Pharmacology - Chloramphenicol, Tetracycline, Clindamycin Flashcards
How are tetracylines formulated and how does this effect them metabolically?
What factor decreases GI absorption?
What is the mechanism of action of tetracyclines?
- They are formulated as hydrochlorides which allow them to be water soluble.
- GI absorption is decreased by the presence of food in the GI and a high pH
- Reversibly blocks the 30s ribosome to prevent protein synthesis
What is the spectrum of anti-microbial activity for tetracycline?
- Broad spectrum with activity against many gram positive and gram negative (Chlamydia, mycoplasmas, Rickettsiae and L-forms. They are also effective against protozoa like amebas.
How do tetracyclines enter susceptible bacteria?
What alternatives are there to fight microbials with tetracycline resistant efflux pumps?
- In part by simple diffusion and through active transport
Doxycucline, minocycline, and tigecycline
What are 3 general ways that resistance can be developed to tetracycline?
1) Impaired influx or enhanced efflux (of tetracycline) by an active transport protein pump
2) Ribosome protection
3) Enzymatic inactivation of the drugs
What is soo freaking special about Tigecycline’s ability to knock off bacteria?
- It is effective even against the Tet (A) efflux-expressing gram negative strains having resistance to the older tetracyclines/
What 3 drugs can overcome Tet (K) resistance to tetracyclines.
doxycyclines, minocycline, or tigecycline
What 3 drugs can overcome Tet (M) ribosomal protection expressed by gram positive strains confers resistance to tetracyclines.
Doxycycline, minocycline, and tigecycline
How is Tigecycline absorbed?
What is the percentage of Doxycline and Minocycline absorption?
- through IV (100%)
- 95-100%
What two tetracyclines are not impaired by food in the GI tract?
What food products or Cations can impair the GI absorption of tetracycline?
- Doxycyline and minocycline
- Concurrent ingestion of dairy products, antacids or the cations like Ca+, Mg2+, Fe2+, or Al3+
What is the distribution range of Tetracyclines?
What is its effects on fetuses and kids?
- Everywhere - except the CNS where only a small portion is present
- Crosses the placenta, found in breast milk, bind calcium and damage bones and teeth especially in children, not good for children younger than 8 years old due to active epiphysis.
What drug attains high concentrations in saliva and tears making it useful for eradication of the meningococcal carrier state?
- Minocycline
How are tetracyclines mainly excreted?
What two tetracyclines are excreted via non-renal mechanisms?
- excreted mainly in the urine and in the bile with enterohepatic circulation.
- Doxycycline and tigecycline
What is the range of T1/2 for some of the top lasting tetracyclines?
- Tigecycline (36 hrs)
- Doxycycline and minocycline (16-18 hrs)
- Demeclocycline and methacycline (12 hrs)
What types of infections is tetracyclines useful in?
- Infections involving Mycoplasma, pneumoniae, Rickettsiae (Rocky mountain fever), Chlamydia, Trachoma, Antrax, and some Spirochetes
- Helcobacter pylori-induced ulcers
What disease caused by vibrio does tetracycline have a rapid response to?
- Cholera
What is Tetracycline’s effects in STDs?
- Effective against most Chlamydial infections but is no longer indicated for gonoccal infections due to resistance.
Tetracyclines are used in combination with aminoglycosides to treat what?
- What Protozoal infections are indicated with tetracyclines?
What tetracycline might be used to treat ADH secreting tumors?
plague, tularemia, and brucellosis
- Entramoeba histolytica or Plasmodium falciparum
- Demeclocycline
What are some other diseases treated with Tetracyclines?
- Acne
- exercitation of bronchitis
- community acquired pneumonia
- Lyme disease
- relapsing fever
- leptospirosis
- Mycobacterium marinum
What types of activity does Tigecycline have against resistant bacteria?
- Coagulase negative staphylococci and Staphylococci aureus and methicillin -resistant strains. Streptococci, penicillin susceptible and resistant, enterococci, vancomycin-resistant strains and gram negative rods. Effective against Enterobacteriacae, multiple resistant strains of Acenitobacter species, Rickettsiae, chlamydia, and legionella.
- ** Proteus and Pseudomonas aeruginosa are resistant
What are the 6 main uses for tetracyclines?
- Cholera
- Malaria
- Parrot Fever
- Lyme Disease
- Rocky mountain spotted fever
- Q-fever
What are the adverse effects of Tetracyclines on the GI tract?
Due to disruption of normal flora giving rise to overgrowth of bacteria what might result?
- nausea, vomiting, and diarrhea
- Anal pruritus, vaginal, or oral candidiasis
Where are tetracyclines deposited in kids less then 8 yrs and pregnant women?
- Administered in high doses could effect intravenously could effect what?
