Pharma 1

Front 1

Sulfonamides: how do they work

Back 1

They competitively inhibit DHPsynthase by acting like PABA and binding to the active site. This will cause a drop in DHP which is needed to work with DHFR to make tetrahydrofolate which is needed to make nucleic acids

Front 2

What is SMX/TMP and how do the active ingredients work

Back 2

Sulfamethoxazole/Trimehtoprim cocktail
Sulfa works by inhibiting DHPsynthase and trimeth works by inhibiting DHFR (DHFR is conserved evo)
TMP is more effective at a lower dose and both are bacteriostatic alone...combined they're bactericidal

Front 3

Which bacteria will sulfonamides work on?

Back 3

Gram neg/pos bacteria requiring denovo synth of folic acid. USED MOSTLY FOR GRAM NEGATIVE RODS
UTI: e coli, proteus mirabilis (cystitis, prostatitis)
GI: salmonella typhi, shigella spp (diarrhea)
RTI: Some Hemophilus influenza (sinusitis),

Front 4

What is Pyrimethamine and what is it used for?

Back 4

Used for Plasmodium and malaria treatment in conjunction with a sulfonamide

This drug itself is not a sulfonamide

Front 5

Mechanism of Resistance Mechanism for SULFA AND TMP

Back 5

SMX: mutation of DHPsynthase or enhanced PABA getting into cell
TMP: mutation of DHFR or overexpression of DHFR

Front 6

Which bacteria are resistant to SMX/TMP

Back 6

CAMPYLOBACTER, p aeruginosa, TB, Bacteroides fragilis and most anerobes, PENICILLIN resistant pneumon, RICKETTSIAE, ENTEROCOCCUS

FOLIC ACID AUXOTROPHS

Front 7

What are main therapeutic usage of SMX/TMP

Back 7

UTI, Treatment/prevention of pneumocystis carinii penumonia (PCP) (Fungal cause of pneumon: pneumocystis jirovecii) for HIV pts
TOXOPLASMOSIS in immunocompromised

Front 8

Adverse Effects of Sulfonamides

Back 8

Kernicterus, hemolytic anemia (especially in pts with inherited G6PD deficiency) due to ox stress causing hemoglobin denaturation and acute hemolysis and red cell loss, stevens johnson syndrome (hypersensitivity), kernicterus (excess bilirubin in brain because you can't get glucuronidation to displace it due to a lack of UGT1A1 in infants)

Front 9

Trimethoprim Birth Defects

Back 9

Causes birth defects because it will inhibit folate activity and this is required during baby making time. though we get our folate through food, we have some folate synthesis biochemical activity. Cause cardiovascular and oral cleft defects.

Front 10

Fluoroquinolone mechanisms of action

Back 10

Enter through porins.
Inhibit dna gyrase (topoisomerasae II) (more for gram negative) and topoisomerase IV (more for gram positive)
TOPO II for unwinding DNA, TOPO 4 for untying replicated DNA

Front 11

Mechanism of Fluoroquinolone Resistance

Back 11

DNA gyrase mutation/topoisomerase mutation
Cellular membrane efflux mechanism
Multidrugresistance and decreased number of porins: channel loss, channel mutation, decreased porin gene expression

Front 12

Usage, names, and bacteria that 1st and 2nd generation fluoroquinolones treat

Back 12

1st gen-Nalidixic Acid-limited spectrum of Activity

2nd gen-Ciprofloxacin (MAIN ONE), (norfloxacin and ofloxacin as secondaries)
Cipro used for GRAM NEGATIVE: Mycoplasma, Chlamydia, Mycobacteria, Legionella
Cipro used for GRAM + : Bacillus anthracis
Cipro for UTI and skin infection and sometime RI
SPECIFICALLY for anthrax, osteomyelitis, febrile neutropenia, typhoid fever, and abdominal infections.

