Microbiology Pharmacology

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Phramaceutical Phase

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The basic principles governing the introduction of drugs into the body

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Drugs

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Substances capable of changing a living system. A.) Topical; B.) Inhaled, C.) Ingested, D. Injected

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Pharmacology

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The study of the interaction between drugs and the body

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Therapeutic effects of a drug

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Drug possess beneficial traits or effects

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Toxix effects of a Drug

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Drug possess detrimental traits or effects

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Toxicology

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The study of poisonous drug effects.

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Pharmacy

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Deals with the formulation, dispensing of and legal aspects of drugs.

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Pharmacotherapeutics

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Is concerned with the use of drugs to treat pathophysiologic conditions.

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Therapeutic agent

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Agent --> provides symptomatic treatment

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Chemotherapeutic agent

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Penicillin --> Treats the cause. Includes antimicrobials which treat infections.

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Antineoplastics

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Chemotherapeutic agents which are anticancer therapies.

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Pharmacokinetics

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The study of movement of drugs between different components in the body.

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Pharmacodynamics

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The study of biochemical and physiologic mechanisms of drug action.

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Chemotherapy

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Treatment of disease with chemicals (drugs) taken into the body.

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Selective toxicity

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Drugs must act with in the host where they kill the harmful organism without damaging the host.

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Synthetic drugs

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Synthesized in the lab (also semisynthetic drugs).

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Antibiotics

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Are produced by microorganisms.

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Dr. Paul Ehrlich

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German who speculated to treat pathogen w/o harming host. Discovered Salvarsan, an arsenic derivative.

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Sulfa drugs

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Chemotherapeutic agents discovered in the 1930's. Inhibits folic acid synthesis.

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Penicillin

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Discovered in 1928, not used until 1940. Produced by pencillum fungi growth. Effective against Gram + organisms like S. aureus.

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Penicillinase (or B-Lactamases)

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Enzyme that breaks down (B-Lactam ring) penicillin and causes resistance to the drug.

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Semisynthetic Penicillins (action)

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Lab made to extend the natural spectrum of penicillin. May also be causing resistence (e.g. methicillin -> MRSA).

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Semisynthetic penicillins (used in treatments)

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Narrow Spectrum: Oxacillin (some resistance developing) and Nafcillin. Broad Spectrum: Ampicillin and amoxicillin

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Penicillin + B-Lactamase Inhibitors

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Combine penicillins w/ clavalanic acid (non-competitive inhibitor of pencillinase) (e.g. Augmentin)

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Cephalosporin

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Structural backbone and mode of action resembles Penicillin. Can be used as substitute.

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Vancomycin

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Used in penicillin-resistant strains of Gram + or Gram - organisms.

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Narron spectrum antibiotic

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Affects relatively few bacteria (as opposed to broad spectrum ones).

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Inhibition of cell wall synthesis

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Antimicrobial drugs that target the peptidoglycan layer. More for Gram + than Gram - b/c thicker layer. Human cells don't have.

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Antimicrobials that effect cell walls

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Include drugs like penicillin, cephalosporins, bacitracin (topical only) -- fight Gram + organisms

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Inhibition of protein synthesis

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Antimicrobial drugs that react with ribosomes of bacteria (different in Eucaryotes)

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Antimicrobials that effect protein synthesis

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Chloramphenicol, gentamicin (toxic), erythromycin (can be toxic), tetracyclines (not for kids), streptomycin

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Injury to Plasma Membrane

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Antimicrobial drugs that effect the membrane permeability of microbes cells. Loss of impt metabolites occur from these changes. (Can effect humans.)

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Chloramphenical (action)

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Broad spectrum inhibitor of protein synthesis.

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Chloramphenical (side effects)

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May cause blood disorder (aplastic anemia).

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Chloramphenical (used to treat)

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Drug of choice for typhoid fever, certain types of meningitis (risks justified).

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First Broad Spectrum Antibiotic

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Chloramphenicol (Toxic). Diffuses into nervous system.

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First Synthetic Antibiotic

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Chloramphenicol: Causes Grey Syndrome: accumulates in newborns blood causing toxic rxn & sudden breakdown of cardiovascular system.

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Aminoglycosides (action)

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Class of antimicrobials that effect protein synthesis.

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Aminoglycosides (side effects)

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Sometimes toxic to the auditory nerve or the kidneys.

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Aminoglycosides (examples)

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Include streptomycin, neomycin, gentamicin, tobramycin.

