acts by inhibiting RNA synthesis. **Indication:** It is co-administered with isoniazid in the management of tuberculosis. **Side effects:** Nausea and vomiting, fever, myalgia (pain in the joint), hemolytic anaemia, shock, orange red colour discolouration, jaundice. **Route of administration:** Oral route **Dose:** It is available alone or as a fixed dose combination with isoniazid (150mg isoniazid and 300mg rifampicin). It combination is the most effective method for managing tuberculosis. It can be administered 1hour before meal or 2hours after meal. For children of 12years the dose is 10-15mg/kg body weight. **Contraindication:** Jaundice due to reduced bilirubin, first trimester of pregnancy, liver disease. **Nursing Responsibility** - Patient should be duly informed that the drug causes a brownish yellow coloruation which will be seen in the secretion such as saliva, urine etc and at such the patient should not discontinue the drug. **ANTI LEPROSY** Leprosy is a chronic disease and is prevalent in tropical countries, especially in India, Philippines, and Brazil, and poses a public health problem. It was first identified and reported by a Norwegian physician G.A. Hansen in 1873 and since then it is also known as "Hansen\'s disease". It is transmitted by close and prolonged contact through inhalation of the bacilli present in nasal secretion or through skin erosions. Early diagnosis and treatment are very important to prevent transmission and for a complete curative therapy without deformities. Leprosy is caused by a rod-shaped slow-growing acid-fast aerobic bacteria called *Mycobacterium leprae* (*M. leprae*). Recently, another species named *Mycobacterium lepromatosis* **Anti-leprosy agents;** the three major antileprosy drugs currently in use are Sulphonamide- diaminodiphenyl sulfone (dapsone), rifampicin, and clofazimine. These three are the first-line antileprosy drugs. Rifampicin is also used as the first-line drug for the treatment of tuberculosis.**Class: Sulfonamide** Pteridine + PABA Dihydrofolic acid Tetrahydrofolic acid Purine, Purimidine Deoxyribonucleic acid Indications: It is used in the management of all forms of leprosy with combination of isoniazid, rifampicin and dapsone acid. It is also used in management of pneumonia caused by pneumocystic jiroveci **Route of Administration:** Oral Route. **Dose:** 100mg per day of 6 months of rifampicin. In children: 1-2mg per day once daily. Prophylactic dose: 50mg per day. **Side effects:** Pancreaitis, nausea and vomiting, insomnia, blood dyscrasia, tinnitus, fever, headache, psychosis, tarchycardia, male infertility, drug induced lupus erythromatosis. **Contraindication:** Hypersensitivity reaction, anaemia, methylhemoglobin reductase deficiency, lactacting mothers. **Nursing responsibility** 1. Monitor for therapeutic effects 2. Determine periodic drug dapsone levels. 3. Monitor temperature within the first few weeks 4. Advice patient not to breast feed while taking dapsone. 5. Advice the patient to use the drug for a very long time. **ANTIFUNGAL AGENT** Infectious disease caused by fungi are called mycoses. Many common mystic infections are superficial. i.e they only involve the skin buy fungi may also penetrate the skin causing subcutaneous infections. Fungi are Eukaryotic in nature, they have a rigid cell wall which contains Chitin (N- acetyl glucosamine rather than peptidoglycan) which is seen in bacteria cell wall. The fungi cell wall contain ergosterol while bacteria is cholesterol (cholesterol is also seen in mammals). DRUG TREATMENT OF FUNGAL INFECTIONS A. Systemic Agents: Anti fungi affecting fungal sterols major group are; Polyenes eg. Amphotericin B, nystatin. Azoles: Econazole, ketoconazole, miconazole, omoconazole, sertaconazole, ticonazole. Inhibitors of β glucan synthesis: