Drugs-to-Control-Infections.pdf

DRUGS TO CONTROL INFECTIONS ANTI-INFECTIVE DEVELOPMENT OF ANTI-INFECTIVE THERAPHY PAUL EHRLICH - 1920s. Ehrlich’s research to develop a synthetic chemical that would be effective only against infection-causing cells, not human cells, led the way for the scientific investigation of anti...

DRUGS TO CONTROL INFECTIONS ANTI-INFECTIVE DEVELOPMENT OF ANTI-INFECTIVE THERAPHY PAUL EHRLICH - 1920s. Ehrlich’s research to develop a synthetic chemical that would be effective only against infection-causing cells, not human cells, led the way for the scientific investigation of antiinfective agents. In the late 1920s, scientists discovered penicillin in a mold sample; in 1935, the sulfonamides were introduced  ALEXANDER FLEMING – WAS A PHYSICIAN– SCIENTIST WHO WAS RECOGNIZED FOR DISCOVERING PENICILLIN. UPON EXAMINING SOME COLONIES OF STAPHYLOCOCCUS AUREUS, HE NOTED THAT A MOLD CALLED PENICILLUM NOTATUM CONTAMINATED HIS PETRI – DISH  Anti-infectives is a general term used to describe any medicine that is capable of inhibiting the spread of an infectious organism or by killing the infectious organism outright. Anti-infective agents are drugs utilized to exert effect on invading foreign organisms on the body, especially those which can cause infection. MECHANISM OF ACTION 1. INTERFERE WITH BIOSYNTHESIS OF BACTERIAL CELL WALL 2. PREVENT THE CELLS OF THE INVADING ORGANISM FROM USING SUBSTANCES ESSENTIAL TO THEIR GROWTH AND DEVELOPMENT. 3. INTERFERE WITH STEPS INVOLVED IN PROTEIN SYNTHESIS 4. INTERFERE WITH DNA SYNTHESIS 5. ALTER THE PERMEABILITY OF THE CELL MEMBRANCE TO ALLOW ESSENTIAL CELLULAR COMPONENTS TO LEAK OUT. CLASSIFICATIONS OF ANTI-INFECTIVES 1) Antibiotics 2) Antivirals 3) Antifungals 4) Antitubercular 5) Antiprotozoal 6) Antimalarial 7) Anthelmintics RESISTANCE Resistance can be natural or acquired and refers to the ability over time to adapt to an antiinfective drug and produce cells that are no longer affected by a particular drug. Because antiinfectives act on specific enzyme systems or biological processes, many microorganisms that do not use that system or process are not affected by a particular antiinfective drug and are said to have a natural or intrinsic resistance ACQUIRING RESISTANCE Producing an enzyme that deactivates the antimicrobial drug. For example, some strains of bacteria that were once controlled by penicillin now produce an enzyme called penicillinase, which inactivates penicillin before it can affect the bacteria. This occurrence led to the development of new drugs that are resistant to penicillinase. Altering binding sites on the membranes or ribosomes, which then no longer accept the drug. Producing a chemical that acts as an antagonist to the drug. → A chemical substance capable of combining with the specific receptor in the cell, and initiating the same reaction or activity typically produced by the binding substance PREVENTING RESISTANCE Limit the use of antimicrobial agents to the treatment of specific pathogens sensitive to the drug being used. Make sure doses are HIGH ENOUGH, and the duration of drug therapy is LONG ENOUGH Be cautious about the indiscriminate use of anti- infective SELECTION OF APPROPRIATE DRUG The aim of anti-infective drug therapy is to choose an agent that is most likely active against the offending pathogen and has at least potential to adverse reactions. 1. Necessity of therapy 1.Many infectious conditions do not require systemic antimicrobial therapy, - And the clinician should make a careful assessment of the patient's status and the location - And severity of the infection before undertaking antibiotic therapy. TREATMENT OF SYSTEMIC INFECTIONS IDENTIFICATION OF THE PATHOGEN Identification of the infecting pathogen is done by culturing a tissue sample from the infected area. Cultures are performed in a laboratory, in which a swab of infected tissue is allowed to grow on an agar plate The correct identification of the organism causing the infection is an important first step in determining which antiinfective drug should be used.  SENSITIVITY OF THE PATHOGEN In many cases, it is necessary to perform sensitivity testing on the cultured microbes to evaluate bacteria and determine which drugs are capable of controlling the particular microorganism. Healthcare providers use a broad- spectrum antiinfective agent that has been shown to be most effective in treating an infection with certain presenting signs and symptoms.  