4.5Nkb_Pharmacology_Antibiotics(2)[1](1).pptx

Pharmacy it is a ppt which explains various antibiotics used in nursing and medicine it allows students to get a better understanding of antibiotics and their application

1. ANTIMICROBIALS Mwangi Daniel BScN SN For KRCHN Consolata School of Nursing 4th April 2022

2. Antimicrobials Definition: Drugs used for treating infections or infestations from different micro-organisms or invasion of micro-organisms Used to treat infections caused by organisms that are sensitive to them usually bacteria or fungi or virus

3. Antimicrobials cont.. Resistance – Degree to which a disease or a disease causing organism remains unaffected by antimicrobials Sensitivity – Degree to which a disease causing organism responds to treatment by antimicrobials or other drugs. Antibacterial/antibiotic – describes a drug that is active against bacteria

4. CLASSIFICATION OF ANTIMICROBIALS Are broadly classified into; The micro-organism affected e.g antifungals, antivirals, antibiotics,antiprotozoals Mechanism of action. Spectrum of activity e.g broad spectrum , narrow-spectrum Type of action ; bectericidal (fast killing),bacterialstatic (inhibit the growth of bacteria keeping them in a stationary ) phase of growth) Chemical structure.

5. ANTIBIOTICS CLASSIFICATION OF ANTIBIOTICS BY MECHANISM OF ACTION Inhibitors of cell wall synthesis Inhibition of cell wall synthesis – cell wall is an essential component of a bacterial wall. Interrupting its synthesis kills the bacteria (bactericidal ) Penicillins Cephalosporin Monobactams

6. CONT’ 2 . Inhibitors of protein synthesis Inhibition of protein synthesis by binding to bacterial ribosomes – Bacteria like all cells require proteins to carry out most functions such as metabolism, cell division, enzyme activities etc. without protein synthesis bacterial cell functions are inhibited thus arresting growth and development. Tetracyclines Macrolides Aminoglycosides Chloramphenicol

7. Classification cont.. 3. Inhibitors of nucleic acid synthesis Inhibition of nucleic acid synthesis – they stop synthesis of nucleic acid precursors and therefore there is no formation of RNA and RNA in the microbes thus leading to no cellular activities Sulphonamides Trimethoprim Quinolones

8. Cont.. 4. Inhibiting metabolism of folic acid and other components essential for bacterial growth. 5. Cause leakage from cell membranes-alters cell membrane permeability thus allow substances to leak out thus destabilizing the cell.

9. Considerations in selection of Antibiotics Site of infection e.g. does drug cross the BBB, is it excreted in breast milk?,renal etc. The causative organism Host characterists e.g renal impairment,hypersensitivity. The general pharmacokinetics and pharmacodynamics of the drug. The severity of the infection in terms of the drug and the dosage.

10. Classes of Antibiotics Beta -lactam antibiotics. Aminoglycosides. Tetracyclines . Macrolides,quinolones / fluoroquinoles . Azoles. Antimycobacterial agents. Sulphonamides ( sulfadoxine ) &pyrimidines(trimethoprim). Lincosamides .

11. 1. Beta - lactam antibiotics. They all poses the beta -lactam ring as a basic chemical structure.Further divided into; Penicillin Cephalosporins Carbapenenerns Monobactams .

12. (a) Penicillins. All penicillins have the basic structure of a thiazolidine ring attached to a - lactam ring that carries an amino group . They have different antibacterial spectrum,which forms a basis for further subdivision. Narrow spectrum - Benzylpenicillin,Nafcillin,Benzathine penicillin G. Antistaphylloccocal (beta-lactamase resistant penicills)- cloxacillin,flucloxacillin,methicillin-not used clinically. Broad spectrum- ampicillin,amoxicillin Antipseudomonal (extended spectrum penicillin) - ticarcillin,temocillin

13. Mechanisms/mode of action. Penicillins inhibit bacterial growth by interfering with the transpeptidation reaction of bacterial cell wall synthesis Cell wall- Rigid outer layer unique to bacterial species It completely surrounds the cytoplasmic membrane, maintains cell shape & integrity & prevents cell lysis from high osmotic pressure Penicillin- binding protein (PBP), bacterial enzymes involved in synthesis of cell wall & in maintenance of morphologic features of the bacterium Penicillins covalently bind to the active site of PBPs inhibiting the transpeptidation reaction, halting peptidoglycan synthesis & the cell dies N/b Penicillins kill bacterial cells only when they are actively growing & synthesizing cell wall Active against gram - ve / + ve bacteria .

