Pharmacology- Antiinfective/Antiviral/Antifungal Drugs

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Why study antiinfective agents?

Infection, after pain management, is the dental problem for which drugs are most often prescribed

Types of dental infections:

-Caries
-Periodontal disease (Biggest problem in adult patients)
-Localized dental infections
-Systemic dental infections

Stages of dental infection "Evolution":

1.) Early stage- Aerobes
2.) Mixed stage- Aerobes and anaerobes
3.) Chronic stage- Anaerobes

If the infection is just beginning in the early stage, what organisms are most likely to be present?

Gram-positive cocci

What is the drug of choice in the early stage?

Penicillin

If a patient has a penicillin allergy, what alternatives may be used?

Erythromycin or clindamycin

What drug is used for anaerobic organisms?

Metronidazole

What drug affects both gram-positive cocci and gram-positive and gram-negative anaerobes?

Clindamycin

Antiinfective agents

Substances that act against or destroy infections (may be synthetic)

Antibacterial agents

Substances that destroy or suppress the growth or multiplication of bacteria (may be synthetic)

Antibiotic agents

Chemical substances produced by microorganisms that have the capacity, in dilut solutions, to destroy or suppress the growth or multiplication of organisms or prevent their action

Antimicrobial agents

Substances that destroy or suppress the growth or multiplication of microorganisms

Antifungal agents

Substances that destroy or suppress the growth or multiplication of fungi

Antiviral agents

Substances that destroy or suppress the growth or multiplication of viruses

Bactericidal

The ability to kill bacteria

Bacteriostatic

The ability to inhibit or retard the multiplication or growth of bacteria

Blood (serum) level

Concentration of the antiinfective agent present in the blood of serum

Infection

An invasion of not only the body by pathogenic microorganisms but also a reaction of the tissues to their presence

Minimum inhibitory concentration (MIC)

Lowest concentration needed to inhibit visible growth of an organism on media after 18-24 hours of incubation
Lower the MIC, Higher the potency!!

Spectrum

Range of activity of a drug

The spectrum of activity of an antibacterial agent may be:

-Narrow
-Intermediate
-Broad

Superinfection/Suprainfection

Infection caused by the proliferation of microorganisms different from those causing the original infection

Superinfection is more often caused by ___ spectrum antibiotics such as ___ and increases when taken for a longer period.

Broad; tetracycline

Synergism

Occurs when the combination of 2 antibiotics produces more effect than would be expected if their individual effects were added

Antagonism

Occurs when a combination of 2 agents produces less effect than either agent alone

Aerobic

Living or active only in the presence of oxygen

Anaerobic

Living or active in the absence of oxygen

Factors determining likelihood of a microorganism causing an infection:

1.) Disease-producing power of the microorganism (virulence)
2.) Number of organisms present (inoculum)
3.) Resistance of the host (immunologic response)

What involves the growing of bacteria from a sample of infective exudate?

Culturing

What involves the exposing of the organism to certain test antibiotics and determining whether the organism is sensitive or resistant?

Sensitivity testing

Natural vs. Acquired resistance

1.) Natural- An organism has always been resistant to an antimicrobial agent because of the bacteria's normal properties
2.) Acquired- An organism that was previously sensitive to an antimicrobial agent develops resistance

Indications for antimicrobial agents:

1.) Therapeutic indications
2.) Prophylactic indications

Therapeutic indications:

-The patient
-The infection

Prophylactic indications:

-Bacteremia

What is a condition in which bacteria are present in the bloodstream?

Bacteremia

The wider te spectrum of the antiinfective agent and the longer the agent is administered, the ____ the chance of superinfection occurring.

Greater

Drug interactions of Antiinfective agents:

-Oral contraceptives (reduce effectiveness)
-Oral anticoagulants
-Other antiinfectives

Oral anticoagulants are ____ _ inhibitors, so interferring with the production of ____ _ could ____ the anticoagulant effect.

Vitamin K; Vitamin K; increase

Adverse reactions:

1.) Gastrointestinal complaints
-Stomach pain, increased motility, diarrhea
2.) Pregnancy considerations
3.) Dose forms
4.) Cost (important factor in deciding antibiotic for patient)

What drug has the highest incidence of gastrointestinal complaints of any of the antibiotics?

Erythromycin

What kind of structure does penicillin include?

