Pharm for bacteria Flashcards
What are anti-invectives effective against
Pathogens
How are anti-invectives classified
According to susceptible organism (antibiotic, antiviral, anti fungal, antiprorozoan)
What determines the mechanism of action for anti-invectives
Chemical structure
Bacteriocidal
Type of anti-infective that kills bacteria
Bacteriostatic
Type of anti-infective that prevents growth and reproduction of bacteria
Mechanisms of antibacterial agents
1) Drugs that damage bacterial cell wall
2) Drugs that damage cell membrane
3) Drugs that inhibit protein synthesis
4) Drugs that inhibit DNA replication or bacterial cell division
What type of drugs damage the bacterial cell wall
Beta-lactam antibiotics inhibit the synthesis of bacterial cell wall; tend tend to be bactericidal
What type of drugs damage the cell membrane
Bactericidal
What type of drugs inhibit protein synthesis
Drugs bind to bacterial ribosomal subunits or bind to transfer RNA; bacteriostatic
Drugs mimic folic acid
Tend to be bacteriostatic
What type of drugs inhibit DNA replication or bacterial cell division
Bacteriostatic
Structure of bacterial cell walls
Peptidoglycan molecules in their cell walls that protect them from the environment
Peptidoglycan molecules form a set of chains called penicillin-binding proteins (PBPs) because penicillins and related antibiotics bind to them.
We can target them because we don’t have peptidoglycan
What do penicillins target
Beta-lactam ring (central ring) structure of penicillin binds PBPs causing lysis of growing by damaging cell walls
How do some bacteria develop resistance to penicillin
They mutate so they lack the PBPs that are the target of penicillins.
or they secrete an enzyme (penicillinase or beta-lactamase) that splits penicillin’s beta-lactam ring, and inactivate it from working, often in response to penicillin.
What type of bacteria do we typically use penicillins for
Gram-positives
What are some types of infections that penicillin G potassium may be used for
Bacterial endocarditis with prosthetic heart valves, rheumatic fever, congenital heart disease, Group B strep, during labour
What is the mechanism of action for Penicillin G Potassium
Inhibits bacteria cell wall synthesis by biding PBPs
What are adverse effects of Penicillin G Potassium
Urticaria, allergies, anaphylaxis
What are the most common drugs to be allergic to
1) Penicillins 2) Sulfa’s
How many cephalosporins are there
20 cephalosporins in 5 generations
What generation of cephalosporins is the most resistant
1st Gen (more broad)
Reserve the 5th Gen (more specific)
Common adverse effects for cephalosporins
allergy, rash, GI complaints
What type of drugs do we typically use with pregnant women
Penicillin’s as we have a lot of data on them
What bacteria do cefotaxime (Claforan) target
They are third generation cephalosporins with a broad spectrum
They target gram-positives and gram-negatives
What type of infections could cefotaxime (Claforan) be used for
Infections of respiratory tract, urninary tract, genital infections, meningitis, septicaemia, endocarditis, bone and joint infections
infection prophylaxis in surgery patients
What is the mechanism of cation for cefotaxime (Claforan)
Inhibit bacterial wall synthesis by biding to specific PBPs
What are the adverse effects of cefotaxime (Claforan)
rash, diarrhea, allergic responses
Potential superinfection (caused by broad spectrum nature of drug)
Painm phlebitis at IM injection sites
What are serious adverse effects for cefotaxime (Clarforan)
Anaphylaxis and seizure
What type of bacteria do carbapenems target
Provide better activity against serious Gram-negative and multi resistant infections than most penicillins and cephalosporins
Given perentually (IV)
What drugs are typically used when there is multi drug resistance
Carbapenems
What are the 3 types of drugs that target the bacterial cell wall
1) Penicillins
2) Cephalosporins
3) Carbapenems
How does protein synthesis (translation) happen in bacteria
Similar tor humans and is carried out in ribsomone’s
