Pharmaceutical Lecture Notes - Antibiotics - PDF

Lecture 5 (MAINLY FOCUSED ON THIS LECTURE AS IT WILL BE MOSTLY TESTED) Common Antibx Classification Brand Dosage Forms Typical Auxiliary Labels Name Dosing...

Lecture 5 (MAINLY FOCUSED ON THIS LECTURE AS IT WILL BE MOSTLY TESTED) Common Antibx Classification Brand Dosage Forms Typical Auxiliary Labels Name Dosing (Cdn) Upper Respiratory Infections Amoxicillin Penicillin - Capsule, suspension, Tid / bid Finish all medication injection/tab Cefuroxime Cephalosporin Ceftin Tab/powder/injection Bid Take with food Azithromycin Macrolide Zithromax Tab/ suspension/ Once a Finish all medication day Ciprofloxacin Fluoroquinolone - Suspension/tab/injection Bid Photosensitivity, Avoid dairy/minerals Levofloxacin Fluoroquinolone Levoquin Tab/injection Once a Photosensitivity, Avoid day dairy/minerals Community Acquired Pneumonia Doxycycline Tetracycline Doxycin Tablet, capsule Once / Photosensitivity, Take with twice daily water Azithromycin Macrolide Zithromax Tablet, suspension Once a Finish all medication day Levofloxacin Fluoroquinolone Levaquin Tablet, injection Once a Photosensitivity, Avoid day dairy/minerals Urinary Tract Infections Nitrofurantoin bid Miscellaneous Macrobid Cap/tab Bid TAKE WITH FOOD Norfloxacin Fluroquinolones noraxin TAB BID Photosensitivity, Avoid dairy/minerals Ciprofloxacin Fluroquinolones - Susp/tab/injection BID Photosensitivity, Avoid dairy/minerals CLASSIFICATION OF ANTIBIOTIC Photosensitivity Photosensitivity, Photosensitivity, Avoid Avoid dairy/minerals dairy/minerals Take on empty Avoid in pregnancy and stomach because lactation food interferes with absorption Antibiotic Brand Name Classification Major Indication(s) Dosage Forms amoxicillin AMOXIL PENICILLIN Bacterial infections (ear, throat, urinary, etc.) Capsules, Tablets, Suspension amoxicillin & AGUMENTIN PENICILLIN Bacterial infections resistant to amoxicillin alone Tablets, Chewable, Suspension clauvulinic acid ampicillin PENBRITIN PENICILLIN Respiratory, urinary, and GI tract infections Capsules, Injection, Suspension azithromycin ZITHROMAX MACROLIDES Respiratory infections, STIs, skin infections Tablets, Suspension, Injection cefaclor CECLOR CEPHALOSPORINS Respiratory and skin infections Capsules, Suspension cefadroxil DURICEF CEPHALOSPORINS Skin, throat, and urinary infections Capsules, Suspension cefazolin ANCEF, KEFZOL CEPHALOSPORINS Preoperative prophylaxis, skin infections Injection cefixime SUPRAX CEPHALOSPORINS Respiratory and urinary infections Tablets, Suspension ceftazidime FORTAZ, TAZICEF CEPHALOSPORINS Severe infections, pseudomonal infections Injection ceftriaxone ROCEPHIN CEPHALOSPORINS Severe infections, STIs, respiratory infections Injection cefuroxime CEFTIN CEPHALOSPORINS Respiratory, skin, and urinary infections Tablets, Suspension, Injection cephalexin KEFLEX CEPHALOSPORINS Skin, throat, and urinary infections Capsules, Tablets, Suspension ciprofloxacin CIPRO FLUOROQUINOLONES Urinary, GI, respiratory infections Tablets, Suspension, Injection clarithromycin BIAXIN MACROLIDES Respiratory infections, peptic ulcer disease Tablets, Suspension clindamycin CLEOCIN LINCOSAMIDES Respiratory, skin, bone infections Capsules, Injection, Suspension cloxacillin ORBENIN Staphylococcal infections Capsules, Injection co-trimoxazole BACTRIM, SEPTRA SULFONAMIDES Urinary, respiratory infections Tablets, Suspension, Injection doxycycline VIBRAMYCIN, TETRACYCLINES Respiratory infections, acne, Lyme disease Tablets, Capsules, Suspension DORYX erythromycin EES, MACROLIDES Respiratory, skin infections Tablets, Suspension, Injection gentamicin GARAMYCIN AMINOGLYCOSIDES Severe infections, often gram-negative bacteria Injection, Topical Imipenem/cilistatin PRIMAXIN CARBAPENEMS Severe infections (multi-drug-resistant bacteria) Injection levofloxacin LEVAQUIN FLUOROQUINOLONES Respiratory, urinary, and skin infections Tablets, Injection minocycline MINOCIN TETRACYCLINES Acne, respiratory infections Capsules, Tablets, Injection nitrofurantoin MACROBID MISCELLANEOUS Urinary tract infections Capsules, Suspension norfloxacin NOROXIN FLUOROQUINOLONES Urinary and GI infections Tablets tobramycin TOBREX AMINOGLYCOSIDES Severe infections, often gram-negative bacteria