14. Pharmacokinetics Absorption : Most penicillins are incompletely absorbed after oral administration & reach the intestine in sufficient amounts to affect the composition of the intestinal flora. Food lowers absorption of all the beta- lactamase resistant penicillins , because, as gastric emptying time increases, the drugs are destroyed by stomach acid Therefore, they should be taken on an empty stomach

15. N/b Poor oral absorption of Nafcillin (NOT suitable for oral administration). Dicloxacillin , ampicillin , and amoxicillin are acid-stable and relatively well absorbed.

16. Distribution: Distribute well throughout the body All penicillins cross the placental barrier, but none have been shown to have teratogenic effects However, penetration into bone or cerebrospinal fluid (CSF) is insufficient for therapy unless these sites are inflamed

17. Metabolism: It’s insignificant, but some metabolism of penicillin G may occur in patients with impaired renal function.

18. Half life Penicillin G is approximately 30 minutes; in renal failure, it may be as long as 10 hours. Ampicillin and the extended-spectrum penicillins are secreted more slowly than penicillin G and have half-lives of 1 hour.  

19. Excretion: Excreted into sputum, milk and by the kidneys( majority). 1 ° route of excretion - unchanged in urine. Dose adjustment with renal impairment. NB- Excretion can be prolonged by giving probenecid – inhibits penicillin secretion by blocking tubular excretion of penicillin,thus increasing blood levels of penicillins.

20. Route of administration: Determined by: Stability of the drug to gastric acid Extent of protein binding Severity of the infection

21. Roots of administration Examples of orally administered penicillins : Penicillin V Ampicillin Amoxicilin Piperacillin Ticarcillin The rest are administered as parenteral preparations i.e. IV or IM

22. Adverse reactions/side effects Penicillins are among the safest drugs & blood levels are not monitored,generally well tolerated and unfortunately bthis encourages their misuse. Most serious adverse effects are due to hypersensitivity.

23. Adverse Reactions: GIT disturbances; Diarrhoea,due to disruption of the normal balance of intestinal flora. Amoxyl & ampicill i n for H . pylori and E . coli Hypersensitivity reactions may occur. All penicillins are cross-sensitizing and cross reacting. This may present as anaphylaxis, serum sickness ( urticaria , fever, joint swelling and intense pruritis ) and skin rash Seizures -high doses in renal failure,also provokes seizures when used intrathecally. Nephrotoxicity may occur. (methicillin). Hematologic toxicities - decreased coagulation may be observed with high doses of piperacillin,nafcillin and ticarcillin. Oral lesions. Vasculitis.

24. Contraindication Hypersensitivity to penicillins ; Approx. 5% of patients have some kind of allergic reactions Include: Rashes Angioedema i.e. marked swelling of the lips, tongue & periorbital area Anaphylaxis NB - Cross-allergic reactions occur among the penicillins & other β-lactam antibiotics. To determine whether treatment with a β-lactam is safe when an allergy is noted, patient history regarding severity of previous reaction is essential.

25. Treatment of anaphylaxis Withdraw product maintain airway administer: epinephrine,aminophylline, oxygen, IV corticosteroids

26. Precautions; Pregnancy Breastfeeding Hypersensitivity to cephalosporins Severe renal disease GI disease Asthma

27. Nursing considerations Assess input output ratio for hematuria , oliguria since its nephrotoxic . Assess bowel pattern before and during treatment – diarrhea, cramping, blood in stool Assess skin eruptions after penicillin administration and anaphylaxis. Assess for allergy through complete hx taking.

28. Cont.. Oral suspension shake well before each dose and discard unused portion after 14 days Adequate fluid intake during diarrhea episodes Teach patient to wear or carry emergency ID if allergic to penicillins

29. b)CEPHALOSPORINS Cephalosporins are similar to penicillins , but active stable to many bacterial b-lactamases hence broader spectrum of activity and hence more expensive than penicillins. β-lactam antibiotics closely related both structurally & functionally to penicillins. Similar MOA to penicillin. Classified into groups or generations, depending mainly on the spectrum of antimicrobial activity.

