ch 86 tetracyclines, macrolides

tetracyclines elimination

-Short and intermediate acting eliminated by kidneys -Long acting eliminated by liver

Which tetracycline may be administered with meals? A. Tetracycline B. Demeclocycline C. Doxycycline D. Minocycline

Answer: D Rationale: Tetracycline, demeclocycline, and doxycycline should be administered on an empty stomach. Minocycline can be administered with meals

tetracyclines distribution

Widely distributed, but poorly crosses blood brain barrier (levels in the CSF are too low to treat meningeal infections)

dalfopristin/quinupristin

-First members of streptogramins (new class of antibiotics) -Inhibit bacterial protein synthesis -When used separately they are bacteriostatic, however when used in combination they are bactericidal. -Principal indication: VRE -Adverse effects: Hepatotoxicity is the major concern - blood should be tested for liver enzymes and bilirubin at least twice during the first week of therapy and weekly thereafter. -Drug interactions: inhibit hepatic drug metabolizing enzymes, specifically CYP3A4

drug and food interaction with tetracyclines****

-Absorption of tetracyclines is decreased if drug is given with: --Milk products --Calcium supplements --Iron supplements --Magnesium-containing laxatives --Most antacids

macrolides

-Antibacterial spectrum similar to penicillin- active against most gram + and some gram - -Treatment of first choice for several infections and may be used as an alternative to penicillin G in patients with a penicillin allergy

linezolid

-Bacteriostatic inhibitor of protein synthesis -Cross-resistance with other agents unlikely -Active against aerobic and facultative gram-positive bacteria -should be reserved for infections caused by VRE and MRSA -Facultative (enabling or capable of permitting something to happen or be done, but not able to force its occurrence)

chloramphenicol

-Broad-spectrum antibiotic -Inhibits protein synthesis -Because of the risk of severe blood disorders, use is limited only for life-threatening infections for which safer drugs are ineffective or contraindicated -Adverse effects:: --Reversible bone marrow depression --Fatal aplastic anemia --Gray syndrome: the syndrome results from accumulation of choramfenicol to high levels. If the drug use is discontinued immediately when early symptoms appear, the syndrome is usually reversible (vomiting, abdominal distention, cyanosis, and gray discoloration of the skin) --GI effects (vomiting, diarrhea) occur occasionally --Peripheral neuropathy develop rarely usually in association with prolonged treatment

macrolides (erythromycin)

-Broad-spectrum antibiotic -Mechanism of action (MOA): inhibition of protein synthesis -Usually bacteriostatic but can be bactericidal against highly susceptible organisms or in high concentrations -Erythromycin is a commonly used antibiotic and may be used as an alternative to penicillin G inpatients with penicillin allergy -Oldest member- erythromycin -Newest Member (Derivatives of Erythromycin): --Azithromycin --Clarithromycin

tetracyclines

-Broad-spectrum antibiotics -Inhibit protein synthesis -Increasing bacterial resistance has emerged --Increased drug inactivation --Decreased access to ribosomes --Reduced intracellular accumulation

other macrolides

-Clarithromycin [Biaxin] -Azithromycin [Zithromax]: Prolonged QT interval

clindamycin ADRs

-Clostridium difficile-associated diarrhea (CDAD): most severe toxicity of clindamycin. The cause is Suprainfection of the bowel with C. difficile. --CDAD is characterized by profuse, watery diarrhea; 10-20 watery stools per day, abdominal pain, fever, and leukocytosis (increase in number of white blood cells). --Patient should be instructed to report significant diarrhea (more than 5 watery stools per day). --If CDAD is diagnosed, clindamycin should be discontinued and the patient given oral vancomycin or metronidazole -Hepatic toxicity -Blood dyscrasias (agranulocytosis, leukopenia, thrombocytopenia) -Diarrhea (not caused by C. Diff) -Hypersensitivity reactions- especially rashes occur frequently -Rapid IV administration can cause electrocardiographic changes, hypotension, and cardiac arrest

drug interactions with macrolides

-Erythromycin increases levels of : Theophylline, carbamazepine, and warfarin- monitor closely for signs of toxicity -Prevents binding of chloramphenicol and clindamycin, antagonzing their antibacterial effects- do not give concurrently -Should not be given with drugs that inhibit erythromycin metabolism including verapamil, diltiazem, HIV protease inhibitors, and azole antifungal drugs

tigecycline (tygacil)

-First in class glycylcycline class -Tetracycline derivative to overcome resistance -Active against broad spectrum of bacteria -Associated with increased mortality (acute pancreatitis) -ADRs similar to tetracycline

linezolid (zyvox)