B-lactam ring

What happens when the B-lactam ring is broken?

(Such as in the presence of penicillinase) The antimicrobial activity of the compound is lost

Pharmacokinetics of Penicillins

-Metabolized by hydrolysis in the liver
-Undergoes tubular secretion in the kidney
-Elimination half-life for both G and V is 0.5 hours

Mechanism of action of Penicillins

-Very potent bactericidal agent
-Attached to penicillin-binding proteins (PBPs) on the bacterial cell membrane

Penicillin inhibits the formation of ___ ___. This destroys cell wall integrity and leads to ___ of the cell.

Cross-linkage; lysis

Adverse reactions of Penicillins

1.) Toxicity- low to almost nonexistent
2.) Allergy and hypersensitivity

What drug is the most common cause of drug allergies?

Penicillin

Types of allergic reactions to penicillin

-Anaphylactic shock
-Rash
-Delayed serum sickness
-Oral lesions

What type of allergic reaction to penicillin accounts for 80-90% of allergic reactions?

Rash

The use of penicillin in dentistry results from its:

-Bactericidal potency
-Lack of toxicity
-Spectrum of action

What is the usual adult dose of penicillin V?

500 mg 4x/day for a min. of 5 days and preferably 7-10 days

Penicillinase-Resistant penicillins should be reserved for use against only penicillinase-producing ____.

Staphylococci

Ampicillins and amoxicillin is mixed with _____ ___, a B-lactamase inhibitor (Augmentin), this combines with and inhibits B-lactamases produced by bacteria.

Clavulanic acid

Types of Macrolides:

-Erythromycin
-Clarithromycin
-Azithromycin

Pharmacokinetics of Erythromycin

-Bacteriostatic
-Broken down in gastric fluid
-Spectrum closely resembles that of penicillin

Adverse reactions of Erythromycin

-Stomatitis
-Abdominal cramps
-Nausea
-Vomitting
-Diarrhea
-Jaundice
Allergic reactions are uncommon!

What is the usual adult dose of Erythromycin?

250-500 mg 4x/day

Azithromycin and Clarithromycin

-Bacteriostatic
-Activity against gram-positive and negative aerobes

Pharmacokinetics of tetracyclines

-Bacteriostatic
-Half-life is 2 hours
-Stored in dentin and enamel of unerupted teeth and concentrated in GCF

Adverse reactions of tetracyclines

-Gastrointesting effects (GI distress is common)
-Effects on teeth and bones
-Hepatotoxicity
-Nephrotoxicity
-Hematologic effects
-Superinfection
-Photosensitivity
-Allergy (low)

What can happen if a patient taking tetracyclines is exposed to the sunlight?

Exaggerated sunburn

What is Minocycline (adverse reaction of tetracyclines)?

CNS side effects including lightheadedness, dizziness and vertigo

What should not be taken within 2 hours of ingesting tetracycline?

Dairy products containing calcium, antacids, and mineral supplements

Drug interactions of tetracyclines

-Cations
-Enhanced effect of other drugs
-Reduced doxycycline effect
-General antibiotic interactions

Uses of tetracyclines:

1.) Medical- Acne and COPD
2.) Dental - ANUG

Pharmacokinetics of Clindamycin

-Bacteriostatic
-Half-life is 2.5 hours

The most commonly observed side effects of clindamycin are:

Gastrointestinal:
-Diarrhea
-Nausea
-Vomitting
-Enterocolitis
-Abdominal cramps

The development of pseudomembranous colitis (PMC), also known as ____ ____ ___, has been a more serious consequence associated with clindamycin. It is characterized by severe, persistent diarrhea and the passage of blood
and mucus.

Antibioticassociated Colitis (AAC)

What is the dose of Clindamycin?

150-300 mg q6h (qid)

Pharmacokinetics of Metronidazole

-Bactericidal
-Has inflammatory effects

Adverse reactions of Metronidazole

-GI tract effects- most common adverse reaction = 12%
-CNS effects
-Renal toxicity
-Oral effects (xerostomia, unpleasant metallic taste)

What should be avoided during Metronidazole administration and for 1 day after therapy is ceased?

Alcohol

Uses of Metronidazole:

1.) Medical- Useful because of its anaerobic spectrum
2.) Dental- Tx of many perio infections

Pharmacokinetics of Cephalosporins

-Bactericidal
-Half-life 50-240 minutes
Structurally related to the penicillins!

