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PHARMACOLOGY – Anti-Microbial Drugs Consider your bugs!

What are you treating or covering empirically?
Basics
• Make sure you try to collect cultures before
starting atntibiotics
• Many antibiotics require renal dosing, such as
vancomycin. If you’re unsure about the dose call
the pharmacist.
ID approval is required for many antibiotics
such as vancomycin, levofloxacin, ciprofloxacin.
Choosing an antibiotic:
• Think about location:
— Where did the patient become ill? Travel?
Exposure?
— Where did the infection anatomically
originate?
— Where in the body, has or will the infection
spread to?
• Think about the bug you are treating

The history of antimicrobial agents

• Chemicals that affect physiology in any manner
• Chemotherapeutic agents
— Drugs that act against diseases
• Antimicrobial agents
— Drugs that treat infections

Antibiotic classes
— Beta-lactams*
— Aminoglycosides
— Quinolones*
— Macrolides*
— Lincosamides*
— Metronidazole*
— Glycopeptides
— Oxazolidinones
— Streptogramins
— Lipopeptides
— Tetracyclines
— Chloramphenicol
— Polymyxins Antimicrobial Drugs
— Sulfonamides ■ Chemotherapy
— Trimethoprim
o The use of drugs to treat a disease
— Rifamycins
— Nitrofurantoin ■ Antimicrobial drugs interfere with the growth of
microbes within a host
Antimicrobial Drugs ■ Antibiotic
— Antimicrobial drugs interfere with the growth of o Substance produced by a microbe that, in small
microbes within a host amounts, inhibits another microbe

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■ Selective toxicity The History of Antimicrobial Agents
o A drug that kills harmful microbes without • Semisynthetics
damaging the host — Chemically altered antibiotics that are more
Figure 10.1 Antibiotic effect of the mold Penicillium chrysogenum
effective than naturally occurring ones
• Synthetics
— Antimicrobials that are completely synthesized in a
lab
Staphylococcus
aureus Clinical Considerations in Prescribing Antimicrobial
(bacterium)
Drugs
• Spectrum of action
— Number of different pathogens a drug acts
Penicillium against
chrysogenum
(fungus) o Narrow-spectrum – effective against few
Zone where
bacterial growth organisms
is inhibited
o Broad-spectrum – effective against many
organisms
Historical Perspective § May allow for secondary or
• Treatment hopeless before 1935 superinfections to develop
• Paul Ehrlich, early 20th century § Killing of normal flora reduces microbial
o Father of chemotherapy organism
• Fleming -- 1929
o Penicillin discovered -- gram positives
• Florey -- 1940
o Penicillin -- first therapeutic use
• Waksman -- 1944
o Streptomycin -- gram negatives
• 1947 -- Chloramphenicol -- broad spectrum
• 1947 - present -- many
• 1928 – Fleming discovered penicillin, Clinical Considerations in Prescribing Antimicrobial
produced by Penicillium. Drugs
• 1940 – Howard Florey and Ernst Chain • Routes of Administration
performed first clinical trials of penicillin. § Topical application of drug for external infections
§ Oral route requires no needles and is self-
administered
§ Intramuscular administration delivers drug via
needle into muscle
§ Intravenous administration delivers drug directly
to bloodstream
§ Know how antimicrobial agent will be distributed
to infected tissues

Properties of an ideal antibiotic

■ broad spectrum
■ stable--long shelf life
■ soluble in body fluids
■ stable toxicity

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■ Nonallergenic Action of Antimicrobial drugs
■ reasonable cost
■ selectively toxic
■ not likely to induce bacterial resistance
Major genera that produce clinically useful
antibiotics
■ Bacillus
■ Streptomyces
■ Cephalosporium
■ Penicillium
Major targets of antimicrobial activity
■ Cell wall synthesis
o penicillins, cephalosporins (beta-lactamase
producing bacteria resistant to both, require
active cell wall synthesis in actively growing
cultures), bacitracin
■ Cell membrane function
o amphotericin B (no growth requirement,
changes membrane permeability by binding to
sterols in fungal membranes, more side effects
since membranes similar in all cells)
■ Protein synthesis
o Aminoglycides, tetracyclines, chloramphenicol
■ DNA synthesis Translation (mRNA--> protein):
o Transcription: rifampin (TB), actinomycin D
§ Block movement of ribosome along
mRNA: streptomycin, tetracycline
§ Prevent peptide bond formation by
binding to ribosome: chloramphenicol,
erythromycin
■ Antimetabolites (structural analogs of natural
substances important in metabolism): PASA, sulfa
drugs, INH
o PASA very similar in structure to PABA,
required by bacteria (but not human cells) for
synthesis of folic acid
o When PASA is used in synthesis of folic acid,
results in nonfuctional folic acid analog and
bacterial cell dies

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Antibacterial Antibiotics Definitions
Inhibitors of Cell Wall Synthesis ■ MIC Minimal inhibitory concentration
■ Penicillin ■ MBC Minimal bactericidal concentration
o Natural penicillins
o Semisynthetic penicillins Broth Dilution Test
■ Penicilinase-resistant penicillins
■ Extended-spectrum penicillins
■ Penicillins + β-lactamase inhibitors
■ Carbapenems
■ Monobactam
■ Cephalosporins
o 2nd, 3rd, and 4th generations more effective
against gram-negatives
■ Polypeptide antibiotics
o Bacitracin
§ Topical application
§ Against gram-positives
o Vancomycin
§ Glycopeptide
§ Important "last line" against antibiotic
resistant S. aureus