Bacteria’s ribosomes have 30S and 50S subunits (humans have a 40S and 60S), they are slightly different so we can target
Ribsomone’s are required for tRNA and mRNA to connect and disrupt translation and prevent reproduction
What type of bacteria are tetracyclines active against
Gram-pos and gram-neg
What type of infections can tetracylines be used for
typhus, cholera, Rocky Mountain spotted fever, Lyme disease, H.pylori ulcers, P.Acnes, Malaria, and chlamydia
How do tetracylines work
They inhibit protein synthesis at the 30S subunit by preventing rRNA from binding to mRNA/ribosome complex
How are tetracylines given
On an empty stomach, as nutrient cation binding interactions (Ca, Mg, Al)
Or
Parenterally (IV) because they are incompletely absorbed in the intestine
How are penicillins and celphasporines absorbed
Very well and fast
Eliminated in the kidneys
How are tetracylines absorbed
They are large molecules so they are absorbed slow and hang around in the bowels longer (interaction with natural bowel flora)
Resulting in more GI side effects
What is a side effect of giving tetracylines parenterally
Can be hepatotoxic and cause photosensitivity (chemical induced reaction to light causing rash)
What happens when a tetracylines is given when it is expired
can cause fatal toxicities
What is the mechanism of action for tetracylines
Inhibits bacterial protein synthesis by interfering with binding of tRNA to the mRNA - 30S ribosome complex
Terminates the growing of amino acid chain prematurely
Adverse effects for tetracylines
superinfections
nausea, vomiting, epigastric burning, diarrhea
discolouration of the teeth and issues with bone development in young kids (strong affinity to Ca2+)
Photosensitivity (may burn quicker or develop a rash)
What are serious adverse effects of tetracyclines
Hepatotoxicity, anaphylaxis, exfoliative dermatitis (very bad photosensitivity), intracranial hypertension also called pseudotumor cerebra (PTC)
What type of drugs are macrolides used against
Gram-positives
Alternative drugs for patients allergic to penicillin
What type of infections are macrolides/erythromycin (Eryc) used for
prophylaxis and treatment of susceptible bacterial infections including legionella, chlamydia, listeria, campylobacter, as well as upper and lower respiratory tract infections, and skin infections
Mechanism of action for macrolides/erythromycin (Eryc)
Inhibits protein synthesis by preventing tRNA from binding to 50S subunit
Considered bacteriostatic but may be bactericidal in high doses
How are macrolides metabolized and what are the effects of this
they are metabolized in the liver and can result in drug interactions (largely CYP 3A4)
Adverse effects for macrolides/erythromycin (Eryc)
Nausea, vomiting, abdominal cramping, phlebitis, intensive pain at IV injection site
What are some serious adverse effects of macrolides/erythromycin (Eryc)
Cholestatic hepatitis,
anaphylaxis
ototoxity (hearing loss, vertigo, dizziness)
Cariotoxicity including palpitations, chest pain, arrhythmias, OT prolongation
What type of bacteria do aminoglycosides target
Gram-neg bacilli caused by aerobic or multi-resistant
A few gram-pos like some strains of MSRA
pseudomonas, enterobacteriaceae family, tuberculosis
What us postanibiotic effect and what drug is it associated with
Activity of drug continues even after serum drug levels drop as drug remains in some tissues despite clearance by kidneys in aminoglycosides
How are aminoglycosides administered
Must be given parenterally and are reversed for serious systemic infections
They are too big to be given orally
Why might there be some serious adverse effects for aminoglycosides
May include nephrotoxicity, ototoxicity, and neuromuscular blockade, thus these drugs are only used when other drugs are not effective
They have a preferential tendency to want to go into organs we don’t want to hurt (endolymph in ear)
Mechanism of action for Gentamicin (Garamycin)/aminoglycosides
Inhibits protein scythes by binding to the 30S ribosomal subunit, causing premature termination of translation.
