Anti-infective The anti- - PowerPoint Presentation

Slide1

Anti-infective Slide2

The anti-infectives Anti-infective agents are drugs that are designed to act selectively on foreign organisms that have invaded and infected the body Anti-infectives- range from antibiotics, antifungals

,

antiprotozoals

,

antihelmintics

,

antivirals

and

antimycobacterialSlide3

Antibiotics Slide4

General Mechanisms of Action of Anti-Bacterial Agent Some interfere with the biosynthesis of bacterial cell WALL Some inhibit protein synthesis Some change the cell membrane permeability Some inhibit DNA synthesis Slide5

Spectrum of Activity of Anti-Bacterial Agent Narrow spectrum anti-infectives affect only a few bacterial types. The early penicillin drugs are examples. Broad-spectrum anti-infectives

affect many bacteria.

Meropenem

is an example.

Because narrow spectrum antibiotics are selective, they are more active against those single organisms than the broad spectrum antibiotics. Slide6

Spectrum of Activity of Anti-Bacterial Anti-Bacterial agents that interfere with the ability of the cell to reproduce/replicate without killing them are called BACTERIOSTATIC drugs. Antibiotics that can aggressively cause bacterial death are called BACTERICIDAL.

These properties (-

cidal

and –static) can also depend on the antibiotic concentration in the blood. Slide7

AntibioticsThe PENICILLINS THE CEPHALOSPORINS

The

Aminoglycosides

The

Macrolides

The

Lincosamides

The

Tetracyclines

The

FluoroquinolonesThe Sulfonamides Slide8

The PENICILLINS Narrow 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 Slide9

Penicillin The structure of Penicillin Penicillin is a beta-lactam drug, with a beta-lactam ring. The group of penicillins is called beta lactam antibiotics.

The action of

Penicillins

:

The penicillin and

penicillinase

-resistant

penicillins

produce BACTERICIDAL effects by interfering with the ability of susceptible bacteria from biosynthesizing the framework of the cell wall.

The bacterium will have weakened cell wall, will swell and then burst from the osmotic pressure within the cell. Slide10

Penicillin Therapeutic Indications of penicillin: The penicillins are indicated for the treatment of streptococcal infections. Adverse Effects of Penicillins

GI system effects- the major adverse effects of penicillin therapy involve the GIT. Nausea, vomiting, diarrhea, abdominal pain,

glossitis

,

stomatitis

, gastritis, sore mouth and furry tongue.

The reason for some of these effects (

superinfection

) is associated with the loss of bacterial flora.

Hypersensitivity reactions- rashes,

pruritus

, fever. These indicate mild allergic reaction. Wheezing and diarrhea may also occur. Anaphylaxis can also happen leading to shock or death. It occurs in 5-10% of those receiving

penicillins

. Pain and inflammation on injection sites Slide11

THE CEPHALOSPORINS First Generation cephalosporins- are largely effective against the same gram-positive organisms affected by penicillin. Second generation cephalosporins

- are effective against those strains as well as

Haemophilus

influenza,

Entreobacter

aerogenes

and

Nesseria

sp. These drugs are less effective against gram positive bacteria

Third Generation

cephlosporins

- are relatively weak against gram-positive bacteria but more potent against gram-negative bacteria, to include

Serratia

marcescens. Fourth generation cephalosporins- are developed to fight against the resistant gram-negative bacteria. The first drug is cefepime. Slide12

THE CEPHALOSPORINS 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

Slide13

THE CEPHALOSPORINS The mechanism of action:The cephalosporins are primarily BACTERICIDAL. They interfere with the cell-wall building ability of bacteria when they divide. They prevent the bacteria from biosynthesizing the framework of their cell wall. The weakened cell wall will swell and burst causing cell death. Pharmacokinetics

Only a few

cephalosporins

are administered orally, most are administered

parenterally

.

Their half-lives are short and

they are excreted mainly in the urine. Slide14

THE CEPHALOSPORINS Contraindications and Precautions The drugs are contraindicated in patients with known allergies to cephalosporins and penicillins. Adverse Effects

GI system- Nausea, vomiting, diarrhea, anorexia, abdominal pain and flatulence are common effects.

CNS – headache, dizziness, lethargy and

paresthesias

have been reported.

Renal system-

nephrotoxicity

in individuals with pre-existing renal disease

Drug-Drug interactions

Aminoglycosides

- if given with

cephalosporins

may increase the risk of kidney toxicity

Anti-coagulants- may experience increased bleeding tendencies .Slide15

The Aminoglycosides The following are the aminoglycosides

1.Gentamycin

2.Tobramycin

3.Amikacin

4.Netilmicin

5.Kanamycin

Mechanism of Action:

These are BACTERICIDAL. They inhibit protein synthesis in susceptible strains of gram-negative bacteria, leading to loss of functional integrity of the bacterial cell membrane, which causes cell death.