COMBINATION THERAPY encouraged to use a smaller dose of each drug, leading to fewer adverse effects but still having a therapeutic impact on the pathogen. Some drugs are synergistic, which means that they are more powerful when given in combination. Sometimes, the combined effects of the different drugs delay the emergence of resistant strains. Resistant strains may be more likely to emerge when fixed combinations are used over time; however, this may be prevented by individualizing the combination. ADVERSE REACTIONS TO ANT-INFECTIVE THERAPY Kidney damage Gastrointestinal (GI) tract toxicity Neurotoxicity Hypersensitivity reactions Superinfections CLASSIFICATIONS - SPECTRUM OF ACTIVITY NARROW SPECTRUM BROAD SPECTRUM of activity of activity Effective against only a few microorganisms with Useful in treating a a very specific metabolic wide variety of infections pathway or enzyme. EMPIRIC THERAPY This utilizes the antibiotic regimen that best treats the common cause of infection This is to initiate an early start in the treatment regimen Note: antibiotic used are broad-spectrum DEFINITIVE THERAPY Utilization of the most sensitive antibiotics to treat the infection by the means of culture and sensitivity Note: antibiotic used are narrow spectrum  PROPHYLAXIS to prevent infections before they occur. For example, when patients anticipatetraveling to an area where malaria is endemic, they may begin taking antimalarial drugs before the journey and continue taking them periodically during the trip. Patients who are undergoing gastrointestinal (GI) or genitourinary surgery, which might introduce bacteria from those areas into the system, often have antibiotics ordered during or immediately after the surgery and periodically thereafter, as appropriate, to prevent infection. TYPES OF ANTIBIOTICS - ANTIMICROBIAL ACTIVITY BACTERIOSTATIC – SUBSTANCES THAT PREVENT THE GROWTH OF BACTERIA. -THEY DO NOT KILL THE CELLS. BACTERICIDAL – SUBSTANCES THAT KILL BACTERIA DIRECTLY SIGNS OF INFECTION 1. Fever 2. Lethargy 3.Classic Signs of Inflammation o redness (rubor), o swelling (tumour), o heat (calor) and o pain (dolor) GOAL OF ANTIBIOTIC THERAPY Decrease the population of the invading bacteria to a point where the human immune system can effectively deal with the invaders. BACTERIAL CLASSIFICATION GRAM POSITIVE – THE CELL WALL RETAINS A STAIN OR RESISTS DECOLORIZATION WITH ALCOHOL. GRAM NEGATIVE – THE CELL WALL LOSES A STAIN OR IS DECOLORIZED BY ALCOHOL AEROBIC – DEPEND ON OXYGEN SURVIVAL ANAEROBIC – DO NOT USE OXYGEN CLASSIFICATION/ CLASSES 1. Aminoglycosides 2. Cephalosporins 3. Fluoroquinolones / Quinolones 4. Macrolides 5. Lincosamides 6. Monobactams 7. Penicillins 8. Sulfonamides 9. Tetracyclines 10. Antimycobacterials 1. AMINOGLYCOSIDES A GROUP OF POWERFUL ANTIBIOTICS USED TO TREAT SERIOUS INFECTIONS CAUSED BY GRAM – NEGATIVE AEROBIC BACILLI THEY ARE USUALLY GIVEN BY INJECTION BUT MAYBE GIVEN AS DROPS FOR SOME EAR OR EYE INFECTION. BACTERICIDAL (E. COLI, PROTEUS, & PSEUDOMONAS) INDICATIONS: TX OF SERIOUS INFECTIONS CAUSED BY SUSCEPTIBLE BACTERIA ACTION: INHIBIT PROTEIN SYNTHESIS IN SUSCEPTIBLE STRAINS OF GRAM – NEGATIVE BACTERIA CAUSING CELL DEATH 1. AMINOGLYCOSIDES PHARMACOKINETICS - POORLY ABSORBED FROM GI TRACT BUT RAPIDLY ABSORBED AFTER IM INJECTION, REACHING PEAK LEVELS WITHIN 1 HOUR -WIDELY DISTRIBUTED THROUGHOUT THE BODY, CROSSING THE PLACENTA AND ENTERING BREAST MILK - EXCRETED UNCHANGED IN THE URINE AND HAVE AN AVERAGE HALF – LIFE OF 2 TO 3 HOURS CONTRAINDICATIONS: KNOWN ALLERGIES, RENAL OR HEPATIC DISEASE, AND HEARING LOSS ADVERSE EFFECTS: OTOTOXICITY AND NEPHROTOXICITY ARE THE MOST SIGNIFICANT DRUG TO DRUG INTERACTIONS: DIURETICS AND NEUROMUSCULAR BLOCKERS 1. AMINOGLYCOSIDES COMMON MEDICATIONS GENTAMYCIN (GARAMYCIN), STREPTOMYCIN AMIKACIN (AMIKIN) KANAMYCIN (KANTREX) NEOMYCIN (MYCIFRADIN) TOBRAMYCIN (NEBCIN, TOBREX) Amikacin should not be used for longer than 7-10 days because it is particularly toxic to the bone marrow, kidneys, and GI. NURSING RESPONSIBILITIES Assess vital signs, electrolyte levels, hearing ability, and renal function studies before and during therapy. Weigh the patient and review baseline renal function studies. Administer an IM dose deep into a large muscle mass (ventral gluteal) SIDE EFFECTS TO REPORT: OTOTOXICITY: damage to the eight cranial nerve can occur as a result of aminoglycoside therapy. This may initially be manifested by dizziness, tinnitus, and progressive hearing loss. NEPHROTOXICITY: monitor urinalysis and kidney function tests for abnormal test results. Report an increasing BUN and creatinine, decreasing urine output, or decreasing specific gravity. 2. CEPHALOSPORINS SIMILAR TO PENICILLIN IN STRUCTURE AND ACTIVITY BACTERIA: 3RD GENERATION (P. AERUGINOSA) ACTION: INTERFERE WITH CELL – WALL – BUILDING ABILITY TO BACTERIA WHEN THEY DIVIDE INDICATION: TX OF INFECTION CAUSED BY SUSCEPTIBLE BACTERIA PHARMACOKINETICS -WELL ABSORBED FROM GI TRACT -METABOLIZED IIN THE LIVER, EXCRETED IN THE URINE CONTRAINDICATIONS: ALLERGIES TO CEPHALOSPORINS OR PENICILLIN ADVERSE EFFECT: GI TRACT - NAUSEA, VOMITING, DIARRHEA DRUG TO DRUG INTERACTIONS: AMINLOGLYCOSIDES, ORAL ANTICOAGULANTS Classification 1. First-generation Cephalosporins – largely effective against the same gram-positive organisms affected by penicillin Cefadroxil, Cefazolin , Cephalexin , Cephalotin , Cephapirin , Cephadrine 2. Second-generation Cephalosporins – effective against those strains as well as Haemophilus influenza, Enterobacte aerogenes, and Neisseria sp. These drugs are less effective against gram- positive bacteria Cefaclor , Cefamandole , Cefonicid , Cefotetan , Cefoxitin , Cefmetazole , Cefprozil , Cefuroxime Classification 3. Third-generation Cephalosporins – relatively weak against gram- positive bacteria but more potent against gram-negative bacteria, to include Serratia marcescens  Cefnidir , Cefixime , Cefoperazone , Cefotaxime, Cefpodoxime, Ceftazidime , Ceftibuten, Moxalactam 4. Fourth-generation Cephalosporins – developed to fight against the resistant gram-negative bacteria Cefditoren , Cefepime , Ceftaroline NURSING RESPONSIBILITIES Take the oral form with food if GI irritation occurs. Watch for signs and symptoms of hypersensitivity and other adverse reactions. Report signs and symptoms of bacterial or fungal superinfection promptly. Don’t consume alcohol in any form within 72 hours of treatment. Eat yogurt or drink buttermilk to prevent intestinal superinfection resulting from the drug’s suppression of normal intestinal flora. 