Macrolides, Clindamycin, Streptogramins Flashcards by Sheng Saladaga

Prototype drug of macrolides

Erythromycin

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Are semisynthetic derivatives of erythromycin

Clarithromycin and azithromycin

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Are a group of closely related compounds characterized by a macrocyclic lactone ring (14 to 16 atoms) to which deoxy sugars are attached

Macrolides

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General structure: macrolide ring and 2 sugar moieties desosamine and cladinose attached to a 14 atom lactone ring

Poorly soluble in water but dissolves readily in organic solvents

Erythromycin

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Is a combination of two streptogramins - _____, a streptogramin B and _____, a streptogramin A in a 30:70 ratio

Quinupristin - dalfopristin

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Shares the same ribosomal binding site as the macrolides and clindamycin and thus inhibit protein synthesis in an identical manner

Streptogramins

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Quinupristin-dalfopristin is rapidly bactericidal for most susceptible organisms except ______, which is killed slowly

Enterococcus faecium

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Streptogramin has resistance to _______ due to modification of quinupristin binding site and enzymatic inactivation of dalfopristin, or efflux

E. Faecalis

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Quinupristin-dalfopristin is active against

Gram positive cocci including
multidrug resistant strains of streptococci, penicillin resistant strains of S pneumoniae, methicillin susceptible and resistant strains of stap and E. faecium

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Quinupristin-dalfopristin is eliminated by what route?

Fecal route

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True or false: dose adjustment is not necessary in Quinupristin-dalfopristin for cases of renal failure, peritoneal dialysis or hemodialysis

True

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True or false: Quinupristin-dalfopristin significantly inhibit CYP3a4 which metabolizes warfarin, diazepam, cisapride, cyclosporine etc

True (dosage reduction of cyclosporin may be necessary)

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Clinical use of Quinupristin-dalfopristin

Treatment of infections caused by staphylococci or by vancomycin resistant strains of E faecium

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Principal toxicities of Quinupristin-dalfopristin

Infusion related events such as pain at infusion site and arthralgia-myalgia syndrome

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Is a chlorine subsituted derivative of lincomycin, an antibiotic that is elaborated by Streptomyces lincolnensis

Clindamycin

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Like erythromycin, it inhibits protein synthesis by interfering with the formation of initiation complexes and with aminoacyl translocation reactions

Clindamycin

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The binding site for clindamycin is on the ____ subunit of the bacterial ribosome identical with erythromycin

50S subunit

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Clindamycin, 0.5-5 mcg/ml inhibits the ff:

Streptococci, staphylococci and pneumococci

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Organisms resistant to clindamycin:

Enterococci and gram negative aerobic organism

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Usually susceptible to clindamycin:

Bacteroides sp and other anaerobes (+ and -)

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Resistance to clindamycin, which generally confers cross resistance to macrolides, is due to:

Mutation of ribosomal receptor site
Modification of the receptor by a constitutively expressed methylase
Enzymatic inactivation of clindamycin

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True or false: clindamycin is about 90% protein bound

True

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Clindamycin penetrates well into most tissues except for _____ and ______.

Brain and CSF

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Clindamycin is metabolized by the _______, and both active drug and active metabolites are excreted in _____ and ______.

Liver
Bile
Urine

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True or false: clindamycin penetrates well into abscesses and is actively taken up and concentrated by phagocytic cells

True

Clinical use of clindamycin

Treatment of skin and soft tissue infections caused by strep and staph Active against community acquired strains of MRSA

True or false: clindamycin is also indicated for the treatment of infections caused by bacteroides sp and other anaerobes

True

Drugs used to treat penetrating wounds of the abdomen and gut; infections originating in the female genital tract (eg PID, septic abortion) and lung abscess

Clindamycin + aminoglycoside or cephalosporin

Clindamycin is now recommended rather than erythromycin for prophylaxis of ______ in pts with specific valvular dse who are undergoing _____ procedures and have allergy to penicillin

Endocarditis | Dental procedures

Is an effective alternative to Trimethoprim-sulfamethoxazole for moderate to moderately severe P. jiroveci pneumonia in AIDS pts

Clindamycin + primaquine

Indicated for AIDS related toxoplasmosis of the brain

Clindamycin + pyrimethamome

Administration of clindamycin is a risk factor for diarrhea and colitis due to ______

C. Difficile

True or false: the antibacterial action of erythromycin and other macrolides may be excitatory or bacteriostatic, particularly at higher concentrations for susceptible organisms.

False. Inhibitory or bactericidal

True or false: erythromycin's activity is enhanced at acidic pH.

False. Alkaline pH

Inhibits protein synthesis occurring via binding to the 50S ribosomal RNA. The binding site is near the peptidyltransferase center and peptide chain elongation is prevented by blocking of the polypeptide exit tunnel

Erythromycin

True or false: in clindamycin, peptidyl-tRNA is dissociated from the ribosome.

False. Erythromycin

Erythromycin is active against susceptible strains of:

Gram positive organisms ( pneumococci, strep, staph and corynebacteria) Gram negative organisms (Neisseria sp, Bordetella pertussis, Bartonella sp, Rickettsia sp.

