Microbiology Lecture Notes: Chemotherapeutic Agents: Antimicrobials and
Antibiotics
Dr. Weis
Definitions:
Chemotherapeutic agents are chemical substances that are used for therapeutic purposes in the body.
Antimicrobials any agent such as a natural or synthetic substances that affect microorganisms by killing or suppression
Antibiotic: a substance that is produced by a microorganism that inhibits another microorganism.
Synthetic drugs are antimicrobial drugs synthesized by chemical procedures in the laboratory.
Selective toxicity is the ability of a drug to injure a target cell/organism without injuring non target cells/organisms
I. History
1930s Penicillin: Alexander Flemming
1940s Streptomycin
1950s CHPC
1960s Cephalosporins
1980s Quinolones
II. Sources for Antimicrobials
Molds / Fungi/ Bacteria
Synthetic : Sulfa drugs
Semisynthetic: pencillins (oxacillin, ampicillin, amoxicillin, carbapenem)
Examples of Antibiotic sources:
Bacteria
Actinomycetes (Streptomyces -> filamentous bacteria)
* CHPC
* Tetracyclines
* -mycin drugs
Bacillus species
* topical drugs : bacitracin, polymyxin
Fungi
Penicillium: penicillin, griseofulvin
Cephalosporium: cephalosporins
Many drugs are available that are effective against prokaryotic cells, since they do not affect eukaryotic cells due to the difference in presence of cell wall, ribosomes, and metabolism.
III. Chemical Classification
Antibiotics
A. Penicillin -cillin
e.g. penicillin G, penicillin V, nafcillin, oxacillin, ampicillin, amoxicillin, carbenicillin, dicloxacillin, methicillin, ticarcillin
B. Cephalosporin cepha-, cefa-
e.g. cephalothin, cefaclor, cefazolin, cephaprin, cefoxitin, cefatriaxone, cefoperazone
C. Aminoglycosides
e.g. streptomycin, neomycin, kanamycin, gentamicin, amikacin, tobramycin
D. Macrolides
e.g. Erythromycin, tylosin, azithromycin, clarithromycin
Semi-synthetic: ketolides
E. Polypeptides
e.g. polymyxin B, vancomycin, bacitracin
F. Tetracyclines
e.g. tetracycline, oxytetracycline (terraymycin), chlortetracycline
semisynthetic: doxycycline, methacycline, minocycine
G. Lincosamides
e.g. lincomycin, clindamycin
H. Antifungals
1. Azoles
Miconazole
Ketaconazole
Clortrimazole
Variconazole
Triazole: Fluconazole, Itraconazole
2. Polyenes
Amphotericin B
3. Nystatin
4. Other
Griseofulvicin
Tolnaftate
I. Quinolones and Fluorquinolones -floxacin
Ciprofloxacin, enterofloxacin, norfloxacin, norfloxacin, Nalidixic acid
Synthetic: moaxifloxacin, gatifloxacin
J. Rifamycins
1. Rifampin
K. Misc.
1. CHPC (chloramphenicol)
2. Isonizid
Other Antimicrobials that are NOT Antibiotics
A. Sulfonamides
e.g. sulfadiazine, sulfamethoxazole, sulfathiazole, sulfacetamide, trimethoprim-sulfamethoxazole
B. Nitrofurans
e.g. nitrofurazone, nifuratel
C. Misc.
Trimethoprim
IV. Method of Action for Antibiotics
Major sites of action are the cell wall, ribosomes, nucleic acids, cell membrane, and metabolites.
1. Inhibition of synthesis of intact peptidoglycan bacterial cell wall
Drugs: Penicillins (natural and semi-synthetic), Cephalosporins, Polypeptides (Bacitracin, Vancomycin), Antimycobacterial (Isoniazid, Ethambutol)
Penicillins: targets synthesis process of active, living cells and prevent the cross linking of the sugars of the peptidoglycan in some of the final stages of cell wall synthesis by binding to the transpeptidase enzymes that add new peptidoglycan monomers and reseal the wall. Lack of linking weakens the wall. They also disinhibit (activate) autolysins which are bacterial enzymes used to break down the wall for synthesis, growth, and division. Disrupting cell wall synthesis and promoting active destruction results in the subsequent osmotic lysis of the bacterium. Molecular targets of the penicillins are known collectively as penicillin-binding proteins (PBPs). PBPs are enzymes located on the outer surface of the bacterial cytoplasmic cell membrane and can include transpeptidases, carboxypeptidases, and endopeptidases. Pencillins must bind to their PBPs to produce their antibacterial effects. PBPs of bacteria differ greatly in size and number and make up less than 1% of the membrane proteins. PBPs also vary greatly in their affinity for the different β-lactams. PBPs are part of the normal membrane proteins of G (+) and G (-) since they are involved in cell wall synthesis during replication processes.