Front 13

3rd Generation Fluoroquinolones: what are they, what are they used for, Indications, ETC

Back 13

Levofloxacin (l isomer of ofloxacin)
More active against Mycoplasma, Chlamydia, and Legionella
Some activity against Gram Positive Cocci: Strepto pneumoniae
USED ESPECIALLY FOR SEPTIC AND PNEUMONIC PLAGUE, PYELONEPHRITIS

Front 14

4th gen Fluoroquinolones: what are they, what are they used for, indications: ETC

Back 14

main one is MOXIFLOXACIN (gemifloxacin is secondary)
Used for Gram Positive Cocci and Bacilli and ANAEROBES
USED ALMOST EXCLUSIVELY for respiratory infections
Uniquely used for anaerobic intra abdominal infection
NO ACTIVITY AGAINST P. aeruginosa

Front 15

Common usages and bacteria affected by 2-4 gen fluoros

Back 15

Enterobacteria, Pseudomonas sp, hemophilius influenza, moraxella catarrhalis

Treatment of osteomyelitis due to gram neg
High bone penetration
effective against sev organisms causing atypical pneumonia (non gram staining ones)

Front 16

Absorption/administration of fluoros

Back 16

Do not take with antacids, magnesium, aluminum, calcium, vitamin, mineral supplements w/iron or zinc because it will make make it harder to absorb
Cipro comes in oral, IV, topical, and eye/ear drops
Levo and Moxi are oral, IV or eye drops
Gemi is only oral

Front 17

Clearance of Fluoros

Back 17

Moxi is primarily hepatic clearance
Cipro is primary renal clearance (50)
Levo is renal -reason why used for GU

Front 18

Complications with fluoros

Back 18

Connective tissue issues: cartilage erosion and arthropathy in children EXCEPT with EYE and EAR DROPS
Tendon rupture in old pts and in pts with tendonitis
PHOTOTOX
Prolonged QT interval-blocking of incoming K thru K channels slowing repolarization (from high to low risk: moxi, gemi, levo)
Peripheral Neuropathy risk with oral, not eye/ear

Front 19

Aminoglycosides: what's a VERY general description of how they work and some VERY general properties and some VERY general uses

Back 19

Protein Synthesis inhibitors of 30S ribosome
Strong base, positive charge, water soluble
Used mostly for empirical therapy (occuring less and less nowadays) and mostly used for specific bacterial infections, zoonotic infections

Front 20

Specific Aminoglycosides: GNATS K

Back 20

gentamicin, neomycin, amikacin, tobramycin, streptomycin, kanamycin

Front 21

Gentamicin uses and half life: what bacteria and which medical conditions

Back 21

Treatment of ENDOCARDITIS, PERITONITIS, INTRA-ABDOMINAL AND PELVIC FUNCTIONS, SEPTIC STATES
Gram negative aerobes
treatment of Tularemia, Brucellosis (with doxycycline combo), Klebsiella (with pipericillin or ticracillin)
Use for serious gram negative bacillary infections
First AG to be used due to low costs, reliability and long experience of use
HALF LIFE OF 2 HOURS

Front 22

Tobramycin: uses and properties

Back 22

Almost used exclusively for P. aeruginosa in combincation with Pipericillin or ticarcilliln

Front 23

Amikacin: uses and properties

Back 23

Used when you have a resistance to gentamicin
NOT AFFECTED BY INACTIVING ENZYMES
use for serious nosocomial gram neg infections withere tobramycin and gentamycin are resisted.
EFFECTIVE for TB and atypical mycobacteria in AIDS pts

Front 24

Kanamycin: uses and properties

Back 24

BAD NEPHROTOX AND OTOTOX and therefore used only with TB and topical forms

Front 25

Neomycin: uses and properties

Back 25

Used for bowel sterilization can also be used topically
Oral-intestinal antiseptic prioer to colonic surg suppressing intestinal folora
Used with antibiotics like bacitracin and polymyxin b to treat topical skin or eye infection (combo helps wide spectrum treatment)
Cream-used alone or combo therapy with other antibio or corticosteroids for burns, wounds, ulcers

Front 26

Streptomycin: uses and properties

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USED FOR TB in hospital
Used for plague treatment (combo with doxycycline)
(plague is called yersinia pestis)