Injection, Ophthalmic vancomycin CANCOCIN MISCELLANEOUS Severe infections (MRSA, C. difficile) Injection, Oral Solution IMPORTANT TO KNOW THIS  Classification of Bacteria Gram Stain: Contains Crystal Violet & Safranin Bacteria are divided into 2 classes based on how they stain Stained Blue: “Gram Positive” + a very thick cell wall (peptidoglycan) Stained Red: “Gram Negative”- thin peptidoglycan, lipopolysaccharides present Type of cell wall will determine which antibiotics are able to attack that type of bacteria Culture and Sensitivity Testing Spectrum of Activity Testing Narrow Spectrum: Drug is effective against only a few specific types of bacteria Broad Spectrum: Drug is effective against a wide range of bacteria Antibiotic Susceptibility Identification of antibacterial drugs that are effective against a specific microorganism Antibiotic Susceptibility  MIC  Minimum Inhibitory Concentration  Lowest concentration of the drug to prevent growth of microorganism culture after 18-24 hours of incubation  MBC  Minimum Bactericidal Concentration  Lowest concentration that kills 99.9% of organisms How do antibiotics generally work? The drug attacks either the cell wall, or the proteins, or the enzymes of the bacterial cell - these are the vital components needed for the bacteria to survive and/or grow/replicate 1. Penicillins Beta- Lactams Bactericidal Derived from mold MOA: Inhibit cell wall synthesis Inhibit transpeptidase enzyme which links the peptidoglycan molecules thus inhibiting cross-linking of cell wall, increased osmotic pressure & cell wall lysis 4 generations –differ regarding: acid stability Spectrum ( how many it’s able to attack) resistance to destruction by penicillinase Penicillins: First Generation Pen V, Pen G Narrow antibacterial Spectrum Effective against common gram-positive organisms Example - ear and throat infections - streptococci, pneumococci Not active against Gram Negative or penicillinase producing bacteria Penicillinase Resistant: Cloxacillin effective for resistant staph aureus infections abscesses, endocarditis, pneumonia  Penicillins: Second Generation AKA: Aminopenicillins Ampicillin, Amoxicillin, Bacampicillin, Pivampicillin Considered broad spectrum ( kills of a lot of things) Effective for: Coverage same as Pen V/G plus common gram-negative organisms E coli, Proteus mirabilis, Haemophilus influenzae Respiratory, urinary, ear infections Not effective vs. penicillinase producing organisms However, Amoxicillin is often combined with clavulanic acid (beta-lactamase inhibitor) to make it more effective Penicillins: Third Generation Ticarcillin (+ Potassium Clavulanate) Poor activity against gram positive organisms Broader spectrum of activity Active against gram negative organisms such as Pseudomonas aeruginosa and Proteus vulgaris More serious urinary, respiratory & bacteremic infections (systemic) Penicillins: Fourth Generation Piperacillin (+ Tazobactam) Broader spectrum of activity Gram Negatives (P. Aeruginosa, P. Vulgaris, Klebsiella) Anaerobic (survive without oxygen) organisms (Bacteroides fragilis) More potent than third generation drugs Indicated for more serious infections (given IV) (systemic infection) Penicillins: Adverse Effects Generally, well tolerated Allergy ( real allergy response) Nausea (side effect) rash, fever, inflammatory response Diarrhea(side effect) anaphylaxis In high doses (overdoses) – convulsions allergy to one = allergy to all What are common Aux labels for a drug in the penicillin class? What is the role of Probiotics with antibiotics? IMPORTANT TO FINISH THIS MEDICATION AS MD PRESCRIBED & TAKE WITH FOOD 2. Carbepenems Beta-Lactams Imipenem/Cilastatin, Meropenem/Cilastatin ✓ Prescribed when there a Life- Broad spectrum (gram positive and negative) threatening infection!!! Beta-lactamase resistant ✓ Longer acting Very potent ✓ Diarrhea, vomiting but much more Reserved for serious life-threatening infections severe Cilastatin blocks the metabolism of antibiotic by the kidney allowing ✓ Better to be given with food antibacterial levels to be maintained Cephalosporins Beta- Lactams Bactericidal Cephalosporins: Adverse Effects Similar structure and MOA to penicillin’s Susceptible to “cephalosporinase” enzyme GI disturbances (diarrhea) Broad-spectrum