30. Classification of cephalosporins. Divided into generations depending on their bacterial susceptibility patterns & resistance to β-lactamases Includes; 1st generation 2nd generation 3rd generation 4th generation (purely parenteral) 5th generation

31. First generation Parenteral Oral Cefazolin Cephalexin Cefadroxil Second generation cephalosporins Parenteral Oral Cefuroxime Cefaclor Cefoxitin * Cefuroxime axetil Cefprozil Third generation cephalosporins Parenteral Oral Cefotaxime Cefixime Ceftizoxime Cefpodoxime proxetil Ceftriaxone Cefdinir Ceftazidime Ceftibuten Cefoperazone Ceftamet pivoxil Fourth generation cephalosporins purely parenteral Cefepime Cefpirome Fifth generation Ceftaroline Ceftibiprol e

32. Pharmacodynamics. >Mechanism of action of cephalosporin is similar to penicillin.

33. Pharmacokinetics; Usually given parenterally, though few may be given orally e.g. cephalexin, cephradine and cefadroxil . Have wide distribution because of lipid solubility. They are metabolized in the liver with half life of 1-4 hours. They excreted unchanged in urine especially by tubular secretion. Dosage reduced for patients with renal impairment. Active secretion in the kidney can be blocked by probenecid.

34. Indications; Septicemia Pneumonia meningitis biliary tract infections Peritonitis urinary tract infections sinusitis. Surgical prophylaxis

35. Unwanted effects. Most common is hypersensitivity , patients who are sensitive to penicillin are also sensitive to cephalosporin i.e. cross-allergy Hemorrhage due to interference with blood clotting factors. Use of cephalosporin for more than two weeks causes thrombocytopenia , neutropenia , and interstitial nephritis . GIT -nausea,vomiting Headache. Dizziness.

36. Drug interactions. Cephalosporin interacts with alcohol to produce disulfiram - like effects. Therefore, you will need to counsel the client to avoid taking alcohol when taking cephalosporins . High ceiling diuretics like furosemide and torsemide with cephalosporins are likely to cause nephrotoxicity . This same effect may be caused when used with amino glycosides. this is because all are predominantly excreted through the renal system.

37. ..cont drug interactions. Oral anticoagulant like warfarin with cephalosporin may cause bleeding. This is because both interfere with clotting factors.

38. Toxicity Local irritation can produce: Pain after IM injection Thrombophlebitis after IV injection Renal toxicity, including interstitial nephritis & tubular necrosis

39. Note; 1st generation; active against gram +ve cocci such as pneumonia,streptococci. 2nd generation; active against -ve bacilli e.g Influenza,E.coli,Neisseria gonorrhea. Cefuroxime i.v- used to treat community acquired pneumonia,gonorrhea infections. Cefuroxime axetil P.O (pulmocef) 3rd generation; Ceftriaxone and Cefotaxime - approved to treat meningitis; active against penicillin - resistant strains of pneumococci. Well absorbed in GIT,cross BBB and placenta,excretion in milk. Cefixime half life 3-4 hrs,ceftriaxone 5-8 hrs. 4th generation; Purely parenteral: cefepime and Cefpirome. 5th generation; Ceftaroline fosamil (TEFLARO™): Active against Gram-positive and -negative bacteria. Ceftibiprole

40. side effects Dizziness Headache Diarrhea Anorexia Pruritus Vaginitis Anaemia Rash Urticaria Anaphylaxis  

41. Contraindications Hypersensitivity to cephalosporins or related antibiotics Seizures Precautions Pregnancy Breastfeeding Children Renal/ GI disease  

42. Nursing consideration Assess nephrotoxicity – increased BUN, creatinine Take tabs or caps on empty stomach 1hr before or 2hrs after; if GI symptoms increases take with food. Teach patient if diabetic to use blood glucose testing No alcohol. To complete full course of therapy. To notify doctor if breastfeeding or of any side effects

43. C )MONOBACTAMS Drugs with a monocyclic b- lactam ring Aztreonam ( azactam )- It resembles aminoglycosides . Active against gram-negative rods (N. gonorrhoeae and H. influenza, including pseudomonas and serratia ).

44. Cont.. Given intravenously every 8 hours in a dose of 1-2 g Half-life is 1-2 hours and is greatly prolonged in renal failure. Uses – UTIs, septicemia, skin muscle and bone infections; lower RTI, intra abdominal infections. Tolerated well in pts with Penicillin-allergy. Occasional skin rashes  

45. Contraindication Hypersensitivity to the product, penicillin, cephalosporins and severe renal disease.

46. d ) CARBAPENEMS Structurally related to b- lactam antibiotics Ertapenem , imipenem , and meropenem are licensed for use in the USA. Carbapenems penetrate body tissues and fluids well, including the cerebrospinal fluid. All are cleared renally , and the dose must be reduced in patients with renal insufficiency. Indicated for infections caused by susceptible organisms, eg, P aeruginosa , highly penicillin-resistant strains of pneumococci .