3. FLUOROQUINOLONES RELATIVELY NEW CLASS OF ANTIBIOTICS WITH A BROAD SPECTRUM OF ACTIVITY INDICATIONS: TX OF INFECTIONS CAUSED BY SUSCEPTIBLE STRAINS OF GRAM – NEGATIVE BACTERIA, INCLUDING URINARY TRACT, RESPIRATORY TRACT, AND SKIN INFECTIONS ACTIONS: INTERFERES WITH DNA REPLICATION IN SUSCEPTIBLE GRAM – NEGATIVE BACTERIA, PREVENTING CELL PRODUCTION PHARMACOKENITICS -ABSORBED IN THE GI TRACT -METABOLIZED IN THE LIVER -EXCRETED IN THE URINE AND FECES 3. FLUOROQUINOLONES CONTRAINDICATIONS: KNOWN ALLERGY, PREGNANCY, AND LACTATION ADVERSE EFFECTS: HEADACHE, DIZZINESS, AND GI TRACT DRUG-TO-DRUG INTERACTION: ANTACIDS AND THEOPHYLLINE BACTERIA: S. PNEUMONIAE, H. INFLUENZAE, P. AERUGINOSA, SALMONELLA, & SHIGELLA INDICATIONS Ciprofloxacin: Lower respiratory tract infections, infectious diarrhea, skin, bone, and joint infections Levofloxacin: Lower respiratory tract infections, skin infections, UTIs Moxifloxacin: Acute bacterial sinusitis, mild to moderate community-acquired pneumonia Norfloxacin: UTIs, Prostatitis Ofloxacin: Selected sexually transmitted diseases, lower respiratory tract infections, prostatitis Gemifloxacin: Chronic bronchitis, mild to moderate community- acquired pneumonia 4. MACROLIDES ANTIBIOTICS THAT INTERFERES WITH PROTEIN SYNTHESIS IN SUSCEPTIBLE BACTERIA INDICATIONS: TX OF RESPIRATORY, DERMATOLOGIC, URINARY TRACT, & GI INFECTIONS CAUSED BY SUSCEPTIBLE STRAINS OF BACTERIA ACTIONS: BINDS TO CELL MEMBRANES CAUSING A CHANGE IN PROTEIN FUNCTION AND CELL DEATH; CAN BE BACTERIOSTATIC OR BACTERICIDAL 4. MACROLIDES PHARMACOKENITICS - ABSORBED IN THE GI TRACT - METABOLIZED IN THE LIVER - EXCRETED IN THE BILE AND FECES CONTRAINDICATIONS: ALLERGY AND HEPATIC DYSFUNCTION ADVERSE EFFECTS: GI SYMPTOMS DRUG-TO-DRUG INTERACTIONS: DIGOXIN, ORAL ANTICOAGULANTS, THEOPHYLLINE, & CORTECOSTERIODS EXAMPLES ARE: AZITHROMYCIN, CLARITHROMYCIN, DIRITHROMYCIN, ERYTHROMYCIN  NURSING RESPONSIBILITIES For best absorption, give the oral form with a full glass of water 1 hour before or 2 hours after meals. Monitor hepatic function (increased levels of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and bilirubin may occur). Monitor the patient’s hydration status if adverse GI reactions occur 5. LINCOSAMIDES SIMILAR TO MACROLIDES BUT MORE TOXIC INDICATIONS: SEVERE INFECTIONS ACTIONS: SIMILAR TO MACROLIDES PHARMACOKENITICS - WELL ABSORBED FROM GI TRACT OR IM - METABOLIZED IN THE LIVER, EXCRETED IN URINE AND FECES CONTRAINDICATIONS: HEPATIC & RENAL IMPAIRMENT ADVERSE EFFECTS: GI REACTIONS EXAMPLES ARE CLINDAMYCIN, LINCOMYCIN 6. MONOBACTAMS UNIQUE STRUCTURE WITH LITTLE CROSS - RESISTANCE INDICATIONS: TX OF INFECTIONS CAUSED BY SUSCEPTIBLE BACTERIA; UTI, SKIN, INTRA- ABDOMINAL, & GYNECOLOGIC INFECTIONS ACTIONS: DISRUPTS BACTERIA WALL SYNTHESIS, WHICH PROMOTES THE LEAKAGE OF CELLULAR CONTENT AND CELL DEATH PHARMACOKENITICS - WELL ABSORBED FROM THE IM INJECTION -EXCRETED UNCHANGED IN THE URINE CONTRAINDICATIONS: ALLERGY ADVERSE EFFECTS: GI & HEPATIC ENZYME ELEVATION EXAMPLES ARE AZTREONAM, AZACTAM 7. PENICILLINS FIRST ANTIBIOTICS INTRODUCED FOR CLINICAL USE INDICATIONS: TX OF INFECTIONS CAUSED BY STREPTOCOCCAL, PNEUMOCOCAL, STAPHYLOC OCCAL, AND OTHER SUSCEPTIBLE BACTERIA ACTIONS: INHIBIT SYNTHESIS OF THE CELL WALL IN SUSCEPTIBLE BACTERIA, CAUSING CELL DEATH PHARMACOKENITICS - WELL ABSORBED FROM THE GI TRACT - EXCRETED UNCHANGED IN THE URINE. -ABSORPTION OF MOST ORAL PENICILLINS (EXCEPT AMOXICILLIN) IS IMPAIRED BY FOOD, AND THE DRUGS SHOULD BE ADMINISTERED AT LEAST 1-2 HOURS BEFORE OR AFTER A MEAL - IV ADMINISTRATION OF PENICILLIN G IS PREFERRED TO THE IM ROUTE BECAUSE OF IRRITATION AND LOCAL PAIN FROM IM INJECTION OF LARGE DOSES 7. PENICILLINS CONTRAINDICATIONS: ALLERGY; CAUTION IN PATIENTS WITH RENAL DISEASE ADVERSE EFFECTS: GI EFFECTS –NAUSEA, VOMITING, DIARRHEA DRUG-TO-DRUG INTERACTIONS: TETRACYCLINES & AMINOGLYCOSIDES Classification: 1.Narrow-spectrum Penicillins – have greatest activity against gram-positive organisms, gram- negative cocci, and non-β-lactamase-producing anaerobes e.g. Penicillin G and Penicillin V 2. Broad-spectrum Penicillins (Aminopenicillin) e.g. Amoxicillin and Ampicillin 3. Penicillinase-resistant Penicillin (Anti-staphylococcal) – resistant to staphylococcal β-lactamases e.g. Cloxacillin, Methicillin and Oxacillin 4. Extended-spectrum Penicillins (Anti-pseudomonal) – retain the antibacterial spectrum of penicillin e.g. Carbenicillin and Piperacillin 5. Beta-lactamase Inhibitors (Clavulanic