drugs Injections: pain and local inflammation Rarely drug of choice Skin rashes Primary uses: Allergic reactions (watch cross-sensitivity to Penicillin allergy penicillin?) however still 10% cross sensitivity Bacterial resistance Certain gram-negative infections Cephalosporins: First Generation Cefazolin, Cephalexin, Cefadroxil Cover gram positive and some gram-negative organisms Useful for common gram positive/negative infections of ear, nose, throat, urinary tract, skin Susceptible to beta-lactamase enzymes Cephalosporin: Second Generation Cefuroxime, Cefaclor, Cefprozil, Cefoxitin Broader spectrum of action than the first-generation drugs Greater potency than first gen drugs vs gram negative Useful for upper respiratory infections caused by H. influenzae ( bacterial infection: viral) Cephalosporins: Third Generation Cefotaxime, Cefixime, Ceftazidime, Ceftriaxone Treatment of serious gram-negative infections not responding to second generation agents Broader spectrum and more potent against gram negative organisms Cross blood brain barrier more easily Useful for some types of meningitis Cefixime oral only – useful for bronchitis, urinary tract, sinusitis, otitis media Many other drugs just as effective for these purposes Other third gen agents available as IV only Cephalosporins: Fourth Generation Cefepime Similar spectrum of activity to third generation drugs Greater resistance to beta lactamase What are common aux labels for cephalosporins? SAME AUXILIARY AS PENICILIN What are some dispensing tips?  Tetracyclines Tetracycline, Doxycycline, Minocycline Bacteriostatic ( prevent growth of the bacteria) Interfere with bacterial protein synthesis Activity against both gram positive & negative organisms Commonly used for bronchitis and acne vulgaris Agents of choice for unusual infections such as: Rickettsiae – Rocky Mountain Spotted Fever Typhus Mycoplasma pneumoniae ( viral) Vibrio cholerae Chlamydia trachomatis – urethritis, STD ( combination of antibiotic to kills it off) Borrelia burgdorferi - Lyme disease (tick bites) Bacterial related acne (Minocycline’s only indication) Tetracyclines : Adverse Effects Nausea, vomiting, and diarrhea Photosensitivity (sunburn) –PT needs to put on sunscreen Fungal superinfection (candida) Taking Probiotic can prevent fungal superinfection Use of expired tetracycline Fanconi syndrome - kidney damage Avoid in children under 8 yrs old discolours teeth yellow may depress bone growth Avoid in pregnancy and lactation Minocycline – not under 13 years old Tetracyclines Labeling Requirements Avoid calcium, dairy products, antacids and mineral supplements at same time as dose, 1 hour before or 2 hours Sunlight warning Avoid in pregnancy and lactation For short course only: take until finished (If for long course…what is the indication?) pt having resistance to the antibiotic Macrolides Erythromycin, Clarithromycin, Azithromycin Bacteriostatic Inhibit protein synthesis Activity varies by drug Gram positive plus some gram-negative organisms Erythromycin Covers similar spectrum as Pen V + can be used to treat Legionella pneumophilia, Mycoplasma pneumoniae, Chlamydia trachomatis Azithromycin Same as erythromycin H. Influenzae – ear and respiratory infections Advantage once daily dosing High tissue affinity – give drug for 5 days and continues to be active in tissue for 10 days  Clarithromycin Same as erythromycin BID dosing and less severity in side effects Penicillin substitute in allergic patients Macrolides Adverse Effects Primarily gastrointestinal – N/V/D Erythromycin Dose related adverse effects (1 g or greater) Various salt forms provided to lessen GI effects Enteric coated pellets attempt to reduce GI irritation Common Aux Labels? “Take with Food” Lincosamides - Clindamycin Indications Clindamycin supplied Infections due to gram positive and anaerobic bacteria Capsules – 150 mg, 300 mg Many dosage forms and routes of admin Oral powder for reconstitution – 75 mg/5 ml Administered topically for Acne and Bacterial Vaginosis Injectables Method of Action Topical solution – 1% Inhibition of protein synthesis Topical creams – face/back (Bacteriostatic) Vaginal cream – 20mg/g Adverse Effects For Topicals: Diarrhea -instruct patients to wash hands before and after