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Streptomycin

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Aminoglycoside that treats TB

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Neomycin

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Aminoglycoside that is a topical ointment. Called Neosporin when combined with Bacitracin and Polymyxin B. Poorly absorbed by GI tract.

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Gentamicin

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Aminoglycoside that is effective against most Gram - (especially Psuedomonas/UTI's). Ototoxic and nephrotoxic.

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Tobramycin

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Aminoglycoside that is an aerosol treatment of Cystic Fibrosis patients with psueodomonads (opportunist)

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Tetracycline (action)

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Broad spectrum inhibitor of protein synthesis.

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Tetracycline (used to treat)

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Effective against atypical pneumonia, syphillis, gonorrhea, pneumococcal pneumonia, some protozoa dz, chlamydia and richettsias, Gram - orgs

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Tetracycline (side effects)

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Can cause tooth discoloration, liver disease, stunted growth (children). Restrict use in pregnant women, children thru teens.

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Antimicrobials that effect Plasma Membranes

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Antifungal agents such as polymycin, nystatin, miconazole, ketaconazole, amphotericin B. These drugs combine w/sterols to disrupt fungal plasma membranes.

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Inhibition of Nucleic Acid Synthesis

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These antimicrobials (More toxic) host DNA and RNA are close to microbial DNA/RNA. These drugs have limited clinical application.

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Antimicrobials effecting nucleic acid synthesis

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Rifampincin (inhibits bacterial RNA polymerase), Quinolones (inhibits bacterial DNA gyrase -- an enzyme).

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Inhibiting the synthesis of essential metabolites

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Antimicrobials that competitively inhibit the synthesis of folic acid (humans don't synthesize, bacteria do). Resembles the metabolite para-aminobenzoic acid that is required to synthesize folic acid.

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Macrolides (action)

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Antimicrobial that inhibits protein syntheis.

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Macrolides (precautions)

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Should not be taken by pregnant women

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Macrolides (examples)

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Class includes Erythromycin and Azithromycin

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Erythromycin (use)

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Macrolide used to treat infections resistent to penicillin.

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Erythromycin (dz treated)

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legionellosis, atypical pneumonia (mycoplasmal), newborns w/neisseria & chlamydia (eyes)

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Azithromycin

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(Zithromax) Macrolide that is more broad spectrum than Erythromycin. Penetrates tissues better.

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Nystatin (used to treat)

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Antifungal drug for Candida albicans (effects intestines, vaginal canal and oral cavity).

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Nystatin (action)

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Changes permeability of cell membrane by combining w/fungal sterol.

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Amphotericin B (used to treat)

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Antifungal for systemic infections. (Ketoconazole is used as a subsitute.)

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Amphotericin B (action/effects)

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Degrades fungal cell membrane. Causes wide variety of side effects. Used in potential fatal cases.

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Acyclovir

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Antiviral. Incorporates in viral DNA during the replication cycle of Herpes Simplex & cyto megalo viruses.

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Interferons (action)

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Natural/synthetically engineered, provokes host cells to produce antiviral proteins and the stimulate NK cells into action.

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Interferons (used to treat)

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FDA approved for use treating Hep B, Genital warts and a type of Leukemia.

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Cell

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Basic unit structure of all living things

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Robert Hooke

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Coined the word cell, which means "box."

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Bacterial cells

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Unicellular organisms

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Humans

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Multicellular organisms

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Viruses

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Psuedo-organism which has a structure, not a cell. Has nucleic acid and protein coat.

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Nucleus

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The brain of a cell. It regulates functions, genes, and instructions inside DNA (found in chromosomes)

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Muscle cell

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An example of a multinucleated cell within animals.

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Red blood cell

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This cell's only job to transport O2 and has its nucleus expelled.

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Bacterial cell (contents)

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It's only contents are nucleoid material plus simple chromosomes

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Prokaryote

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Literally means "Pre"-nucleus/ "no" nucleus. Organisms which are only bacteria

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Eubacteria

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Name means"true" bacteria.

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Archeobacteria

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Name means "ancient" bacteria (found in unusual places).

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Linnaeous

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Developed binomial system of naming organism by Genus and species.

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Characteristics of a cell

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Its characteristics are: 1.) Reproduction 2.) Food for an energy source, 3.) "Food" --> synthesize things, 4.) Excretes waste, 5.) Respond to a stimulus, 6.) Mutateable

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Taxonomy

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Science of the classification of an organism

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Taxonomic order

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The order would include: Kingdom, Phyllum, Class, Order, Family, Genus (Homo), and Species (sapiens).

