antibiotik 2.ppt

8/13/2019 antibiotik 2.ppt

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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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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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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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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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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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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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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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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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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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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



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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

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antibiotik 2.ppt