micofungin, amidulafungin, casofungin. Allylamines: terbinafine, naftifine, amorolfin, Butenafine. **POLYENES** Amphotericin B. Group: Anti- fungi Mechanism of Action: the drugs binds to ergosterol that is present in cell membrane of sensitive fungi and alters the permeability of the cells by forming Oligodendromes which is toxic to the fungi. Thus leading to leakage of intracellular cons which brings about the eventual death of the cell. Clinical Indication: Used in the management of cryptococcal meningitis. Protozoa infection (leishmaniasis). Side effects: Nausea, vomiting, headache, fever chill. It affects the body haematology, GIT upset, it is extremely bound to plasma protein. Hypotension accompanied by hypokalemia Contra Indication: Heart disease, diabetes, kidney disease, electrolyte imbalance (such as low level of potassium or magnesium I your blood) mastocytosis. Route: IV infusions. Dosage: dosage forms and strengths powder for injection= 50mg/vial. Systematic fungal infections: Test dose: 1 mg iv infused over 20-30mins. Load: 0.25-0.5mg/kg IV infused over 2-6 hours. Maintenance 0.25-1 mg/kg IV qday or up to 1.5mg/kg IV qOD (may increase gradually by 0.25 increment/day) NURSING RESPONSIBILITIES: (1) Ensure patient is adequately hydrated before and during therapy. (2) Obtain baseline FBC, serum electrolyte, renal and liver function tests. Repeat these measurements regularly during therapy (3) Monitor and document vital signs including blood pressure and fluid balance.(4) Assess IV site carefully before and during infusion of amphotericin.(5) Observe for adverse effects during the first 30 minutes of administration especially for cardiotoxity **AZOLES** Ketoconazole. Group: Antifungal Class: Azoles Mechanism of Action: The antifungal result due to reduction of ergosterol synthesis by binding to cytochrome P450, the reduction is dependent on 14 alpha demethylase which prevent conversion of lanosterol to ergosterol. This prevention leads to the accumulation of methylsterol which is toxic to the fungi. Clinical Indication: the azoles is used for; Candida spp, candida aspergillus, neofomas. Side effects: Nausea and vomiting, headache, dryness, diarrhea, dyspepsia, taste disturbances, internal bleeding. At high dose: adrenal insufficiency, decrease in testosterone levels, decrease in sperms production. Contra Indication: Hepatotoxicity, QI prolongation, arrhythmia adrenal insufficiency, alcoholism, HSR. Route: topical, oral. Dosage: 200mg once a day (for adult) 3.3-6.6mg/kg/day as a single dose 2yrs). Nursing Intervention: (1). Do not administer with antacids, H~2~blockers, proton pump inhibitors, ketoconazole requires an acidic environment for absorption, if antacids are required, administer at least 2hrs apart. (2). Continue administration for long term therapy until infection is eradicated. (3). Monitor hepatic function more frequently throughout treatment. **ALLYLAMINES** Allylamines: amorolfin, terbinafin, naftifine. Group: Antifungal, antimycotic agent. Class: Allylamine Mechanism of Action: it inhibits ergosterol synthesis by inhibiting the enzyme called squalene epoxidase (the enzyme that makes way for the parasynthesis of ergosterol). Clinical Indication: onchomycosis of toe and ringworm infection, dematophyte infection. Side Effects: abdominal pain, anorexia, diarrhoea, dyspepsia, rash, vomiting, headache, neutropenia. Contra Indication: chronic or active hepatic disease, hypersensitivity, lactating mothers. Route: topical, oral. Dosage: 250mg/qds for 6 weeks. Nursing Responsibility: (1). Do not give to breast feeding mothers. (2). Notify physician if drug causes increased skin irritation on sensitivity. (3). Learn correct technique for application. **INHIBITORS OF BETA GLUCAN SYNTHESIS**: They are made up of 3 groups