Front 27

Spectrum of coverage of AMGs

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aerobic Gram neg bacilli
WHEN USED WITH A COMPLEMENTARY AGENT (SUCH AS A CELL WALL INHIBITOR), CAN EXTEND TO GRAM POSITIVE COCCI

Front 28

Clinical Indications of AMG: empirical and direct

Back 28

Empirical usages with rapid bactericidal activity with dose limited to 48 hr and with combo of cell wall inhibitor (b lactam or vancomycin)
AG have low levels of resistance (hospital gram neg pathogens)
Direct therapy: antibiotic for gram negative infection resistant to safer antimicrobials (what does this mean?)
Combo therapy used for p. aeruginosa, brucellosis, tulaermia, and the plague
Synergistic treatment with cell wall inhibitor (blacatam) for strepto and enterococcal endocarditis.
Oral neomycin for bowel sterilization before bowel surg or colonoscopy (works because AMG are highly polar and poorly absorbed) (usually oral to reduce hepatic tox)

Front 29

Mechanism of Action for AMG

Back 29

1. Passive diffusion through porins
2. O2 dependent active transport to cytosol via O2 dependent active transporter on inner membrane
3. Binding to 30S subunit (binds irreversibly and distorts rRNA/mRNA interaction to the poitn where you don't get a proper anticodon set. This causes wrong AA to insert making the bacteria dyslexic and creating bactericidal and post antibiotic effect)
4. Disrupt Protein Synthesis (reading errors)
Irreversible binding and residual bactericidal activity present even after drug is cleared
Will produce aberrant proteins caused by misreading and premature termination of mRNA at ribosome which favor bacteria cell death

Front 30

Mechanism of Drug Resistance for AMGs

Back 30

1. Depletion or deficit of porin
2. O2 Deficit/Anerobic Organism (like facultative bacteria in an anaerobic environment) (Gram+clostridia Gram-Bacteroides/fusobacteria)
3. Enzyme alteration of AMG impairing AMG binding to 30s or ability to enter cell (acetylation-less h20 soluble, phosporylation-distort ribosomebinding/porinentry, adenylation-make less water soluble)
4. Mutation of 30s ribosome

Front 31

Dosing of AMG

Back 31

Daily dose usually admin as a single injection (IM injection) with less toxicity and equal efficacy as multi dose
YOU'D RATHER HAVE A HIGH CONCENTRATION THAN LOWER MORE FREQUENT DOSES

Front 32

Absorption and elimination of AMG

Back 32

Rapid with peak plasma in 60-90 min
does not cross BBBarrier
Doesn't penetrate eye
Elimination via glomerular filtration with half life of 2-3 hrs
Accumulation in Renal cortex and inner ear perilymph

Front 33

Toxicity of AMG and Risk factors and how to manage neuromuscular risk

Back 33

Nephrotoxicity and Ototoxicity/Vestibular TOX (8th cran nerve effects and accumulation occurs due to pH diff)
Ototox/vestitox will damage hair cells, can cause hearing loss, and physical instability and damage to vestibular nerve

Risk factors for nephrotox-low bp, loop diuretics like furosemide, old age, use of other nephrotox agens like cyclosporin in transplate pts or amphotericin in severe fungal infections

Fetal exposure-AMG accumulating in fetal plasma/amniotic fluid. (strepto and tobramycin can cause deafness in children during preg and gentamycin cause renal damage

Neuromuscular blockade with highest risk during intrapleural/intraperitoneal admin, large dose, rapid iv infusion (can cause resp arrest, aggravate/reveal MG or cause transient myasthenia syndrome----managed with neostigmine or ventilator

Front 34

GENERAL PNEUMONICS AND SMALL CHART FOR MECH/CLINCIAL USE/TOX/RESISTANCE

Back 34

see picture

Front 35

Tetracyclines: Mechanism of Actions

Back 35

Protein synthesis inhibitor on 30s rRNA
1. Passive diffusion into Bacterial Cytosol
2. Bind to 30S rUnit
3. Block Binding of Aminoacyl tRNA
4. Inhibit prot synth
5. Exert Bacteriostatic effect which is reversible unlike AMG