47. Cont.. The most common side effects of carbapenems are nausea, vomiting, diarrhea, skin rashes, and reactions at the infusion sites, seizures ( imipenem pts with renal failure given in high dose) . NB - Patients allergic to penicillins may be allergic to carbapenems as well.  

48. 2.) AMINOGLYCOSIDES Aminoglycosides have a hexose ring to which various amino sugars are attached. They have a broad antibacterial spectrum of activity. They are water-soluble, stable in solution, and more active at alkaline than at acid pH. NB _ admin Parenteral and topical only.

49. Examples Includes ; S treptomycin Kanamycin Neomycin Netilmycin Tobramycin Gentamicin A mikacin F ramycetin .

50. Mechanism of action Acts by binding to 30s ribosomal sub unit leading to formation of non- functional initiation complex which leads to inhibition of bacterial protein synthesis and misreading the genetic code such that incorrect acid sequence are entered into peptide chain. From these abnormal peptides, abnormal proteins are formed which are fatal to the microbe. Under aerobic conditions these antibiotics are rapidly bactericidal since they penetrate cell wall through active processes which requires oxygen. However, if the concentrations of the drugs or oxygen concentration is low, aminoglycosides will be bacteriostatic

51. PHARMACOKINETICS These drugs are very water soluble and therefore, highly polar. Consequently, they are not absorbed through the gut. They are primarily given parenterally e.g. through IV or IM. They are narrowly distributed, hence do not cross blood brain barrier. Metabolism is in the liver with half life of 2-5 hours. Excretion is usually through kidney in unchanged form, therefore one need to take caution in renal impairment.

52. Once-daily dosing of aminoglycosides. N/b_ Traditionally, aminoglycosides have been administered B.D or TID in patients with normal renal function.But, administration of entire daily dose, once daily preferred in many clinical situations due to 2 reasons: Exhibit concentration-dependent killing ( increasing concentrations kill an increased proportion of bacteria & at a more rapid rate) Have a significant postantibiotic effect, such that the antibacterial activity persists beyond the time during which measurable drug is present.

53. Indications Basically active against gram -ve aerobic bacilli such as E. coli hence indicated for; septicemia, pelvic and abdominal sepsis, brucellosis, bacterial endocarditis, ophthalmic infections, Pneumonia meningitis N/b_ Neomycin is toxic for systemic use but can be used for gut sterilization for surgery.

54. SIDE EFFECTS Ototoxicity & nephrotoxicity – all aminoglycosides More likely to be encountered when Treatment is continued for >5 days Higher doses Elderly Renal insufficiency Note: Concurrent use with: Loop diuretics e.g. furosemide, ethacrynic acid Other nephrotoxic antimicrobial agents e.g. vancomycin, amphotericin

55. Ototoxicity can present as either:Auditory damage, resulting in tinnitus & high-frequency hearing loss initially Vestibular damage , evident by vertigo, ataxia & loss of balance Nephrotoxicity results in either; Rising serum creatinine levels Reduced creatinine clearance Nb_Earliest indication of nephrotoxicity include; R ise in serum aminoglycoside concentrations/levels Neomycin, kanamycin & amikacin - most ototoxic Streptomycin & gentamicin - most vestibulotoxic Neomycin, tobramycin & gentamicin - most nephrotoxic

56. Curare - like effect with neuromuscular blockage that results in respiratory paralysis. Occurs in very high doses Reversible by:Calcium gluconate (given promptly) Hypersensitivity - infrequently,Contact dermatitis - common reaction to topically applied neomycin

57. Other side effects Confusion Depression Numbness Hypo or hypertension Muscle twitching Splenomegaly Rash Alopecia Dermatitis Tremors

58. CONTRAINDICATION Bowel obstruction (oral use- neomycin) Pregnancy_they damage the 8th cranial nerve(vestibulocochlear) may cause hearing problems and balance problems. Myasthenia gravis- since they can cause neuromuscular damage. Mild to moderate infections – a strong antibiotic Hypersensitivty to aminoglycosides. Infant botulism and Parkinsonism.

