Anti-Infective Agent



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Anti infective agents:

-Are drugs that designed to act selectively on foreign organisms that have invaded and infected the body
-They range from antibiotics, antifungal, antiviral, antibacterial, and antiprotozoals.

Mechanism of actions:
· Some interfere with biosynthesis of bacterial cell wall

· Some inhibit protein synthesis
· Some change cell membrane permeability
· Some inhibit DNA synthesis
Spectrum of activity:
Narrow spectrum: effect only few bacterial type
Broad spectrum effect many bacteria
Bacteriostatic drugs: interfere with ability of the cell to reproduce and replicate without killing them ex: tetracycline
Bactericidal: aggressive causing of bacterial death

Adverse effect:

1- Nephrotoxicity : kidney damage
2- GI toxicity: nausea, vomiting, stomach pain, diarrhea, hepatitis, liver failure.
3- Hypersensitivity: allergic response
4- Superinfection: opportunistic infection that develop during the course of antibiotic therapy.

Antibiotics:
· disrupts proteins or enzymes within a bacterium.
v bacteriostatic – prevents multiplication
v bactericidal – kills bacteria

· Goal : to reduce the number of bacteria à immune system can deal with infection.


Antibiotic resistance
:
· bacteria mutate that they become resistant to certain antibiotics.



common in nosocomial infectionswffFeb2007_clip_image002.jpg

cause: indiscriminate antibiotic


Microbial Resistant Diseases
HAART= High activity antiretroviral therapy

General adverse reactions to antibacterials:
1. allergy / hypersensitivity reactions
2. superinfections
3. organ toxicity

Penicillins & Penicillinase Resistant Antibiotics
v
Amoxicillin
a. Natural Penicillins
· penicillin G
· penicillin V

b. extended- spectrum penicillin
· amoxicillin
· ampicillin

c. penicillinase – resistant antibiotics
· cloxacillin
· nafcillin
· oxacillin

Indications: Tx broad spectrum respiratory & urinary tract infections

Action: inhibit cell wall synthesis (bactericidal)

Monitor for:
§ GI effects
§ superinfections
§ hypersensitivity reactions




Couple_of_Bacteria.jpg
Drug interactions:

Almost all antibiotics can potentiate the effects of warfarin by inhibiting intestinal flora that produce vitamin K. Inhibition of the hepatic metabolism of warfarin is another possible mechanism for increased bleeding.

Carbamazepine (Tegretol), phenobarbital and phenytoin (Dilantin) are commonly prescribed for the management of epilepsy and other disorders. These agents are eliminated through hepatic metabolism. Thus, their effects may be

potentiated by drugs that inhibit cytochrome P450 hepatic metabolism, such as macrolide antibiotics

Oral Contraceptives- Although insufficient evidence is available to make a firm conclusion, it appears possible that oral contraception may fail while patients are taking an antibiotic. Thus, patients should be encouraged to consider using an alternative method of contraception for the duration of the cycle



Adverse reactions — "Adverse reaction" is the medical term for any undesireable reaction caused by a medication. Allergic adverse reactions are less common than non-allergic adverse reactions. Another important difference is that allergic reactions are caused by the immune system. Stomach upset and diarrhea are examples of non-allergic adverse reactions.
It is important to distinguish non-allergic adverse reactions from true allergic reactions. Some people report that they are allergic to penicillin when actually they have had a non-allergic side effect. As a result, the person may be treated for a particular infection with a less-effective or more toxic antibiotic. This can lead to antibiotic failure or resistance, which can be costly and prolong illness.
When reporting past problems with antibiotics, it is important to provide as much detail as possible about the reaction. Anyone who is uncertain if a past allergic reaction was truly caused by allergy should avoid the antibiotic until they have discussed the situation with their healthcare provider.
Rashes — Several different types of rashes can appear while people are taking penicillin. Rashes that involve hives (raised, intensely itchy spots that come and go over hours,
show picture 1) suggest a true allergy.
However, some people, especially young children, can develop flat, blotchy rashes that spread over days but do not change by the hour (
show picture 2). These rashes typically start after several days of treatment. This type of rash is less likely to indicate a dangerous allergy, although it can be difficult to distinguish between different types of rashes that occurred in the past. Taking a photograph of a rash is always helpful.
Allergic reactions — An allergic reaction occurs when the immune system begins to recognize a drug as something "foreign". Several different symptoms can indicate that a person is allergic to penicillin. These include hives (raised, intensely itchy spots that come and go over hours) (
show picture 1), angioedema (swelling of the tissue under the skin, commonly around the face), wheezing and coughing from asthma-like reactions (narrowing of the airways into the lungs).
A past history of these types of reactions is important because the person might develop a more severe reaction, such as anaphylaxis, if they were to take the antibiotic again. Mild to moderate allergic reactions to penicillins are common, occurring in 1 to 5 percent of people.

Anaphylaxis — Anaphylaxis is a sudden, potentially life-threatening allergic reaction. Symptoms include those of an allergic reaction, as well as very low blood pressure, difficulty breathing, abdominal pain, swelling of the throat or tongue, and/or diarrhea or vomiting. Fortunately, anaphylaxis is uncommon. (See "Patient information: Anaphylaxis symptoms and diagnosis").





Fungal diseases usually mainfest in areas such as skin, mucous membranes or internally in organs.
Hygienist need to be aware of the oral manifistations such as those caused by the infamous "
Candida Albicans", so that they can ensure their Doctor is made aware and and proper medication can be prescribed. If the cause of the fingal infection can not be identified such as, a denture that is not routinely removed and cleaned causing denture stomatitis, the clinician should suspect a more serious underlying condition and be referred to a physician. Most of these medication will be used topically, so it is important for hygienist to become familiar with how these medications are used.