Adverse effects of Gentamicin (Garamycin)/aminoglycosides
Nausea, vomiting, rash, fatigue
Serious adverse effects of Gentamicin (Garamycin)/aminoglycosides
Ototoxicity, nephrotoxicity, neuromuscular blockage, neurotoxicity
What type of bacteria do lincosamides (Clindamycin)/aminoglycosides target
Anaerobic infections (live in bowels typically) and gram positive organisms
What type of infections do lincosamides (Clindamycin)aminoglycosides target
Oral infections (especially when PCN allergic), Septicemia, skin and soft tissue infections, GI infections, abscess (skin, ovarian), pelvic inflammatory disease
What is the mechanism of action for lincosamides (Clindamycin)aminoglycosides
Work by biding to the 50S ribosomal subunit of bacteria
This agent disrupts protein synthesis by interfering with the protein synthesis by transpeptidation reaction, which thereby inhibits early chain elongation
Adverse effects for lincosamides (Clindamycin)aminoglycosides
GI related (Nausea, vomiting, diarrhea): diarrhea quite common given broad spectrum activity
Poor taste in mouth (take with lots of water, stay up right 20 mins after admin) try cold and tarte combo
Serious adverse effects for lincosamides (Clindamycin)
Most common antibiotic to cause C. Diff diarrhea especially with high doses
What are the steps in bacterial DNA replication
1) DNA gyrase relaxes supercoil
2) DNA helocase unwinds stands of helix
3) DNA polymerase replicates DNA strands
4) Topoisomerase IV separates newly replicated strands into daughter cells
Drugs can block bacterial DNA replication in three ways
1) Inhibit synthesis of precursor bases or nucleotides
2) Interact with or bind to DNA, preventing uncoiling or relaxation
3) Bind to enzymes of replication, stopping the formation of new DNA strands
How many gernerations are there for fluoroquinolones
4 with activity on all Gram-negs and some gram-positives
What type of infections are Fluoroquinolones used to treat
Uriniary tract infections, GI, respiratory and skin infections
Ciprofloxacin (Cipro)/Fluoroquinolones mode of action
Inhibits bacterial topoisomerase IV and DNA gyrase, preventing DNA replication
Adverse effects for Ciprofloxacin (Cipro)/Fluoroquinolones
Nausea, vomiting, diarrhea
phototoxicity, headache, dizziness
tendonitis
Serious Adverse effects for Ciprofloxacin (Cipro)/Fluoroquinolones
Pseudomembranous colitis (wide scale inflammation of intestines)
Seizures, toxic psychosis
What type of treatment is used for pneumonia
need parenteral administration (IV)
may be toxicity in other tissues bc doses are too high when taken orally
What types infections are sulfonamides/trimethoprim-sulfamethoxazole used to treat
UTI prophylaxis and UTI
Prophylaxis and treatment of p. carinii and shigella
Acute episodes during chronic bronchitis
Off-label for other indications depending on sensitivity of microbe
Mechanisms of action for sulfonamides/trimethoprim-sulfamethoxazole
Both drugs inhibit different steps of folate synthesis (necessary for thymine metabolism), thereby inhibiting DNA replication
Adverse effects for sulfonamides/trimethoprim-sulfamethoxazole
Nausea, vomiting
Skin rash, pruritus
Fever
Photosensitivity
Severe adverse effects for sulfonamides/trimethoprim-sulfamethoxazole
Anaphylaxis, allergic myocarditis
Stevens-Jognson syndrome (exfoliated dermatitis, life threatening AKA skin is dying), epidermal necrolysis
Agranulocytosis, aplastic anemia
What infections is vancomycin (Vancocin) used for
Severe gram-postive infections resistant to safer antibiotics
Off-label uses for meningitis and antibiotic-induced pseudomembranous colitis
Mode of action for vancomycin (Vancocin)
Inhibits synthesis of bacterial cell wall
Increases permeability of bacterial cell membrane
Alters RNA synthesis
How is vancomycin (Vancocin) administered
Not well absorbed (molecule size is too big) so often given parenterally unless bowel issues give oral
Need to give slow
What are adverse effects for vancomycin (Vancocin)
“red man” syndrome: flushing, hypotension, tachycardia, rash on upper body
Nausea, rash, fever, chills
What are serious adverse effects for vancomycin (Vancocin)
Confusion, seizures, and hallucinations
Extravasation leading to tissue necrosis (infusion site reactions)
Ototoxicity and Nephrotoxicity
Anaphylaxis
What type of infections are Metronidazole (Flagyl) used for
Anaerobic infection and protozoal infections
Mechanism of action for Metronidazole (Flagyl)
Reductive activation by intracellular transport proteins that exist only in obligate anaerobes
Metronidazole in the cellular environment, its nitro group acts as an electron sink shutting down ATO production
Formation of intermediate compounds and free radials occurs that are toxic to the cell, energy production is interfered with.