Antibacterial Antibiotics
Inhibitors of Protein Synthesis Antibiotic Resistance
■ Chloramphenicol § A variety of mutations can lead to antibiotic
o Broad spectrum resistance.
§ Binds 50S subunit, inhibits peptide bond § Mechanisms of antibiotic resistance
formation 1. Enzymatic destruction of drug
■ Aminoglycosides 2. Prevention of penetration of drug
o Streptomycin, neomycin, gentamycin 3. Alteration of drug's target site
§ Broad spectrum 4. Rapid ejection of the drug
o Changes shape of 30S subunit
§ Resistance genes are often on plasmids or
■ Tetracyclines
o Broad spectrum transposons that can be transferred between bacteria.
§ Interferes with tRNA attachment § Misuse of antibiotics selects for resistance mutants.
■ Macrolides Misuse includes:
o Gram-positives • Using outdated, weakened antibiotics
§ Binds 50S, prevents translocation
• Using antibiotics for the common cold and other
■ Erythromycin
inappropriate conditions
o Gram-positives
§ Binds 50S, prevents translocation • Use of antibiotics in animal feed
• Failure to complete the prescribed regimen
Disk Diffusion Test • Using someone else's leftover prescription

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– Protease inhibitors interfere with an enzyme
HIV needs in its replication cycle
• Inhibition of Nucleic Acid Synthesis
– Several drugs block DNA replication or
mRNA transcription
– Drugs often affect both eukaryotic and
prokaryotic cells
– Not normally used to treat infections
– Used in research and perhaps to slow cancer
cell replication
– Nucleotide or nucleoside analogs
o Interfere with function of nucleic acids
Effects of Combinations of Drugs o Distort shapes of nucleic acid molecules
■ Synergism occurs when the effect of two drugs and prevent further replication,
together is greater than the effect of either alone. transcription, or translation
■ Antagonism occurs when the effect of two drugs o Most often used against viruses
together is less than the effect of either alone. o Effective against rapidly dividing cancer
cells
– Quinolones and fluoroquinolones
o Act against prokaryotic DNA gyrase
– Inhibitors of RNA polymerase during
transcription
– Reverse transcriptase inhibitors
o Act against an enzyme HIV uses in its
replication cycle
o Do not harm people because humans lack
reverse transcriptase
• Prevention of Virus Attachment
– Attachment antagonists block viral
attachment or receptor proteins
– New area of antimicrobial drug development
The Future of Chemotherapeutic Agents
• Antimicrobial peptides Clinical Considerations in Prescribing Antimicrobial
o Broad spectrum antibiotics from plants and Drugs
animals • Ideal Antimicrobial Agent
§ Squalamine (sharks) – Readily available
§ Protegrin (pigs)
– Inexpensive
§ Magainin (frogs)
– Chemically stable
• Antisense agents
– Easily administered
o Complementary DNA or peptide nucleic acids that
– Nontoxic and nonallergenic
binds to a pathogen's virulence gene(s) and
– Selectively toxic against wide range of pathogens
prevents transcription
• Safety and Side Effects
Mechanisms of Antimicrobial Action – Toxicity
• Inhibition of Metabolic Pathways o Cause of many adverse reactions poorly
– Antiviral agents can target unique aspects of viral understood
metabolism o Drugs may be toxic to kidneys, liver, or
o Amantadine, rimantadine, and weak organic nerves
bases prevent viral uncoating
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o Consideration needed when prescribing drugs Most Commonly Prescribed Antifungal and Antiviral
to pregnant women Medications
– Allergies ANTIVIRALS
o Allergic reactions are rare but may be life Influenza:
threatening • Oseltamivir
o Anaphylactic shock Herpes Simplex/ Herpes Zoster:
• Acyclovir
Resistance to Antimicrobial Drugs • Valacyclovir
• Mechanisms of Resistance • Famciclovir
– At least seven mechanisms of microbial
resistance VIRAL UPPER RESPIRATORY INFECTIONS OR
o Produce enzyme that destroys or “THE COMMON COLD”
deactivates drug — Virus replicates in upper respiratory epithelium,
o Slow or prevent entry of drug into the cell sloughs of superficial cells which leads to virus
o Alter target of drug so it binds less shedding
effectively o Caused by more than 200 viruses
o Alter their metabolic chemistry
• Rhinovirus, influenza, coronavirus, respiratory
o Pump antimicrobial drug out of the cell
syncytial virus, etc.
before it
o Virus replicates and “sheds”
can act
• Symptoms and shedding usually last 3-7 days
o Biofilms retard drug diffusion and slow
• Most contagious the day before fever begins
metabolic rate
through 24 hours after fever ends
o Mycobacterium tuberculosis produces
o Symptoms
MfpA protein
• Nasal congestion, non-productive cough, fever,
• Multiple Resistance and Cross Resistance
muscle aches, sore throat
– Pathogen can acquire resistance to more
than one drug
WHEN TO TREAT THE COMMON COLD?
– Common when R-plasmids exchanged
– Develop in hospitals and nursing homes • Empiric use of antibiotics
o Constant use of drugs eliminates sensitive o More harm than good? Unnecessary adverse
cells effects? Increase bacterial resistance?
– Superbugs • “My snot’s yellowish-green, not clear. Is it
– Cross resistance bacterial?”
• Retarding Resistance • Should we culture, and is it an infection or normal
– Use antimicrobials only when necessary colonization?
– Develop new variations of existing drugs o Cultures may take a few days to return from lab, pt
o Second-generation drugs often already has begun antibiotic treatment
o Third-generation drugs o Rapid tests for influenza- results in 1 hr
– Search for new antibiotics, semisynthetics, § Can’t use if symptoms > 3 days, or recent
and synthetics LAIV
o Bacteriocins § False negatives and low sensitivity
o Design drugs complementary to the § Expensive
shape of microbial proteins to inhibit • Antibiotic therapy does help those infections with a
them positive culture for the “big three” bacterial suspects
o H. influenzae, M. catarrhalis, or S. pneumoniae
• Antibiotics are important to prevent secondary
infections
o Pneumonia, otitis media, bronchitis, sinusitis
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§ LAIV nasal vs. IM § Defined by CDC as high risk populations, more at
§ Most viral infections have a resolution of symptoms risk from complications of influenza
in 3-7 days and fully clear within 1-2 weeks. § Pregnancy category C
Bacterial infections can clear as well but may § No spleen, can’t remove capsulated bacteria- risk
require antibiotics if they do not appear to be for secondary bacterial infection
clearing on their own, are associated with too many § Empirically-without laboratory confirmation
symptoms, or are in an individual with many
ANTIVIRALS FOR INFLUENZA
comorbid conditions.
¢ Oseltamivir (Tamiflu®)
§ colored nasal discharge is a normal self-limited
— Oral capsule
phase of the uncomplicated common cold. Treating
— Oral suspension
with antibiotics in clinical trials does reduce the
risk of persistent purulent discharge but adverse MECHANISM OF ACTION
effects of antibiotics outweighed benefit of o Oseltamivir: inhibits influenza virus neuraminidase
treatment. which stops viral particle release
§ Some of us are natural colonizers of the big three o LAYMEN’s terms: prevents the infected host cell
bugs that cause complications of the common cold: from releasing new virus
H. influenzae, M. catarrhalis, or S. pneumoniae. So OSELTAMIVIR INDICATIONS
is it a positive culture or was always there? There is
still controversy regarding whether diagnostic tests Prophylaxis Treatment
and treatment for influenza are cost-effective in
¢  Influenza A & B ¢  Influenza A & B
healthy individuals who will likely resolve
¢  H1N1 ¢  H1N1
anyways. Diagnostic tests are expensive and many
¢  Avian (H5N1) ¢  Avian (H5N1)
patients present after the time period If we take a
culture and send the patient home on antibiotics
¢  Prophylaxis should begin ¢  Treatment should begin
then it comes back viral what do we do? Tell them 24-48hr after exposure for ASAP, or 12-48 hr after onset
best effect of symptoms
to stop antibiotics, unforeseen risks of developing
¢  Continue for 10 days ¢  Continue for 5 days
resistance either way?
¢  QD therapy ¢  BID therapy
§ Each situation must be weighed individually for ¢  Prophylaxis is NOT ¢  Oseltamivir resistance?
risk vs. benefit. Generally all treatment should be replacement for vaccine —  Zanamivir