acid, Sulbactam, Tazobactam) e.g. Clavulanic acid, Sulbactam and Tazobactam 8. SULFONAMIDES DRUGS THAT INHIBIT FOLIC ACID SYNTHESIS INDICATIONS: TX OF INFECTIONS CAUSED BY GRAM – NEGATIVE BACTERIA AND GRAM POSITIVE BACTERIA ACTIONS: INTERFERES WITH CELL-WALL- BUILDING ABILITY OF DIVIDING BACTERIA PHARMACOKENITICS - WELL ABSORBED FROM THE GI TRACT - METABOLIZED IN THE LIVER & EXCRETED IN THE URINE CONTRAINDICATIONS: ALLERGY & PREGNANCY ADVERSE EFFECTS: GI SYMPTOMS & RENAL EFFECTS RELATED TO THE FILTRATION OF THE DRUG DRUG-TO-DRUG INTERACTIONS: CROSS SENSITIVITY WITH THIAZIDE DIURETICS; SULFFONYLUREAS EXAMPLES ARE SULFAZALAZINE ,SULFAMETHOXAZOLE , SULFADIAZINE, SULFIXOXAZOLE 9. TETRACYCLINES CLASSIFICATION: 1. SHORT-ACTING TETRACYCLINES TETRACYCLINE AND OXYTETRACYCLINE 1. INTERMEDIATE-ACTING TETRACYCLINES DEMECLOCYCLINE AND METHACYCLINE 2. LONG-ACTING TETRACYCLINES DOXYCYCLINE AND MINOCYCLINE 9. TETRACYCLINES DEVELOPED AS SEMISYNTHETIC ANTIBIOTICS BASED ON THE STRUCTURE OF COMMON SOIL MOLD INDICATIONS: TX OF INFECTIONS CAUSED BY SUSCEPTIBLE STRAINS OF BACTERIA AND ACNE, WHEN PENICILLIN IS CONTRAINDICATED FOR ERADICATION OF SUSCEPTBLE ORGANISM ACTIONS: INHIBIT PROTEIN SYNTHESIS IN SUSCEPTIBLE BACTERIA, PREVENTING CELLL REPLICATION PHARMACOKENITICS - ADEQUATELY ABSORBED FROM THE GI TRACT - CONCENTRATED IN THE LIVER & EXCRETED UNCHANGED IN THE URINE 9. TETRACYCLINES CONTRAINDICATIONS: ALLERGY, PREGNANCY, & LACTATION ADVERSE EFFECTS: GI , SKELETAL: DAMAGE TO BONES & TEETH DRUG-TO-DRUG INTERACTIONS: PENICILLIN G, ORAL CONTRACEPTIVE THERAPY, METHOXYFLURANE, & DIGOXIN  NURSING RESPONSIBILITIES Give water with the oral drug Don’t give the drug within 1 hour of bedtime to prevent esophageal reflux Monitor the patient for bacterial and fungal superinfection Monitor IV injection sites and rotate them routinely to minimize local irritation 10. ANTIMYCOBACTERIALS CONTAIN PATHOGENS CAUSING TUBERCULOSIS AND LEPROSY INDICATIONS: TX OF ACID-FAST BACTERIA (MYCOBACTERIUM TUBERCULOSIS) ACTIONS: ACT ON THE DNA OF THE BACTERIA, LEADING TO LACK OF GROWTH AND EVENTUAL BACTERIAL DEATH PHARMACOKENITICS - ADEQUATELY ABSORBED FROM THE GI TRACT - METABOLIZED IN THE LIVER & EXCRETED IN THE URINE CONTRAINDICATIONS: ALLERGY & RENAL OR HEPATIC FAILURE ADVERSE EFFECTS: CNS EFFECT & GI IRRITATION DRUG-TO-DRUG INTERACTIONS: RIFAMPIN AND INH(ISONIAZID) CAN CAUSE LIVER TOXICITY CARBAPENEMS − Are relatively new class of broad-spectrum antibiotics effective against gram- positive and gram-negative bacteria INDICATIONS Serious intra-abdominal, urinary tract, skin and skin structure, bone and joint, and gynecological infections. Infections caused by susceptible strains: S.pneumoniae, H.influenzae, CONTRAINDICATIONS: Seizure disorders, Meningitis, Lactation. Ertapenem is not recommended for use in patients younger than 18 years of age. Meropenem is associated with development of pseudomembranous colitis and should be used in caution in patients with inflammatory bowel disease CARBAPENEMS ADVERSE EFFECTS: C.DIFFICILE DIARRHEA, NAUSEA, VOMITING, DEHYDRATION AND ELECTROLYTE IMBALANCE EXAMPLES ARE ERTAPENEM AND MEROPENEM ANTIVIRALS Antivirals are medications that help your body fight off certain viruses that can cause disease. Antiviral drugs are also preventive First experimental antivirals were developed in the 1960s, mostly to deal with herpes viruses, and were found using traditional trial- and-error drug discovery methods. Only in the 1980s, when the full genetic sequences of viruses began to be unraveled, did researchers begin to learn how viruses worked in detail, and exactl what chemicals were needed to thwart their reproductive cycle CLASSIFICATIONS OF ANTIVIRALS 1. Agents for Influenza A and Respiratory Viruses 2. Agents for Herpes and Cytomegaloviruses 3, Agents for HIV and AIDS (Antiretroviral Drugs) a) Nonnucleoside Reverse Transcriptase Inhibitors b) Nucleoside Reverse Transcriptase Inhibitors (NRTIs) c) Protease Inhibitors d) Integrase Inhibitors 4. Anti-Hepatitis B and C Agents 5. Agents for COVID-19 WHAT ARE VIRUSES? Viruses are tiny (microscopic) infectious agents that grow and multiply only inside living cells of an organism. Viruses have receptors that allow them to attach to healthy (host) cells in your body. Once a virus attaches to and enters a host cell, it can replicate (make copies of itself). The host cell dies, and the virus infects other healthy cells. HOW DO ANTIVIRAL MEDICATIONS WORK? Antiviral medicines work differently depending on the drug and virus type. Antivirals can: Block receptors so viruses can’t bind to and enter healthy cells. Boost the immune system, helping it fight off a viral infection. Lower the viral load (amount of active virus) in the body WHAT IS ANTIVIRAL RESISTANCE? Skipping doses or starting and stopping an antiviral medicine can allow a virus to change/adapt so that the antiviral is no longer effective. People who take antivirals for extended periods are more prone to antiviral resistance. 