- Deposited in the bones and the teeth
- The liver resulting in hepatic necrosis
Tetracyclines cause nitrogen resulting in the renal buildup of all tetracyclines except?
What does local tissue toxicity result in?
Doxycycline and tigecycline
- Venous thrombosis, pain, and local irritation in muscles
What tetracycline especially has photosensitivity?
What vestibular reaction can result?
- Demeclocycline
- Dizziness, vertigo, nausea, and vomiting have been noted particularly with doxycycline.
What is the Mechanism of action of Clindamycin?
What microbes are susceptible to Clindamycin and what are resistance?
- Binds exclusively to the 50S ribosome and inhibits protein synthesis
- Susceptible: Streptococci, staphylococci, pneumococci, and bacteriodes species
Resistant: enterococci and gram negative aerobic organisms
What mechanism of resistance is used against Clindamycin?
1) Mutation of the ribosomal receptor site
2) Constitutive expression of METHYLASE–> modification of the receptors
3) Enzymatic inactivation of clindamycin
- Gram negative aerobic species are intrinsically resistant due to poor permeability of the outer cell wall.
What is the % of protein binding in Clindamycin?
- What type of cells does clindamycin concentrate in?
- 90% protein bound and has good penetration in to the tissues (except for the CNS)
- Concentrates in phagocytic cells via active transport
Where is Clindamycin metabolized in, excreted with, and does an adjustment need to occur with renal insufficiency?
- metabolized in the liver, excreted in the urine and bile, and dose adjustment is not necessary in renal insufficiency
What types of infection are treated with clindamycin?
Clindamycin is used in combination with cephalosporin or aminoglycosides to treat what?
- Anaerobic infections by bacteroide species
- To treat penetrating wound of the abdomen
Clindamycin provides prophylaxis against what in patients with valvular hear diseases?
What Clindamycin is combined with what drug does it form an effective alternative to trimethoprim-sulfamethozazole against moderate to severe pneumocystitis jirovei in AIDS patients?
- Prophylaxis against endocarditis
- Primaquine
Clindamycin is also used in combination with pyrimethamine for AIDS-related what of the brain?
toxoplasmosis
What are the adverse effects of Clindamycin?
- Diarrhea, nausea, vomiting, and skin rashes
- Impaired liver function (possible jaundice) and NEUTROPENIA may also occur
- SEVERE DIARRHEA and PSEUDO MEMBRANOUS COLITIS have been reported following admin. of clindamycin most likely due to Clostridium difficile
What is the mechanism of action of chloramphenicol?
What is Chloramphenicol’s spectrum range?
- inhibits bacterial 50S ribosomes and prevent protein synthesis
- Has a broad spectrum with activity against both gram negative and gram positive bacteria
What microbacteria is Chloramphenicol active against?
- Active against Rickettsia but not Chlamydia. Active against haemophilus influenza, N. meningitis and some strands of bacteriodes are highly susceptible.
What is resistance to chloramphenicol due to?
The production of CHLORAMPHENICOL ACYL TRANSFERASE, a plasmid encoded enzyme
Where is Chloramphenicol distributed? - Where is it metabolized and excreted? - How does dosing change with renal insufficiency? - How would dosing be reduced in newborns and premature infants?
- Widely distributed throughout the body including the CNS and body fluids.
- Conjugated in the liver (glucuronic acid) and eliminated in urine.
- Dosing MUST be reduced in hepatic but not renal insufficiency.
- Dose must also be reduced in newborns and premature infants
How does chloramphenicol treatment effect cholera, Rickettsia diseases?
- What is disease is it an alternative to beta-lactam?
- It is a second line drug for cholera, and is indicated for serious Rickettsial infection such as typhus and Rocky Mountain Spotted Fever
- Meningococcal meningitis (in patients either hypersensitive to penicillin or if the infection is penicillin-resistant
Used for Brain abscesses and topically for treatment of eye infection.
Just didn’t feel like making a questions out of that!!
What are the adverse effects in the GI tract?
- Adults (no kids) commonly develop nausea, vomiting, and diarrhea
- Risk of oral or vaginal candidiasis may occur due to alteration of normal flora
What bone marrow disturbances might occur with chloramphenicol?
- Bone marrow disturbances: decreased production of red blood cells. Aplastic anemia (idiosyncratic - no explanation) may be reversible but could be fatal
What is the toxicity in newborn infants?
- Gray baby syndrome ( vomiting flaccidity, hypothermia, gray color shock and collapse). Must be used with caution in infants
What are the drug interactions of Chloramphenicol?
- (Chloramphenicol is a CYP inhibitor that reduces the rate of metabolism of) phenytoin, tolbutamide, chlorpropamide, and warfarin, thereby increasing their half lives
- Can also antagonize the effect of penicillin and aminoglycosides.