namely; Echinocandins, aculeacins, papilafungins. Echinocandins are also made up of three drugs which are; micafungins, anidulufungin, capsofungin. MICAFUNGINS GROUP: Antimycotic agent. CLASS: inhibitors of beta glucosynthesis MOA: it inhibits the beta (1-3) glucagon synthesis this enzyme, glucan synthase makes way for the integrity of the fungal cell wall. This leading to the death of lysis of the pathogen. CLINICAL INDICATION: Candida its spectum of activity is limited, it is the second line drug for patients who cannot tolerate the azoles or amphotericin B. Side effect: rash, GIT disturbances, fever headache, flushing, plebitis. ROUTE: IV DOSAGE: 150mg/day. Contra Indication: Hepatic insufficiency, intravascular hemolytic, hypersensitivity. Nursing Responsibility: 1.Monitor for signs of anaphylaxis (rash, pruritis, wheezing, laryngeal edema, abdominal pain) (2).Check for hepatic disease before administration.(3) Assess for injection site reaction (phlebitis, thrombophlebitis). **INHIBITORS OF NUCLEIC ACID, ANTIMETABOLITE** GROUP: Antifungal. CLASS: Inhibitors of nucleic acid anti metabolites MOA: it is converted to 5\' fluorodeoxuride 5\' monophosphate which is further hydrolysed to which is incorporated into RNA of the fungi leading to destruption of nucleic acid and protein synthesis. CLINICAL INDICATIONS: it is used in combination with itracolazole in the treatment of chromo -blastomycosis and in combination with amphoterin B in the treatment of candidiasis. SIDE EFFECTS: GIT disturbances bone marrow depression, thrombocytopenia, nausea, vomiting and rash. CONTRA INDICATION: hypersensitivity, bone marrow, depression, anaemia. ROUTE: Oral. DOSAGE: Neonate 80-160mg/kg/day orally in 4 divided doses. Children; 50mg-150mg/kg/day orally in 4 divided doses. Adult; 0.5-1 g/day NURSING RESPONSIBILITY: Do not give to patient who are Contra indicated above. **ANTI-PROTOZOA:** Trichomonas, Amoebic Dysentry and Giardiasis**.** Trichimonas Vaginalis discharge (occasionally causes urethritis in both sexes) giadia lamblia is a flagella pear shaped protozoa causing flatulence and diarrhea. Amoebiasis is caused by an infection with the Entamoeba histolystica diloxanide furoate the agent, giardia, and tricho and amoeba to metronidazole. Classification of Amebicidal Agent (1). Luminal Amebieide: Action parasites/ lumen of bowel: Paromomycin. (2). Systemic Amebicide: effective against Ameba in intestinal wall and liver: chloroquine, emerin, dehydroemetin. (3). Mixed amebicide (liminal and Systematic activity) metronidazole, trinidazole. **METRONIDAZOLE**: metronidazole is the drug of choice on the treatment of extraluminal amebiasis. Mode of Action: the Nitro group of metronidazole is chemically reduced in aerobic bacteria and sensitive protozoan that target DNA altering the cell permeability with loss of intracellular constituents. Clinical indication: Amebiasis: neither drug is reliably effective against parasite and so must be used with the lumina amebicide to ensure eradication of the infection, amebic liver abscess. Giardiasis Trrichomoniasis \_2g is effective, metronidazole resistant organisms can lead to treatment failures. Anaerobic cocci anaerobic gram -ve bacilli, brain abscesses. A/E: Nausea, headache, drymouth or metallic taste in dry mouth occurs commonly, infrequent A/E include vomiting, insomnia, rash, dark urine, vertigo, parenthesias, it has disulfrain like effect so that nausea and vomiting occur when taken with alcohol. Dosage: MTz 750mg tds or 500mg IV every 6 hours for 10 days or trinidazole 2g daily for 3 days plus luminal agent 650mg tds. Contra Indication: CNS disease, blood dyscrasias, pregnancy, phenytoin and phenobarbital, lithium. **Diloxanide furoate**. Dosage: 500mg tds daily x 10 days Mechanism of Action: inhibit protein synthesis. Side effects: flatulence, nausea, abdominal cramp and rashes. Contraindication: pregnancy. Nursing Responsibility: (1) Discontinue if symptoms of CNS toxicity develop.