12.comprehensive ofantimicrobial agents and chemotherapy ( classification and mechanism)

BYBY

Dr. Dr. SAMINATHAN KAYAROHANAMSAMINATHAN KAYAROHANAM

M.PHARM, M.B.A, PhDM.PHARM, M.B.A, PhD

COMPREHENSIVE OF CHEMOTHERAPHY (CLASSIFICATION AND MECHANISAM)

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III. MECHANISMS OF ANTIMICROBIAL AGENTS

1.INHIBITION OF CELL WALL SYNTHESIS

2.INHIBITION OF FUNCTIONS OF CELLULAR MEMBRANE

3. INHIBITION OF PROTEIN SYNTHESIS

4.INHIBITION OF NUCLEIC ACID SYNTHESIS

5.INHIBITION OF FOLIC ACID SYNTHESIS

CON ...

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BACTERIAL CELL STRUCTURE

Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

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MECHANISMS OF ANTIBACTERIAL RESISTANCE

1.Inhibition of drug uptake or blocking the entry (Change their cell membrane and cellwall permeability to the drug)

2. Produce enzymes that destroy the chemical structures of drugs

3.Alter or modified the target molecule.

4. Activation of drug efflux pump.

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RESISTANCE TO ANTIBIOTICS

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A) TRANSFERMATIONWhen naked DNA (Antibiotic-resistance Gene) is released on lysis of an organism and is taken up by another organism.

B) TRANSDUCTION Antibiotic-resistance genes are transferred from one bacterium to another by means of bacteriophages.

C) CONJUGATION Direct contact between two bacteria: Plasmids form a mating bridge across the bacteria and DNA is exchanged, which can result in acquisition of antibiotic-resistance genes by the recipient cell. Transposons can also carry antibiotic-resistance genes

GENETIC TRANSFER


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VI. IDEAL ANTIMICROBIAL DRUG

Have highly selective toxicity to the pathogenic

microorganisms in host body

Have no or less toxicity to the host.

Low propensity for development of resistance.

Not induce hypersensitive in the host.

Have rapid and extensive tissue distribution

Be free of interactions with other drugs.

Be relatively inexpensive7 Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

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VII. PREVENTION OF ANTIBIOTIC RESISTANCEPatients :•Take antibiotics exactly as the doctor prescribes. •Do not skip doses. •Complete the prescribed course, even when you feeling better.•Only take antibiotics prescribed for you. •Do not save antibiotics for the next illness. •Discard any leftover medication once the treatment is completed.•Do not ask for antibiotics to your doctor. •Prevent infections by practicing hygiene and recommended vaccines.

Health professionals:•Do not treat viral infections with antibiotics.•Prescribe antibiotics only when they are absolutely necessary – giving them at the right dose and only for as long as they are needed.•Avoid unnecessary overlaps in antibiotics. •Become familiar with resistance trends in your region.


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7.CLASSIFICATION OF CELL WALL INHIBITORS


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1.Natural Penicillins:

Aqueous penicillin GPenicillin GPenicillin VK

2.Beta lacatamse resistant Penicillins

•Methicillin •Nafcillin •Oxacillin •Cloxacillin •Dicloxacillin

3. Aminopenicillins /extended spectrum

•Ampicillin •Amoxicillin

4. Carboxypenicillins/ antipseudomonal penicillins /extended spectrum

•Carcenicillin •Ticarcillin

5. Ureidopenicillins / antipseudomonal penicillins / extended spectrum

•Mezlocillin •Piperacillin

6. Penicillins/inhibitor combination

•Ampicillin/sulbactam •Ticarcillin/clavulanate •Piperacillin/tazobactam •Amoxicillin/clavulanate

8.CLASSIFICATION OF PENICILLIN

Con…Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

10. MECHANISM OF ACTION OF PENICILLINS

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1.Penicillin-binding proteins:

Penicillins inactivate numerous proteins on the bacterial cell membrane. These penicillin-binding proteins (PBPs) are bacterial enzymes involved in the synthesis of the cell wall and in the maintenance of the morphologic features of the bacterium.

2.Inhibition of transpeptidase:

Penicillins inhibit this transpeptidase-catalyzed reaction, thus hindering the formation of cross-links essential for cell wall integrity. As a result of this blockade of cell wall synthesis.

3.Production of autolysins:

Many bacteria, particularly the gram-positive cocci, produce degradative enzymes (autolysins) that participate in the normal remodeling of the bacterial cell wall.