1. AGENTS FOR INFLUENZA A AND RESPIRATORY VIRUSES These agents are used to treat the signs and symptoms of respiratory flu caused by influenza A and B viruses as well as respiratory syncytial viruses (RSV). INDICATIONS: Respiratory flu, especially in health care workers and high-risk individuals - Oseltamivir is the only antiviral agent that has been shown to be effective in treating H1N1 and avian flu. - Zidovudine has been safely used in pregnant women CONTRAINDICATIONS: Renal impairment- Alters metabolism and excretion of drugs, particularly amantadine, zanamivir, and oseltamivir, Pregnancy, Lactation ADVERSE EFFECTS: light- headedness, dizziness, insomnia, orthostatic hypotension, urinary retention 2. AGENTS FOR HERPES AND CYTOMEGALOVIRUSES These agents are used to the infections caused by herpes (e.g., cold sores, encephalitis, shingles, and genital infections) and CMV/cytomegaloviruses (e.g., infections affecting the eyes, respiratory tract, and liver) INDICATIONS: Infections caused by DNA viruses herpes simplex, herpes zoster, and CMV Effective in immunocompromised individuals (e.g., patients with AIDS and multiple infections) Acyclovir is the drug of choice for children with herpes virus or CMV infections CONTRAINDICATION: Renal impairment, Pregnancy and lactation, Severe CNS disorders, Children with AIDS, Cidofovir has potential carcinogenic effects and effects on fertility 2. AGENTS FOR HERPES AND CYTOMEGALOVIRUSES ADVERSE EFFECTS: headache, depression, paresthesias, neuropathy, nausea, vomiting. renal dysfunction and failure, rash, inflammation, burning sensation Cidofovir is associated with severe renal toxicity and granulocytopenia. Ganciclovir and valganciclovir are associated with bone marrow suppression. Foscarnet has been associated with seizures, especially in patients with electrolyte imbalance 3. AGENTS FOR HIV and AIDS (ANTIRETROVIRAL DRUGS) a. NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS INDICATIONS: Treatment of patients with documented AIDS who have decreased numbers of helper T cells and evidence of increased opportunistic infections in combination with other antiviral drugs. CONTRAINDICATIONS: Pregnancy, Children ADVERSE EFFECTS: dizziness, blurred vision, headache, dry mouth, constipation or diarrhea, nausea, abdominal pain, dyspepsia Flu-like syndrome may occur but this may also bebecause of the underlying disease b. NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs) This antiretroviral drug was the first class of drug developed to treat HIV infections. This competes with the naturally occurring nucleosides within a human cell that the virus would need to develop INDICATIONS: Combination therapy for the treatment of adults and children with HIV Lamivudine as an oral solution can be used in treatment of chronic hepatitis B Zidovudine is used in prevention of maternal transmission of HIV CONTRAINDICATIONS: Pregnancy. No adequate studies of NRTIs so use should be limited, except for zidovudine, which has been proven to be safe, Hepatic dysfunction, severe renal impairment, Bone marrow suppression  ADVERSE EFFECTS Abacavir: serious-to-fatal hypersensitivity reactions (fever, chills, rash, fatigue, GI upset, flu-like symptoms can occur and drug must be discontinued immediately Didanosine: serious pancreatitis, hepatomegaly, and neurological problems Emtricitabine, tenofovir: severe and fatal hepatomegaly with steatosis Zidovudine: severe bone marrow suppression Tenofovir: changes in body fat distribution, with loss of fat from arms, legs, and face and deposition of fat on the trunk, neck, and face. c. PROTEASE INHIBITORS − Block protease (which is essential for the maturity of the virus) activity within the HIV INDICATIONS: Combination therapy for the treatment of HIV infections CONTRAINDICATION: Pregnancy, lactation, Hepatic dysfunction, Patients taking antidiabetic drugs. Darunavir should not be used in children younger than 3 years of age because of the potential for toxic effect ADVERSE EFFECTS: nausea, vomiting, diarrhea, anorexia, changes in liver function (elevated cholesterol and triglyceride), rashes, pruritus, Steven Johnson syndrome d. INTEGRASE INHIBITORS This antiretroviral drug was released in late 2007 INDICATIONS: Reserved for use in patients who have been treated with other antivirals and have evidence of a return to viral replication CONTRAINDICATIONS: hypersensitivity to any component of the drug, as initial treatment for adults, for use in children, and for nursing mothers. ADVERSE EFFECTS: headache, dizziness, rhabdomyolysis, myopathy 4. ANTI-HEPATITIS B AND C AGENTS Hepatitis B is a serious-to-potentially fatal viral infection of the liver. It can be spread by blood or blood products, sexual contact, or contaminated needles or instruments. Individuals affected may develop a chronic condition or become a carrier. Hepatitis C is the leading cause of most liver transplants due to progressive liver disease. After initial infection with hepatitis C virus (HCV), most people develop chronic hepatitis C while some will develop cirrhosis of the liver. Mode of transmission is similar with HBV. INDICATIONS: Treatment of adults with chronic hepatitis B and C who have evidence of active viral replication and either evidence of persistent elevations in serum aminotransferase or histologically active disease  