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Ways nutrients obtained

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1.) Absorption, 2.) Photosynthesis, 3.) Ingestion

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Five Kingdoms

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1.) Monera , 2.) Protista, 3.) Fungi, 4.) Plants and 5.) Animals

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Whitaker

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Came up w/clasification system based on how nutrients are obtained.

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Kingdom of Monera

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Bacteria (eu- & archeo). Mostly absorb nutrients, some use photosynthesis (cynobcteria)

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Animal Kingdom

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Multicellular organisms that injest nutrients

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Fungi Kingdom

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Organisms that mainly absorb nutrients

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Plant Kingdom

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Organisms that mainly use photosynthesis for nutrients. (Higher algae)

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Endosymbiotic Theory

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The theory that a bacterial cell found its way into a primitive eukaryote animal/plant cell and eventually became mitochondria/chlorophyll.

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Major groups of microorganisms

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Protozoa, Fungi, Algae, Bacteria (and viruses are an add-on)

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Rigid outer cell wall

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Helps prevent organisms that absorb their nutrients from bursting (plants & bacteria)

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Protozoa (defined)

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Animal-like (injest nutrients) microorganisms

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Protozoa (characteristics)

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The characteristics of these include: Mostly H2O based, lack chlorophyll, lacks rigid cell wall, may have cilia or flagella (can be mobile).

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Protozoa (examples)

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Amoebas and Sporozoans are examples of these.

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Amoebas

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A protozoan that moves by endoplasmic streaming, psuedopods.

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Sporozoans

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A life stage within certain types of protozoas (dormancy stage) in order to survive harsh conditions.

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Algae

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Microorganism that is water-based, Eukaryote. Can be unicellular or multicellular (macroscopic), like pond scum

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Algae (pros & cons)

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Can cause plumbing problems. Can be used as thickeners/emulsifier. Create antiinflammatory drugs. Used for agar.

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Fungi (characteristics)

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Eukaryotes, rigid walled (absorb nutrients), Lacks chlorophyll

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Fungi (examples)

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Mold and yeast

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ariel state

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Non-metabolically active state of mold where organism becomes a spore to survive harsh environment.

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bacteria

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Prokaryotes, rigid cell wall (absorb nutrients), do not have many organelles (only ribosomes)

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bacteria (types)

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eubacteria or archeobacteria

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bacteria (shapes)

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rod (bacillus), round (coccus), rod with wiggle (spirillium), rod with comma (vibrio)

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Clostridium

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Spore forming genus name

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Bacillus subtilis

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Spore forming genus name

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Streptococcus pyrogenes

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Can cause many diseases depending on portal of entry: scarlet fever, strep throat.

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ratio of human: bacteria cell

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1:10 (>50% of feces is bacteria)

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Chemistry

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Science that deals with the interaction of atoms and molecules

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matter

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made up of repeating units called atoms

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atoms

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combine to form molecules, which combine to form compounds,

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atomic nucleus

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composed of protons (positively charged) and neutrons (no charge)

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orbit / energy shells

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area of electrons (negatively charged)

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neutrons

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neutral particles, equal with the number of electrons

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atomic number

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number of protons

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atomic weight

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# protons plus # neutrons

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isotope

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#protons stays same, #neutrons changes, atomic weight chgs

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valence electrons

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# electrons in outermost shell

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octet rule

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atom content if outer shell is full

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ionic bond

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one atom transfers electrons from one atom to another

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covalent bond

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atoms share a pair of electrons

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hydrogen bond

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attraction of H nucleus to a negatively charged O or N atom

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ionic bonds (examples)

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NaCl

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polar covalent bond (example)

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H2o

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synthesis reaction

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A + B = AB (endergenic)

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decomposition

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AB = A + B + energy (exogenic)

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exchange

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AB + CD = AC + BD (part decomposition/part synergy)

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chemical energy

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occurs when old bonds destroyed, new formed.

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charge of bacteria

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slightly negative

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carbon skeleton

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substance has a carbon-based framework with a "R group" as its functional group.

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carbohydrates

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Water carbon C6H12O6 divide by 6--> CH2O (polysaccharides, disaccharides, monosacharides)

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lipids

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C, H, O w/o 2:1 ratio btwn H and O. Simple lipids are dietary fats like triglycerides. Complex lipids have N, O, P attached, like phospholipids, cell membranes, or sterols.

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mycoplasm

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bacteria that lack a cell wall, but has sterols to back the walls, which effects the outcome of staining techniques

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proteins

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Chains of amino acids (amine groups) linked togethter with peptide bonds. C, H, O, and N grouped together.

