Pharmacology Flashcards
What is the MOA of Dopamine?
- Has direct alpha, beta, and dopaminergic effects
- Effects likely to be dose related;
- Dopaminergic vasodilatory effects at low dosages
- Beta effects at mid-range dosages
- Alpha effects at high dosages
- Dopamine generally causes a moderate vasoconstriction and increase in BP with little change/modest increase in cardiac output
What is the MOA of Dobutamine?
- Synthetic analogue of dopamine
- Strong beta-1 agonist activity
- Mild beta-2 and alpha-1 receptor activity
- NO dopaminergic effects
- Generally causes moderate vasodilation and a marked increase in cardiac output with little change in blood pressure
What is the MOA of ephedrine?
- Acts by increasing the release of norepinephrine from sympathetic nerve endings
- Has MILD direct beta agonist effects
- Modest decrease in heart rate, increase in cardiac output, vascular resistance and arterial blood pressure
- Prolonged use can deplete norepinephrine stores, resulting in tachyphylaxis
What is the MOA of norepinephrine?
- Primarily an alpha-receptor agonist
- Minimal beta-1 receptor activity
- Generally causes vasoconstriction and increases BP with variable effects on HR.
- CO may increase, decrease, or remain unchanged
- Animals with an effective circulating volume but with vasodilation would likely have an increase in CO dt venoconstriction of capacitance vessels
- CO may increase, decrease, or remain unchanged
What is the MOA of phenylephrine?
- Strict alpha receptor agonist
- NO beta activity
- Causes vasoconstriction and an increase in arterial BP, decrease in HR
What is the MOA of vasopressin (with regards to vascular actions…)?
- Acts via vasopressin V1 receptor increasing intracellular calcium and vasomotor tone
- PURE vasoconstritor with no diret effect on heart
- Increase in systemic vascular resistance
- Baroreceptor reflex decrease in HR
No change in contractility - No change or a decrease in CO
- Baroreceptor reflex decrease in HR
What is the MOA of epinephrine?
- Potent beta-1, 2 and alpha-1,2 receptor agonist
- Positive inotrope, chronotrope, arteriolar and venular vasoconstrictor
- Can be used in critically ill patients, but therapeutic margin may be much lower due to higher incidences of sinus tachycardia, ventricular arrythmias and increased lactate levels
What is the MOA of isoproterenol?
- Potent beta agonist with NO alpha action
- Potent vasodilator and hypotensive agent
- Increases heart rate and cardiac output, decreases blood pressure
- If administered very carefully while BP is monitored and maintained, can provide potent augmentation of forward blood flow and tissue perfusion
Define breakpoint.
The highest achievable MIC that still inhibits growth of the micro-organism.
Based on achievable serum concentrations, not tissue, which are typically slightly less than serum.
Define MIC
The lowest concentration of an antimicrobial that inhibits growth of a micro-organism.
An organism is susceptible to the antimicrobial if the MIC is below the breakpoint for that antimicrobial.
What are the 3 types of bacterial resistance?
- Intrinsic resistance
- Inherent feature of a microorgnaism that results in lack of activity of an antimicrobial drug or class of drugs.
- Circumstantial resistance
- When an in vitro test predicts susceptibility, but in vivo, the antimicrobial lacks clinical efficacy
- May be due to lack of the drug to penetrate the site of infection or inability to work because of a local pH
- When an in vitro test predicts susceptibility, but in vivo, the antimicrobial lacks clinical efficacy
- Acquired resistance
- Change in the phenotypic characteristics of a micro-organism (compared to wild type) which confers decreased efficacy of an antimicrobial against that microorganism (MULTIPLE mechanisms!)
What defines an MDR infection?
Organisms that are not susceptible to at least one agent in three or more classes of drugs to which they are usually susceptible
What are the 3 primary mechanisms of acquired resistance?
- A decrease in intracellular drug entery from efflux pumps or altered membrane structure
- Enzymes that modify or destroy antimicrobials
- Modification of the target of the antimicrobials (DNA gyrase mutation)
Genes imparting resistance are shared among organisms by integrins, plasmids and transposons that facilitate rapid transfer of multidrug resistance.
What is a beta-lactamase?
An enzyme that hydrolyzes and disrupts the beta-lactam ring in the beta-lactam group of antimicrobials. This confers resistance to many penicillins.
Discuss escalation versus de-escalation protocols.