(2)Monitor patient on lithium for elevated lithium levels. (3).Repeat feaces examination up to 3 to ensure it has been eliminated. (4). Refrain from intercourse drug therapy for unless the male partner wears a condom to prevent reinfection. (5). Do not drink alcohol, drug therapy may include reaction (6) Do not breast feed while taking the drug **MALARIA**: is an acute infection dx caused by four sports of the protozoa genus \"plasmodium\". It is transmitted to humans through the bites of a female anopheles mosquito, which thrives in humid swampy areas. Plasmodium falciparum is the most dangerous spy causing an acute rapidly fulminating dx. Characterised by persistent high fever, orthostatic hypotension and massive erythrocytosis. P. Falc infection is not instituted promptly. Classification of anti-malaria agents 1. Aryl amino compounds; Quinine, quinidine, chloroquine, amoduauine, mefloamine, halofantrin, lumefantrin, pipequine, tafenaquine. Antifolates compounds: pyrimetanine, proguquil, chloroproguanil, trimetropim. Artemisinin compounds: artemisinin, dehydroartemisinin, artemeter and artesunate. Others: atovaquone. Antibacteria: cindamycin, tetracycline. Chloroquine is a synthetic Blood schizonticide, is 4 amino quinolone that has been the mainstay of antimalaria, is a drug of choice in treatment of erythrocytic P. Fal malaria, except in resistant strains is less effective against P.Vivax malaria, it is highly specific for sexual form of plasmodia. MOA: after transferring the erythromycin and plasmodia/ membrane chloroquine (diprotic weak base) is conc in the organism acidic food vacoule primarily by ion tapping. It is in the organism acidic food vacoule that the parasite digest host all haemoglobin to obtain essential amino acid. Chloro specifically bind to home, preventing it polymerization to hemazoin, the increase pH and accumulation of home lead to oxidative damage to the membrane, leading to both lysis of both the parasite and red blood cells Therapeutic Use /lndication. It is effective in the treatment of extra intestinal amebiasis.-Used in rheumatoid Arthritis and discoid lupus erythromatosus. Falcipa malaria, combination metronidazole. A/E: at lower doses side effect are minimal. At high doses effect such as GIT upset, pruritus, headache and blurred vision discolouration of nailed and mucus members may be seen or chronic administration, dermatitis. C/l: in patients with GIT problems or in patients with neurologic or blood disorders. Impaired renal/liver function. Resistance: Resistance of plasmodia to available drugs has become a serious medical problem I Africa, Asia. Chloroquine resistant P.Falc exhibit level of resistance. Chloroquine Route/ **Dose:** assignment. **ARTEMISININS AND DERIVATIVE:** Artemisinin is derived from the plant quinghaosu plant which had been used in Chinese medicine for more than 2 millenia in the treatment of malaria. One of its derivative is available for the treatment of severe multi drug resisting P.Falc. Artemisinin is a Blood schizonticide MOA: involves the production of free radical within the plasmodium food vacoule. Following cleavage of the drugs endoperoxide-bridge by heme ion in parasynthesized erythrocyte. It also covalent binds to and damage specific malaria proteins Route: Oral, rectal and IV Artesunate (oral, rectal and IV). Artemeter (1M, rectal) Dosage: Artemisinin 100mg b.d on first day, 50mg b.d for next 5 days. IV 60mg /vial daily for 5-7days. The vial of malamine powder mixed with 1 ml of N/s add 5% N/s to make concentration or Artesin in 10mg Quinine dose: Oral 600mg t.d.s for 4 days Sever cases IV 10mg/kg 8hrs followed by one of the following: Sul 3 