Therapeutic Use of the

Aminoglycosides

These drugs are used to treat serious infections caused by gram-NEGATIVE bacteria. Slide16

The Aminoglycosides Contraindications and PrecautionsThese drugs are contraindicated in known allergies to aminoglycosides, in patients with renal failure, hepatic disease, pre-existing hearing loss, myasthenia gravis, Parkinson’s, pregnancy and lactation.

Drug to drug interactions

Diuretics- increased incidence of

ototoxicity

,

nephrotoxicity

and neurotoxicity.

Anesthetics and

Neuromusular

blockers- increased neuromuscular blockage and paralysis may be possible

Penicillin- synergistic action Slide17

The Aminoglycosides Adverse Effects of Aminoglycosides CNS- irreversible deafness, vestibular paralysis, confusion, depression,

disorietnation

, numbness, tingling and weakness related to drug effects.

Kidney- renal toxicity, which may progress to renal failure caused by the direct toxicity of the

aminoglycosides

.

Hema

- bone marrow depression resulting from direct drug effect may lead to immune suppression and

superinfection

.

GI system- nausea, vomiting, diarrhea, weight loss,

stomatiits

and hepatic toxicity. The effects are due to the direct GI irritation, loss of bacterial flora and toxicity to

mucucs

membrane and liver as the drugs are metabolized. Skin effects- photosensitivity, purpura, rash, urticaria and exfoliative dermatitis Cardiac- palpitaions, hypotension or hypertension Slide18

The Macrolides

The

macrolides

are

Azithromycin

Clarithromycin

Dirithromycin

Erythromycin

Mechanism of Action :

The

macrolides

are primarily BACTERICIDAL and sometimes bacteriostatic. They exert their effect by binding to the bacterial cell ribosomes and changing or altering protein production/function. This will lead to impaired cell metabolism and division. Slide19

The Macrolides Pharmacokinetics Erythromycin is destroyed by the gastric juice, which is why slats are added to stabilize the drug. Food does not interfere with the absorption of the macrolides.

Therapeutic Use:

These are indicated for the treatment of the following conditions:

Steptococcal

infection,

Mycoplasma

infection,

Listeria

infection and group A beta hemolytic strep infection.

Contraindications and Precautions

These agents are contraindicated in the presence of known allergy to any

macrolide

, because cross-sensitivity occurs.

Caution should be used in patients with hepatic dysfunction that could alter the metabolism of the drug;

in lactating women because of drug excretion in breast milk in pregnant women because potential adverse effects on the developing fetus. Slide20

The Macrolides Adverse Effects:GI system- abdominal cramping, anorexia, diarrhea, vomiting and pseudomembranous colitis. HEPATOTOXICITY can occur if the drug is taken in high doses with other hepatotoxic drugs.

CNS- confusion, abnormal thinking and uncontrollable emotions.

Hypersensitivity reactions

Drug-Drug Interactions

Digoxin

- increased level of dioxin can occur

Anticoagulants,

theophyllines

and corticosteroids- increased effects of these drugs due to impaired hepatic metabolism

Astemizole

- when used with

macrolides

, will cause fatal cardiac arrhythmias

Clindamycin

or lincomycin – should not be given with erythromycin because they compete for receptor sites. The Nursing Process and Macrolides Slide21

The Lincosamides

These agents are similar to the

Macrolides

but are more toxic.

They are bactericidal and

bacteriostatic

depending on the dose.

The following are the

Lincosamides

:

Clindamycin

lincomycin

The Mechanism of Action :These agents penetrate the cell membrane and bind to the ribosome in the bacterial cytoplasm to prevent the protein production Slide22

The Lincosamides Side effects and Adverse Reactions GIT- GI irritation, nausea, vomiting and stomatitis Allergic reactions

Drug Interactions

Lincomycin

and

clindamycin

are incompatible with

aminophyline

,

phenytoin

, barbiturates and

ampicillin

. Slide23

The Tetracyclines

The following are the

tetracyclines

Short-acting

tetracyclines

tetracycline

oxytetracycline

Intermediate acting

tetracyclines

demeclocycline

methacycline Long acting tetracyclines doxycycline minocycline The Mechanism of Action:The tetracyclines inhibit protein synthesis in susceptible bacteria leading to the inability of the bacteria to multiply. Slide24

The Tetracyclines Therapeutic indications of the Tetracycline Tetracyclines are effective against a wide range of bacteria. They are primarily BACTERIOSTATIC.

Contraindications and Precautions:

These agents are contraindicated in the presence of known allergy to

tetrayclines

.

It is not recommended for use in pregnancy and lactation because the drug can affect the bones and teeth, causing permanent discoloration and sometimes arrest of growth.