59. PRECAUTION Neonates Mild renal disease Breastfeeding Hearing deficits Parkinson’s disease Geriatrics  

60. NURSING CONSIDERATION Assess weight before treatment – dosage Assess for dehydration. Assess for renal impairment and vestibular dysfunction (nausea, vomit, headache,dizziness ). Assess blood electrolytes levels Assess injection sites for redness, swelling, abscess – warm compresses

61. Cont.. Teach pt to report hypersensitivity (rash, itching, trouble breathing facial edema). Teach pt to report headache, dizziness, renal impairment. Teach pt to report loss of hearing, ringing roaring in the ears and feeling of fullness in the head.

62. TREATMENT OF HYPERSENSITIVITY Hemodialysis Exchange transfusion in newborns May give ticarcillin or carbenicillin ( antipseudomonal carbepenicillin

63. 3.TETRACYCLINES (oral susp,tabs , caps) Broad spectrum antibiotics whose value has decreased due to bacterial resistant. Examples include: T etracycline D oxycycline M inocycline Oxytetracycline Lymecycline D emecloycline hydrochloride, E thacycline

64. Pharmacodynamic Broad-spectrum bacteriostatic antibiotics They act by binding reversibly to 30s ribosomal subunit of bacteria ribosomes which inhibits protein synthesis.

65. Pharmacokinetics Partially absorbed except minocycline and doxycycline which have a good absorption. Absorption is increased in the absence of food. Antacids and milk decrease the absorption of tetracycline because they contain metal like magnesium, and calcium which chelate with them. They have a narrow distribution but they cross placental barrier. Metabolism takes place in the liver and excreted in urine via glomerular filtration in unchanged. Hence you need to avoid them in renal impairment except for doxycycline and minocycline which are excreted via feces.

66. Caution All tetracyclines chelate with metals & none should be orally administered with milk, antacids, or ferrous sulfate Contraindications To avoid deposition in growing bones or teeth, tetracyclines should be avoided in: Pregnant women Children younger than 8 years

67. Drug interaction Interactions Lowers clearance of warfarin & increase prothrombin time

68. Indications Syphillis , bronchitis, pneumonia, brucellosis, acne Chlamydia trachomatis ( urethritis , cervicitis , rectal infection),typhus, Q fever, abortus fever. Travellers diarrhea – doxycycline Uncomplicated gonorrhea in pts allergic to penicillin Malaria prophylaxis – 100mg daily 1-2 days prior to travel, during travel and 4 wks after return. Anthrax Periodontitis  

69. SIDE EFFECTS Gastric discomfort- nausea,diarrhoea,vomiting . Fever Headache Dysphagia Glossitis Vestibular dysfunction - dizziness,vertigo and tinnitus. Diarrhea Nausea abdominal pain

70. Cont.. Pruritus Flatulence Photosensitivity - severe sunburn may occur wth patients receiving tetracycline when exposed to UV rays. Epigastric disturbance Vomiting Effects on calcified tissues -discoloration of deciduous teeth, damage bones - avoid from 4 th month of preg until child is 12 yrs    

71. 4. MACROLIDES These are broad spectrum antimicrobials like: Erythromycin Azithromycin clarithromycin.

72. Erythromycin – 1st of these drugs to find clinical application, both as a drug of first choice & as an alternative to penicillin in individuals with an allergy to β-lactam antibiotics

73. Mode of action Bind irreversibly to a site on the 50S subunit of the bacterial ribosome, thus inhibiting translocation steps of protein synthesis May also interfere with other steps, such as transpeptidation Generally considered to be bacteriostatic May be bactericidal at higher doses

74. PHARMACOKINETIC Administration Erythromycin base is destroyed by gastric acid. -Thus, either enteric-coated tablets or esterified forms of the antibiotic are administered Clarithromycin & azithromycin are stable in stomach acid & are readily absorbed

75. N/b_ Food interferes with the absorption of erythromycin & azithromycin but can increase that of clarithromycin.

76. Indications   Infections caused by neisseria gonorrhea and chlamydia trachomatis. Mild to moderate upper and lower respiratory tract, skin, soft tissue infections Intestinal amoebiasis - erythomycin ) Syphilis - erythro Endocarditis prophylaxis, PID, Acute OM and gonorrhea - azithromycin

77. SIDE EFFECTS Hearing loss Tinnitus Nausea Vomiting Diarrhoea Abdominal pain Stomatitis Vaginitis Rash Pruritus  

78. Cont.. Anaphylaxis Hepatotoxicity Dysrhythmias

79. CONTRAINDICATIONS Hypersensitivity to macrolides Pre existing hepatic disease    

80. PRECAUTIONS Pregnancy Hepatic disease Breastfeeding GI disease Seizure disorder Geriatric pts

81. DRUG INTERACTION Interaction with digoxin -inactivates digoxin. Serious dysrrhythmias – ketokonazole , itraconazole , protease inhibitors, verapamil Increase action of warfarin , diazepam, felodipine , midazolam , quinidine .  