tab as a single dose. Adverse. E: Nausea, vomiting and diarrhea but overall, it is remarkably safe. Extremely high dose may cause neurotoxicity and prolongation of interval. Tinnitus and vertigo, epigastric pain, visual disturbances, delirium, confusing, hypotension. Clinical Indication: Used in cerebral malaria. Recrudescence is common due to short half-life. Combining with mefloquine avoid this acute attack of P. F A/E: cinchonism: syndrome cause Nausea, vomiting, timitus and vertigo, epigastric pain, visual disturbances, delirium, confusion, hypotension. D/lnteraction: potentiation of neuromuscular blocking agents and elevation of dioxin level if taken concurrently with Quinine action is retarded if taken with Aluminium containing antacids. **ANTI-TRYPANOSOMIASIS** Trypanosomiasis: It is caused by spp of trypanosoma African. Sleeping Sickness and American Sleeping Sickness. African trypanosoma brucei gambense and trypanosoma Brucei rhodiense. The cause of Chagas disease is the parasite Trypanosoma cruzi, which is spread from an insect known as the triatomine bug, or \"kissing bug.\" Agents: Melarsoprol, Pentamidine Isethionate, Nifurtimox, Suramin, Benzinidazole Class: Antiprotozoa agent Mechanism of Action: Mel is a prodrug which is metabolised to melarsen oxide (Mel oxide) as the active form. Mel oxide is an arsenic oxide that irreversibly binds to sulfhydryl group on which disrupt energy production in the parasite. Clinical Indication: African trypanosoma (sleep Sickness) Route of Administration: IV. Dose: 2-3.6 mg/kg/day IV x3days. After 1 week 3.6mg/kg/day IV x3days, repeat again after 10-21 days 3.6mg/kg/d Side effects: Hypertension, tachycardia (damage, vomiting, peripheral neuropathy, fever Contraindications: Patient with G6PD deficiency Nursing Considerations:(1)Pre hospital care of Sleeping Sickness centers on management of the acute symptoms of fever and malaise in conjunction with monitoring patients neurologic state.(2) If CNS symptoms are severe, airway mgt to prevent aspiration becomes important along with immediate admission, in the late stage ICU staff need to administer treatment. (3) Do not administer to contraindicated patients **Nifurtimox.** Class: Anti protozoa Mechanism of Action: it undergoes reduction and generates intracellular oxygen radicals such as superoxide radicals and H~2~0 which are toxic to T. Cruzi which lack catalase. Clinical Indication: Acute T. Cruzi Infection Side effects: anaphylaxis, delayed HSR dermatitis, Icterus and GIT problems, peripheral neuropathy, CNS disturbances, nausea, anorexia, vomiting, headache etc Route: Oral, IV. Dose: Oral 30mg and 120mg. 8-10mg/kg/day qt 8hr for 90-120 days Contraindications: severe liver or kidney disease as well as people with neurological or psychiatric disorders, HSR NB: *mammalian cell are partially protected from such substances by the presence of enzymes \_ catalase* **ANTIVIRAL AGENT** Virus are obligate intercellular parasite, they are the smallest infection agent which is made up of double or single stranded DNA or RNA that is enclosed in a protein core called Capsid. Viruses do not have a cell wall or a cell membrane and then do not engage in metabolic processes. They usurp the machinery of the host cell to replicate. They leave within the living host cells. Antiviral agents block the entering into or exist outside the host cell. **DRUG TREATEMENT OF HERPES** Virus such as chicken pox, shingles, grandular fever are DNA virus. Acyclovir, Valcyclovir, Penciclovir, Trifluridine, Ganciclovir, Folscanet, Primantidine **ACYCLOVIR. Group: antiviral. Class:** **MOA:** After conversion by herpes virus, thymidine kinase, the enzyme helps in the conversion of acyclovir to acyclovir monophosphate which is then converted by the host cellular kinase enzyme (amp kinase) to