use Overgrowth of clostridia difficile -read dispensing instructions for mixing and storing, Causes pseudomembranous colitis review with patient (some are refrigerated, and some are Severe abdominal cramps mixed just prior or after dispensing) Happens with Oral and IV administration After rubbing into eyes, nose, mouth – may cause burning sensation Topical – dalacin, benzaclin, clindoxyl Aminoglycosides Bactericidal Spectrum: gram negative bacilli Inhibition of bacterial protein synthesis at the ribosome Gentamicin Tobramycin Amikacin Paramomycin amebicide Streptomycin (anti tubercular) Not absorbed well through GI Topical preps for ocular/otic infections Given IV or IM for systemic effect Multiple vs single daily dosing is questionable Effectiveness / toxicity is questionable Adverse Effects: Ototoxicity – hearing (high frequency), vestibular – balance Nephrotoxicity – kidney Drug levels may be monitored in high-risk patients( blood test)  Sulfonamides Synthetic antibiotic ( not naturally occurring) Competitive antagonists of PABA (para-amino-benzoic acid), a compound needed by bacteria for folic acid production Inhibits bacterial growth-Bacteriostatic Widespread early use led to resistance Currently, use is limited to selected infections Sulfamethoxazole + Trimethoprim = “Cotrimoxazole” – oral tabs/susp Sulfacetamide: ocular infections (drops/oint) Sulfapyridine combined with 5-amino salicylic acid to form sulfasalazine (IBD/ulcerative colitis) Sulfonamides: “Cotrimoxazole” Combo drug: Sulfamethoxazole + Trimethoprim Trimethoprim also interferes with folic acid synthesis within bacteria Synergistic effect ( works better when there two or more combined rather than by itself) Broad spectrum, very popular product USES: Respiratory, urinary, GI, otitis media (children and adults) Treatment of choice and prophylaxis for Pneumocystis Carinii Pneumonia – infection often seen in HIV/Chemo patients Cotrimoxazole - Adverse Effects GI intolerance – N/V/D Sulfonamides – Drug Interactions crystalluria – rare with hydration photosensitivity Sulfonamides are highly protein bound drugs… allergic reactions Therefore, increase free concentration of other highly pruritis, rashes ( extreme rash and should be stop taken bound drugs such as: immediately) Anticoagulants – increase bleeding rarely Stevens-Johnson Syndrome Hyperglycemic drugs – lower blood sugar exfoliative dermatitis, can be fatal blood disorders in patients with G6PD deficiency anemia, thrombocytopenia, leukopenia Sulfonamides – Labelling Sulfamethoxazole + Trimethoprim ❑ Water – drink lots of fluid ❑ Sun protection ❑ Acute infection: take until finished  Fluoroquinolones ❑ Ciprofloxacin Synthetic ❑ Norfloxacin Broad spectrum ❑ Ofloxacin Mechanism of Action: Inhibit DNA gyrase, an enzyme essential to bacterial ❑ Levofloxacin replication ❑ Moxifloxacin Bactericidal ❑ Trovafloxacin (Trovan) ❑ Altrofloxacin (Trovan IV) Fluoroquinolones - Indications Ciprofloxacin Used in urinary, respiratory, skin, soft tissue, bone, GI infections Very commonly used, many available strengths and dosage forms Norfloxacin Indicated in urinary tract infection only Not available in sufficient concentrations at other sites Levofloxacin & Moxifloxacin “Respiratory fluoroquinolones” Altarofloxacin/Trovafloxacin Indicated for serious life-threatening infections in hospitalized adult patients Fluoroquinolones - Adverse Effects ✓ Headache ✓ Dizziness ✓ GI disturbance (N/V/D) ✓ Skin rash ✓ Photosensitivity* ✓ Joint swelling* (Symptoms of joint swelling , you should immediately STOP ) ✓ Cartilage defects in animal studies Not recommended in children and pregnancy *new restrictions and precautions for use due to very rare reports of disabling and potentially long-lasting or irreversible adverse effects affecting musculoskeletal and nervous systems have been reported very rarely with fluoroquinolones, therefor treatment should be discontinued at the first signs of a serious adverse reaction, including tendon pain or inflammation. Fluoroquinolones – Labeling For all: Avoid Minerals, calcium, aluminum, magnesium, iron at time of administration (drug interaction which reduces the absorption of antibiotic) Take until finished Norfloxacin (UTI) Take on empty stomach because food