Con…

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4. CLASSIFICATION OF PROTEIN SYNTHESIS INHIBITORS


3. GENERAL MECHANISM OF ANTIBIOTIC


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1) Effective against many organisms.

2) Well-absorbed orally.

3) Well-distributed in tissues.

4) Relatively long serum half-lives and minimal toxicity.

5) Deep-tissue and cell penetration.

6) Urinary tract infections, prostatitis.

7) Infections of the skin and bones.

8) Penicillin-resistant sexually transmitted diseases.

9) lower cost in synthesis with the excellent activities.

2. ADVANTAGES OF QUINOLONES


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4. CLASSIFICATION OF QUINOLONES


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7. MECHANISM OF QUINOLONES


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10.CLASSIFICATION OF SULFONAMIDE


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12. MECHANISM OF SULFONAMIDES AND TRIMETHOPRIM


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8. CLASSIFICATION OF ANTIMYCOBACTERIALS


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8. CLASSIFICATION OF ANTIMYCOBACTERIALS


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9. MECHANISM OF ANTIMYCOBACTERIALS


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9. MECHANISM OF ANTIMYCOBACTERIALS


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5.CLASSIFICATION


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6.SITES OF ACTION OF COMMON ANTIFUNGAL DRUGS

Con…

POLYENES

IMIDAZOLESTRIAZOLE

ALLYLAMINES

OTHER

GLUCAN

SYNTHASE

INHIBITORS

BIND TO ERGOSTEROL AND FORM PORES (CHANNELS)


FLUCYTOSINE

IMIDAZOLES

TRIAZOLES

POLYENES

CANDINS

GRISEOFULVIN

OTHERS

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7. ANTI FUNGAL DRUGS MECHANISAM


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5.CLASSIFICATION OF ANTIVIRAL DRUGS1

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6.MECHANISM OF ANTIVIRAL AGENTS


8.HIGHLY ACTIVE ANTIRETROVIRAL (HIV) THERAPY (HAART)

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9.DRUGS USED TO PREVENT HIV FROM REPLICATING

Con…29 Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

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6. ANTHELMINTIC DRUGS

roundworms

(flukes) are leaf-shaped flatworms

tapeworms


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Diethylcarbamazine is used in the treatment of filariasis because of its ability to immobilize microfilariae and render them susceptible to host defense mechanisms.

Combined with albendazole, diethylcarbamazine is effective in the treatment of Wuchereria bancrofti and Brugia malayi infections.

It is rapidly absorbed following oral administration with meals and is excreted primarily in urine.

Symptoms include fever, malaise, rash, myalgias, arthralgias, and headache, and their severity is related to parasite load.

Most patients have leukocytosis. Antihistamines or steroids may be given to ameliorate many of the symptoms.

6.1. DIETHYLCARBAMAZINE


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Ivermectin is the drug of choice for the treatment of onchocerciasis (river blindness) caused by Onchocerca volvulus and for cutaneous larva migrans and strongyloidiasis.

Ivermectin targets the parasite’s glutamate-gated chloride channel receptors. Chloride influx is enhanced, and

hyperpolarization occurs, resulting in paralysis of the worm.

The drug is given orally. It does not cross the blood-brain barrier and has no pharmacologic effects in the CNS.

Ivermectin is also contraindicated in pregnancy.The killing of the microfilaria can result in a Mazotti-like reaction (fever, headache, dizziness, somnolence, and hypotension).

6.2. IVERMECTIN


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Mebendazole a synthetic benzimidazole compound, is effective against a wide spectrum of nematodes.

It is a drug of choice in the treatment of infections by whipworm (Trichuris trichiura), pinworm (Enterobius vermicularis), hookworms (Necator americanus and Ancylostoma duodenale), and roundworm (Ascariasis lumbricoides).

Mebendazole acts by binding to and interfering with the assembly of the parasites' microtubules and also by decreasing glucose uptake. Affected parasites are

expelled with the feces.

Mebendazole is relatively free of toxic effects, although patients may complain of abdominal pain and diarrhea. It is, however, contraindicated in pregnant women ,because it has been shown to be embryotoxic and teratogenic in experimental animals.

6.3. MEBENDAZOLE


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Pyrantel pamoate along with mebendazole, is effective in the treatment of infections caused by roundworms, pinworms, and hookworms. Pyrantel pamoate is poorly absorbed orally and exerts its effects in the intestinal tract.

It acts asa depolarizing, neuromuscular-blocking agent, causing persistent activation of the parasite’s

nicotinic receptors.