symptomatic (fluids, APAP for fever, etc) unless a

secondary bacterial infection is suspected. § Prophylaxis can continue for longer than 10 days in
immunocompromised individuals or in H1N1 if they
WHEN TO PROPHYLAX/TREAT INFLUENZA have continued exposure. (Continue 10 days past last
WITH AN ANTIVIRAL? exposure)
o High risk populations: § There are oseltamivir resistant influenza strains
— ≥65 years old particularly with Influenza A strain. Pandemic H1N1
— Pregnant women less resistant than seasonal H1N1 There is another
— Chronic medical conditions neuraminidase inhibitor Zanamivir (nasal inhalation)
§ Diabetes, asthma, COPD, cardiovascular that can be used and has shown less resistance. There
disease, etc is also a class of antivirals called adamantanes which
— Asplenic patients includes amantadine and rimantadine but they are
— Influenza requiring hospitalization only effective against Influenza A.
o Prevent outbreak
— Nursing homes, long-term care facilities, OSELTAMIVIR PATIENT INFORMATION
correctional facilities Administration:
— Take with or without food
§ Influenza A gains resistance very quickly, don’t
o Food may decrease GI upset
want to use in everyone
— Suspension:

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o Shake well — Famciclovir: Prodrug converted to penciclovir (acts
o Store in fridge similarly to acyclovir)
Contraindications LAYMEN’s terms: interferes with viral DNA
o No live vaccines w/in 2 weeks before or 48 replication by terminating the DNA chain
hours after
What to expect:
— Improvement of symptoms
— May shorten duration of flu symptoms by 1-3 days
— May decrease risk of transmission to others
— Reduction in secondary antibiotic use

HERPES INFECTIONS
¢ HSV1
— Herpes labialis or “cold
sores”, fever blisters
— HSV2
§ Prodrug- administered in inactive form and is
— Genital herpes
activated in the body by metabolism or some
— Acquired through sexual contact, lifelong
other metabolic process to the active drug
recurrent infection
— Can by asymptomatic, still transmissible
INDICATIONS
¢ Herpes Zoster
o Acyclovir
— Varicella zoster virus
— Herpes Labialis (topical)
— Causes chicken pox in
— Genital Herpes
children, shingles, and
§ Initial, Recurrent, Chronic Suppression
postherpetic neuralgia
— Herpes Zoster (shingles)
— Varicella-zoster (chicken-pox)
§ HSV1- what learned from OTC
o Valacyclovir
§ Postherpetic neuralgia is pain after shingles
— Herpes Labialis
— Genital Herpes
ANTIVIRALS FOR HERPES INFECTIONS
§ Initial, Recurrent, Reduction of
¢ Acyclovir (Zovirax®)
Transmission, Chronic Suppression
• Oral capsule, tablet, and IV
— Herpes Zoster
• Oral suspension — Varicella-zoster
• Topical cream, ointment o Famciclovir
¢ Valacyclovir (Valtrex®) — Herpes Labialis
• Oral tablet — Genital Herpes
¢ Famciclovir (Famvir®) § Initial, Recurrent, Chronic Suppression
• Oral tablet — Herpes Zoster