Basic structure of the pencillins is thiazolidine ring (C-S-N), a β-lactam ring (C-N) and a side chain. This common core structure containing a β-lactam ring called the nucleus. The group is differentiated by the chemical side chains attached to their nuclei which determine the spectrum of activity and pharmacological properties (absorption, distribution, elimination). The β-lactam ring is essential for antibacterial properties. Penicillins can be produced naturally or semi-synthetically.
a) Natural Penicillin
Penicillin G: narrow spectrum à Staph, Strep, Spirochetes
IM, Oral, Potentiated (procaine or benzathine)
Penicillin V: narrow spectrum, oral administration
Some bacteria (staph) produce penicillinase that cleaves the β-lactam group at
the C-N bond to open the ring structure to produce penicilloic acid
b) Semisynthetic Penicillins à change or add different side chains to the β-lactam group nucleus that can determine additional pharmacokinetic properties:
1) Affinity for binding to PBPs
2) Resistance to penicillinases
3) Ability to penetrate the G (-) bacteria cell wall through porins
based on size, change and hydrophilic properties
4) Resistance to stomach acids
Penicillinase Resistant: designed to evade the pencillinase of staph
methacillin, oxacillin, nafcillin
Now resistance to methacillin, esp S. aureus (MRSA)
Extended Spectrum: G (+) and many G(-), not penicillinase resistant
Aminopenicillin :Ampicillin, amoxicillin
Carboxypenicllins: carbenicillin, ticarcillin
Ureidopenicllins: mezlocillin, azlocillin
Pencillins + β-lactamase inhibitors (Augmentin)
Combine penicillins with potassium clavulanate which functions as
a noncompetitive inhibitor of pencillinase by binding to the enzyme it forms an intermediate that causes destruction of the enzyme. It has no known antimicrobial activity
Carbapenems (Primaxin)
Changes in the β-lactam: substitutions (C for S, double bond)
Broad spectrum
Monobactams (Aztreonam)
Synthetic antibiotic with only one ring rather than the double ring
Primarily G (-) such as E. coli and
Pseudomonas
Cephalosporins : nucleus of drug resembles pencillin as it contains a modified β-lactam ring, but has a different second ring (thiazolidine 5 member ring is a 6 member ring) and three areas for various R groups which create the different major groups. Cephalosporins are resistant to penicillinase, but are susceptible to β lactamases. Several generations created with each generation having more broad spectrum due to the changes in the R groups, and each successive generation has more spectrum of activity, especially against G (-) bacteria and more resistance to bacterial enzymatic destruction.
Polypeptides
Bacitracin: inhibit cell wall synthesis of linear strands
of the peptidoglycans, an earlier stage than the penicllins and cephalosporins as
it prevents the peptidoglycan precursors from being carried to the cell membrane
to be linked. Drug is synthesized by Bacillus. These drugs are restricted
to topical use for G (+) staphylococcus and streptococcus.
Glycopeptides
Vancomycin: inhibition of cell wall synthesis by binding directly to the cell wall peptides and block the transpeptidase enzymes from cross-linking the sugar chains and blocks transglycolation, the bonding of the NAMs to the NAGs. Results= weak cell wall and subsequent osmotic lysis of the bacterium. It also impairs RNA synthesis. This drug has a narrow spectrum, used as a last line of defense in MRSA
2. Alteration of cell membrane permeability
Permeability changes result in loss of important metabolites.
Drugs: Polymixin B, Nystatin, antifungal drugs
Polymixin B: attach to the phospholipids of the cell membrane and act like detergents
Since they increase cellular permeability to disrupt osmotic integrity
Bacteriocidal, Spectrum G(-), topical
use
Antifungals: bind to the ergosterols in the fungal membrane
3. Inhibition of Protein Synthesis
Based on the difference in bacteria ribosome structure, 70S (50S + 30S)
Most are considered broad spectrum
Drugs are either bacteriocidal or bacteriostatic
Bacteriocidal = abnormal proteins, which are then inserted into the cell wall
Bacteriostatic = inhibition of protein synthesis
Drugs: CHPC, Tetracycline, Aminoglycosides, Macrolides, Lincomycin, Streptogramins, Oxazolidinones
CHPC : acts at the 50S portion to inhibit formation
of peptide bonds of the protein chain.
