113 terms

Pharmacology- Antiinfective/Antiviral/Antifungal Drugs

Why study antiinfective agents?
Infection, after pain management, is the dental problem for which drugs are most often prescribed
Types of dental infections:
-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?
If a patient has a penicillin allergy, what alternatives may be used?
Erythromycin or clindamycin
What drug is used for anaerobic organisms?
What drug affects both gram-positive cocci and gram-positive and gram-negative anaerobes?
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
The ability to kill bacteria
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
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!!
Range of activity of a drug
The spectrum of activity of an antibacterial agent may be:
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
Occurs when the combination of 2 antibiotics produces more effect than would be expected if their individual effects were added
Occurs when a combination of 2 agents produces less effect than either agent alone
Living or active only in the presence of oxygen
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?
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:
What is a condition in which bacteria are present in the bloodstream?
The wider te spectrum of the antiinfective agent and the longer the agent is administered, the ____ the chance of superinfection occurring.
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?
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?
Types of allergic reactions to penicillin
-Anaphylactic shock
-Delayed serum sickness
-Oral lesions
What type of allergic reaction to penicillin accounts for 80-90% of allergic reactions?
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 ____.
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:
Pharmacokinetics of Erythromycin
-Broken down in gastric fluid
-Spectrum closely resembles that of penicillin
Adverse reactions of Erythromycin
-Abdominal cramps
Allergic reactions are uncommon!
What is the usual adult dose of Erythromycin?
250-500 mg 4x/day
Azithromycin and Clarithromycin
-Activity against gram-positive and negative aerobes
Pharmacokinetics of tetracyclines
-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
-Hematologic effects
-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
-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
-Half-life is 2.5 hours
The most commonly observed side effects of clindamycin are:
-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
-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?
Uses of Metronidazole:
1.) Medical- Useful because of its anaerobic spectrum
2.) Dental- Tx of many perio infections
Pharmacokinetics of Cephalosporins
-Half-life 50-240 minutes
Structurally related to the penicillins!
Adverse reactions of Cephalosporins
-GI effects- most common
-Local reaction
-Impair hemostasis and disulfiram-like-reaction-parenteral (injections)
Various types of hypersensitivity reactions have been reportred in approx. ___% of patients receiving cephalosporins.
The degree of cross-hypersensitivity reported is about ___%.
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
Aminoglycosides include:
1.) Neomycin
2.) Gentamicin
3.) Tobramycin
4.) Amikacin
Adverse reactions of Aminoglycosides
Uses of aminoglycosides
Serious gram - infections
-Not used in dentistry
-Inhibits synthesis of folic acid from PABA
Adverse reactions of sulfonamides
-Allergic skin reactions
-Possibility of renal crystallization
-Inhibits DNA involved in DNA synthesis
-Half-life is 4 hours (Cipro)
What bacteria causes TB?
Mycobacterium tuberculosis
Because of the problem of resistance, at least ___ drugs are administered concurrently in all active cases.
-Half-life is 1.5-3 hours
-Adverse reactions in 5% of patients
-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
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?
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 is ___ and ___ against a variety of yeasts and fungi.
Fungicidal; fungistatic
-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
-Binds to phospholipids in cell membrane which produces an alteration of cell membrane permeability
-Alters cellular membranes and interferes with intracellular enzymes
-Most serious adverse reaction is hepatotoxicity
Amphotericin B
-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?
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?
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.
What antiviral agent is used prophylactically for prevention or in tx of influenza A?
What antiviral agent is used for hep C and multiple sclerosis?