Front 36

CHART OF TETRACYCLINES with potency, absorption, disruption of gut, phototox, others

PNEUMONIC OF TETRA: it's a palindrome from lowestpot/highest disruption to highestpot/lowestdisruption

Back 36

TDMDT
tetracycline, demeclocycline, minocycline, doxycycline, tigecyline

Front 37

tetracyline (specific drug) properties

Back 37

low potency but disrupts the gut more than any other organ

Front 38

Demeclocycline properties

Back 38

medium potency and most phototoxic

Front 39

minocycline properties

Back 39

high potency and can reach therapeutic levels CNS for meningeal carriers and HIGH phototox

Front 40

doxycycline properties

Back 40

high potency and perferred parenteral agent especially during renal impairment with high levels of phototox

Front 41

tigecycline

Back 41

ONLY USED WHEN ABSOLUTELY NECESSARY TO PREVENT RESISTANCE TO THIS NEWER DRUG
Highest potency, least gut disruption
Considered a Glycylcycline
overcomes resistance and MRSA
Structural modification to minocycline which improves spectrum of activity
No drug interactions
Use biliary excretion so is safe in pt with renal impariment
Decreased susceptibility to TetA efflux pump and ribosomal protection
Works on gram positive aerobes including MRSA and VRE (vancomycin resistant enterococci) and gram negative bacteria and anaerobes including c perfringens and bacteriodes sp.

Front 42

Spectrum of Activity for Tetracyclines

Back 42

Broad Spec: gram negative bacteria, atypical organisms, intracellular organisms, gram positive and negative myccoplasma and ricketsia

Front 43

Treatment Indications for Tetracyclines (mostly doxycycline)

Back 43

Rickettsia (intracellular)-tick bornw infection causing rocky mountain fever, q fever, and typhus
Borrelia Burgdorferi-tick born infection causing lymeD
Chlamydia trachomatis-STD causing urethritis, PID, lymphogranuloma venereum
Chlamydia psittaci- causes psittacosis pneumonia
Mycoplasma-causing pneumonia in Young adults and ppl living in close quarters
vibrio cholera-cholera (single dose of doxy to treat)
Brucellosis, tularemia, and plauge-combo cocktail with gentamicin for brucellosis and tularemia or cocktail with strepto for plague

Front 44

tetracylines mechanism of action in a picture form

Back 44

Front 45

Resistance Mech for TETRACYCLINES

Back 45

1. TetA efflux pump-pumps tetracyclines out of cell allowing ribo to stay intact
2. Ribosomal protection - via methylation of ribosome- can be mediated by a chromosome or plasmid encoding for a protecting prot

Front 46

Absorption of Tetracyclines

Back 46

Good entry to most fluids and compartments
TET can enter placenta and CNS (usually CNS levels don't get high enough for tox or probs)
Minocycline can reach therapeutic levels in CNS

Any antacids, magnesium, calcium, dairies will chelate tet and not cause proper absorption

Front 47

Metabolism and excretion of Tetracyclines

Back 47

Phase 2 conjugation produces glucuronide metabolites....metabolism occurs in the liver and excretion occurs via biliary mechanism
it can also be cleared somewhat renaly with the exception of Doxycycline which is the only TET safe to use in renal impaired people (almost entirely biliary cleared)

Front 48

Adverse Effects of Tetracyclines on GI

Back 48

GI DISTURBANCE-irritiate mucosa and case epigastric distress
Super infection by disrupting commensal flora of gut and causing pathogenic organisms to thrive causing a SUPER infection: C difficile thrives causing psuedomembranous colitis which can be life threat----treated by metronidazole first, vancomycin second, or fidaxomicin when c difficile is ICU acquired.
metronidazole-damages DNA via reductive metabolism

Front 49

Other Adverse Effects of Tetracyclines

Back 49

Disulfiram like reaction: severe symptoms like with intake of alcohol and medication: abdominal distress vomiting flushing headache alcohol withdrawal symptoms: Accumulate acid aldehyde instead of acetic acid and will make you sick as a dog

Accumulation in teeth and bone causing discoloration due to calcium chelation.