§ Acyclovir is only one available topically. Topical use § Note that Famciclovir is not approved to be used in
should only be for Shingles or cold sores. CDC chickenpox in children
discourages topical acyclovir use for genital herpes
except in immunocompromised individuals COMMON COUNSELING POINTS
• Take with or without food
MECHANISM OF ACTION • Take with extra fluids
¢ Acyclovir: acts as a purine nucleotide analog to — Tell patients to drink enough to urinate every few
interfere with herpes viral DNA polymerase hours
— Valacylovir: Prodrug converted to acyclovir
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• Topical application: § Superficial involves the skin, hair and nails. Does
— Use gloves, wash hands anyone remember another name for onychomycosis?
— Cover lesion, rub on gently (tinea unguium) All tinea infections can be treated
• Adverse Effects with oral medication: topically except….. Capitus and onychomycosis
— Headache, fatigue § Subcutaneous is confined to the dermis or adjacent
— N/V/D/constipation structures, very rare unless in tropical or exotic
¢ More SE with Herpes Zoster treatment locations
(increased dose) § Sebborrheic dermatitis: inflammatory condition,
overproduction of cells and sebum, overgrowth of
§ Shingles lesions or genital lesions normal skin fungus (yeast). Dandruff is a symptom of
§ Eliminated completely by kidneys, will prevent kidney sebborrheic dermatitis but not all dandruff is caused by
problems fungal overgrowth. Dandruff is always confined to
scalp, whereas s.d. can be around nose and eyebrows
SPECIFIC PATIENT INFORMATION as well.
o Valacyclovir and famciclovir have longer half-lives § Do you remember some OTC treatments:
than acyclovir, take less frequently clotrimazole cream and tablet, miconazole. When
— Example: Acyclovir 5 times a day x 5 days would someone have complicated yeast infection?
Valacyclovir 2 times a day x 3 days Diabetes (high blood sugar, yeast may flourished),
— May increase patient adherence to chronic med immunocompromised, pregnancy, recurrent infxn.
o Acyclovir and valacyclovir § Oral and topical treatment are therapeutically
— Drug-Drug Interaction with probenicid equivalent, oral preferred due to convenience
— May increase levels of these antivirals, increase
side effects FUNGAL INFECTIONS, CONT.
¢ Oropharyngeal (thrush) and Esophageal candidiasis
§ Acyclovir needs to be taken much more frequently — Infection can spread from oral mucosa into
depending on the infection, anywhere from four to 5 esophagus
times a day for shingles and chickenpox, 2-5 times a o Risk factors include antibiotics, inhaled
day for suppressive therapy in genital herpes steroids, dentures, smoking,
depending on the strength. Valacyclovir and immunocompromised patients
famciclovir are max bid in genital herpes. Systemic and Opportunistic Infections
§ Probenecid: used in gout and some STD treatments. — Can gain entry through GI, lungs, or IV
¢ Systemic candidiasis
ANTIFUNGALS — Can include peritonitis, pneumonia, and others
§ Individuals can be carriers of Candida, and these risk
FUNGAL INFECTIONS factors give the yeast an opportunity to flourish
Superficial Infections § Systemic is an infection involving the whole body,
¢ Tinea (dermatophyte) infections blood and internal organs. Opportunistic is an
— Named for site of infection infection only occurring in immunocompromised
— Tinea pedis, corporis, cruris, capitus, etc individuals such as HIV infected individuals
¢ Onychomycosis § Peritonitis is inflammation of the peritoneum, which is
— Infection of finger/toenails by dermatophytes the tissue that covers the abdominal organs.
¢ Sebborrheic dermatitis
COMMON COUNSELING POINTS
¢ Vaginal candidiasis (yeast infection)
o If taking chronically, explain importance of
— Most common species is C. albicans, though
adherence to prevent outbreaks
other spp are on the rise
— Cost of therapy? Covered by insurance?
— Antibiotic treatment can lead to overgrowth
— Reduction of stressors (may increase risk of
— OTC treatment possible if uncomplicated
outbreak)