CONTRAINDICATIONS Anti-hepatitis B: known allergy to drugs to prevent hypersensitivity reactions; lactation to prevent potential toxicity to the infant; renal and liver impairment, because of increased risk of toxicity. Anti-hepatitis C: pregnancy, hepatitis B, and HIV infections, as safety is not established ADVERSE EFFECTS Anti-hepatitis B: should not be stopped immediately because of potential risk of hepatitis B exacerbation CNS: headache, dizziness, nausea GI: diarrhea, elevated liver enzymes, severe hepatomegaly with steatosis Anti-hepatitis C CNS: headache, fatigue GI: nausea, diarrhea Immunological: bone marrow suppression, severe skin reaction  AGE CONSIDERATIONS IN GIVING ANTIVIRALS Children This age group is very sensitive to the effects of mostantivirals and therefore more severe reactions can be expected. In addition, many antivirals do not have proven safety and efficacy in children. Caution must be applied, and smaller doses are given for children. Adults This age group should be educated about the dangers of using antibiotics for viral diseases. Emphasis is given on patients with HIV about the limitations of antiviral drugs with regards to the curative aspect of the disease. Pregnant women Generally, pregnant women are not given antivirals unless the benefits clearly outweigh the risks to the fetus or neonate. Women of childbearing age should be advised to use barrier contraceptives if they take any of these drugs. The Centers for Disease Control and Prevention (CDC) advises that women with HIV infection should not breast-feed to protect the neonate from the viruses. Older adults Older patients are more susceptible to adverse effects of antiviral therapy, particularly those with hepatic and renal dysfunctions. ANTIFUNGALS Antifungal medicines are used to treat fungal infections, which most commonly affect your skin, hair, and nails Fungi can be single-celled or very complex multicellular organisms They are found in just about any habitat. They mostly live on the land, mainly in soil or on plant materials rather than in sea or freshwater. A very small number of fungi causes disease in animals. In humans, this includes skin diseases such as athlete’s foot, ringworm, and thrush. Antifungals are used to treat mycosis, or infections caused by fungi. Fungi are different from bacteria in the sense that their cell walls are made up of chitin and various polysaccharides rendering these organisms resistant to antibiotic.  Antifungals can be systemic and/or topical: o Systemic antifungals are used to treat systemic mycoses and can be toxic to the host and not to bem used indiscriminately o Topical antifungals are used to treat a variety of mycoses of skin and mucous membranes. Some systemic antifungals have topical forms. Antifungals work by either killing the fungus or preventing the fungus from growing  INDICATIONS ringworm athlete's foot fungal nail infection vaginal thrush some types of severe dandruff Some fungal infections can grow inside the body and need to be treated in hospital. Examples include: o aspergillosis, which affects the lungs o fungal meningitis which affects the brain  TYPES OF ANTIFUNGAL MEDICINE a cream, gel, ointment, or spray a capsule, tablet, or liquid an injection a pessary: a small and soft tablet you put inside the vagina COMMON ANTIFUNGAL MEDICINES clotrimazole (Canesten) econazole miconazole terbinafine (Lamisil) fluconazole (Diflucan) ketoconazole (Daktarin) nystatin (Nystan) Amphotericin  Drugs for systemic antifungal treatment include the following: Various azole derivatives (fluconazole, isavuconazole, itraconazole, posaconazole, and voriconazole) Echinocandins (anidulafungin, caspofungin, and micafungin) Flucytosine  PHARMACOKINETICS Route Onset Peak Duration Oral Slow 1-2 h 2-4 d IV Rapid 1h 2-4 d Metabolism: liver Excretion: kidney (urine) SIDE EFFECTS These are usually mild and do not last long. Side effects include: itching or burning, redness, feeling sick, tummy (abdominal) pain, diarrhea, rash Occasionally, antifungal medicines may cause a more severe reaction, such as: an allergic reaction, a severe skin reaction, liver damage (very rarely) AGE CONSIDERATIONS IN GIVING ANTIFUNGALS Children More sensitive to the effects of antifungals so more severe adverse reactions may be expected Only fluconazole, ketoconazole, terbinafine, and griseofulvin have established pediatric doses. Adults can be very toxic so usage is only justified when causative organism is identified. Pregnant and lactating women should be advised that usage of this drug should only be in situations where the benefits clearly outweigh the risks.  