antibiotik 2.ppt
TRANSCRIPT
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Pharmacology of the
Antibiotics
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The anti-infective drugs
Anti-infective agents are drugs thatare designed to act selectively on
foreign organismsthat have invadedand infected the body
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The anti-infective drugs
Anti-infective drugs - range from
Antibacterials
Antifungals
Antiprotozoals
Antihelminthics Antivirals
Antimycobacterial
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Spectrum of Activity of Anti-infectives
Narrow spectrum anti-infectivesaffect only a few bacterial types
The early penicillin drugs areexamples.
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Spectrum of Activity of Anti-infectives
Broad-spectrum anti-infectives affectmany bacteria.
Meropenem is an example.
Because narrow spectrum antibioticsare selective, they are more activeagainst single organismsthan thebroad spectrum antibiotics.
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Spectrum of Activity of Anti-infectives
Anti-infective agents can also be:
Bacteriostatic
Erythromycin, tetracyclines,
clindamycin, chloramphenicol,
spectinomycin, sulfonamides
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Bactericidal
- Penicillins, Cephalosphorins,
Metronidazole, Aminoglycosides,
Vancomycin, Polymyxin
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Common Adverse Reactions to
Anti-infective Therapy1. Nephrotoxicity
Antibiotics that are metabolizedand excreted in the kidney mostfrequently cause kidney damage..
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Common Adverse Reactions to
Anti-infective Therapy2. Gastro-intestinal toxicity
Direct toxic effect to the cells of the
GI tract can cause nausea, vomiting,stomach pain and diarrhea.
Some drugs are toxic to liver cells
and can cause hepatitis or liverfailure.
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Common Adverse Reactions to
Anti-infective Therapy3. CNS toxicity
When drugs can pass through the
brain barrier and accumulate in thenervous tissues, they can interferewith neuronal function.
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Common Adverse Reactions to
Anti-infective Therapy4. Hypersensitivity
Most protein antibiotics can induce
the bodys immune system toproduce allergic responses.
Drugs are considered foreign
substances and when taken by theindividual, it encounters the bodysimmune cells.
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Common Adverse Reactions to
Anti-infective Therapy5. Super-infections
Opportunistic infections that develop
during the course of antibiotictherapy are calledSUPERINFECTIONS.
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The PENICILLINSNarrow spectrum penicillins
Penicillin G
Penicillin V
Broad Spectrum Penicillins (aminopenicillin)
Amoxicillin
Ampicillin
Bacampicillin
Penicillinase-resistant Penicillin (anti-staphyloccocal penicillins)
Cloxacillin Nafcillin
Methicillin
Dicloxacillin
Oxacillin
Extended-Spectrum penicillins (Anti-pseudomonal penicillins)
Carbenicillin
Mezlocillin
Piperacillin
Ticacillin
Beta-lactamase inhibitors
Clavulanic acid
Sulbactam
Tazobactam
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Penicillin
Penicillin is a beta-lactam drug,with a beta-lactam ring.
The group of penicillins is calledbeta lactam antibiotics.
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PenicillinThe action of Penicillins
The penicillin and penicillinase-
resistant penicillins produceBACTERICIDAL effects byinterfering with the ability ofsusceptible bacteria from
biosynthesizing the framework ofthe cell wall.
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Penicillin
The bacterium will haveweakened cell wall, will
swell and then burst fromthe osmotic pressure withinthe cell.
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Penicillin
Pharmacokinetics:
Amoxicillin is well absorbed in theGIT. This in NOT affected by foodintake!!
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Penicillin
Therapeutic Indications ofpenicillin
The penicillins are indicatedfor the treatment ofstreptococcal infections
Syphilis Tetanus
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Adverse Effects of Penicillins
GI system effects- the major adverseeffects of penicillin therapy involvethe GIT.
Nausea, vomiting, diarrhea,abdominal pain, glossitis, stomatitis,gastritis, sore mouth and furrytongue.
The reason for some of these effects(superinfection) is associated withthe loss of bacterial flora.
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Adverse Effects of Penicillins
Hypersensitivity reactions- rashes,pruritus, fever and urticaria
These indicate mild allergic reaction.