Broad spectrum but has high toxicity
as it suppresses the bone marrow causing aplastic anemia.
Macrolides: have macrocylic lactone ring, large carbon rings attached to unusual carbohydrates.
Macrolides act at the 50S portion affecting protein synthesis by preventing the elongation of the protein since they inhibit the enzyme that forms peptide bonds between the amino acids and in turn, prevents the ribosome from translocating down the mRNA.
Erythomycin: mainly G(+) bacteria, Not able to penetrate cell walls of most G(-) bacteria.
Broad Spectrum macrolides: azithromycin, clarithromycin
Streptogramins: combination of two cyclic peptides,
attaches to the 50S portion to achieve a synergistic reaction. One portion
of the ring acts at an earlier stage, the other at a later step in protein
synthesis resulting in inhibition of translocation of the ribosome along
the mRNA so that an incomplete peptide chain is released.
Aminoglycosides: Two(+) amino-sugars with glycoside bonds to a ring. They are
transported into the cell via a proton pump via electrochemical gradient
and will bind to the proteins on the smaller ribosomal subunit to affect
the shape of 30S portion of the ribosome. This prevents the 50S subunit from
attaching to the translation initiation complex so that code is read incorrectly
on the mRNA, resulting in tRNA inserting the wrong
amino acids into the protein. Bacteriocidal since
the abnormal protein synthesis causes cell death. Does cause some toxicity to the auditory nerve and the kidneys. Used
for G(-).
Tetracyclines gain entry to the bacteria interior
by way of an energy dependant transport in system used by bacteria. As the
drug accumulates inside the bacteria, it binds to the 30S subunit to distort
it in a way that interferes with the attachment of tRNA anticodons to
the ribosomes, thus preventing addition of amino acids to the growing peptide
chain. Broad Spectrum: used for G(+), G(-), Rickettsia, Chlamydia,
especially for urinary and reproduction infections. Bacteriostatic.
Oxazolidinones: synthetic antibiotic produced
in response to vancomycin resistance. Drug binds
to the 50S subunit of the ribosome at the junction point for the 30S subunit.
Lincomyocins: Bacteriostatic drugs that inhibit protein synthesis by binding to the 50S subunit at a site that overlaps other drugs (CHPC and the macrolides) therefore can antagonize each other effects.
4. Inhibition of Nucleic Acid Synthesis
Interfere with the process of DNA replication and transcription of RNA
Some drugs will also interfere with mammalian DNA and RNA
Drugs: Quinolones, Fluroquinolones, Griseofulvicin, Rifampin, Metronidizole
Rifamycins: Rifampin. Structurally
related to macrolides. Inhibit syntheis of
mRNA. Primary use to treat mycobacteria. Side
effects include orange red color change to body waste fluids.
Quinolones and Fluoroquinolones:
Inhibit activity of topoisomerases. DNA gyrase (topoisomerase II) is need
for the replication of DNA as it breaks and rejoins the strands of bacterial
DNA to relieve the stress that occurs during the unwinding of DNA during
replication and transcription. Not intended for use in growing individuals.
Metronidizole is a drug that is activated by the microbial proteins (flavodoxin and feredoxin) found in microaerophilic and anaerobic bacteria and certain protozoans. Once activated, the drug puts nicks in the microbial DNA strands.
5. Inhibition of synthesis of essential metabolites
Competitive inhibition of enzymatic activity, so that while the enzyme is bound to the drug, it is unable to bind to its natural substrate and that blocks that step in the metabolic pathway to disrupt biochemical synthesis.
Drugs: Sulfonamides, Trimethoprim
Sulfanilamide: prevents enzyme from converting PABA to folic acid ( a B vitamin that functions as a coenzyme in the synthesis of N-bases for NA. It blocks the initial step in which a synthetase enzyme links PABA with pteridine to form dihydropteroic acid (one of the precursors to making folic acid).