-First member of a newer class of antibiotics: oxazolidinones -It is active against multidrug-resistant gram-positive pathogens (eg, vancomycin-resistant enterococci [VRE], methicillin-resistant Staphylococcus aureus [MRSA]) --To delay emergence of resistance, should be reserved only for VRE and MRSA even though it is approved for other uses******

telithromycin

-First representative of ketolide class of antibiotics -It is effective against strains of Streptococcus pneumoniae that are resistant to penicillin and macrolides -Adverse effects:: --GI effects (diarrhea, nausea, vomiting and loose stools) --Severe liver injury, so should only be used when necessary --Worsen muscle weakness in myasthenia gravis patients, therefore it is contraindicated --About 1% experience Visual disturbances (blurred vision, double vision, and difficulty focusing). Females and patients under 40 years are at highest risk. They can persist for hours - symptoms may or may not recur with subsequent doses --Prolonged QT interval

linezolid agaim

-Generally well tolerated -Most common side effects Diarrhea, Nausea and vomiting, Headache -Oral suspension contains phenylalanine so cannot be used on patients with phenylketonuria -May also cause reversible myelosuppression manifesting as anemia, leukopenia, thrombocytopenia, pancytopenia -Dependant on length of tx; should monitor CBC weekly -Reversible optic neuropathy and irreversable peripheral neuropathy:: --Prolonged therapy- 5 months or more

clindamycin (cleocin)

-Inhibits protein synthesis -Can induce severe Clostridium difficile-associated diarrhea (CDAD) (can be fatal) -Indicated only for certain anaerobic infections located outside the central nervous system (CNS) -does not cross blood brain barrier --drug of choice for Severe Group A Streptococcal infection, gas gangrene, and infections of abdomen and pelvis caused by B. fragilis.

macrolides (erythromycin)

-Oral erythromycin available in three forms:: --Erythromycin base, and two derivatives of base: erythromycin stearate and erythromycin ethylsuccinate -Food decreases the absorption of erythromycin base and erythromycin stearate -Erythromycin lactobionate is IV form -Distributes to most tissues and body fluids- poor penetration to CSF -Crosses placenta, but no ADRs known from this -Primarily eliminated by hepatic mechanisms

administration of tetracycline

-PO preferred method, IV, -IM rarely given bc very painful -As a rule, give on empty stomach (1 hour before or 2 hours after meal) and with full glass of water -2 hours between administration of medication and any chelating products (milk calcium, iron supplements, antacids, or magnesium) -IV only if when oral therapy cannot be tolerated or has proved inadequate (IV therapy has been associated with severe liver damage, particularly in pregnant and postpartum women with kidney disease) -IM injection is extremely painful and is rarely used -Dosage variable by the nature and intensity of the infection

therapeutic uses for macrolides

-Preferred tx for pneumonia caused by Legionella pneumophilia -Drug of first choice for Whooping cough, bordetella pertussis, acute diphtheria, Corynebacterium diphtheriae, chlamydial infections, M. pneumoniae, group A Streptococcus pyogenes -May be used as an alternative to penicillin G in patients with penicillin allergy

tetracyclines use for which they are first line therapy

-Rickettsial disease -Infections caused by -Chlamydia trachomatis -Brucellosis -Cholera -Pneumonia caused by Mycoplasma pneumoniae -Lyme disease -Anthrax -Gastric infection with Helicobacter pylori (used in combo with metronidazole and bismuth subsalicylate) -Acne (topically and orally) -Peptic ulcer disease -Periodontal disease -Rheumatoid arthritis

four members of the tetracycline family available for systemic therapy

-Tetracycline -Demeclocycline -Doxycycline -Minocycline

summary of major precautions with tetracyclines

-Tetracycline and demeclocycline are eliminated primarily in urine; they accumulate in patients with kidney disease -Tetracyclines can cause discoloration of deciduous and permanent teeth*** -Diarrhea may indicate a potentially life-threatening suprainfection of the bowel -High-dose IV therapy has been associated with severe liver damage

tetracyclines absorption: chelation

-Tetracycline, demeclocycline, and doxycycline absorption reduced by food. Minocyclone is not -All form insoluble chelates with calcium, iron, magnesium, aluminum, and zinc causing decreased absorption -They should not be administered with calcium supplements, milk products, iron supplements, magnesium containing laxatives, and most antacids*****