acyclovir di and triphosphate. The acyclovir di and triphosphate inhibits DNA and RNA synthesis by: Inhibiting DNA polymerase, Deoxyuridine triphosphate. **Indications** - It is used in management of herpes simplex virus and varicella zoster virus infection. - Also used for prophylaxis in transplant recipient with cytomegalo virus (CMV) infection though it is inefficient in the treatment of CMV. **Side effect:** Rash, neurotoxicity, nausea, dizziness, diarrhea, headache, renal insufficiency. **Contra indication:** Dehydration, renal impairment, hypoxemia, hepatic insufficiency, pregnancy, hypersensitivity. **Route:** Oral, IV. **Dosage: Adult:** 10mg/kg/ 8 hrly (IV)**. Children:** 12-17 years: 10mg/kg/ 8 hourly (IV) **Nursing responsibility:** Do not administer to lactating patient. Do not administer to patient who are hypersensitive. Monitor for phlebitis and hypoxemia. **GANCICLOVIR** **Group: antiviral agent. Class:** **Mechanism of Action:** It inhibits DNA synthesis. **Clinical indications-** Used in management of CMV infections, also used in prophylaxis of transplant recipient to prevent CMV**.** Used in the treatment of CMV infection in immune compromised patient. **Side effects:** Neuro toxicity, embryotoxicity, Hepato-toxicity, and dose related neutropenia. **Contraindication:** Anaemia, thrombocytopenia, hepatic insufficiency, hypersensitivity. **Route: Oral, IV, Dosage:** Adult: 1000mg/ 3x/dly or 500mg/ 6x/dly. Children: 5mg/kg/body weight/ dly. **Nursing responsibilities** - Avoid direct contact of powder in capsules or solution with skin and mucous membrane - Maintain frequent hematologic monitoring - Inspect IV insertion site throughout infusion for signs and symptoms of phlebitis - Monitor FBC **TRIFLURIDINE** **Group: Anitiviral agent. Class:** **Mechanism of action:** It acts by inhibiting viral DNA synthesis in HSV 1, HSV 2 and CMV infection by producing defective synthesis of DNA leading to no production of the DNA. **Clinical indications:** - Kerato conjunctivitis, keratitis due to HSV 1 and 2. The drug is too toxic for systemic used as such is administered by ophthalmic route (eye) - combining trifluridine/tipiracil with oxaliplatin enhances anti-tumour activity **Side effects:** Transient irritation of the eye, eye edema (palpebral edema). **Contra indication:** Pregnancy, neutropenia, thrombocytopenia. **Route:** Oral, ophthalmic or instillation. 30 and to 35 mg/m^2^ twice daily, days 1--5, q14 days, together with a fixed dose of 85 mg/m^2^ of oxaliplatin day 1, q14 days. **Nursing responsibilities** - Monitor for hepatic eye infection during therapy. - Do not administer to lactating mothers. - Do not administer to same time with other eye drops. Drug treatment to influenza **--**Rimantadine**,** Amantadine **AMANTADINE. Group:** Antivirus. **Class:** Anti --influenza virus **Mechanism of action:** The drug acts by blocking M~2~ proton ion channel of RNA within infected host cells, thus preventing replication. *M~2~ ion channel can promote the transfer of ions, most likely protons, across the virus membrane. The M~2~ protein is a transmembrane ion channel responsible for both ***the release of viral RNA from the virion after entry as well as regulating viral maturation*** * **Clinical indication: -**Prevention and treatment of influenza patient. For seasonal prophylaxis of influenza virus. **Side effect:** GIT disturbance, neurotoxicity which is characterized by hallucination, seizures, delirium, and combing with cardiac arrhythmia, CNS side effect such as insomnia which is dose related. Amantadine helps treat the symptoms of Parkinson disease by increasing the effect of dopamine. Amantadine is teratogenic in animals. Its safety profile in pregnancy has not been determined. The drug should not be co-administered with psycho-tropic agent, anticholinergic agent, anti-histamine agent. **Contraindication:** glaucoma, cancer, low blood pressure, other static hypotension, cardiac insufficiency. **Route:** Oral. **Dosage:** 200mg/dl in 1 or 2 divided doses. Nursing responsibility: ***HUMAN IMMUNE VIRUS*** Life cycle: Is a retrovirus, the 3 enzymes which the virus use to genetically encode, replicate and assemble new virus with cells are called *Reverse Transcriptase, intergrase, and protease.