Adverse reactions of Cephalosporins

-GI effects- most common
-Nephrotoxicity
-Superinfection
-Local reaction
-Impair hemostasis and disulfiram-like-reaction-parenteral (injections)
-Allergy

Various types of hypersensitivity reactions have been reportred in approx. ___% of patients receiving cephalosporins.

5%

The degree of cross-hypersensitivity reported is about ___%.

10%

Use of cephalosporins

Prophylaxis for patients with "at-risk" joints who are undergoing dental procedures likely to produce bleeding

Rational use of antiinfective agents:

1.) Stage I- Acute infection (Gram + aerobes)
2.) Stage II- Mixed infection (Aerobes and anaerobes)
3.) Stage III- Chronic infection (Anaerobes)

Why an antiinfective may be ineffective:

-Patient compliance
-Wrong antibiotic
-Poor debridement
-Resistant organism
-Concentration did not reach site of infection
-Host defense inadequate

Vancomycin is used intravenous for ____ effect; orally for ___ effect.

systemic; local
Bactericidal

Aminoglycosides include:

1.) Neomycin
2.) Gentamicin
3.) Tobramycin
4.) Amikacin

Adverse reactions of Aminoglycosides

-Ototoxicity
-Nephrotoxicity
Bactericidal

Uses of aminoglycosides

Serious gram - infections

Chloramphenicol

-Bacteriostatic
-Not used in dentistry

Sulfonamides

-Inhibits synthesis of folic acid from PABA
-Bacteriostatic

Adverse reactions of sulfonamides

-Allergic skin reactions
-Possibility of renal crystallization
*DRINK PLENTY OF WATER!!*

Quinolones

NEW
-Inhibits DNA involved in DNA synthesis
-Half-life is 4 hours (Cipro)
-Bactericidal

What bacteria causes TB?

Mycobacterium tuberculosis

Because of the problem of resistance, at least ___ drugs are administered concurrently in all active cases.

3

Isoniazid

BACTERICIDAL
-Half-life is 1.5-3 hours
-Adverse reactions in 5% of patients

Rifampin

-Half-life is 1.5-5 hours
-Most common adverse reaction if GI
-Causes a red-orange color to body fluids

Adverse reactions of Pyrazinamide

-Hepatotoxic
-GI

Adverse reactions of Ethambutol

-Optic Neuritis- decrease in visual acuity

Topical antibiotics include a combination of...

Neosporin and triple antibiotic ointment
-Used topically for scratches

What drug is used in the treatment of impetigo and angular cheilitis?

Mupirocin

Factors to consider for using prophylactic antibiotics:

1.) The specific dental procedure being performed
2.) The cardiac and medical condition of the patient
3.) The drug and dose that may be needed

What is the most common oral fungus?

Candida albicans
Fungal infections are often difficult to treat

What is the most common used antifungal drug?

Nystatin

Nystatin is ___ and ___ against a variety of yeasts and fungi.

Fungicidal; fungistatic

Nystatin

-Taken orally it is poorly absorbed from the GI tract
-Available as aqueous suspension or lozenge

What are the 3 imidazoles?

1.) Clotrimazole
2.) Miconazole
3.) Ketoconazole

Clotrimazole

-Binds to phospholipids in cell membrane which produces an alteration of cell membrane permeability

Ketoconazole

-Alters cellular membranes and interferes with intracellular enzymes
-Most serious adverse reaction is hepatotoxicity

Amphotericin B

*"Amphoterrible"*
-Macrolide antibiotic
-Tx of many serious systemic fungal infections

What drug is indicated in the treatment of susceptible infections of the skin, hair and nails?

Griseofulvin

What is the problem with finding a drug useful for viral infections?

It must be able to kill the host and the virus

Antiviral agents inhibit ___ ____.

DNA synthesis

What drug interferes with the DNA polymerase and inhibits DNA replication?

Acyclovir

What are Famciclovir and Valacyclovir?

Prodrugs that are converted to penciclovir and acyclovir as they pass through the intestinal wall

Antiretroviral agents are used in combinations called ___ to manage AIDS.

"cocktails"

What antiviral agent is used prophylactically for prevention or in tx of influenza A?

Amantadine

What antiviral agent is used for hep C and multiple sclerosis?

Interferons

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