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— Pts concerned should know toxicity of long-term OTHER ANTIFUNGALS
therapy is minimal o Terbinafine (Lamisil®)
— Explain that that this is not a cure, give realistic — Oral tablets
expectations — Topicals: cream, gel, solution
o If taking medication episodically for genital herpes, o Nystatin (Nystat-RX®)
take within 24 hours of outbreak symptoms — Oral tablets
(tingling) to suppress or reduce duration and — Oral suspension
severity — Vaginal tablets
— Reduces pain, length of time to healing, viral — Topical powder
shedding
o Practice SAFE SEX
§ Lamisil also OTC for treatment of athletes foot
— Chronic therapy does reduce transmission risk
(tinea pedis) or jock itch and ring worm (tinea
— Use condom, avoid sex during outbreak
corporis, tinea cruris)
ANTIFUNGAL MEDICATIONS § There are multiple brand names for Nystatin. This
o Azoles is just one of them
— Imidazoles: ketoconazole
— Triazoles: fluconazole, itraconazole, MOST COMMON INDICATIONS
voriconazole, posaconazole Tinea Infections (1-4 wks)
o Terbinafine o Ketoconazole § By no means ALL of
o Nystatin the indications that they
o Terbinafine
can be used for.
MECHANISM OF ACTION Onychomycosis (6wks-1yr) Additionally, in each
¢ Triazoles: inhibition of CYP450 enzyme o Itraconazole case the provider must
dependent ergosterol synthesis o Terbinafine have an understanding
¢ Ketoconazole and Terbinafine: interfere with Vaginal Candidiasis (1d-2wks) that the fungi they are
fungal ergosterol biosynthesis o Fluconazole treating will be
¢ Nystatin: binds to sterols in cell membrane and o Nystatin susceptible to the drug,
changes permeability otherwise resistance
Oropharyngeal Candidiasis
will prevent treatment.
¢ LAYMEN’s terms: prevents proper production of (7-14d) Resistance will likely
fungal cell membrane resulting in cell death o Fluconazole lead to reoccurrence
§ Ergosterol is main sterol component of fungal cell o Itraconazole and treatment failure.
o Nystatin § Ketoconazole is not
membranes, inhibiting production of this allows
Esophageal Candidiasis often used systemically
increased permeability and leakage because the other azoles
§ Disruptions in the biosynthesis of ergosterol cause (14-21d)
because have less drug
significant damage to the cell membrane by increasing o Fluconazole interactions, higher
its permeability, resulting in cell lysis and death. o Itraconazole safety profiles, and
Despite this mechanism of action, the triazoles are o Voriconazole higher efficacy for
generally considered fungistatic against Candida Systemic Infections invasive infections
species. o Fluconazole
o Voriconazole
AZOLES o Nystatin
o Ketoconazole (Nizoral®)
— Oral tablet & topicals: cream, gel, shampoo, foam PATIENT INFORMATION FOR ALL
— Fluconazole (Diflucan®) ANTIFUNGALS
— Oral tablet and IV ¢ Administration
o Itraconazole (Sporanox®) — Superficial fungal infections may take a LONG
— Oral capsule time to effectively treat (weeks to months)
o Voriconazole (VFEND®) o Exception-Fluconazole for vaginal yeast
— Oral tablet and IV infection
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— Important to counsel on adherence and time to How do bacteria become resistant to antibiotics?
effect
o Onychomycosis
¢ Side Effects
— Oral: Headache, dizziness, changes in taste
— GI upset: N/V/D
o Can take with food to prevent
§ Exception- take voriconazole 1-2 hrs before
meal
— Topical: Irritation, burning, and dryness
o Reminder to wash hands after administration
§ Counseling is crucial for fungal infections because
patient adherence is directly linked to therapeutic
outcome. If the patient has realistic goals initially,
that there will be slow improvement over time, they
are more likely to follow-through with therapy than
give up after a week with no change. In
onychomycosis which takes months to treat due to
Mechanisms Responsible for Resistance to
slow growing toenails, let the patient know that
Antimicrobial Drugs Include the Following:
sometimes the nail will not return to normal
• Resistance to antibiotics can be caused by four
appearance even when the fungus has been
general mechanisms:
eradicated.
Ø Inactivation or modification of antibiotic;
§ Fluconazole for vaginal yeast infection is a one
inactivating enzymes that destroy the drug (e.g., β-
time dose, flu has half-life of 30 hours, vaginal
lactamases).
concentrations are roughly equivalent to plasma.
Ø Decreased drug accumulation (e.g., tet).
Symptoms begin to improve in 24 hours
Ø Altering the target site/binding site that reduces its
§ Itraconazole capsules should be taken with food to
binding capacity (e.g., aminoglycosides and
increase absorption
erythromycin).
§ Voriconazole should be taken 1-2 hours before
Ø The modification/development of alternative
food to maximize absorption
metabolic pathways to circumvent the antibiotic
ANTIMICROBIAL RESISTANCE effect: sulphonamides (dihydropteroate synthease)
} The ability of bacteria or other microbes to resist the and trimethoprim (dihydrofolate reductase).
effects of an antibiotic. Ø The reduced intracellular antibiotic accumulation by
} Antibiotic resistance occurs when bacteria change in decreasing permeability and/or increasing active
some way that reduces or eliminates the effectiveness efflux of the antibiotic.
of drugs, chemicals, or other agents designed to cure
Drug inactivation or modification
or prevent infections.
• for example, enzymatic deactivation of penicillin G
} The bacteria survive and continue to multiply causing
in some penicillin-resistant bacteria through the
more harm. production of B-lactames.
Why are bacteria becoming resistant to antibiotics? • Most commonly, the protective enzymes produced
} Antibiotic use promotes development of antibiotic- by the bacterial cell will add an acetyl or phosphate
resistant bacteria. Every time a person takes group to a specific site on the antibiotic, which will
antibiotics, sensitive bacteria are killed, but resistant reduce its ability to bind to the bacterial ribosomes
germs may be left to grow and multiply, and disrupt protein synthesis.
} Repeated and improper uses of antibiotics are
primary causes of the increase in drug-resistant
bacteria.
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Alteration of target site Penicillin – beta lactamase inhibitor combinations
• for example, alteration PBP – the binding target site • Amphicillin – sulbactan (unasyn) – used in
of penicillins-in MRSA and other penicillin-resistant infections that are caused by bacteria that are
bacteria. resistant to beta-lactam antibiotics
• Another protective mechanism found among bacterial Things to consider
species is ribosomal protection proteins.
• Oral penicillin should be taken with 6-8 ounces of
• These proteins protect the bacterial cell from
antibiotics that target the cell’s ribosomes to inhibit water. Do not take with acidic fluids as these will
protein synthesis. destroy the drug.
• The mechanism involves the binding of the ribosomal • Oral penicillin should be taken on an empty
protection proteins to the ribosomes of the bacterial stomach for best absorption. The following can be
cell, which in turn changes its conformational shape. taken with or without food: penicillin V (Pen Vee
• This allows the ribosomes to continue synthesizing K), amoxicillin (Amoxicillin – amoxil),
proteins essential to the cell while preventing
clavulanate – augmentin, and bicampicillin –
antibiotics from binding to the ribosome to inhibit
protein synthesis. spectrobid)
• Take full course of medication.
Alteration of metabolic pathway
• Take at evenly spaced interval around the clock to
• for example, some sulfonamide-resistant bacteria do
not require para-aminobenzoic acid (PABA), an maintain blood levels
important precursor for the synthesis of folic • Should not be taken if a previous allergic reaction
acid and nucleic acids in bacteria inhibited by has been experienced
sulfonamides, instead, like mammalian cells, they • Liquid penicillin should be shaken well before
turn to using preformed folic acid. taken
Reduced drug accumulation Cephalosporins
• By decreasing drug permeability or increasing • Bactericidal and posses low toxicity
active efflux (pumping out) of the drugs across the
• They have 4 generations
cell surface.
• Well distributed to most body tissues and fluids &
• These specialized pumps can be found within the
cellular membrane of certain bacterial species and are eliminated by the kidney
used to pump antibiotics out of the cell before they Cephalosporins – broad spectrum & used to kill both
are able to do any damage. These efflux pumps are gram+ and gram - bacteria
often activated by a specific substrate associated with
• First generation – ( Cefazolin sodium – Ancef ) –
an antibiotic.
effective against Streptococci and staphylococci .
Used for infections of soft tissue, bone, skin, urinary
and biliary tracts, bactermia and endocarditis
• Also used for surgical prophylaxis
Second generation
• Cefoxitin sodium ( mefoxin )- effective against
• gram – negative bacteria
• Used for infections of urinary tract , skin , bone ,
joints , lower respiratory & septicemia
• Also used for surgical prophylaxis in orthopedic and
cardiovascular surgery and gynecological infections
Third generation
• Greater activity against gram –negative bacteria
• Ceftazidime ( fortaz ) – effective against citrobacter ,
serratia , providencia , enetrobacter, haemophiluz
influenzae , n. meningitidis