82. NURSING CONSIDERATION Assess input output ratio and report hematuria , oliguria in renal disease. Assess hepatic studies – LFTs. Assess for allergies before treatment and reaction of each medication. Do not break, crush or chew caps or tabs. Do not administer by IV or IM push – erythromycin. Administer oral product with a full glass of water. Teach pt to report sorethroat , fever, fatigue – indicate superinfection .

83. Cont.. Teach pt to complete dose regimen Teach pt to take without food unless if GI symptoms are severe. Teach pt to notify nurse of diarrhea, dark urine, jaundice and severe abdominal pain. Teach pt to notify doc if pregnancy is suspected or planned.  

84. 6) SULPHONAMIDES & Pyrimidines. Examples; Sulfadoxine Sulfadiazine Sulfamethoxazole Sulfisoxazole Slfamethizole Sulfapyridine

85. MOA Inhibits folate s y n t h e s i s . Sulphonamides competes with microorganisms for the enzyme dihydropteroate synthase because the organisms needs the enzyme to synthesize the folic acid.Sulphonamides inhibits the process of folic acid synthesis hence the micro organism don't survive. Are bacteriostatic.

86. Cont.. Divided into three major groups: (1) oral, absorbable – Sulfisoxazole ( gantrisin ) and sulfamethoxazole ( gantanol , urobak ), sulfadiazine ( coptin ), sulfadoxine.( 2 ° agent - antimalarial + pyrimethamine) (2) oral, nonabsorbable - Sulfasalazine ( azulfidine ) - IBD,ulcerative colitis,enteritis. (3) topical - Sodium sulfacetamide ophthalmic solution or ointment, silver sulfadiazine  N/b Sulfisoxazole and Sulfamethoxazole - UTIs.

87. Indications UTI. URTs - Sulfisoxazole and sulfamethoxazole Acute toxoplasmosis – 1 st line treatment is Sulfadiazine in combination with pyrimethamine (a potent inhibitor of dihydrofolate reductase Malaria – 2 nd line agent Sulfadoxine combined with pyrimethamine ( Fansidar ). Meningitis - sulfadiazine Sulfasalazine ( salicylazosulfapyridine ) used in ulcerative colitis, enteritis, and other inflammatory bowel disease.

88. Cont.. Sulfisoxazole and Sodium sulfacetamide ophthalmic solution or ointment is effective treatment for bacterial conjunctivitis and as adjunctive therapy for trachoma. Silver sulfadiazine, sulfasalazine for prevention of infection of burn wounds.

89. SIDE EFFECTS Nausea Rashes Fatigue Anxiety Dermatitis Photosensitivity Urticaria

90. ADVERSE EFFECTS Blood dyscrasias - constituents of the blood are abnormal or are present in abnormal quantity. Reduced sperm count – sulfasalazine ; stop drug Precipitation in the urinary tract – sulfadimidine ( give plenty of fluids 2-3L of ).

91. Contraindications Hypersensitivity to sulfonamides, sulfonylureas , thiazide , loop, salicylate , sunscreen with PABA. Pregnancy at term Infants < 2 months - danger of kernicterus.

92. Precaution Pregnancy Breastfeeding Geriatrics Impaired renal/ hepatic function Severe allergy.  

93. Nursing consideration   Assess input output ratio – note color, pH if drug is used for UTIs Administer on an empty stomach. Administer with full glass of water to maintain adequate hydration and prevent crystalluria . Avoid sunlight Notify doctor of skin rash, sore throat, fever, mouth sores, unusual bruising.

94. Pyrimidines Examples; Oral trimethoprim. Pyrimethamine . Oral trimethoprim - given alone 100 mg Bd in acute UTIs. NB : sulfamethoxazole - trimethoprim combination = Cotrimoxazole ( septrin )

95. 7) Quinolones/fluoroquinolones Examples; Coprofloxacin -Anthrax rx of choice. Levofloxacin Ofloxacin - BBB Perfloxacin - BBB Norfloxacin Enoxacin Nalidixic acid.

