Transcript pharm4e-chapter 04

Chapter 4
Antibiotics
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Chapter 4 Topics
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Fighting Bacterial Infections
Major Classes of Antibiotic Drugs
Storage of Liquid Antibiotics
Ophthalmic Antibiotics
Treating Complications of Infections
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Learning Objectives
• Identify the major types of antibiotics by
drug class.
• Know which auxiliary labels to use when
dispensing major types of antibiotics.
• Define therapeutic effects side effects, and
administration routes of major antibiotics.
• Use antibiotic and general drug
terminology correctly in written and oral
communication.
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Fighting Bacterial Infections
• Bacteria
– Single-celled organisms occurring in
most environments
• Infection
– Condition in which bacteria grow in body
tissues and cause tissue damage by
their presence or by toxins they produce
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Types of Bacteria
• Aerobic
– Needs oxygen to survive
• Anaerobic
– Survives in the absence of oxygen
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Bacteria Shapes
(a) Round cocci
(b) Rod-like bacilli
(c) Spiral-shaped spirochetes
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Gram Stain
(a) Gram-positive bacteria turn purple
(b) Gram-negative bacteria appear red
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Gram Stain Results and
Related Diseases
Shape Gram Stain
Bacteria
rods
grampositive
Corynebacteria endocarditis
rods
gramnegative
E. Coli
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Related
Disease
UTI
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Gram Stain Results and
Related Diseases
Shape Gram Stain Bacteria
Related
Disease
cocci
grampositive
Staphylococcu toxic
s
shock
syndrome
cocci
gramnegative
Neisseria
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Gonorrhea
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Gram Stain Results and
Related Diseases
Shape
Gram
Stain
Bacteria
curved or
spiral rods
gramCampylobacter septicemia
negative
spirochetes gramTreponema
negative palladium
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Related
Disease
syphilis
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How Antibiotics Work
• Prevent folic acid synthesis
– Sulfonamides
• Inhibit cell wall formation
– Penicillins
– Cephalosporins
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How Antibiotics Work
• Block protein formation
– Macrolides
– Tetracyclines
– Aminoglycosides
• Interfere with DNA formation
– Quinolones
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How Antibiotics Work
• Disrupt cell membranes
– Cyclic lipopeptides
• Disrupt DNA structure
– Metronidazole
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How Antibiotics Work
• Bactericidal Agent:
– Kills invading organisms
• Bacteriostatic Agent:
– Inhibits the growth or multiplication of
bacteria
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Antibiotic TX
• Ideal: Tx starts after a culture
• No time for Culture
– Tx with Broad-spectrum antibiotics
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Dispensing Issues of
Antibiotics
Warning!
• Mix exactly as directed by manufacturer
• Swab counting tray with alcohol
between drugs to prevent crosscontamination
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Side Effects of Antibiotics
• Most antibiotics taken on an empty
stomach to attain faster absorption
• Exceptions
– nitrofurantoin (Macrobid, Macrodantin)
– cefuroxime (Ceftin, Zinacef)
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Antimicrobial Resistance
• Developing largely because of
– Overuse
– Misuse
• Superinfection may occur
– Bacteria produce enzyme that
destroys the molecular integrity of
the drug
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Antimicrobial Resistance
• Pharmacy technician—place a
label on antibiotics advising
patient to take all of the medication
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Terms to Remember
bacteria
infection
aerobic
anaerobic
Gram staining
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Terms to Remember
bactericidal agent
bacteriostatic agent
superinfection
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Discussion
How might the widespread use of
antibacterial soaps affect the
population?
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Disinfectants not safe to
use systemically
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Major Classes of Antibiotic
Drugs
• Sulfonamides
• Ketolides
• Pencillins
• Quinolones
• Cephalosporins
• Streptogramins
• Tetracyclines
and Tigecycline
• Aminoglycosides
• Macrolides
• Cyclic
Lipopetides
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Sulfonamides
• AKA “sulfa drugs”
• Effective against a broad range of
microorganisms
• Block specific step in biosynthetic
pathway of folic acid
• Interfere with PABA and folic acid
formation, thereby destroying bacteria
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Allergy to Sulfonamides
• If patient is allergic to sulfa, then
drug of choice is nitrofurantoin
(Macrobid, Macrodantin)
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Therapeutic Uses of
Sulfonamides
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Urinary tract infections (UTIs)
Otitis media
Ulcerative colitis
Lower respiratory infections
Prophylaxis in Pneumocystis carinii
pneumonia in immunocompromised
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Side Effects of Sulfonamides
• Rash
• Jaundice
• Nausea
• Kidney damage
• Drug fever
• Blood
complications
• Vomiting
• Stevens-Johnson
Syndrome: fatal
marked by large
red blotches on
skin
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Dispensing Issues of
Sulfonamides
• Avoid sun
• Maintain adequate fluid intake
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Penicillins
• Low toxicity
• Kills bacteria by preventing them from
forming rigid cell wall
• Because human cells do not have rigid cell
walls, they are not affected
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Therapeutic Uses of
Penicillins
• Abscesses
• Beta-hemolytic streptococcus
• Meningitis
• Otitis media
• Pneumonia
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Therapeutic Uses of
Penicillins
• Respiratory infections
• Strep throat
• Tooth and gum infections
– Prophylaxis prior to dental
procedures
• Sexually transmitted diseases (STDs;
syphilis and gonorrhea)
• Endocarditis due to streptococci
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Side Effects of Penicillins
• Diarrhea
• Allergies in 7% to 10% of population
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Dispensing Issues of
Penicillins
• Take on an empty stomach
– Food slows absorption
– Acids in fruit juices or colas could
deactivate drug
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Resistance to Penicillins
• Penicillinase-resistant penicillins work
against gram-positive aerobes
• Extended-spectrum penicillins are
more resistant to gram-negative
bacteria
• Penicillin combinations improve effect
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Cephalosporins
• Mechanism of action similar to
penicillins
• Person allergic to penicillin has about
1% chance of being allergic to
cephalosporins
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Dispensing Issues of
Cephalosporins
Warning!