Wheezing and diarrhea may alsooccur.
Anaphylaxis can also happen leadingto shock or death. It occurs in 5-10%of those receiving penicillins.
Pain and inflammation on injectionsites
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THE CEPHALOSPORINS
The cephalosporinsalso belong to thebeta lactam groupof antibiotics
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THE CEPHALOSPORINS
First Generation cephalosporin
Second generation cephalosporin
Third Generation cephalosporin
Fourth generation cephalosporin
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THE CEPHALOSPORINS
First Generation cephalosporins- arelargely effective against the samegram-positive organisms affected bypenicillin.
Second generation cephalosporins-are effective against those strains aswell as Haemophilus influenza,
Entreobacter aerogenes and Nesseriasp. These drugs are less effectiveagainst gram positive bacteria
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THE CEPHALOSPORINS
Third Generation cephlosporins- arerelatively weak against gram-positivebacteria but more potent againstgram-negative bacteria, to include
Serratia marcescens.
Fourth generation cephalosporins-are developed to fight against the
resistant gram-negative bacteria. Thefirst drug is cefepime.
Fi t ti h l i
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First generation cephalosporins
cefadroxil
Cefazolin
Cephalexin
Cephalotin
Cephapirin
Cephadrine
Second Generation cephalosporins
Cefaclor
Cefamandole
Cefonizind
Cefotetan
Cefoxitin Cefmetazole
Cefprozil
Cefuroxime
Third Generation Cephaosporins
Cefnidir
Cefixime
Cefoperazone Cefotaxime
Cefpodoxime
Ceftazidime
Ceftibuten
Moxalactam
Fourth Generation Cephalosporin Cefepime
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Cephalosporin The mechanism of action The cephalosporins are primarily
BACTERICIDAL.
They interfere with the cell-wallbuilding ability of bacteria when theydivide.
They prevent the bacteria from
biosynthesizing the framework oftheir cell wall. The weakened cell wall will swell and
burst causing cell death.
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Cephalosporin PharmacokineticsOnly a few cephalosporins are
administered orally, most are
administered parenterally. Their half-lives are short and they
are excreted mainly in the urine.
Contraindications and Precautions The drugs are contraindicated inpatients with known allergies tocephalosporins and penicillins.
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Cephalosporin
Adverse Effects GI system- Nausea, vomiting,
diarrhea, anorexia, abdominal pain
and flatulence are common effects. CNSheadache, dizziness, lethargy
and paresthesias have been reported. Renal system- nephrotoxicity in
individuals with pre-existing renaldisease
Hypersensitivity
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Cephalosporin
Drug-Drug interactionsALCOHOL- many patients experience
a disulfiram-like reactions when taken
with some specific cephlosporins( cefamandole, cefoperazone ormoxalactam).
The patient may experience flushing,
headache, nausea, vomiting andmuscular cramps. This may occureven up to 72 hours of cephalosporindiscontinuance.
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The Aminoglycosides
The following are the aminoglycosides1. Gentamycin
2. Tobramycin3. Amikacin4. Netilmicin5. Kanamycin
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The Aminoglycosides
Mechanism of action These are BACTERICIDAL.
They inhibit protein synthesis insusceptible strains of gram-negative bacteria, leading to lossof functional integrity of thebacterial cell membrane, whichcauses cell death.
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The Aminoglycosides
Therapeutic Use of the Aminoglycosides These drugs are used to treat serious
infections caused by gram-NEGATIVEbacteria.
These drugs are contraindicated inknown allergies to aminoglycosides,
in patients with renal failure, hepaticdisease, pre-existing hearing loss,myasthenia gravis, Parkinsons,pregnancy and lactation.
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The AminoglycosidesAdverse Effects of Aminoglycosides CNS- irreversible deafness, vestibular
paralysis, confusion, depression,disorientation, numbness, tingling and
weakness related to drug effects. Kidney- renal toxicity, which may
progress to renal failure caused by thedirect toxicity of the aminoglycosides.
Hema- bone marrow depressionresulting from direct drug effect maylead to immune suppression and super-infection.