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Fourth generation • Drug of choice for acne, Rocky mountain spotted
• Cefepine ( maxipime ) – effective against fever, cholera , typhus ,chanchroid, trachoma , lyme
staphylococci & streptococci diease and gastric infections to helicobacter pylori
• Used for infections of the skin and urinary tract and • Well distributed in body fluids and tissues except in
in pneumonia CSF
Aminoglycosides • They act by inhibiting protein synthesis in bacteria by
attaching to the 30s ribosomes unit , which in turn
prevents the binding of transfer RNA to messenger
RNA ( the process impedes the function of bacteria )
Prototype drug and Related Drugs
Action of the drugs Tetracycline (Acromycin)
• Interfere with protein synthesis • Demeclocycline (declomycin)
• Enter bacterial cell walls and bind to 30S and 50S • Doxycycline (Vibramycin)
ribosomes (important for protein synthesis) • Minocycline (minocin)
• As this process is disturbed, cells cannot live • Oxytetracycline (terramycin)

Aminoglycosides Reminders
• Natural as well as synthetic, bactericidal antibiotics • Each dose should be taken with 8 ounces of water
• Usually used against gram –negative bacteria • Take on empty stomach
(aerobic – Proteus, Klebsiella , E. coli, • Cannot be taken with or within 2 hours of antacids ,
Pseudomonas) iron preparations or dairy products
• Parenteral administration provides good absorption • Avoid exposure to sun
of drug, poorly absorbed orally Macrolides
• Can also be used to cleanse the tract before bowel • Used primarily for gram-positive bacterial
surgery infections.
• Reserved to treat serious infections due to its • Erythromycin is the drug of choice for the treatment
powerful side effects of pertussis , diptheriae, chlamydia & urethritis
• Frequent monitoring is necessary • When combined with rifampin (rifadin) is the
Prototype drug and related drugs treatment of choice for legionnaires disease
Gentamycin (garamycin) • It is a good substitute for clients who are allergic to
• Amikacin (amikin) penicillin
• Kanamycin • The opthalmic preparation is contraindicated in
• Neomycin fungal, viral and mycobacterial eye infections
• Netilmicin (netromycin) • Should be taken on empty stomach
• Paromomycin (humatin) Fluoroquinolones
• Streptomycin • Has powerful bactericidal effect but having few
• Tobramycin (nebcin) adverse effects
Reminders • Can be given orally, parenterally & topically
• Should not be taken if previous allergic reaction has • Well absorbed by G I tract & well distributed in the
been experienced body
• Oral form should be taken on an empty stomach • Kill bacteria by changing their DNA , they interfere
• Take full course of medication with DNA gyrase which is an enzyme needed to
synthesize bacterial DNA
Tetracyclines
• They are useful in the treatment of multidrug
• Composed of 3 drugs derived from soil mold
resistant tuberculosis, gonorrhea , infections due
(Streptomyces genus of actinobacteria)
AIDS, fever in clients with cancer with nuetrophenia

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VGFV - 2/2/17
Prototype drug and related drug Antifungals
Ciprofloxacin (Cipro) • Used to treat infections due to fungi (mold & yeast)
• Alatrofloxacin • They may cause systemic & superficial infection
• Enoxacin • Treatment maybe for extended time
• Gatifloxacin • Act by changing the permeability of the cell wall
• Levofloxacin • Treatment of the following fungal infections:
• Lomefloxacin aspergillosis , blastomycosis, cryptococcal
• Moxifloxacin meningitis, histoplasmosis , moniliosis ,tinea
• Norfloxacin infections & candida infections
• Orfloxacin
Antifungals
• Sparfloxacin
Prototype Related Drug
• Trovafloxacin drug drugs classification
Vancomycin (glycopeptide)
Amphoterecin Nystatin/ Systemic
• Have only one member vancomycin (vancocin) B ( fungizone ) griseofulvin antifungals
• Can produce severe toxic effects
• Given IV since orally has poor absorption Fluconazole Clotrimazole/ Azoles
• Prevents cell wall synthesis in bacteria (diflucan) ketoconazole
• Drug of choice for pseudomembranous colitis caused
No prototype Tolnaftate/ topicals
by C. defficile haloprogin
Antitubercular drugs
Prototype drug Related drugs Drug Antimalarials
classification • Antimalarials depend on the family of chemical
isoniazid ethambutol Antitubercular agents with which they associated, attaches to
agents
nucleoproteins and interrupts protein synthesis.
ethionamide
• It also prevents reproduction by interfering with DNA
pyrazinamide and RNA polymerase and interferes with the
parasite’s ability to use erythrocyte hemoglobin
rifampin