• Alert pharmacist if patient who is allergic to
penicillin is receiving a cephalosporin Rx
• If patient wants cephalosporin dispensed,
document communication in case of crossreaction
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First-Generation
Cephalosporins
• Similar to penicillinase-resistant
penicillins but have greater gramnegative coverage
• Used for
– Community-acquired infections
– Mild to moderate infections
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Second-Generation
Cephalosporins
• Increased activity, especially against
Haemophilus influenzae
• Used for
– Otitis media in children
– Respiratory infections
– Urinary tract infections (UTIs)
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Third-Generation
Cephalosporins
• Active against wide spectrum of
gram-negative organisms
• Long half-life, so once-a-day dosing
for some
• Used for
– Ambulatory patients
– Children (dosing before or after school)
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Fourth-Generation
Cephalosporins
• Broad-spectrum coverage, such as
cefepime (Maxipime)
• Used for
– Pneumonia
– UTIs
– Sepsis
• IV form mixed in NS or D5W
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Side Effects of
Cephalosporins
• Share side effects of penicillin
• A few may initiate unique toxic
reactions
• Lower frequency of toxicity than
many other antibiotics
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Dispensing Issues of
Cephalosporins
Warning!
• All cephalosporins look alike when
written in the generic form
• Watch dosing and indications for use
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Drugs Related to Penicillins
and Cephalosporins
• New beta-lactam drugs differ slightly
in structure
• Carabpenems, carbacephems, and
monobactam
• Some used for serious infections
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Tetracyclines
• Broad-spectrum bacteriostatic
antibiotics
• Inhibit protein synthesis in bacteria by
binding to ribosomes
• Suppress infection, but require
phagocytes to eradicate bacteria
completely
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Therapeutic Uses of
Tetracyclines
• Acne
• Anthrax
• Chronic bronchitis & pulmonary
infections
• Lyme disease
• Mycoplasma pneumoniae infection
• Rickettsia infection
• Some sexually transmitted diseases, such
as Chlamydia infection
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Side Effects of Tetracyclines
• Gastrointestinal upset with nausea
and vomiting
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Dispensing Issues of
Tetracyclines
• Avoid antacids to avoid chelation with
minerals
• Photosensitization
• Pregnant women and children up to
age 9 must avoid- teeth discoloration
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Dispensing Issues of
Tetracyclines
Warning!
• Expired drugs can be toxic, can
cause fatal renal syndrome
• Pharmacy technician always watch
the expiration date
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Dispensing Issues of
Tetracyclines
Warning!
• Government agencies stockpiling
tetracyclines due to concern over
terrorist attack
• Due to toxicity: must be rotated;
destroy when out of date
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Tigecycline
• New drug class: glycylcycline
• Similar to tetracyclines
• Used for
– Skin infections
– Intra-abdominal infections
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Macrolides
• Inhibit protein synthesis by combining
with ribosomes
• Used primarily to treat pulmonary
infections
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Dispensing Issues of
Macrolides
• Most antibiotics taken on empty
stomach
• Some forms of erythromycin can
cause severe GI distress and should
be taken with food
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Dispensing Issues of
Macrolides
Warning!