Ototoxicity
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The Aminoglycosides
Adverse Effects of Aminoglycosides GI system- nausea, vomiting,
diarrhea, weight loss, stomatitis andhepatic toxicity Skin effects- photosensitivity,
purpura, rash, urticaria and
exfoliative dermatitis Cardiac- palpitations, hypotension
or hypertension
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The Aminoglycosides
Drug to drug interactions Diuretics- increased incidence of
ototoxicity, nephrotoxicity andneurotoxicity.Anesthetics and Neuromusular
blockers- increasedneuromuscular blockage andparalysis may be possible Penicillin- synergistic action
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The Macrolides
The macrolides are
AzithromycinClarithromycinDirithromycinErythromycin
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The MacrolidesMechanism of Action of the Macrolides
They exert their effect by bindingto the bacterial cell ribosomes and
changing or altering proteinproduction/function
This will lead to impaired cell
metabolism and division.
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The Macrolides
Pharmacokinetics
Erythromycin is destroyed
by the gastric juice, whichis why slats are added tostabilize the drug.
Food does not interferewith the absorption of themacrolides.
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The Macrolides
Therapeutic Use of Macrolides These are indicated for the
treatment of the followingconditions: Steptococcal infection,
Mycoplasma infection, Listeria
infection and group A betahemolytic strep infection.
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The MacrolidesContraindications and Precautions in the Use
of Macrolides These agents are contraindicated in
the presence of known allergy to anymacrolide, because cross-sensitivity
occurs. Caution should be used in patients
with hepatic dysfunction that couldalter the metabolism of the drug; inlactating women because of drugexcretion in breast milk and inpregnant women because potentialadverse effects on the developingfetus.
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The Macrolides
Adverse Effects of Macrolides GI system- abdominal cramping, anorexia,
diarrhea, vomiting and
pseudomembranous colitis.HEPATOTOXICITY can occur if the drug istaken in high doses with other hepatotoxicdrugs.
CNS- confusion, abnormal thinking anduncontrollable emotions. Hypersensitivity reactions
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The Lincosamides
These agents are similar to theMacrolides but are more toxic.
Clindamycin
lincomycin
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The Lincosamides
Pharmacodynamics: The Mechanism ofAction of Lincosamides
These agents penetrate the cellmembrane and bind to the ribosome inthe bacterial cytoplasm to prevent theprotein production
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The Lincosamides
Side effects and Adverse Reactions
GIT- GI irritation, nausea, vomiting andstomatitis
Allergic reactions
Drug Interactions
Lincomycin and clindamycin areincompatible with aminophyline,phenytoin, barbiturates and ampicillin.
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The Tetracyclines
These agents were first isolated fromStreptomyces aureofaciens
The following are the tetracyclines Short-acting tetracyclines
tetracycline oxytetracycline
Intermediate acting tetracyclines
demeclocycline
methacycline Long acting tetracyclines
doxycycline minocycline
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The Tetracyclines
Pharmacodynamics
The tetracyclines inhibit
protein synthesis insusceptible bacterialeading to the inability of
the bacteria to multiply.
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The Tetracyclines
Contraindications and Precautions in the use of Tetracyclines It is not recommended for use in
pregnancy and lactation because thedrug can affect the bones and teeth,causing permanent discoloration andsometimes arrest of growth.
Tetracyclines are also avoided inchildren less than 8 (eight) years ofage because of the potential damageto the bones and permanentdiscoloration of the teeth.
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The Tetracyclines
Adverse Effects of the Tetracycline GI system- nausea, vomiting, diarrhea, abdominal
pain, glossitis and dysphagia.
Fatal hepatotoxicity related to tetracyclinesirritating effect on the liver cells has beenreported.
Musculoskletal- Tetracyclines have an affinity forteeth and bones; they accumulate there, leadingto weakening of the bone/teeth and permanentstaining and pitting.
Skin- photosensitivity and rash are expected. Less frequent- bone marrow depression,
hypersensitivity, super infections, pain andhypertension
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The Tetracyclines
Drug-Drug Interactions Penicillin- if taken with tetracyclines, will
decrease the effectiveness of penicillin. Oral contraceptives- if taken with
tetracycline, will have decreasedeffectiveness.