streptomycin aminoglycoside Antiprotozoals

Prototype Related Drug
Antivirals drug drugs classification
• They prevent viruses from reproducing and this Chloroquine Hydroxychloro antimalarials
allows the body’s immune system to kill them ( aralen ) quine/ quinine
• Virus lives in the human cells by placing its own
RNA or DNA into a healthy cells thus gaining
control of the cell Metronidazole Pentamidine/ antiprotozoals
( flagyl ) tinidazole
Antiviral drugs
Prototype drug Related drugs Drug
classification Antihelmintics
Rimantadine Amantadine Drugs for • Works on various metabolic processes in the specific
( flumadine ) (symmetrel) influenzae worm.
Acyclovir ( zovirax ) Cidofovir ( Vistide ) Drugs for CMV and
• The prototype drug, mebendazole (vermox) prevents
herpes
Saquinavir Amprenavir Protease inhibitors the uptake of glucose and other and other nutrients
(fortovase ) ( agenerase) which in turn prevents reproduction
Zidovudine Abacavir ( ziagen ) Nucleoside reverse
(retrovir) transcriptase
inhibitors
Nevirapine Delaviridine Non-nucleoside
(viramune) ( rescriptor ) reverse 14
transcriptase
inhibitors
 Prototype drug Related drugs Drug
VGFV - 2/2/17 classification
• Combat infections caused by flukes, tapeworms and Imipramine Amitriptyline Tricyclic
roundworms. (tofranil) (Elavil)/ antidepressants
nortriptyline
Alpha-Adrenergic Blocking agents (alpha blockers) Phenelzin Isocarboxazid Monoamine
• Blocks the effects of the cathecolamines epinephrine (nardil) (marplan) oxidase
and norepinephrine on alpha-adrenergic receptors on inhibitors
the autonomic nervous system, preventing the Fluoxetine Sertraline (zoloft) Selective
vasoconstriction normally caused by cathecolamines (prozac) serotonin
• Primary action is the smooth muscle of the blood reuptake
inhibitors
vessel wall-causing relaxation of the wall thus
Bupropion Trazodone Miscellaneous
increasing blood flow
(wellbutrin) (desyrel) antidepressants
• Used to treat blood vessel spasm
Antiseizure drugs
• Treat hypertension and sweating caused by
• Are used to control seizures but not to cure the cause
pheochromocytoma (tumor in the adrenal medulla)
of the seizures
Analgesics • The first drug to treat tonic-clonic seizures effectively
• Are drugs that help to alleviate pain without loss of was Phenobarbital (luminal)
consciousness • The objective of the drug is to remove or decrease
• Opioid analgesics were originally obtained from the seizure activity while causing few side effects
opium plant • Adjunct antiseizures drugs – used in combination
• There are 3 groups of opioid analgesics that interact with other antiseizure drugs to treat partial seizures,
with opioid receptors to bring pain relief simple or complex absence seizures and Lennox-
• Opioid agonist – stimulate the activity of opioid Gastaut syndrome
receptors sites in the body An#seizure drugs
• Opioid agonists- antagonist, obstruct some receptors Prototype drugs Related drugs Drug classification
sites and stimulate others (less addictive) Phenytoin ( dilantin ) Ethotoin ( peganone ) hydantoins
• Opioid antagonist – reverse the effects of the opioids Phenobarbital Mephobarbital Barbiturates and
( luminal ) ( mebaral ) / barbiturate like drugs
and are given for opioid overdose primadone ( mysoline
Analgesics Diazepam ( valium ) Clonazepam benzodiazepines
(klonopin)/
Prototype drug Related drugs Drug clorazepate
classification ( tranxene )
Morphine ( roxanol) Codeine / fentanyl/ Opioid agonist Ethosuximide Methusuximide succinimides
levorphaol/ ( zarontin ) ( celontin )
meperidine - Carbamazepines Oxcarbazepine Miscellaneous anti-
demerol ( tegretol ) ( trileptal ) seizure drugs
Pentazocine Buprenorphine Opioid agonist- Valproic acid Adjunct antiseizure
(talwin) (buprenex) antagonist (depakene)/ drugs
Butorphanol Nalbuphine Opioid agonist- gabapentin
(stadol) (nubain) antagonist ( neurontin )

Naloxone (narcan) Nalmefene (revex) Opioid antagonist

Anesthetics
Acetaminophen No related drug Nonopiod • General anesthetics – used for surgical procedures
(tylenol) analgesic involving major body parts or systems and for
Antidepressants certain invasive procedures
• Drug used to treat depression • Local anesthetics – are used in situations when
• They activated the CNS and disguised the clients generalized CNS depression is not warranted
depressed behavior but has the potential to be abused (suture, lacerations)
• They also help regulate sleep and appetite, enhance • Are group of drugs that result in differing amounts
mental alertness and lessen suicidal thoughts of loss of sensation in the body