CONTRAINDICATIONS Hepatic dysfunction. Ketoconazole, fluconazole, posaconazole, and terbinafine can cause serious hepatic toxicity. Patients are carefully monitored for bone marrow suppression and GI and liver toxicity if using these drugs, particularly posaconazole. Endocrine or fertility problems. Ketoconazole is absolutely contraindicated in patients with this condition because of its effects on these processes. Fluconazole can be the alternative drug but it can cause liver and/or renal toxicity. Caution is exercised. Pregnancy and lactation. Not known whether most azoles cross placenta or enter breastmilk. However, terbinafine is known to do so. ADVERSE EFFECTS liver toxicity and severe effects on a fetus or a nursing babies PATIENT EDUCATION Instruct patient in the correct method of administration, depending on the route, to improve effectiveness and decrease the risk of adverse effects. o Troches should be dissolved slowly in the mouth o Vaginal suppositories, creams, and tablets should be inserted high into the vagina with the patient remaining recumbent for at least 10-15 minutes after insertion. o Topical creams and lotions should be gently rubbed into the affected area after it has been cleansed with soap and water and patted dry. Advise patient to stop the drug if a severe rash occurs,especially if it is accompanied by blisters or if local irritation and pain are very severe. This development may indicate drug sensitivity or worsening of condition being treated. Educate client on drug therapy to promote understanding and compliance. ANTITUBERCULAR Antitubercular medications are a group of drugs used to treat tuberculosis Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis (TB) is a disease caused by germs that are spread from person to person through the air. TB usually affects the lungs, but it can also affect other parts of the body, such as the brain, the kidneys, or the spine. There are two forms of TB, namely: o Latent TB: germs are present in the body; however, there are no symptoms as the immune system is actively working to fight against it. It is a noncontagious state. o Active TB: germs multiply and symptoms are developed. It is a contagious state  Antitubercular agents work in the following ways: Antitubercular agents work by stopping the growth of the bacteria that causes TB (which is the Mycobacterium tuberculosis). They act by reversibly inhibiting DNA- dependent RNA polymerase, which further inhibits bacterial protein synthesis and transcription. TB bacteria die very slowly, and so, the drugs must be taken for quite a few months until all bacteria are dead INDICATIONS Patients diagnosed with TB Multidrug-resistant pulmonary TB (a serious infection that affects the lungs and other parts of the body and cannot be treated with other medications that are usually used to treat the condition) Urinary tract infection TB treatment for human immunodeficiency virus exposed/infected First Line Second Line Antitubercular Drugs Antitubercular Drugs Kanamycin (discontinued use in the USA) Streptomycin Rifampicin Capreomycin Isoniazid Amikacin Pyrazinamide Levofloxacin Moxifloxacin Ethambutol Gatifloxacin MDR-TB Bedaquiline Delamanid Linezolid Pretomanid TREATMENT DURATION 6 MONTHS OR 9 MONTHS although the 6-month regimen is used for the majority of patients TOXICITY All first-line anti-tubercular medications, rifampin, isoniazid, pyrazinamide, and ethambutol can exert hepatotoxic effects. A continual rise in liver functions test should prompt discontinuation of treatment. NURSING RESPONSIBILITIES Liver function tests should be monitored routinely A CBC is also required to regularly monitor patients taking rifampin, as it can lead to thrombocytopenia and neutropenia. Isoniazid can cause pyridoxine deficiency that may lead To peripheral neuropathy in patients. The patient can supplement vitamin B6 to prevent this from happening. Monitor uric acid concentrations routinely for patients managed with pyrazinamide. Counseling and careful monitoring should be conducted during pregnancy, as some second-line medications are teratogenic. Educate the patient. Educating patients about TB disease helps ensure their successful completion of therapy. ANTIPROTOZOAL Antiprotozoals are agents used to treat protozoan infections. Protozoan infections are common in tropical areas. Protozoans are single-celled organisms that pass through several stages in their life cycles, including at least one phase as a human parasite. While protozoans thrive in tropical climate, they may also survive and reproduce in any area where people live in very crowded and unsanitary conditions. DISEASE SPOTLIGHT: PROTOZOAL DISEASES 1. Amoebiasis It is an intestinal infection caused by Entamoeba histolytica. It is often known as amoebic dysentery. The disease is transmitted through fecal- oral route. 2. Leishmaniasis Is a disease caused by a protozoan that is passed from sand flies to humans. It is characterized by serious lesions in the skin, viscera, and mucous membranes of host. 3. Trichomoniasis Is caused by T. vaginalis, a common cause of vaginitis (reddened, inflamed vaginal mucosa, itching, burning, and yellowish-green discharge), transmitted through sexual intercourse. 