Tetracyclines

are also avoided in children less than 8 (eight) years of age because of the potential damage to the bones and permanent discoloration of the teeth. Slide25

The Tetracyclines Adverse Effects:GI system- nausea, vomiting, diarrhea, abdominal pain, glossitis

and

dysphagia

.

Fatal

hepatotoxicity

related to tetracycline’s irritating effect on the liver cells has been reported.

Musculoskletal

-

Tetracyclines

have an affinity for teeth and bones; they accumulate there, leading to weakening of the bone/teeth and permanent staining and pitting.

Skin

- photosensitivity and rash are expected.

Less frequent- bone marrow depression, hypersensitivity, super infections, pain and hypertension Slide26

The Tetracyclines Drug-Drug Interactions Penicillin- if taken with tetracyclines, will decrease the effectiveness of penicillin. Oral contraceptives- if taken with tetracycline, will have decreased effectiveness (must advise alternative methods of contraception ).

Digoxin

-

digoxin

toxicity rises when

tetracyclines

are used together

Drug-Food Interaction

Dairy products- can complex with tetracycline and render

unabsorbable

.

Tetracyclines

should then be given on an EMPTY stomach 1 hour before meals or 2-3 hours after any meal or other medications. Slide27

The Fluoroquinolones

The

fluoroquinolones

are broad-spectrum antibiotics.

The examples are:

1.

Nalidixic

acid

2. ciprofloxacin

3.

oxacillin

4.

norfloxacin

5.Levfofloxacin 6.Sparfloxacin Slide28

The Fluoroquinolones

Mechanism of action

These agents enter the bacterial cell by diffusion through cell channel.

Once inside they interfere with the action of DNA enzymes (DNA

gyrase

) necessary for the growth and reproduction of the bacteria.

This will lead to cell death.

Therapeutic Use:

These agents are indicated for the treatment of infections caused by susceptible strains

of gram-negative bacteria

including E. coli., Proteus, pseudomonas, Strep and Staph

spp

Contraindications and Precautions

Known drug allergy to these agents contraindicate their use.

Pregnancy and lactation .These agents are found to cause significant damage to the cartilages such that they are given cautiously to growing children and adolescents less than 18 years of age. Slide29

The FluoroquinolonesAdverse Effects: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 on the GIT

Hema

-

bone marrow depression related to the direct effect of the drug on the cells of the bone marrow that rapidly turn over.

Other effects-

skin reactions, rash, fever and photosensitivity

Drug-Drug Interaction

Iron salts,

Sucralfate

, mineral supplements and antacids- all of these will

decrease the effectiveness of the

fluoroquinolones

Quinidine

, Procainamide, terfenadine, henothiazines- can prolong the QT interval when used with the fluoroquinolones Slide30

The Sulfonamides These are called sulfa drugs that inhibit folic acid synthesis. Folic acid is necessary for the synthesis of purine and pyrimidine

precursprs

of DNA and RNA. Humans cannot produce folic acid and must

obtin

it form the diet. While bacteria need to manufacture their own folic acid inside their cell structure.

The following are the sulfonamides:

1.Sulfazalazine

2.Sulfamethoxazole

3. Sulfadiazine

4.Sulfixoxazole Slide31

The Sulfonamides The Mechanism of Action:The sulfa drugs competitively block the para-amino benzoic acid to prevent the synthesis of folic acid in susceptible bacteria that synthesize their own folates for the production of RNA and DNA.

Therapeutic indications:

The spectrum of activity includes the following bacteria-

Chlamydia,

Nocardia

,

Haemophilus

, E, coli and Proteus.

Sulfa drugs are used to treat trachoma and brain abscess.

Contraindications and precautions

These agents are contraindicated to patients with known

allergy

to sulfa drugs,

sulfonylureas and thiazide diuretics because they share similar structures. It is not recommended for use in pregnancy because it can cross the placenta and cause birth defects and kernicterus. Lactating women who take these drugs will excrete them in the breast milk potentially causing kernicterus, diarrhea and rash in the newborn. Slide32

The 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 the GIT and death of normal flora.

Renal system-

crystalluria

,

hematuria

and

proteinuria

which can progress to a

nephrotic

syndrome.

CNS-

headache, dizziness, vertigo, ataxia, convulsions and depression related to drug effects on the nerves

Hema

-

bone marrow depression related to drug effects on the cells of the bone marrow that turn over rapidly. Dermatologic effects- photosensitivity and rash and hypersensitivity Drug-Drug Interaction Tobultamide, tolazamide, glyburide, glipizide, acetohexamide or chlorpropamide (all are oral Anti-diabetic agents) can increase the risk of hypoglycemia if taken with the sulfa drugs Slide33