FATAL HEPATOTOXICITY- TETs concentrate in liver and can also disrupt mitochrondrial processes leading to excess lipid production. Fatty liver deposition in pregnancy leading to fatal hepatitis
SHOULD NOT BE USED WITH PREG and BREAST FEEDING

Phototox
Vestibular issues
Diabetes Insipidus by demeclocyline

Front 50

IMAGE OF A COMPREHENSIVE ANTIMICROBIAL THERAPY REVIEW

Back 50

Front 51

How do macrolides and Ketolides work?

Back 51

Binding to bacterial 50S ribosomes

Front 52

Names of Macrolides

Back 52

Erythromycin, Clarithryomycin, Azithromycin

Front 53

Erythromycin: description/properties

Back 53

Acid Labile, poor oral absorption (esters of it are absorbed well), used in patients with penicillin allergy

Acts mainly on gram positive cocci and TREPONEMA PALLIDUM (SYPHILLIS)

Front 54

Clarithromycin: description/properties

Back 54

Intestinally absorbed and has an active metabolite allowing for a longer effect (HALF LIFE OF 3-4 HRS)

Acts on same bacteria as erythromycin: gram positive cocci...also acts on gram negative COCCI bacteria and Chlamydia, legionella, pneumophila, moraxella

Front 55

Azithromycin: description and properties

Back 55

Intestinally absorbed which highly active metabolites (HALF LIFE OF 40 HOURS)

Extended activity over clarithro and erythro to include more gram negative cocci: DRUG OF CHOICE FOR LEGIONNAIRES DISEASE

least number of drug drug interactions
USED ONCE DAILY FOR 5 days being as effective as a 10 day regimen of other macs: MORE COMPLICANCE

Front 56

Which drugs make up Ketolides and is this drugs general properties/description?

Back 56

Telithromycin: intestinally absorbed, active metabolite for longer effect (half life of 10 hours)

Used for multidrug resistant S. Pneumonia

Front 57

Clinical indications of Macs and Ketos

Back 57

Active against many Gram Postive organisms including S Aureus but not MRSA
Active against Group ABCG streptococcus

Used heavily for upper resp tract inf (particularly CAP) because they will distribute/concentrate in lung tissue and phagocytic cells, lung tissue. (serum concentrations that is lower than concentration in epithelial lining, alveolar macrophages)

SPECIFIC PATHOGENS: S pneumonia, H influenza, Moraxella, Legionella, Chlamydophila, mycoplasma

Front 58

Mechanism of Action for Ketolides and Macrolides

Back 58

1. Binds IRREVERSIBLE to 50S subunit and inhibit translocation step of prot synth (bacteriostatic manner)
2. Stops the ribosome from getting RATCHET
3. Growing peptide cannot be moved along ribosome for the next rTNA to roll thru

Front 59

Mechanisms of Resistance for Macrolides and Ketolides

Back 59

Cross resistance for Macs are high b/c of drug similarities
1. Methylation of ribosomes- methylases encoded via ERM A/B/C genes alter macrolides (erm-erythromycin ribosome methylase) VERY COMMON METHOD OF RESISTANCE
2. Macrolide efflux pumps, just like TetA pumps but prefer macs...encoded by Macrolife Efflux Genes (mef E).
Enterobacteriaceae, Pseudomonas, Acinetobacter are intrinsically resistant due to decreased perm of outer envelope

Front 60

Adverse effects of Macs/Ketos (see another note card for drug drug interactions)

Back 60

Reversible Hearing loss
Nausea, vomitting, diarrhea (time spent in GI tract determines this)
Hepatotox-rare, but serious:
1.Cholestatic jaundice caused by hypersensitivity to Erythromycin Estolate
2. Fatal hepatotoxicity caused by Telithroymycin