• Can be misread
– erythromycin
– azithromycin
• Dosing should help identify drug
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Ketolides
• Bind to ribosomal subunits and block
protein synthesis
• May inhibit newly forming ribosomes
• Bacteria resistant to macrolides,
lincomycin derivatives, and streptogramins
is also resistant to ketolides
• Used to treat bacterial infections in lungs
and sinuses
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Quinolones
• Strong, rapid bactericidal action
against
– Most gram-negative bacteria
– Many gram-positive bacteria
• Antagonize enzyme responsible
for coiling and replicating DNA,
causing DNA breakage and cell
death
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Therapeutic Uses of
Quinolones
• Bone and joint infections caused by
gram-negative organisms
• Infectious diarrhea
• Ophthalmic infections (ciprofloxacin)
• Some sexually transmitted diseases
• Upper respiratory infections
• Urinary tract infections (UTIs)
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Side Effects of Quinolones
• Primarily gastrointestinal, with nausea and
vomiting
• Some joint swelling, dizziness, and
unpleasant taste
• Can cause joint problems and
malformations
• Patients have tendency to injure tendons
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Dispensing Issues of
Quinolones
• Not to be given with theophylline
• Antacids interfere with absorption
• Avoid sun
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Streptogramins
• Inhibit protein synthesis within the
bacterial ribosomes
• Alternative to vancomycin
• Side effects similar to quinolones:
nausea, vomiting, joint swelling,
dizziness
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Aminoglycosides
• Used to treat serious infections:
– Sepsis
• Inhibits bacterial protein synthesis by
binding to ribosomal subunits
• After first dose, dosage adjusted
according to plasma concentrations
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Side Effects of
Aminoglycosides
• Nephrotoxicity (destructive to kidney)
• Ototoxicity (damage organs of
hearing)
– Equilibrium problems
– Tinnitus
– Permanent deafness
• Neuromuscular blockade
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Dosing of Aminoglycosides
• Dosed 1x/daily instead of 2 to 3x/daily
• Less frequent dosing may reduce toxicity
– Less drug accumulates in kidneys and ears
– Simplifies drug monitoring
• Trough levels should be checked before
second dose to confirm drug elimination
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Cyclic Lipopetides
• Bind bacterial membranes causing
cell membrane to depolarize
• Leads to
– Inhibition of DNA and RNA synthesis
– Bacterial death
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Drug List
Cyclic Lipopetides
– daptomycin (Cubicin)
Warning!
• Do not take with statins: causes
hypotension
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Terms to Remember
sulfonamides
penicillin
cephalosporin
community-acquired
NS
D 5W
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Terms to Remember
tetracycline
chelation
macrolide
ketolide
quinolone
streptogramin
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Terms to Remember
aminoglycoside
sepsis
nephrotoxicity
ototoxicity
cyclic lipopeptide
hypotension
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Other Antibiotics
• Five important antibiotics are
structurally distinct from
– Those in other classes
– Each other
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vancomycin (Vancocin)
Warning!
• Bacterial resistance increasing
due to overuse
• Strict CDC guidelines for handling
and use
• Adverse effect: Red man
syndrome
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clindamycin (Cleocin)
• Broad-spectrum antibiotic used for
– Acne
– Penicillin alternative in dental
prophylaxis
– Anaerobic pneumonia
– Bone and bowel infections
– Female genital and intra-abdominal
infections
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clindamycin (Cleocin)
Warning!
• If patient develops diarrhea, drug
must be discontinued
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linezolid (Zyvox)
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First oxazolidinone approved by FDA
Inhibits bacterial protein synthesis
Drug must be protected from light
TX: MRSA, VRE, other gram positive
IV, oral, tablet
Cannot go in the IV with other drugs
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metronidazole (Flagyl)
• Effective against Fungi,
protozoa and bacteria
• Pharmacy technician—place No
Alcohol warning sticker on
medication
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pentamidine (NebuPent,
Pentam)
• Second-line agent for Pneumocystis
carinii
• Mechanism of action unknown
• Patient may develop sudden
hypotension (low blood pressure)
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Storage of Liquid Antibiotics
• After lyophilized (powdered)
antibiotics are mixed
– Some need refrigeration
– Others stored at room temperature
• Pharmacy technician may tell storage
information to patient
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Ophthalmic Antibiotics
• Some antibiotics have ophthalmic
(eye) dosage forms
• Very few antibiotics have otic forms
– Very painful in the eye
– Otic medicines have different pH than
the eye
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Dispensing Issues of
Ophthalmic Antibiotics
• Newer eye drops very expensive,
often rejected by insurance
companies
• Pharmacy technician will need to let
prescriber know
– What eye drops are available
– Which ones insurance most likely cover
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Terms to Remember
ophthalmic
to be used in the eye
otic
to be used in the ear
pH
a measurement of acidity or alkalinity;
pH 7 neutral
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Treating Complications of
Infections
• drotrecogin alfa (Xigris)
– Not an antibiotic
– Used in treating some complications
of sepsis (life-threatening result of
serious infections)
– Anticoagulant and anti-inflammatory
– High cost, strict guidelines limit use
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Drug List
Adjunct in Treating Sepsis
– drotrecogin alfa (Xigris)
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Discussion
• Why is resistance developing to
antibiotics? Is this a problem?
• What role can the pharmacy
technician play in regard to this
problem?
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