96. Mode of action Active against gram - ve and + ve bacteria . Inhibits DNA synthesis by inhibiting DNA gyrase ( topoisomerase II ) .

97. Pharmacokinetics Well absorbed orally and distributed widely in body fluids and tissues. Excreted by the kidneys.   Mode of action . Inhibition of n u c l e i c synthesis .

98. Indications Meningococcal meningitis prophylaxis – Ciprofloxacin Uncomplicated UTI – Norfloxacin and nalidixic acid To prevent inhalation anthrax Treat acute sinusitis caused by gram negative and positive organisms Bone and joint infections. Chronic bacterial prostatitis .

99. Cont.. Infectious diarrhea Treat cysttis caused by E. coli, enterococcus faecalis Treat lower respiratory tract infections. Treat uncomplicated urethral or cervical gonococcal infections caused by Neisseria gonorrhoea  

100. Side effects Headache Flatulence Heartburn Tremor GI upset Rashes Crystalluria Tendon rupture

101. Adverse effects Seizures Steve Johnsons Syndrome Anaphylaxis Contraindication Hypersensitivity to ciprofloxacin,or quinolones . Dm patients on oral hypoglycemic agents. Under 18 years.

102. Precaution Pts with epilepsy – potential of causing seizures - Ciprofloxacin Children – damages joints - Ciprofloxacin Elderly or pts with tendon pain – pain and inflammation of the tendons – Ciprofloxacin Pregnancy Hypokalemia Renal disease

103. Nursing consideration Obtain culture and sensitivity test. Pt should be well hydrate during therapy to prevent crystalluria and nephrotoxicity. Teach pt to complete prescribed course of therapy. Teach pt not to take drug with dairy products or calcium fortified juices.

104. Cont.. Teach pt to shake oral suspensions for 15 secs , not to chew or crush tablets. Teach pt that photosensitivity may occur – avoid sunlight or use sunscreen cream to prevent burns. Take drug 2hrs before or after eating, drinking milk, taking antacids.

105. 8) Azoles Metronidazole Tinidazole Both have antibacterial & antiprotozoal actions. Penetrates well in CSF and brain. Metabolized in liver,accumulates in hepatic insufficiency.

106. 9) Urinary Antiseptics. Are oral agents that exert antibacterial activity in urine but have little or no systemic antibacterial effect. Concentrated in urine,microorganisms at this site can be eradicated effectively. Usefulness limite to lower UTIs Examples are; Nitrofurantoin.(dx of choice/cheap) Methanamine.

107. MISCELLANEOUS ANTIBIOTICS CLINDAMYCIN - Dalacin (class- lincomycin derivative) MOA – Bind to bacterial ribosomes , suppresses protein synthesis. Clindamycin is a chlorine-substituted derivative of lincomycin , an antibiotic that is elaborated by Streptomyces lincolnensis . Effective against gram positive organism Well absorbed orally, penetrate into bones Uses – Complicated bowel surgeries, bone infections Side effect - Diarrhoea

108. GLYCOPEPTIDES E x a m p l e : Vancomycin . MOA – inhibits bacterial cell wall synthesis Uses – Severe staph infections resistant to other antibiotics; pseudomembranous colitis; endocarditis prophylaxis for dental procedures Given by slow IV infusion and blood levels are measured to control dose. Adverse effects – Ototoxicity, nephrotoxicity, venous thrombosis - often given into a central line.

109. ANALGESICS Drug that relieves pain; act at various sites along the pain pathways:- Act on the brain and spinal cord and reduce the appreciation of pain – site of action of opioids analgesics Suppress conduction in nerves carrying impulses from the painful area. This is where local anaesthetics act.

110. Cont.. Reduce inflammation and other causes of pain in the painful area. Site of action of NSAIDs. Classified into:- Opioid analgesics Non opioids analgesics

111. OPIOID ANALGESICS Aka narcotics or narcotic analgesics because of their soporific / hypnotic effects (drug that induces sleep by depressing brain function). Opioid is a psychoactive chemical that binds to opioids receptors found in the CNS, Peripheral NS and GIT. OR Opioid is applied to any substance which has an opium like action.  