interferes with absorption Take with lots of water  Miscellaneous Antibacterial Agent: Nitrofurantoin (Macrobid) Used only in urinary tract infections and cystitis MOA Interferes with protein synthesis, cell wall synthesis and DNA/RNA synthesis of bacterial cells Bacteriostatic but may be bactericidal at higher concentration E. Coli and Staph saprophyticus Adverse Effects: GI intolerance – nausea, vomiting Pulmonary reactions – fibrosis, pneumonitis Rare, seen more often in long term therapy Labeling ❑ Plenty of water ❑ Discoloration of urine/feces ( reddish colour) ❑ Take with food ❑ Take until finished Miscellaneous Antibacterial Agents: Vancomycin Indications IV - serious gram-positive infections Oral – treatment of C. difficile infections MOA Interferes with cell wall synthesis ( bactericidal) Supplied Injections Capsules – 125 mg, 250 mg (not commonly seen) Adverse Effects ❑ Ototoxicity ❑ Nephrotoxicity ❑ Flushing – “red man syndrome” infusing drug too rapidly causes histamine release How does prescriber choose? Role of Pharm Tech with Antibiotics Published guidelines/charts as per type of bacteria and Dispensing accurately infection, indicating 1st line, 2nd line, etc Reconstitution (oral susp, creams, IV admixtures, etc.) Should “swab” and identify bacteria Labeling requirements – sig, aux labels, expiries Based on antibiotic susceptibility Insurance coverage (LU needed? Criteria met?) or non- (spectrum) formulary within hospital What is the risk of prescribing wrong agent? Checking the accuracy of dispensed antibiotics Degree of infection – mild to severe, or resistant Correct antibiotic, appropriate dosage Type of infection – topical or systemic form, reconstituted properly, labelled, Patient factors etc. age Flagging issues to pharmacist of possible… dosage form preference Inappropriate dosing on Rx coverage, criteria SE and non-compliance of patient contraindications: allergies, pregnancy, drug Potential allergy or drug interaction or interactions, liver/kidney disease contraindication (pregnant) Resistant infections if patient returns Train patients with the administration steps Bactericidal Antibiotics Bacteriostatic Antibiotics Tetracyclines Beta lactam (penicillin’s, cephalosporins, carbapenems) Macrolides Aminoglycosides Sulfon Fluoroquinolones Lincosamides Vacomycin Erythromycin (macrolid) LECTURE 6 Tuberculosis DEFINITIONS: CHARACTERISITCS An infection caused by Mycobacterium Can lie dormant in the body and reemerge when immune Usually involving the lungs, but may also affect other parts system is weak of the body including different organs and the brain Humans are the only reservoir of microorganisms Once it reaches the lymph nodes, the circulation of TB spreads even more Tuberculosis (TB) is primarily transmitted through the air when an infected person coughs, sneezes, speaks, or sings. GOALS OF THERAPY Why are healthcare workers screened for TB? Prevent progress of infection not to become clinically active Risk of Exposure: Healthcare workers are often in close Prevent person-to-person transmission by early diagnosis contact with patients who may have active TB and initiation of treatment Preventing Transmission Treat active disease - eradicate the bacteria from affected Protecting Vulnerable Populations: compromised immune organs (Streptomycin in combination) systems or existing health conditions.’ Public Health Relieve symptoms of fever, sweats, weight loss and cough Strategy: public health initiatives to control and reduce the incidence of TB TUBERCULOSIS DRUGS Isoniazid 1st choice for prophylaxis of tuberculosis (TB) Rifampin Specifically used for treating Mycobacterium tuberculosis (TB), as they are highly effective against this bacteria Rifabutin Specifically used for treating Mycobacterium tuberculosis (TB), as they are highly effective against this bacteria Ethambutol can be used for other mycobacterial infections beyond TB Pyrazinamide Streptomycin Streptomycin (IV, in combo for active) For latent and active infections, there is a long course (6-24 months) of a combination of meds Streptomycin is an aminoglycoside antibiotic and is considered a second-line TB treatment. It’s generally reserved for cases where first-line drugs cannot be used, such as drug-resistant TB