adverse effects of tetracyclines

-Tetracyclines irritate the GI tract - as a result oral therapy is frequently associated with gastric burning, cramps, nausea, vomiting, and diarrhea - these reactions can be reduced by giving tetracyclines with meals - although food may decrease absorption. -Occasionally, tetracyclines cause esophageal ulceration - Risk can be minimized by avoiding dosing at bedtime. -Because diarrhea may result from Suprainfection of the bowel, it is important that the cause of diarrhea be determined (adverse drug reaction) -Tetracyclines bind to calcium in developing teeth, resulting in yellow or brown discoloration; Hypoplasia of the enamel may also occur (enamel may not develop on the teeth) -When taken after the fourth month of gestation, tetracyclines can cause staining of deciduous teeth of the infant. However it will not affect permanent teeth. -Discoloration of permanent teeth occurs when tetracyclines are taken by patients ages 4 months - 8 years (the time frame when tooth enamel is being formed) so should not be used in children less than 8 years old --Tooth discoloration is less likely with doxycycline -Because tetracyclines are broad-spectrum agents the risk of superinfection are greater. Such as C-diff and Candida -Liver damage is most likely when tetracyclines are administered IV in high doses (greater than 2 gm/day) --Pregnant and postpartum women with kidney disease is especially at risk. (eliminated by the kidneys) -Tetracyclines may exacerbate renal impairment in patients with pre-existing kidney disease. Short and intermediate are eliminated by the kidneys so if a patient with renal impairment requires a tetracycline either doxycycline or minocycline (long acting) should be used. - Photosensitivity: All tetracyclines can increase the sensitivity of the skin to ultraviolet light. Educate client to avoid prolonged exposure to sunlight, wear protective clothing, and apply a suncreen to exposed skin.

bacteriostatic inhibitors of protein synthesis

-These drugs inhibit bacterial protein synthesis -Largely bacteriostatic -Most of these are 2nd line agents, used primarily for infections resistant to 1st line agents

retapamulin and mupirocin

-Topical antibiotics indicated for impetigo -Mupirocin: also for MRSA in nostrils

drug interactions with linezolid

-Weak inhibitor of monoamine oxidase, hence, poses a risk of hypertensive crisis -Can cause severe hypertension if combined with indirect acting sympathomimetics (ephedrine, cocaine etc) or with foods containing large amounts of tyramine (aged and fermented foods- cheese, meats treated with salt, cured meats) -Combo with SSRIs can increase risk of serotonin syndrome resulting in death (Serotonin syndrome symptoms usually occur within several hours of taking a new drug or increasing the dose of a drug you're already taking. Severe signs and symptoms include high fever, seizures, irregular heartbeat, unconsciousness)

tetracyclines duration of action

-divided in 3 groups:short acting, intermediate and long acting. These differences are related to differences in lipid solubility

macrolides (erythromycin) ADR

-one of safest antibiotics -Erythromycin is one of the safest antibiotics GI disturbances: epigastric pain, nausea, vomiting, diarrhea are most common side effects. --Can minimize by giving with food (if absorption not affected by food) -QT prolongation and sudden cardiac death --In high concentrations erythromycin can cause QT prolongation posing a risk of Torsades de pointes (tor·sades de pwant) a potential fatal ventricular dysrhythmia. Sudden death can occur. -Erythromycin should be avoid in patient with congenital QT prolongation and those taking antidysrhythmic drugs and CYP3A4 inhibitors -By killing off sensitive gut flora, erythromycin can promote Suprainfection of the bowel

A patient is prescribed doxycycline [Vibramycin]. If the patient complains of gastric irritation, what should the nurse do? A. Instruct the patient to take the medication with milk B. Tell the patient to take an antacid with the medication C. Give the patient food, such as crackers or toast, with the medication D. Have the patient stop the medication immediately and contact the health care provider

Answer: C Rationale: Tetracyclines form insoluble chelates with calcium, iron, magnesium, aluminum, and zinc; absorption is decreased. Tetracyclines should not be administered together with milk or antacids. Long-acting tetracyclines, such as doxycycline, may be taken with food; food does not affect absorption.

A patient recently began receiving clindamycin [Cleocin] to treat an infection. After 8 days of treatment, the patient reports having 10 to 15 watery stools per day. What will the nurse tell this patient? A. The provider may increase the clindamycin dose to treat this infection. B. This is a known side effect of clindamycin, and the patient should consume extra fluids. C. The patient should stop taking the clindamycin now and contact the provider immediately. D. The patient should try taking Lomotil or a bulk laxative to minimize the diarrheal symptoms.

Answer: c Clostridium difficile-associated diarrhea (CDAD) is the most severe toxicity of clindamycin; if severe diarrhea occurs, the patient should be told to stop taking clindamycin immediately and to contact the provider so that treatment with vancomycin or metronidazole can be initiated. Increasing the dose of clindamycin will not treat this infection. Consuming extra fluids while still taking the clindamycin is not correct, because CDAD can be fatal if not treated. Taking Lomotil or bulk laxatives only slows the transit of the stools and does not treat the cause.