4. Giardiasis Is caused by G. lamblia, the most commonly diagnosed intestinal parasite in the United States, transmitted through contaminated water or food, and trophozoites. COMMON ANTIPROTOZOAL DRUGS METRONIDAZOLE Atovaquone Benznidazole Emetine Fenbendazole Pentamidine Suramin Tinidazole THERAPUETIC ACTION DNA synthesis in susceptible protozoa, interfering with cell’s ability to reproduce, subsequently leading to cell death. INDICATIONS Treatment of infections caused by susceptible protozoalike Balantidial dysentery, Trichomoniasis (genital infection), Giardiasis (diarrhea), Leishmaniasis, African sleeping sickness, Chagas disease METRONIDAZOLE is effective in the treatment of vaginal trichomoniasis, giardiasis, and all forms ofamebiasis CONTRAINDICATIONS Known allergy to the drug. Pregnancy - can cause fetal abnormalities and even death. CNS disease. Possible disease exacerbation due to drug effects on the CNS. Hepatic disease. Possible exacerbation when hepatic drug effects occur. Lactation. Can pass breast milk and cause severe adverse effects to the infant. Tinidazole should never be combined with alcohol. ADVERSE EFFECTS CNS: headache, dizziness, ataxia, loss of coordination, peripheral neuropathy GI: nausea, vomiting, diarrhea, unpleasant taste, cramps, Superinfections  NURSING RESPONSIBILITIES Arrange for appropriate culture and sensitivity tests before beginning therapy to ensure proper drug for susceptible species. Administer the complete course of the drug to get the full beneficial effects. Monitor hepatic function before and periodically during treatment Provide comfort and safety measures if CNS effects occur Educate client on drug therapy to promote understanding and compliance. ANTIMALARIALS Antimalarials are agents used to attack Plasmodium at various stages of its life cycle. Through this, it becomes possible to prevent acute malarial reaction in individuals who have been infected by the parasite. These agents can be: o schizonticidal (acting against the red-blood-cell phase of the life cycle), o gametocytocidal (acting against the gametocytes), o sporontocidal (acting against the parasites that are developing in the mosquito). − Quinine (Qualaquine) was the first drug found to be effective in the treatment of malaria.  Malaria is caused by a single-cell protozoa, the plasmodium. There are over 50 species of plasmodia, but only four are infectious to humans: Plasmodium malariae, Plasmodium ovale, Plasmodium vivax, and Plasmodium falciparum. − Plasmodium vivax is the most prevalent, but P. falciparum is the most serious and lethal form of malaria INDICATIONS Treatment of malaria, prevention of relapse, and other protozoal diseases like extraintestinal amoebiasis (chloroquine) and toxoplasmosis (pyrimethamine) CONTRAINDICATIONS Known allergy to the drug. Liver disease or alcoholism. Lactation. Pregnancy. Associated with birth defects. Pregnancy should be avoided two months after completion of therapy using mefloquine. Retinal disease or damage. Psoriasis ADVERSE EFFECTS Use of antimalarials may result to these adverse effects: CNS: headache, dizziness Immunological: fever, shaking, chills, malaise GI: nausea, vomiting, dyspepsia, anorexia, hepatic dysfunction Dermatological: rash, pruritus, loss of hair associated with changes in protein synthesis Eyes: visual changes, possible blindness Ears: ototoxicity related to nerve damage COMMON ANTIMALARIAL DRUGS Chloroquine Mefloquine Primaquine Pyrimethamine Quinine ANTIHELMINTICS Antihelminthics are used to treat parasitic infections. They work by preventing the parasite from absorbing any nutrients which will weaken it and kill it. COMMON ANTHELMINTICS Generic Name Brand Name Albendazole Albenza Ivermectin Stromectol Mebendazole Vermox Praziquantel Biltricide Pyrantel Antiminth, Pin-Rid HELMINTHIC INFECTIONS These are infections in the GI tract or other tissues due to worm infestations. Infestations are very common in tropical areas. Most common infectious helminths are nematodes (roundworms) and platyhelminths (flatworms) which invade the intestines and the tissues THERAPEUTIC ACTION They act on metabolic pathways present in the invading worm but are absent or significantly different in human INDICATIONS Albendazole - active lesions caused by pork tapeworm and cystic disease of the liver, lungs, and peritoneum caused by dog tapeworm. Ivermectin - used for threadworm disease or strongyloidiasis and onchocerciasis or river blindness. Mebendazole - for diseases caused by pinworms, roundworms, whipworms, and hookworms. Praziquantel - for a wide number of schistosomes or flukes. Pyrantel is for treatment caused by pinworms and roundworms. CONTRAINDICATIONS Known allergy to the drug. Lactation. Drug can enter breast milk. Renal and hepatic disease. Interfere with drug metabolism and excretion. Severe diarrhea and malnourishment. Pyrantel has not been established as safe for use inchildren younger than 2 years. ADVERSE EFFECTS GI: abdominal discomfort, diarrhea, pain CNS: headache, dizziness, Immunologic: fever, shaking, chills, malaise, rash, pruritus, loss of hair Albendazole is associated with severe bone marrow depression and renal failure  Albendazole, ivermectin, and praziquantel are more toxic so they are avoided in children. Instead, a chewable preparation of mebendazole is usually given. Obtain a culture of stool for ova and parasites to determine the infecting worm and establish appropriate treatment. Assess the abdomen to evaluate for any changes from baseline related to the infection, identify possible adverse effects, and monitor for improvement