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proteins (examples)

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Can serve as enzymes, transportation, regulation, motility, antibodies, hormones, sterools, anything that gives structure, actin, myosin, collagen, bacteriocinogens (to kill bacteria), exotoxins

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proteins (role for AA)

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Serve as the building blocks for amino acids - 20 different (10 essential/10 nonessential)

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L-form of amino acid

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the most common natural form of an amino acid found in nature, which grows in a spherical shape and bends light to left

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D-form of amino acid

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mirror image of the L-form of amino acid, bends to the right, referred to as a steroisomer, sometimes are bacteria or drug.

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glycine

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simplest amino acid (no mirror image possible)

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1° Primary structure

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Structure like shoe laces. A genetically determined exact sequence of amino acids that make up the protein.

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2° Secondary structure

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Structure like string through the shoe. Twisting and folding of the polypeptide chain that may be due to H-bonds or ionic bonds or hydrophobi/philic characteristics of the protein structure.

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3° Tertiary structure

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Structure like tieing a bow. The 3-D structure determines function. The functional product is based on the 3-D shape due to hydrogen, covalent or ionic bonds.

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4° Quarternary Structure

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Structure not present in all proteins. At least 2 polpeptide chains in 3 structure combine to form object. Linked together with disulfide bridges, like hemoglobin.

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lipids (examples)

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Include fats, phospholipids, and steroids

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fats

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Category of lipids that include a (3) carbon alcohol (glycerol) plus one (+) fatty acid: one FA= monacylglycerol, 2 FA= diacylglycerol, 3 FA= tricylglycerol

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saturated fatty acid

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A category of lipids that contains all the hydrogens it can have.

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unsaturated fatty acid

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A category of lipids that has lost at least (2) H atoms and contains a double bond btwn at least 2 C atoms.

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Phospholipid

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A lipid that substitutes phosphoic acid (H2PO4) for one fatty acid. HPO4 gets attached to another charged group, making that end able to attach to H2O.

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Steroid

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A lipid that has a four ring C structure. It includes cholesterol, steroid hormones, vitamin D, found in the cell membranes of animal cells and in the bacteria mycoplasms.

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Hydrocarbons

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Chains of C atoms with their associated H.

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alcohol

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A class of organic compound that contains one or more hydroxyl group -OH.

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aldehyde

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a class of organic compound that contains one or more carboNyl group -COH.

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Organic acid

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a class of organic compound that contains one or more carboXyl group -COOH.

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Ketone

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a class of organic compound that contains one or more ketone C=O

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amino group

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The functional group without the O, or -NH2. Found in amino acids, account for the N in proteins.

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monosaccharide

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Carbon chain plus several alcohol groups plus one other functional group. Several have isomers.

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disaccharides

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Two monosaccharides combine (H2O byproduct) forming a glycosidic bond.

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polysaccharide

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Multiple monosaccharide combine linked by glycosidic bonds.

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Nucleic acids

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DNA (double helix) and RNA (the single strands: messenger, transfer and rRNA- replicative)

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Nucleotides

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(5) - C sugar plus phosphate plus nitrogenous base.

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DNA (N-bases)

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Pyrimindines: Thymine (T) and Cyosine (C); and Purines: Adenine (A) and Guanine (G)

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RNA (N-bases)

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Pyrimindines: Uracil (U) instead of Thymine (T), along with Cyosine (C); and Purines: Adenine (A) and Guanine (G)

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Complementary Nucleic Acid Base Pairs

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Adenine (A) pairs with Thmine (T) or Uracil (U) with RNA; Cyosine (C) pairs with Guanine (G)

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Mutations

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Changes in the sequence in Nitrogenous bases.

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ATP

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Adenosine tri-phosphate: stores cellular energy in phosphate bonds

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ADP

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Adenosine di-phosphate: lowered formed of stored cellular energy in phosphate bonds from ADP.

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Heat fix bacteria slide

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The process of adhering microorganisms to a slide by air drying then flaming to kill them.

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Chromophore

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The ion that contains the pigment.

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Basic dye

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Dye which contains positively charged chromophores - will adhere to bacterial cells which are generally slightly negative on surface.

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Acidic dye

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Dye which contains negatively charged chromophores - will repel from the surface of bacterial cells which are generally slightly negative.