* The virus enters the cell through CD4 molecule or cell surface. Virus uncoat with the help of Reverse Transcriptase enzyme, a singles stranded viral RNA is converted into DNA, the form in which cells carries its gene. The viral DNA migrates to the nucleus of the cell where it is spliced into the host DNA, which helps the enzyme (Intergrase). Once incorporated, HIV DNA is called a Provirus and is duplicated with the cell gene every time it divides. Protease assists in the assembly of newly formed viral particles **Classification of *Antiretroviral Agents.* The agents are:** \(i) NRTI's: **Zidovudine, Abacavir, Lamivudine, Emcitritabine, Tenofovir, stavudine** **(ii)** NNRTI's: delavirdine (DLV), doravirine (DOR), efavirenz (EFV), etravirine (ETR), nevirapine (NVP), and rilpivirine (RPV) \(iii) Protease inhibitors: Lopinavir, Indinavir, Nelfinavir, Amprenovir, Ritonovir, Atezanavir. \(iv) Integrase Inhibitor-, bictegravir (BIC), dolutegravir (DTG), elvitegravir (EVG), and raltegravir (RAL) \(v) Entry/fusion- Inhibitors: Maraviroc, Eufuvirtide- CCRT5 a co- receptor, located in human helper T-cells. **NB:** The treatment strategy is the combination of HAART (2 NRTI with either one NNRTI's or 1 or 2 protease inhibitors). Integrase is responsible for integration of viral DNA into the DNA of infected cells. Entry/fusion- Inhibitors: Maraviroc, Eufuvirtide- CCRT5 a co- receptor, located in human helper T-cells. The main difference lies in their molecular composition as Nucleosides contain only sugar and a base whereas Nucleotides contain sugar, base and a phosphate group as well. A nucleotide is what occurs before RNA and DNA, while the nucleoside occurs before the nucleotide itself. **CLASS:** NRTIS's Trade name: AZT, Retrovir. **MECHANISM OF ACTION:** Inhibition of viral enzyme reverse transcriptase, an enzyme necessary for HIV replication. **CONTRA-INDICATIONS:** Allegy to Zidovudine. **CAUTION:** Bone marrow compromises Renal and hepatic dysfunction, decreased hepatic blood flow. **INDICATIONS:** Management of clients with HIV infection, prevention of maternal- fetal HIV transmission. **SIDE EFFECTS:** Numbness, Tingling, Burning and pain in lower extremities, Abdominal pain, Rash, G.I incontinence, Fever, Sore throat, Headache, Difficulty in swallowing, Insomnia, Confusion. **DOSE:** Prophylaxis; Maternal therapy PO- 100mg 5x/d, initiated at 14-34 weeks of gestation through pregnancy. Newborn (Syrup): PO 2mg/ kg q6h; I.V, 1.5 mg/ kg over 30 min q6h. **TREATMENT:** ADULTS: PO 200mg, q8h or 200mg, q12h; I.V, 1mg/kg, q4h. CHILDREN: I.V -- neonatal, 1.5mg/kg, q6h. 12 YEARS: Intermittent infusion 120mg/ m2, q6h max/ 160mg/ m^2^ per dose. **Non Nucleoside Reverse Trancriptase Inhibitors: efavirenz, nevirapine.** **CLASS:** NNRTI's. **TRADE NAME:** Sustiva. **MODE OF ACTION:** Binds to reverse transcriptase blocking RNA dependent DNA polymerase activity including HIV-1 replication. **INDICATIONS:** Treatment of HIV infection in combination with at least two other ART. **CONTRA- INDICATIONS:** Life threatening allergies, efavirenz or component of preparation; concurrent use of midazolam, triazolam, ergot alkaloids. **SIDE EFFECTS:** CNS, dizziness, insomnia, abnormal dream, impaired concentration, amnesia, agitation, hallucination, euphoria, anxiety, diarrhoea. **DOSE:** PO: 600mg/daily, CHILDREN: PO: 10-\