Adverse effects for Metronidazole (Flagyl)
GI related (Nausea, vomitin, diarrhea)
Metallic taste in mouth
Thrombophlebitis common with IV administration
Serious adverse effects for Metronidazole (Flagyl)
Seizure threshold is lowered
Disulfiram like reaction with alcohol (MUST avoid combination)
Leukopenia with high dose/long term use
What is the most important question to ask in the health history when picking an antibiotic
Allergies
Common UTIs
Urethritis, Cystitis
Prostatitis in males
Pyelonephritis
Common therapies for UTIs
Nitrofurans
Sulfonamides
Fluoroquinolones
How are UTI drugs administered
Drugs specific for UTIs are given by oral route and only each effective concentrations in kidney
Food improves absorption by 30-40% so meals are important for effective absorption
What is Nitrofurantoin/Macrobid, Macrodantin used for
Uncomplicated acute cystitis, usually prophylaxis of recurrent UTIs
Rapid absorption and renal eliminate, concentrating drug in the bladder
What is the mechanism of action for Nitrofurantoin/Macrobid, Macrodantin
Intermediates attack bacterial ribosomal proteins, prevent DNA and RNA synthesis, and prevent protein synthesis, also inhibits cell wall synthesis
Are Nitrofurantoin/Macrobid, Macrodantin effective for systemic infections like pyelonephritis (kidney infection)
NO
What is a note worthy serious adverse effect for Nitrofurantoin/Macrobid, Macrodantin
Acute and chronic pulmonary toxicity (++ in renal impairment)
What is tuberculosis cause by
Mycobacterium tuberculosis, spread by airborne droplets
How does mycobacterium tuberculosis cause infection
Immune system response leads to formation of tubercles in lungs that surround mycobacteria
Mycobacteria can remain dormant for awhile
What are the two major goals of therapy
- Eliminate all tubercle mycobacteria
- Avoid emergence of resistant strains
What are the two phases of pharmacotherapy for TB
- Initial phase - active cells are killed
- Continuation phase - dormant mycobacteria are killed (may last 6-12 months)
What is necessary for patients that are at high risk for TB
Directly observed therapy (DOT), its a pill
what is Isoniazid used to retreat
M. tuberculosis prophylaxis and treatment
What is the mechanism of action for Isoniazid
Inhibits the synthesis of mycelia acid, a critical component of mycobacterial cell wall
Is Isoniazid bactericidal or bacteriostatic
Bactericidal for rapidly dividing organisms
bacteriostatic for dormant mycobacteria
Adverse effects for Isoniazid
Numbness of hands and feet
Serious adverse effects for Isoniazid
Tend to have drug interactions
Neurotoxicity related to decrease in vitamin B6
Blood dyscrasias
Assessment for Isoniazid
Understand the importance of drug-drug interactions, may need to change other drugs like BP meds.
What is Leprosy used to treat
Chronic infection caused by Mycobacterium leprae
Targets the nervous tissues, leading to nerve thickening, skin lesions, loss of sensation disfiguration
Infection is thought to be spread via respiratory route
What are the two types of disease associated with Leprosy
- Lepromatous - slow, progressive form of disease requiring 2-5 years of therapy
- Tuberculoid - less progressive with long remissions, requiring 2-3 years of therapy
What is the main drug used to treat Leprosy
Dapsone
What is the mode of action for Dapsone
Inhibits folic acid metabolism