- Escalation
- Protocols that involve a single antibiotic, carefully chosen to treat what is thought to be the most likely source of infection
- After C&S results return, either to be continued or changed if it is wrong
- De-escalation
- Protocols that involve broad-spectrum antibiosis with the intent to rapidly narrow the spectrum to the most appropriate antibiotic (possibly only a single antibiotic) as soon as culture results return
What are the beta-lactam antimicrobials? What is their MOA? Are they static or cidal? Can they readily cross biologic membranes?
- Penicillins, cephalosporins, carbapenems
- MOA
- Interfering with bacterial cell wall synthesis by binding and inhibiting PBPs that catalyze the cross-linking of the glycopeptides that form the bacterial cell wall
- Bactericidal
- Do a poor job of crossing biologic membranes; concentrations in eyes, testes, brain, prostate typically low
- Can penetrate BBB if there is meningeal inflammation
- Excreted actively by kidney into urine, concentrations in urine can be several times higher than serum
What are the different generations of the cephalosporins?
- First generation
- Cefazolin, cephalexin
- Mainly gram positive, some gram negative
- Second generation
- Cefoxitin, cefuroxime
- Gram positive, more gram negative
- Third generation
- Cefovecin, ceftazidime, cepodoxime
- Vary greatly in efficacy, however, some have extremely high gram negative coverage (i.e. ceftazidime)
What are the aminoglycoside antimicrobials? What is their MOA? What is their spectrum? Are they static or cidal? Concentration or time dependent?
- Gentamicin, amikacin
- Best choices for severe gram negative infections
- MOA
- Impair protein synthesis by ribosomal 30s binding
- Spectrum
- Most community acquired gram negative aerobes, select gram positives
- Bactericidal
- Do not readily cross biologic membranes (no good for abscesses).
- Concentration dependent (therefore once daily dosing)
What are the fluoroquinolones? What is their MOA? What is their spectrum? Are they static/cidal?
- Enrofloxacin, marbofloxacin etc
- MOA
- Inhibition of DNA gyrase and topoisomerase
- Highly effective against aerobic gram negative organisms
- Bactericidal
- Excellent tissue distribution–concentration in tissues ofen exceeds that in serum
- Concentration dependent
What are the macrolide antimicrobials? What is their MOA? Spectrum? Are they static or cidal?
- Azithromycin, erythromycin
- MOA
- Reversible binding of the 50s ribosome
- Spectrum
- Gram positives, mycoplasma, anaerobes
- Azithromycin has a strong gram negative spectrum however
- Bacteriostatic
- Highly tissue distributed
What is amphotericin B? MOA, uses, adverse effects?
- A polyene antibiotic used to treat systemic mycoses
- “Gold standard” for antifungal therapy
- Binds to ergosterol in fungal cell membranes, increasing membrane permeability to cause cell death
- Major toxicity is nephrotoxicity
What are the azole anti-fungals?
- Inhibit the fungal P-450 enzyme necessary for development of ergosterol in fungal cell walls
- Of the commonly used azoles, ketoconazole is the most likely to induce mammalian P450 enzymes to cause elevations in liver enzymes; clinical hepatitis, which may be fatal, has also been recognized
What is the MOA of metronidazole? Spectrum? Cidal/static? Other properties?
- MOA
- Not well understood; thought to disrupt DNA and inhibit nucleic acid synthesis
- Broad spectrum anaerobic coverage, some protozoal coverage
- DIffuses well into tissues and body fluids
- Bactericidal
- Has some immunomodulatory effects which may help ameliorate clinical signs in animals with inflammatory enteropathies
What is the MOA of chloramphenicol? Spectrum? Static/cidal? Other properties?
- MOA
- Acts on ribosomal 50s subunit, supressing activity of peptidyl transferase
- Spectrum
- Gram positive and negative aerobes/anaerobes, spirochets, rickettsia, mycoplasma…
- Either static or cidal depending on the organism
- Can cause reversible bone marrow suppression and GI upset
- Associated with aplastic anemia in people
What is the MOA of the tetracyclines? Spectrum? Cidal/static?
- MOA
- Bind to 30s subunit
- Bacteriostatic
- Wide spectrum (at least for doxy)–positive, negative, aerobes, anaerobes
- Also has effects on inflammation, immunomodulation, inhibition of collagenase activity and wound healing
What is the MOA of the sulfonamides? Spectrum? Static/cidal?
- MOA
- Inhibition of 2 consecutive steps in bacterial folic acid synthesis
- Bactericidal against gram negatives, staphylococci (+)
- Unpredictable against strep
- NO activity against anaerobes or enterococci
What is the MOA of clindamycin? Spectrum? Static/cidal?
- Lincosamide
- MOA
- Binds 50s ribosomal subunit
- Wide distribution
- Bactericidal in some cases
- Gram positive spectrum, anaerobes