112. Cont.. Opioids can be :- either weak or strong Strong - Pethidine , Morphine, Fentanyl,Meperidine Weak- Codeine Tramadol Pentazocaine They are also either; Opioid agonist – morphine, diamophine , methadone, pethidine ( meperidine ) – 3-4hrs, codeine, dihydrocodeine , fentanyl ( sulfentanil , alfentanil , remifentanil ). Partial agonist – Buprenorphine , meptazinol , nalbuphine , tramadol (7-8hrs) Opioid antagonists – Naloxone ( narcan ), naltrexone , nalmefene

113. Mechanism of action Opioids – Binds with opiate receptors in the spinal cord and higher levels of the CNS; which alters perception and emotional response to pain. Partial agonists – Bind with mu receptors and inhibits reuptake of norepinephrine and serotonin accounting for analgesic effects. Antagonist – antagonizes mu and opiate receptors in the CNS thus reversing the analgesia, hypotension, respiratory depression and sedation

114. Pharmacokinetic Well absorbed after oral, Im and SC administration, Protein binding vary. Distributed to most tissues but remain highly perfused eg liver, kidney and brain. Metabolized by liver. Excreted in urine

115. Indications Mx of moderate to severe pain (preoperatively and postoperatively) Cough – codeine syrup Mx of respiratory depression induced by opioids - antagonists. Mx of asphyxia neonatorum , coma and hypotension – antagonists ( naloxone )

116. FFECTS OF OPIOID USE CNS effects Analgesia Respiratory depression Depress cough centres Anaesthesia - Mild hypnotics (drowsiness and sleep)

117. CNS stimulant effects Nausea/ vomit Miosis (Constrict pupil) – effect on 3 rd nerve. Bradycardia and hypotension – stimulates vagus nerve

118. Peripheral effects Constipation – decreased peristaltic activity of the bowel and increase tone. Decrease renal function Bronchoconstriction – histamine release.

119. Cont.. Side effects Restlessness Hyperactivity Nausea and Vomiting Constipation

120. Adverse effects Tolerance Dependence Postural hypotension Urinary retention Increased intracranial pressure

121. NON OPIOIDS ANALGESICS They include:- NSAIDs(Non steroid anti-inflammatory drugs) Acetaminophen

122. NSAIDs Two enzymes are concerned with the formation of prostaglandins:- Cyclooxygenase – 1 (COX - 1) – have a protective effect on stomach lining. Cyclooxygenase – 2 (COX - 2) – responsible for pain and inflammation; can cause stomach ulceration.

123. Pharmacokinetics Well absorbed orally. Food does not interfere with absorption. Protein bound. Metabolized in liver. Excreted by kidneys. Pharmacodynamic Block both cox – 1 and 2 which causes pain, inflmtn and infection.. They also have general effects:-

124. Cont.. Anti inflammatory effect Analgesic effects Antipyretic effects Antiplatelets NSAIDs can be broadly classified into:-

125. Acetylated NSAIDs eg aspirin( acetylsalicyclic acid) Pharmacokinetic Given by mouth, rapidly absorbed from stomach and ileum. Distributed in tissues and blood. In high doses, some salicylate become bound to plasma proteins (causing allergy). Metabolised in liver and excreted in urine. Half life 15-20 mins

126. Pharmacodynamics Analgesic effects – blocks pain impulses. Anti inflammatory effects – a nonselective inhibitor of both COX hence reduces inflammation by inhibiting prostaglandin synthesis. Antipyretic effects – vasodilation of peripheral vessels); antiplatelets – decrease platelet aggregation.

127. Indication Relieves moderate and mild pain Relieves fever Long term use of aspirin lowers incidences of colon cancer Osteoarthritis Rheumatic fever Prophylaxis of myocardial infarction

128. Contraindication 3 rd trimester of pregnancy. GI bleeding Bleeding disorders. Breastfeeding Precaution Pts with gastritis, peptic ulcers, asthma. Hypersensitivity to ASA. Chidren <12yrs

129. Side effects Drowsiness Dizziness Headache Rapid pulse  

130. Cont.. Tinnitus Hearing loss Rash Urticaria Wheeze

131. Adverse effects Reye syndrome Laryngeal edema Thrombocytopenia seizures

132. Treatment of overdose Lavage Activated charcoal Monitor electrolytes

133. Nonacetylated NSAIDs COX -2 selective inhibitors Celecoxib Etoricoxib Valdecoxib Meloxicam .

134. Non selective COX inhibitors (pg 152) Diclofenac Diflunisal Etodolac Fenoprofen Ibuprofen

135. Cont.. Indomethacin Ketoprofen Ketorolac Mefenamic acid Naproxen