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VGFV - 2/2/17
• There are 2 groups: general anesthetics and local • Benzodiazepines is safer than barbiturates
anesthetics • Representative drugs are phenobarbital
• General anesthetics are able to produce amnesia, (luminal), Diazepam (valium)
analgesia and unconsciousness by creating
Antipsychotics
widespread depression in the CNS. They are given
• Are used to treat disease that interferes with thought
parentally or by inhalation
processes
• Local anesthetics are able to block sensation in a
• They are also called neuroleptic agents due to their
specific area of the body.
neurologic side effects and at one time major
• Lidocaine (xylocaine) is the most widely use local
tranquilizers
anesthetics
• Two types are: typical and atypical antipsychotics
• These drugs are potent nerve blockers and cause
• Typical antipsychotics have been used for the past
toxicity if they were absorbed systematically
50 years and considered principal drug for
5 types of local anesthetics schizophrenia
• Topical • Atypical antipsychotics are newer drugs and have
• Infiltration low side effects
• Nerve block • Eskalith (lithium) is a mood stabilizer used to treat
• Epidural mood swings in bipolar disorder
• Spinal
• Representative drugs are chlorpromazine (thorazine)
Prototype Drugs: Thiopenta (pentothal), halothane
(nitrous oxide – laughing gas), Lidocaine which is typical antipsychotics & clozapine (clorazil)
is atypical antipsychotics
Antacids
• Examples: aluminum hydroxide and magnesium Antianemics
hydroxide, calcium carbonate and sodium • Iron salts – ferrous fumarate, ferrous gluconate,
bicarbonate ferrous sulfate
• Partially neutralize gastric acids thereby raising the • Water soluble vitamins – cyanocobalamin, folic
pH acid, hyrdroxocobalamin
• Inactivate pepsin when pH gets above 4
• Used to treat peptic ulcer or due to stress, Anemia
indigestion, and esophagitis • Disorders characterized by a decreased number of
• Used in treatment of hyperphosphatemia in patient RBC, reduced Hgb and Hct
with chronic renal failure • Caused by increased RBC destruction or decreased
• Aluminum hydroxide – binds with phosphates in production of RBC, due to hepatic, nephrotic or
the bowel, causing phosphates to be excreted. Best cancers.
given after meals because they may bind phosphates • Absorption of iron is decreased when given with
found in saliva antibiotic – tetracyclines, antacids, coffee, tea, milk,
• Aluminum and magnesium hydroxide – mixed or eggs. These all bind to iron causing an insoluble
together to achieve a balance between the compound
constipation caused by aluminum preparations and • Vitamin C – increases the absorption of iron salts
the diarrhea caused by magnesium preparations
Antianginals
Anxiolytic and Sedative Hypnotics • Beta-adrenergic Blockers - atenolol, metoprolol,
• Are drugs that have depressant effects on the central nadolol, propanolol
nervous system • Calcium Channel Blockers – Bepridil, diltiaem,
• Hypnotics caused sleep to occur, while anxiolytics nicardipine, nifedifine, verapamil
and sedatives induce relaxation • Nitrates – erythrityl tetranitrate, isosorbide dinitrate,
• High dose of hypnotics caused sedation, while nitroglycerin, pentaerythritol tetranitrate
anxiolytics & sedative caused sleep

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VGFV - 2/2/17
Action: General Use:
• Angina pectoris is a syndrome characterized by • Group IB and IC suppress and prevent ventricular
sudden chest pain resulting from an imbalance arrhythmias, both acute and chronic where IC useful
between O2 supply and demand of heart muscle for atrial arrhythmias
• Arteries become pliable due to arterioschlerosis – • Group II – are beta adrenergic blockers, which slow
lessing the blood flow to heart muscle leading to MI ventricular rates in patients with atrial flutter & atria;
Beta-adrenergic blockers fibrillation. Effective in the treatment of
tachycardias activated in the bundle branches.
• Make the heart more resistant to the effects of
cathecolamines such a sepinephrine and • Bretylium (Group III) is used in life threatening
norephinephrine ventricular arrhythmias that have not responded to
• Decreases heart rate and oxygen consumption lidocaine and procainamide
• Verapamil (Group IV) – used primarily to correct
Calcium Channel Blockers the rapid heart rate of paroxysmal supraventricular
• Relieve angina by dilating coronary arteries and tachycardia
preventing vasopasm
• Dilate peripheral arteries, lessening afterload and Anticholinergic drugs
decreasing oxygen demand on heart muscle • Interfere or block the effects of acetylcholine (Ach)
Nitrates in the parasympathetic nervous system (PSNS)
• Universal vasodilators • They are also called parasympatholytics or
• Act directly on coronary blood vessels to cause cholinergic blockers
dilation and also decrease afterload by causing • These drugs vie with Ach to attach to the muscarinic
peripheral vasodilation receptors in the PSNS. After they affix themselves to
• Their action relieve anginal pain these receptors, nerve transmission is interrupted.
• Sublingual forms work within seconds to dilate • Atropine is the representative drug
coronary arteries and reduce pain
Individual Agents:
Interactions:
• Atropine, benztropine, cyclopentolate,
• May cause hypotension when used with
glycopyrrolate, propantheline, scopolamine,
antihypertensive agents
trihexyphenidyl
• Ingestion with large amount of alcohols will cause a
• Atropine – used primarily to treat bradycardia
shard drop in blood pressure
• Scopolamine – used to control the nausea and
Antiarrhythmics vomiting related to motion sickness and vertigo
• Group IA – disopyramide, procainamaide,
quinidine
• Group IB – lidocaine, mexiletine, phenytoin,
tocainide
• Group IC – flecainide, propafenone
• Group II – acebutolol, esmolol, propanolol
• Group III – amiodarone, bretylium
• Group IV - verapamil
Action:
• Arrhythmias characterized by any deviation from the
normal rate or rhythm of the heart
• Abnormal rhythms after occur after a heart attack or
cardiac surgery
• Antiarrhythmic are used to treat and prevent
disorders of cardiac rhythm
17