Digoxin- digoxin toxicity rises when
tetracyclines are used together
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The Tetracyclines
Drug-Food Interaction Dairy products- can complex with
tetracycline and renderunabsorbable.
Tetracyclines should then be givenon an EMPTY stomach 1 hour before
meals or 2-3 hours after any meal orother medications.
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The Fluoroquinolones
The fluoroquinolones are broad-spectrumantibiotics. They are usually manufacturedsynthetically and are associated with mildadverse reactions.
The examples are:1. Nalidixic acid2. ciprofloxacin
3. ofloxacin4. norfloxacin5.Levfofloxacin6.Sparfloxacin
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The Fluoroquinolones
Pharmacodynamics: Mechanism ofaction of the Fluoroquinolones
These agents enter the bacterialcell by diffusion through cellchannel.
Once inside they interfere with the
action of DNA enzymes (DNAgyrase) necessary for the growthand reproduction of the bacteria.This will lead to cell death.
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The Fluoroquinolones
Contraindications and Precautions
Pregnancy and lactation are alsocontraindications.These agents are found to cause
significant damage to the cartilagessuch that they are given cautiously to
growing children and adolescents lessthan 18 years of age
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The Fluoroquinolones
Adverse Effects of the Fluoroquinolones CNS- dizziness, insomnia, headache, and
depression related to possible effects on
the CNS membrane. GI system- nausea, vomiting, diarrhea and
dry mouth related to the direct effect onthe GIT
Hema- bone marrow depression related tothe direct effect of the drug on the cells ofthe bone marrow that rapidly turn over.
Other effects- skin reactions, rash, feverand photosensitivity
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Sulfonamides
The following are thesulfonamides:
1. Sulfazalazine2. Sulfamethoxazole3. Sulfadiazine4. Sulfixoxazole
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Sulfonamides
Pharmacodynamics
The sulfa drugs competitively
block the para-amino benzoicacid toprevent the synthesisof folic acidin susceptiblebacteria that synthesize their
own folates for the productionof RNA and DNA.
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Sulfonamides
Contraindications and precautions
These agents are contraindicated to patientswith known allergy to sulfa drugs,
sulfonylureas and thiazide diuretics becausethey share similar structures.
It is not recommended for use in pregnancybecause it can cross the placenta and causebirth defects and kernicterus.
Lactating women who take these drugs willexcrete them in the breast milk potentiallycausing kernicterus, diarrhea and rash in thenewborn.
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Sulfonamides
Adverse Effects of the Sulfonamides GI system- nausea, vomiting, diarrhea, abdominal
pain, anorexia, stomatitis and hepatic injury,which are all related to the direct irritation of theGIT and death of normal flora.
Renal system- crystalluria, hematuria andproteinuria which can progress to a nephroticsyndrome.
CNS- headache, dizziness, vertigo, ataxia,convulsions and depression related to drugeffects on the nerves
Hema- bone marrow depression related to drugeffects on the cells of the bone marrow that turnover rapidly.
Dermatologic effects- photosensitivity and rashand hypersensitivity
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COTRIMOXAZOL
TRIMETOPRIM + SULFAMETOKSAZOL
KEMIRIPAN FARMAKOKINETIK
MEKANISME KERJA : INHIBISI 2 LANGKAHBERURUTAN PD SINTESIS ASAMTETRAHIDROFOLAT
1. SULFAMETOKSAZOLMENGHAMBATPENGGABUNGAN PABA KE DLM AS.FOLAT
2. TRIMETOPRIM MENCEGAH REDUKSIDEHIDROFOLAT MJD TETRAHIDROFOLAT
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SPEKTRUM KERJA : LBH LUASDIBANDING SULFA
RESISTENSI : JARANG TERJADI
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The anti tubercular
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
M h i f ti
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Mechanisms of action
Isoniazid Menghambat enzim utk
penyusunan as.mikolat ke dlmlap.luar mikobakteri. Asammikolat penting utk sifattahan asam dr mikobakteri