Cardiac tox: can cause PROLONGED QT interval (esp complicated in pts with long qt syndrome) because macs and ketos can block inward rectifying K channel

ORDER of worse to least side effects: Erythro, Clarithro, Azithro

Front 61

Drug Drug Interactions with Macs and Ketos and pregnancy usage

Back 61

Macs and Ketos interact with CYP3A
Erythro and Clarithro have interactions related to inhibition of hepatic CYP3A enzymes: NOT AZITHRO
Pts who are on drugs that inhibit CYP3A enzymes are at a five fold increase risk of SUDDEN CARDIAC death
Erythro and Azithro are CLASS B: safe for preggos in contrary to Tetracyclines

Front 62

Great chart for Macrolides including a PNEUMONIC!

Back 62

Front 63

Clindamycin: what type of drug is it considered and general properties

Back 63

IS A LINCOSAMIDE
similar to erythromycin in terms of mech of action, mech of resistance, and efficacy against nonenteric gram positive cocci

Front 64

Anti Microbial Spectrum of Clindamycin

Back 64

UNLIKE EYRTHRO: used primarily in clinical settings for ANAEROBES, mostly for those associated with abdominal anaerobic infections from trauma like bacteroides fragilis

Front 65

Adverse Effects of Clindamycin

Back 65

Increased risk for pseudomembranous colitis because of activity in gut (overgrowth of c difficile) (can be treated via metronidazole, vancomycin, or (fidaxomycin-ICU acquired PC))

Front 66

Mech of Action of Clindamycin

Back 66

Front 67

Small Chart for Clindamycin

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Front 68

Chloramphenicol: general properties

Back 68

Considered a broad spec antibiotic with limited clinical use...wide range of gram positive and negative organism
RESTRICTED USE for life threatening infections with no alternatives such as meningitis infection because of ability to cross BBB

Front 69

Adverse effects of Chloramphenicol

Back 69

Lethal side effects
Aplastic anemia:rare/idiosyncratic-individuals with G6PD def have tendency to put stress on RBC causing hemolytic anemia

Gray baby syndrome: b/c chloramp penetrates human cells and disrupts mitochondrial prot synth: abdominal distension, diarrhea, vomitting, dusky gray color which can lead to circulatory collapse and death . Syndrome is drug concentration dependent and caused by IMPAIRED GLUCURONIDATION AND RENAL CLEARANCE IN INFANTS (30 DAYS FOR RENAL CLR TO DEV AND 60 DAYS FOR GLUCURON TO DEV)

Front 70

Mechanism of Action and resistance of Chloramphenicol (checccck out the pic here)

Back 70

Binds to 50s subunit inhibiting peptidyl transferase step of prot synthesis in a bacteriostatic fashion. Also has ability to enter host cell impairing mitochondiral prot synthesis enabling toxicity

Resistance: enzymatic modif of Acetyltransferase (CAT) acetylates two hydroxyl groups causing drug to be less active and reduce binding to 50s

Front 71

Chloro Chart

Back 71

Front 72

Linezolid: what kind of drug is it considered and general properties

Back 72

Considered a OXAZOLIDINONE and used in instances of bacterial resistance
In penicillin resistant S. aureus, use Isoxazole Penicillins, in methicillin resistant S. aureus, use Vancomycin, in vancomycin resistant S. aureus/enterococci (VRSA/VRE) use Linezolid

Front 73

Mech of Action for Linezolid

Back 73

Bacteriostatic protein synthesis inhibitor
binds to 50s ribosome and interferes with its binding to initiation complex

Front 74

Linezolid Clearance and Toxicity

Back 74

Does not induce CYP450, inhibit, or act as substrate for CYP450

Cleared renally
With long term use: increased ALT (alanine aminotransferase) decreased platelet count, interaction with MAO (monoamine oxidase) which can lead to peripheral neuropathy

Front 75

GREAT REVIEW SLIDE OF PROTEIN SYNTH INHIBITOR

ALSO GREAT PNEUMONIC

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