Antifungal agents

Yagiela page. 661

Antifungal Agent
Mechanism of action
Clinical uses
Amphotericin B
Binding to ergosterol of fungal membrane
Topical: superficial candidiasis
intravenous: severe and
proggressive systemic fungal infection.

Nystatin
Binding to ergosterol of fungal membrane
Topical: oral candidiasis.
Clotrimazole

Fluconazole

Inhibition of ergosterol synthesis
Topical: oral candidiasis and superficial candidiasis.

Oral: systemic and localized candidiasis, cryptococcal meningitis, systemic blastomycosis, and coccidioidomycosis.

Ketoconazole

Itraconazole

Inhibition of ergosterol synthesis
Topical: superficial fungal infections; Oral: systemic fungal infections; Mucocutaneous candidiasis, severe, unresponsive cutaneous dermophyte infections.

Oral: systemic fungal infections, dermophyte infections.

Miconazole
Inhibition of ergosterol synthesis
Topical: cutaneous candidiasis ans vulvovaginitis, superficial fungal infections.
Flucytosine
Inhibition of necleic acid synthesis
Oral: systemic candidiasis and cryptococcosis.
Griseofulvin

Caspofungin

Disruption of mitotic spindle

Inhibition of fungal cell wall synthesis

Oral: fungal infections of skin, hair and nails.

Intravenous: severe, invasive aspergillosis.






Antiviral Agents:

Because the replication of viruses was known to use metabolic machinery essential for the function of normal cells, it seemed nearly impossible to find agents that would inhibit viral growth without killing the host. Potential points of attack include virus encoded enzymes and other proteins taht appear during viral replication and are different from corresponding cellular enzymes in noninfected cells. However, selective toxicity is still a major challenge. More than three dozen antiviral agents have been approved by the FDA.

1. amantadine and rimantadine- prophylaxis and tx of influenza A infections
2. idoxuridine, vidarabine, trifluidine- ocular herpetic diseases
3. acyclovir, ganciclovir, foscarnet- various systemic and localized herpes group infections
4. ribavirin- respiratory syncytial bronchitis, pneumonia
5. interferons- human papillomavirus and chronic hepatitis infections
6. three casses of antiviral agents- control of HIV infection


Antiviral Spectrum, Mechanisms of Action, and clinical uses of antiviral agents:

Yagelia pg. 666


Agent
Antiviral Spectrum
Mechanism of action
Clincal Uses
Amantadine, rimantadine
Influenza A virus
Blockade of uncoating process
prophlyaxis of influenza A infection
Idoxuridine
HSV
Inhibition of DNA synthesis
Topical treatment of herpetic keratitis
Vidarabine, trigluridine
HSV
Inhibition of DNA synthesis
Topical treatment of herpetic keratitis and keratoconjunctivits.
Acyclovir, valacyclovir
HSV and VZV
Inhibition of DNA synthesis
Treatment of primary and recurrent herpes genitialis, herpetic encephalitis, mucocutaneous herpetic infection in immunocomprmised patients, neonatal herpetic infection, and VZV infection, CMV prophylaxis.
Famciclovir, penciclovir
HSV and VZV
Inhibition of DNA syntheis
Treatment of acute VZV infection and recurrent herpes infections.
Cidofovir
CMV and HSV
Inhibition of DNA synthesis
Treatment of CMV keratitis and HSV lesions
Foscarnet
HSV, VZV and CMV
Inhibition of DNA synthesis
Treament of CMV retintis and acylovir resistant HSV amd VZV infections.
Ganciclovir
CMV
Inhibition of DNA synthesis
Treatment of CMV retintis and prevention of CMV disease.
Interferon a and a2b
HCV and PHV
Stimulation of synthesis of antiviral proteins
Treament of HBV and HCV and refractory genital warts
Ribavirin
RSV
Inhibition of mRNA synthesis, inhibits purine synthesis
Treatment of RSV pnemonia and bronchitis
Reverse transcriptase inhibitors
HIV
Inhibition of viral DNA synthesis
Treament of HIV infection and AIDS
Protease Inhibitors
HIV
Blockade of HIV protease
Treatment of HIV infection and AIDS




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ANTI-INFECTIVE DRUGS

Anti-infective drugs are classified as antibacterials, antivirals, or antifungals depending on the type of microorganism they combat. Anti-infective drugs interfere selectively with the functioning of a microorganism while leaving the human host unharmed.
Antibacterial drugs, or antibiotics-sulfa drugs, penicillins, cephalosporins, and many others-either kill bacteria directly or prevent them from multiplying so that the body's immune system can destroy invading bacteria. Antibacterial drugs act by interfering with some specific characteristics of bacteria. For example, they may destroy bacterial cell walls or interfere with the synthesis of bacterial proteins or deoxyribonucleic acid (DNA)-the chemical that carries the genetic material of an organism. Antibiotics often cure an infection completely. However, bacteria can spontaneously mutate, producing strains that are resistant to existing antibiotics.
Antiviral drugs interfere with the life cycle of a virus by preventing its penetration into a host cell or by blocking the synthesis of new viruses. Antiviral drugs may cure, but often only suppress, viral infections; and flare-ups of an infection can occur after symptom-free periods. With some viruses, such as human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), antiviral drugs can only prolong life, not cure the disease.
Vaccines are used as antiviral drugs against diseases such like mumps, measles, smallpox, poliomyelitis, and influenza. Vaccines are made from either live, weakened viruses or killed viruses, both of which are designed to stimulate the immune system to produce antibodies, proteins that attack foreign substances. These antibodies protect the body from future infections by viruses of the same type.
Antifungal drugs selectively destroy fungal cells by altering cell walls. The cells' contents leak out and the cells die. Antifungal drugs can cure, or may only suppress, a fungal infection.