Rifampicin Interferes with RNAsynthesis. Antilepra yg plgaktif
Pyrazinamide
Interferes with bacterial wallsynthesis bakterisid
Ethambutol Prevent multiplication
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Common Side effects
Isoniazid Interferes with B6
Peripheral neuritis
Rifampicin Red-orange discoloration of
the secretionsHepatitis
Pyrazinamide Hyperuricemia
Ethambutol Optic neuritis
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Precautions
Isoniazid Liver impairment
Rifampicin Liver impairment
Pyrazinamide Liver impairment
Gout
PregnancyEthambutol Liver impairment
Children less than 6 years
old
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General Responsibilities
Advise patient to take the DRUGS asprescribed
Multiple drugs are taken to preventRESISTANCE
Periodically check the liver function tests
Supplemental Intake of Vitamin B6
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ANTILEPRA
Penyebab M.leprae
Patofisiologis :
Basil-basil dr lesi kulit/sekret hidung pasienlepra masuk melalui kulit/saluran nafas
TERAPI MNRT WHO :
Kombinasi Dapson, Clofazimin danRifampisin selama 6-24 bulan
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DAPSON
BAKTERIOSTATIK
Mekanisme : bekerja sbg antagonis PABA
utk menghambat biosintesis folat Efek Samping :
Hemolisis terutama pd penderita dg
defisiensi Glukosa-6-fosfatdehidrogenaseMethemoglobinemia
Neuropati perifer
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KLOFAZIMIN
Mekanisme : mengikat DNA danmenghambat fungsi template
Bakterisidal thd M.leprae
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ANTI-FUNGALS
Jamur mempunyai dinding sel kaku ygmengandung kitin+polisakarida danmembran selnya terdiri dr ergosterol
Berinteraksi dengan enzim P-450 sitokromuntuk menghambat demetilasi lanosterol
menjadi ergosterol yg mrp sterol pentingutk membran jamurmengganggu fungsi
membran dan meningkatkan permeabilitas
OBAT OBAT MIKOSIS SISTEMIK
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OBAT-OBAT MIKOSIS SISTEMIKDAN SUBKUTANEUS
AMFOTERISIN B
FLUKONAZOL
FLUSITOSIN
ITRAKONAZOL
KETOKONAZOL
OBAT OBAT MIKOSIS
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OBAT-OBAT MIKOSISSUPERFISIALIS
KLOTRIMAZOL
EKONAZOL
GRISEOFULVIN
MIKONAZOL
NISTATIN
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Anti-fungals
The AZOLES
Ketoconazole
CLotrimazole Miconazole
IV: AMPHOTERICIN
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Antifungals
Indications
Fungal infections
Candidiasis
Tinea
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Antifungals
Important side effects
Hypersensitivity
Headache Dizziness
Pruritus
Irritation AMPHOTERICIN: HYPOKALEMIA,
arrhythmia and kidney damage
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General Responsibilities
Take the oral drugs with food
Evaluate the liver test, kidney test and
CBC Institute safety measures
FOR amphotericin: Evaluate ECG and
Potassium, administer steroid, evaluate IVsite, give with INFUSION pump
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Antivirals
General Action
These agents interfere with the DNA or
RNA synthesis and replication of thevirus
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Antivirals
The Vir
Acyclovir
FamcyclovirValacyclovir
Gancyclovir
AIDS anti-viral Zidovudine (AZT)
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Antivirals
Precaution with use
Hypersensitivity
Pregnancy Renal and hepatic impairment
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Antivirals
Adverse effects
Anorexia
NauseaVomiting
Bleeding
Phlebitis Reportable : bone marrow depression
and nephrotoxicity
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KEMOTERAPI AMEBIASIS
MALARIA
TRIPANOSOMIASIS LEISHMANIASIS
TOKSOPLASMOSIS
GIARDIASIS
ANTI PROTOZOA
KEMOTERAPI AMEBIASIS
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KEMOTERAPI AMEBIASIS
KLOROQUIN
METRONIDAZOL
DEHIDROEMETIN DILOKSANID FUROAT
EMETIN
PARAMOMISIN
MALARIA
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MALARIA
KLOROQUIN
MEFLOQUIN
PRIMAKUIN PIRIMETAMIN
KUININ
Penyebab : Plasmodium falciparum.
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y pP.vivax, P.malariae
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TRIPANOSOMIASIS
MELARSOPROLOL
NIFURTIMOKS