TMPS: synergistic combination of trimethoprim and sulfamethoxazole. Sulfa portion works as a normal sulfa drug (see above). Trimethoprim inhibits the conversion of folic acid to its active form
by preventing the enzymatic reduction of dihydropteroic acid to tetrahydrofolic acid (active form).
6. Antimycobacterial Antibiotics
Mycobacterium cell wall differs from other bacteria as it incorporates mycolic acids that cause them to have a more waxy cell wall that will stain as acid-fast.
Isoniazid: inhibit synthesis of mycolic acid, used to treat tuberculosis
Ethambutol: inhibit incorporation of mycolic acid into the cell wall
V. Antiviral Drugs
Targets for antiviral drugs are various points in viral reproduction:
attachment, penetration, uncoating, DNA or RNA synthesis, maturation (assembly).
Nucleoside and Nucleotide Analogs: are synthetic compounds which resemble nucleosides, but have an incomplete or abnormal deoxy-ribose or ribose group. Once activated by phophorylation, the drug competes with normal nucleotides for incorporation into viral DNA or RNA. Incorporation into the growing nucleic acid chain results in irreversible association with the viral polymerase and chain termination.
Examples: Acyclovir, Famcyclovir, Gancicyclovir, Ribavirin, Lamivudine, Cidofovir
Antiretrovirals: some are nucleoside/nucleotide anaologs that inhibit reverse transcriptase
Examples: Zidovudine, Tenofovir
Enzyme Inhibitors:
Block enzyme neuraminidase to treat influenza ( Relenza and Tamiflu)
Block protease inhibitor enzymes controlling last stage of viral reproduction
to treat HIV (Indinavir, Saquinavir)
Interferons: Three classes à alpha-, beta-, gamma-
Alpha and Beta interferons are cytokines produced by virally infected cells to inhibit spread of viral infection by binding to specific receptors on adjacent cells and enhancing the expression of class I and class II MHC molecules on the surface of infected cells.
Gamma interferon is a cytokine secreted by TH-1 CD4 cells to enhance specific T-cell mediated immune responses.
VI. Antifungal Drugs
More potential for toxicity since fungi share the same mechanisms to synthesize proteins and nucleic acids as other Eukaryotes. Many antifungals target the ergosterol of fungal membranes. When synthesis is interrupted, the membrane becomes excessively permeable, killing the cell.
Antifungal Agents affecting Sterols:
Polyene Antibiotics: Amphotericin B. Used for systemic fungal infections (histoplasmosis, coccidiomycosis, and blastomycosis). Toxic to the kidneys. Are liposized to aid in delivery and avoid toxicity.
Azole Antibiotics: Imidizoles for topical and oral; Triazoles
Allylamines: inhibit the biosynthesis of ergosterols, different than other classes
Antifungal Agents Affecting Fungal Cell Walls
Inhibition of syntheis of β-glucan results in an incomplete cell wall and results in the lysis of the fungal cell.
Echinocandins: drugs used to treat secondary fungal infections
in immunosuppressed individuals.
Antifungal Agents Inhibiting Nucleic Acids: Flucocytocine
Interfers with
the biosynthesis of RNA by acting as a pyrimidine analog
to cytosine. The fungal cell wall activates the drug and it is incorporated
into the RNA which eventually disrupts protein synthesis. Toxicity includes
renal and bone marrow suppression.
Other Antifungal Drugs
Griseofulvin: oral route of administration,
works on superficial dermatophyte infections since
it selectively binds to the keratin found in hair, nails, and skin. Blocks microtubule
assembly which interferes with mitosis and thereby inhibits fungal reproduction
Tolnaftate: MOA unknown. Topical treatment
VII. Spectrum of Activity
Defined as the range of different microbial types they affect
Narrow spectrum antibiotics are active against only a few microorganisms.
Broad spectrum antibiotics affect a wide range of G(+) and G(-) bacteria. However, the disadvantage of choosing these drugs are that normal microbiota of the host are destroyed. Normal flora usually compete and keep in check the growth of other microbes, especially pathogens. Sometimes treatment allow for normal flora to flourish and become opportunistic pathogens.
An overgrowth of normal or pathogen resistant bacteria is called a superinfection.
Primary factor involved with the selective toxicity of antibacterial
action lies in the lipopolysaccharide outer layer
of G(-) bacteria and the porins that form water-filled
channels across this layer. Drugs that are lipophilic and
large do not pass through the porins, therefore
the drugs need to be small and hydrophilic.