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Basic dye (examples)

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Dyes that adhere to bacteria include: crystal violet (purple), safranin (pink/red), methylene blue (blue), Malachite green, and Carbol fuschin (deep pink)

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Acidic dye (examples)

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Dyes repeled by organisms include: India ink (grey background), Eosin (reddish) and Acid fusion

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Types of staining

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Simple stain (one dye, like methylene blue); differential stain (2+ stains, like a Gram or Acid fast stain); Special Stain (capsule, spore, flagella stains)

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Gram stain (steps)

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Steps: 1.) HFBS, 2.) Primary stain (CV) 30-60 secs; 3.) Iodine (mordant) 10 - 30 secs; 4.) Decolorization (Acetone-alcohol) 10 drops; 5.) Counter stain (safranin) 30-60 secs; rinse w/H2O after steps.

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Gram stain (results)

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After stain: Gram + retain 1st stain, look purple, b/c thicker peptidoglycan layer; Gram - loose 1st stain, look pink, thiNNer peptidoglycan layer; Gram variable - pink/purple

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Gram non-reactive

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These cells do not stain easily b/c there is no peptidoglycan wall, e.g. gum cells (squamous cells) s/b pink after Gram stain.

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Acid fast stain (steps)

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Steps: 1.) HFBS, 2.) Primary stain (carbol fuschin) place 5 min over boiling water; 3.) Decolorize (ACID-alcohol) 10 drops; 4.) Secondary stain (methylene blue); rinse after steps

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Acid fast stain (results)

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If org has mycolic acid (waxy protein), then retains primary stain (deep pink/purple); if non-acid fast, takes secondar stain only (blue).

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Capsule stain

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Creates a halo in organisms with capsules or have slime layers -- which tend to be slippery org (e.g. pneumococcal pneumonia)/have polysac polpept, or both layers

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Brightfield microscope

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This microscope uses a light source, view stained specimens, not useful for viruses.

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Dark field microscope

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This microscope used for viewing microorganisms that are still alive to get a sense of size and shape.

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Electron microscope

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This microscope views objects @ 100K - 200K x. Kills org w/electrons. Good for dead specimens, viruses, & internal structures

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Scanning microscope

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This microscope enables you to see the surface features of a cell like a relief map. Can also see viruses. (Not to be confused w/power.)

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prokaryote cells (features)

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1.) Genetic material (DNA), 2.) single circular chromosome, not contained nucleus, lack membrane bound organelles, 3.) lacks certain proteins, 4.) most have cell wall (peptidoglycan layer), 4.) divide by binary fission process.

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eukaryotic cell (features)

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1.) Has nucleus w/nuclear membrance, 2.) DNA associated w/stabilization proteins (histones), 3.) mitotic spindles, 4.) cytoplasm has organelles, 5.) may/may not have cell wall, never a peptidoglycan layer.

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monomorphic

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to maintain a single characteristic shape

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pleomorphic

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exhibits irregular morphology (shape) - probably getting old

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glycocalyx (dental plaque)

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Can be either: capsule (indicates virulence). Composed of polysaccharide, polypeptide or combo of both - organized. Or slime layer - disorganized, loosely attached to cell wall.

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monotrichous

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one flagella at either end of pole

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lophotrichious

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two + bundle of flagella at one end

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amphitrichous

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two flagella: one at each end

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peritrichous

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flagella surrounding the organism

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atrichous

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no flagella

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org. movement

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clockwise/counterclockwise rotation, synchronized (directional), towards/away, run/swim, random (tumble)

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taxis

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movement to or from a stimulus

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chemotaxis

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swim towards or away from a chemical

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phototaxis

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swim towards or away from light

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a run

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movement lasting longer than a tumble (1 sec - 10-20x length of body)

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serovar

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a strain or subspecies/ variations w/in a species (e.g. H-antigen - certain type of protein marker)

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axial filaments (endoflagella)

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spirochete: rotates like a corkscrew

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fimbrae (pili)

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hairlike appendages, adheres to a surface protein - indicate virulence

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sex pilus

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extra packet of DNA that makes it drug resistant (MRSA, C. diff)

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sediment

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settling in the bottom of a test tube

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flocculent

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thick with a lot of cloudy growth in a test tube

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pellicle

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skin or film at the top of liquid surface in a test tube (org needs O2)

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relative size (typical bacteria)

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red blood cell about 7.5um vs largest bacteria about 2-5 um

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Glycan portion

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CHO portion of peptidoglycan layer - 2 sugars N-acteylmuranic acid (NAM) and N-actylglucosomine (NAG)

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Peptide portion

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Peptide portion of peptidoglycan "bonds" to NAM to create "cross linkages"