The paralyzed worm is then expelled from the host’s intestinal tract. Adverse effects are mild and include nausea, vomiting, and diarrhea.

6.4. PYRANTEL PAMOATE


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Thiabendazole another synthetic benzimidazole,is effective against strongyloidiasis caused by Strongyloides stercoralis (threadworm), cutaneous larva migrans, and early stages of trichinosis (caused by Trichinella spiralis;

Thiabendazole, like the other benzimidazoles, affects microtubular aggregation.

Although nearly insoluble in water, the drug is readily absorbed on oral administration.

It is hydroxylated in the liver and excreted in urine. The adverse effects most often encountered are dizziness, anorexia, nausea, and vomiting. There have been reports of central nervous system (CNS) symptomatology.

There have been a number of fatalities among thecases of erythema multiforme and Stevens-Johnson syndrome reportedly caused by thiabendazole. Its use is contraindicated during pregnancy.

6.5. THIABENDAZOLE


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Trematode infections are generally treated with praziquantel. This drug is an agent of choice for the treatment of all forms of schistosomiasis and other trematode infections and for cestode infections like cysticercosis.

Permeability of the cell membrane to calcium is increased, causing contracture and paralysis of the parasite.

Praziquantel is rapidly absorbed after oral administration and distributes into the cerebrospinal fluid. High levels occur in bile. The drug is extensively metabolized oxidatively, resulting in a short half-life.

Common adverse eff ects include drowsiness, dizziness, malaise, and anorexia as well as gastrointestinal upsets. The drug is not recommended for pregnant women or nursing mothers. Drug interactions due to increased metabolism have been reported .

Praziquantel is contraindicated for the treatment of ocular cysticercosis, because destruction of the organismin the eye may damage the organ.

6.6. PRAZIQUANTEL


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Broad spectrum Drug of choice for treatment of hydatid disease and

cysticercosis. Used for the treatment of ( intestinal nematodes )

e.g. ascariasis , tricurasis and strongyloidiasis, pinworm, hookworm Inhibits microtubule synthesis that irreversibly

impairs glucose uptake , intestinal parasites are immobilized and die slowly.

larvicidal in : hydatid ,cysticercosis , ascariasis and hook worm infections.

Ovicidal in ascariasis ,hookworm , trichuriasis

6.7. ALBENDAZOLE


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Niclosamide is the drug of choice for most cestode (tapeworm) infections.

Its action has been ascribed to inhibition of the parasite’s mitochondrial phosphorylation of adenosine diphosphate, which produces usable energy in the form of adenosine triphosphate. anaerobic metabolism may

also be inhibited.

Alcohol should be avoided within 1 day of niclosamide.

6.8. NICLOSAMIDE


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4. CLASSIFICATION OF ANTIPROTOZOAL DRUGS


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6.LIFE CYCLE OF ENTAMOEBA HISTOLYTICA


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7.LIFE CYCLE OF THE MALARIAL PARASITE


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3. RISK FACTORS

1.Tobacco

2.Sunlight

3.Ionizing radiation

4.Certain chemicals and other substances

5.Some viruses and bacteria

6.Certain hormones

7.Family history of cancer

8.Alcohol

9.Poor diet, lack of physical activity, or being overweight


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categorized based on the functions/locations of the cells from which they originate:

Carcinoma: a tumor derived from epithelial cells, those cells that line the surface of our skin and organs (80-90% of all cancer cases reported)Sarcoma: a tumor derived from muscle, bone, cartilage, fat or connective tissues. Leukemia: a cancer derived from white blood cells or their precursors. Lymphoma: a cancer of bone marrow derived cells that affects the lymphatic system. Myelomas: a cancer involving the white blood cells responsible for the production of antibodies (B lymphocytes)

6. CANCER TYPES


13.ANTI CANCER DRUG CLASSIFICATION


14.CHEMOTHERAPEUTIC DRUGS AFFECTING RNA /DNA PRECURSORS.


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2.B. TYPE OF ACQUIRED IMMUNITY

Con…


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11. CLASSIFICATION OF IMMUNOSUPPRESSANTS


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16.ACTION OF IMMUNOSUPPRESSANTS


12.comprehensive ofantimicrobial agents and chemotherapy ( classification and mechanism)

Health & Medicine

development of resistance

inexpensive7 dr

cell membrane

bacterial cell structure

inhibition of drug uptake

inhibition of functions

recipient cell

cell wall permeability