True or false: T. Pallidum and Campylobacter sp. are susceptible to erythromycin.

True

True or false: H. influenzae is less susceptible to erythromycin

True

Resistance to erythromycin is usually ________-encoded?

Plasmid-encoded

_____ and _____ are the most important resistance mechanisms in gram positive organisms

Efflux and Methylase production

Constitutive methylase production confers resistance to structurally unrelated but mechanistically similar compounds such as clindamycin and streptogramin B called ______, which share the same ribosomal binding site

Macrolide-lincosamide-streptogramin B or MLS type B

Erythromycin base is destroyed by _________ and must be be administered with ______ coating

Stomach acid, enteric coating

True or false: food does not interfere with absorption while taking erythromycin

False

_____ and ____ are fairly acid resistant and somewhat better absorbed

Stearates and esters

Is the best absorbed oral preparation for erythromycin

Erythromycin estolate (lauryl salt of propionyl ester of erythromycin)

True or false: dialysis can removed erythromycin

False. Large amount is excreted in the bile and lost in feces and only 5% excreted in the urine

True or false. Erythromycin is distributed widely except to the brain and CSF

True

True or false: erythromycin is taken up by PMN leukocytes and macrophages

True

True or false: erythromycin does nit traverse the placenta and reaches the fetus

False

Traditional drug of choice in corynebacterial infections ( diphtheria, sepsis, erythrasma) and in respiratory, neonatal, ocular or genital chlamydial infections

Erythromycin

True or false. Macrolide resistance is increasing in pneumococci and M. pneumoniae

True

True or false. Erythromycin resistance in staph and in strains of Group A strep has made macrolides less attractive as first line agents for treatment of pharyngitis and skin and soft tissue infections

True

Although ________ is the best absorbed salt, it imposes the greatest risk of adverse reactions

Erythromycin estolate

Oral erythromycin is sometimes combined with ______ or ________ for preoperative preparation of the colon

Oral neomycin or kanamycin

__________ is the most common reason for discontinuing erythromycin and substituting another antibiotics

Gastrointestinal intolerance

Erythromycin estolate can produce _______, probably as a hypersensitivity reaction

Acute cholestatic hepatitis

True or false: most pts can recover from acute cholestatic hepatitis, but it recurs if the drug is readministered

True

Erythromycin metabolites inhibit CYP P450 enzymes and thus increase serum concentrations of:

``` Theophylline Warfarin Cyclosporine Methylprednisolone Oral digoxin (increase bioavailability) ```

Is derived from erythromycin by addition of a methyl group and has improved acid stability and oral absorption compared with erythromycin

Clarithromycin

Clarithromycin is similar with erythromycin with respect to antibacterial activity except it is more active against:

Mycobacterium avium complex

Clarithromycin also has activity against:

M. leprae T. gondii H. influenzae

True or false: clarithromycin has a longer half life (6 hr) compared with erythromycin which permits twice daily dosing

True

Clarithromycin is metabolized in the _____. The major metabolite is ______.

Liver | 14 hydroxyclarithromycin

True or false: clarithromycin is eliminated in the urine

True

True or false: in clarithromycin, dosage requirement is not needed for patients with creatinine clearances of less than 30 ml/min

False. Dosage reduction is recommended

What is the advantage of giving clarithromycin compared with erythromycin?

Lower incidence of GI intolerance and less frequent dosing

Is a 15 atom lactone macrolide ring compound, is derived from erythromycin by addition of a methylated nitrogen into the lactone ring

Azithromycin

Azithromycin is: a A. active against: B. slightly less active than erythromycin and clarithromycin against: C. Slightly more active against: D. Highly effective against:

A. M. avium complex and T. gondii B. Staph and strep C. H. influenzae D. Chlamydia sp.

Azithromycin may prolong ________ due to an effect on potassium ion channels

QT interval ( prolongation of the QT interval can lead to torsades de pointes arrythmia

True or false: recent studies have suggested that azithromycin may be associated with a small increased risk of cardiac death

True

True or false: azithromycin is slowly released from tissues ( half life 2-4 days ) to produce an elimination half life approching 3 days

True

Has unique properties that permit once daily dosing and shortening of the duration of treatment in many cases

Azithromycin

When should azithromycin be administered:

1 hr before or 2 hrs after meals

True or false: azithromycin is rapidly absorbed and well tolerated orally

True

True or false: Because azithromycin has a 15 member lactone ring, it does not inactivate CYP P450 enzymes and therefore free of drug interactions

True

Are semisynthetic 14 membered ring macrolides, differing from erythromycin by substitution of a 3 keto group for neutral sugar L-cladinose

Ketolides

E.g of ketolides approved for limited clinical use

Telithromycin

Telithromycin is now indicated only for the treatment of ______ in the USA

Community acquired bacterial pneumonia

Telithromycin was removed as an indication for respiratory tract infections due to:

It can result in hepatitis and liver failure

Telithromycin is also contraindicated in pts with _________

Myasthenia gravis ( it may exacerbate this condition)