Narrow Spectrum:
g(+), some g(-)
penicillin, first generation cephalosporins, macrolides, lincosamides, vancomycin
g(-) aerobes, some g(+)
aminoglycosides, polymixin B, third
generation cephalospoins, Quinolones
Broad Spectrum
CHPC, tetracyclines, sulfonamides, ampicillin, amoxicillin, 2nd generation cephalosporins
Pseudomonas :: polymixin B, gentamicin, some penicillins
VIII. Cidal vs. Static
Antimicrobial drugs are have one of two actions, they are either
Bactericidal = kill microbes directly at clinically achievable concentrations
Bacteriostatic = prevent microbes from growing, slows growth, but does not kill.
Therefore elimination of the bacteria must be accomplished by the host’s immune system.
cidal antimicrobials kill : penicillin, cephalosporins, aminoglycosides, bacitracin, polymyxin
static antimicrobials inhibit growth : tetracyclines,
CHPC, macrolides, sulfonamides
Interaction between drugs on a homogenous bacterial population can happen one of three ways :
1. Indifference
2. Synergism
3. Antagonism
Synergism happens when cidal drugs are used together but never with a cidal and static drug, where the activity is additive at best.
NEVER combine a static and cidal drug for treatment of the same pathogen in
the same patient.
More likely to
get an antagonistic effect if this is done.
MIC = minimum (in vitro) concentration of a drug that inhibits growth.
Zone of inhibition is a factor of the Log Base 2 of the MIC
Results are given as :
S sensitive
I intermediate
R resistant
and are dependent on the type of media used, temperature, and pH.
IX. Bacterial Resistance
Defined as mechanisms by which a change in DNA base sequence via mutation or genetic recombination results in bacterial resistance to chemotherapeutic agents. Exposure to antibiotics selects for strains of the organism that have become resistant through natural processes. Also, not taking the prescribed amount of the antibiotic at the proper intervals or time also plays a role in resistance or tolerance.
Resistance is acquired by spontaneous mutation and conjugation.
Spontaneous mutations confer resistance to only one drug.
Conjugation can result in multiple drug resistance as extrachromosomal DNA is transferred from
one bacterium to another. Conjugation takes place primarily
between G(-) bacteria.
Hereditary drug resistance is often carried by plasmids or small pieces of DNA called transposons.
R (resistance) plasmids: genes that code for multiple antibiotic resistance
Conjugative transposons: can excise and transfer themselves from donor to
recipient
Methods of Resistance:
A. Low permeability membrane barriers and thereby intrinsically resistant to many antibiotics.
B. Mechanisms to become resistant to antibiotics:
1) Producing an enzyme capable of destroying or inactivating the antibiotic
2) Altering the target site receptor for the antibiotic to reduce or block its binding
3) Preventing the entry of the antibiotic into the bacterium
4) Actvely transporting
the antibiotic out of the bacterium
Producing enzymes that destroy or inactivate the antibiotic
* β-lactamases break the β-lactam ring of the penicillin antibiotics at the amide bond
G(+) have plasmid mediated β-lactamases as an inducible exoenzyme
G(-) can have either chromosomal or plasmid mediated β-lactamases as a
constitutive or inducible enzyme in the periplasmic space
Enzyme stability also plays a role in its effectiveness against the β-lactam ring
* Enzymatically adding a new chemical group to aminoglycosides
Altering the target site receptor for the antibiotic
* Produce slightly altered 50S ribosomal subunit that still functions but does not let the macrolide antibiotics bind
* Produce altered transpeptidases which alter the binding of beta lactam antibiotics
* Alter cross linking of the peptidoglycan so that vancomycin can not bind
* Produce altered topoisomerases that are resistant to fluoroquinolones
* Alter PBPs that affect pencillin binding
(Methicllin)
Altering membranes and transport systems
* Altered porins in the outer membrane of G(-) bacteria
* Alter carrier transport proteins used to transport the drug through the PM
* Altered transporter that is capable of an energy-driven efflux
that pumps the antibiotic out
Antibiotic use can also promote drug resistance
* Broad spectrum kills off competing organisms
* More antibiotics that are used, faster resistance: allows for overgrowth of normal flora
that can transfer resistance to pathogens.
X. Tests for Microbial Susceptibility
A. Diffusion Methods
1) Disk Diffusion Method or Kirby Bauer
Medium is evenly inoculated with microorganism and chemotherapeutic agent impregnated in filter paper are spaced evenly around the plate. Because of diffusion, the antibiotic- containing zone becomes established around each of the disks. If agent is effective, a zone if inhibition forms around the disk. The diameter can be measured and compared to a standardized table for that drug to report if the organism is sensitive, intermediate, or resistant.
2) E test : diffusion method
to measure Minimal Inhibitory Concentration (MIC) which is the lowest antibiotic
concentration that prevents visible bacterial growth.
B. Broth Dilution Tests
Determines MIC and minimal bacteriocidal concentration (MBC).
MIC : the lowest concentration of an antibiotic that will produce complete inhibition of growth.
MBC: lowest concentration of a drug that produces a 99.9% decrease in the number of bacterial colonies.
MIC is determined by making decreasing concentrations of the drug in the broth which is then inoculated with the test bacteria.
If no growth, then MIC can be determined, if growth, then MBC can be determined. Process is highly automated by computers. It is a more precise measurement of the drugs sensitivity since the drug concentration is known.
XI. Selection of Antibiotics for patients
Select appropriate antibiotic for the individual patient
a) identify the infecting organism
b) determine drug sensitivity
c) identify host factors
: location of infection, host defenses
Appropriate antibiotic is one that
1) greater efficacy
2) lower toxicity
3) Narrower spectrum
Alternate choices should only be considered when
* host allergy to the drug of choice
* inability of the drug to penetrate the site of infection
* changes in patient susceptibility
to drug toxicity
Bottom line: Match the drug with the bug!
XII. Host Factors that Modify Drug choice, Route of Administration, or Dosage
A. Host Defenses
Nonspecific and Specific Immune System Dependent
Goal of most Antibiotic therapy is suppress microbial
growth to the point at which the balance is tipped
in favor of the host.
B. Site of Infection
To be effective the antibiotic must be present at the site of infection in a concentration greater than the MIC.
Drug access may be impeded by body barriers
a) Blood Brain Barrier
b) Decreased circulation (poor vascularity)
c) Abscesses (CT walled off areas of infection)
d) Presence of excess exudate / pus
C. Other Host Factors
1) Age: Drug toxicity increases with the very young and very old due to changes in
drug excretion, drug levels can accumulate to the point of toxicity.
2) Pregnancy and Lactation
Antiotics can be toxic to the mother
Antibiotics can cross the placental membrane and accumulate in the fetus
Antibiotics can enter the breast milk and affect a nursing infant
3) Previous Allergic Reactions
Type I Hypersensitivity causing anaphylaxis
4) Genetic Factors
Enzyme deficient pathways can make them more sensitive to AB Tx (antibiotic treatment)
Affect rates of metabolism
Hepatic or Renal disease can predispose a patient to drug toxicity.
XIII. Therapy with Antibiotic Combinations
Should be reserved as initial treatment for severe mixed infections of unknown etiology
If two antibiotics are used together, the result can be: additive, synergistic or antagonistic
Additive: antimicrobial effect of the combination equals the sum of the effects of the two drugs alone.
Synergistic: antimicrobial effect of the combination is greater than the sum of the individual drugs alone.
Antagonistic: antimicrobial effect of the combination is less than the sum of the two drugs alone.
XIV. Prophylactic Use of Antimicrobial Drugs
Agents give to prevent an infection only if appropriate and known efficacy
a) Presurgical
b) Valvular Heart disease patients undergoing any procedure
c) High risk individuals à neutropenia
d) Possible exposure to organisms à STDs
XV. Misuses of Antibiotics
* Attempts at treating an untreatable infection (i.e. certain viral infections)
* Treating FUO (fever of unknown origin)
* Improper dosage or failure to monitor therapeutic dosages or clinical responses
* Failure to identify the agent causing the infection
* Failure to establish adequate drainage or cleansing as antibiotics do not work in exudate
(i.e. necrotic tissue, pus, foreign material)
FYI for your future success in the Health Sciences in general and specifically for nursing students will have to know the following regarding drugs: (look into getting a drug formulary book which will have most all of the information you need.)
Chemical Name and Trade Name
Chemistry (structures of importance)
MOA (mechanism of action)
Pharmakokinetics: absorption, distribution, elimination
Adverse Side Effects
Drug Interactions
Therapeutic Uses
Dosage and Administration