Pharmacology Exam II

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tetracyclines are named for their

four hydrocarbon rings
Free tetracyclines are _____ substances of ____ solubility
- amphoteric
- low
Tetracyclines are generally available as ____ which are more soluble and fairly stable

hydrochlorides
Interferance with absorption of tetracyclines

chelation of divalent metal ions
Introduced to treat infections which are resistant to other antimicrobics including tetracyclines

tigecycline
Mechanism of action for tetracyclines

protein synthesis inhibition by binding the 30s subunit of the bacterial ribosome
Activity of tetracyclines
- broad specturm bacteriostatic
- gram positive and negative
tetracycline resistant strains may be susceptible to ____ because they are______
- doxycycline
- minocycline
- tigecycline
- poor substrates for efflux pump
tetracyclines enter cells via

passive diffusion and active transport
3 mechanisms of resistance to tetracyclines
- impaired influx or increased efflux
- ribosome protection by proteins that interfere with tetracycline binding
- enzymatic inactivation of tetracycline
most important mechanisms of resistance to tetracyclines
- production of an efflux pump
- ribosomal protection
Confers resistance to older tetracyclines such as doxycylcine and minocycline

Tet(AE) efflux pump-expressing gram negative species
TET(AE) efflux pump expressing species are susceptible to

tigecycline
Tet (K) efflux pump of staphylococci confers resistance to tetracycline but not
- doxycycline
- minocycline
- tigecycline
proteus pseudomonas is resistant to all tetracyclines (including tigecycline) due to the

multidrug efflux pumps
# of classes of ribosomal protection genes/proteins

6 classes
mechanisms of action of ribosomal protective proteins
- block tetracylcines from binding to the ribosome
- distort structure of ribosome to allow t-RNA binding while TCN is bound
- binding the ribosome to dislodge the TCN
Tet (M) expressed by gram positive bacteria produces resistance to
- tetracycline
- doxycycline
- minocylcine
Tet (M) does not confer resistance to ____ because of its _____
- tigecycline
- bulky t-butylglycylamido group
Rarest type of TCN resistance
- enzymatic inactivation
- acetyl group is added to the TCN which results in inactivation
chlortetracycline oral absorption

30%
TCN, oxyTCN, demeclocycline and methacycline absorption

60-70%
Absorption of 95-100%
- doxycycline
- minocycline
Tigecycline administration

IV only
Absorption of TCNs occurs in
- small intestines
- impaired by food and divalent cations
TCN should be taken

1 hr before or 2 hrs after eating with a full glass of water
Reaches very high concentrations in tears and saliva which makes it useful for eradication of the meningococcal carrier state

minocycline
TCN excretion
- cross placenta and milk
- bind to bones and teeth (growing)
- excreted mainly in bile and urine
TCN metabolism induced by
- carbamazepine
- phenytoin
- barbiturates
- chronic alcohol consumption
TCNs that require no dosage adjustments based on renal function
- doxycycline
- tigecycline
Naturally occuring TCNs
- TCN
- chlortetracycline
- oxytetracycline
- demeclocycline
Semi-synthetic TCNs
- doxycycline
- lymecycline
- meclocycline
- methacycline
- minocycline
- rolitetracycline
Short acting TCNS (6-8hr half life)
- TCN
- chlortetracycline
- oxytetracycline
Intermediate acting half life 12 hr
- Demeclocycline
- methacycline
Long acting TCNs (16 hrs or more)
- doxycycline
- minocycline
- tigecycline (36hrs)
TCN is the drug of choice for infections with
- mycoplasma pneumoniae
- chlamydiae
- rickettsiae
- spirochetes
TCNs are used in combo regimens to treat

gastric and duodenal ulcer disease caused by H. Pylori
TCN in combo with aminoglycoside is indicated for
- plague
- tularemia
- brucellosis
TCN are no longer recommended for treatment of

gonococcal disease because of resistance
Oral TCN of choice
- Doxycycline
- once daily dosing
- absorption not significantly affected by food
Adverse reactions with TCN
- chelation with metals
- avoid in pregnant and children less than 8 due to deposition in growing bones and teeth
- mostly due to direct toxicity or alteration of microbial flora
GI adverse effects of TCN
- n/v
- diarrhea
Avoiding GI ADRs associated with TCNs
- administer with food or carboxymethycellulose
- reduce dose
- discontinue therapy
Liver toxicity with TCN may occur when:
- used in pregnancy
- used in pt with hepatic insufficiency
- high doses given IV
Hepatic necrosis has been reported with daily doses of TCN of ____ or more IV

4g
Fanconi Syndrom
- potentially fatal disease affecting proximal tubular function in the nephrons caused by breakdown products from expired TCN.
- Discard drugs when expired
usage of expired tetracycline can result in
- fanconi syndrome
- renal tubular acidosis
- renal nitrogen retention
TCN + Diuretics may produce

renal nitrogen retention
TCNs other than doxycycline with impaired renal function

may accumulate to toxic levels
Intravenous injection of TCN can lead to

venous thrombosis
IM injection of TCNs can lead to

local painful irritation
TCNs espcially demecloclycline can lead to these other reactions
- photosensitization
- vestibular reactions (35-70% of minocylcine pt)

Author

Rx2013

65138

Card Set

Pharmacology Exam II

Description

Tetracyclines

Updated

2011-02-09T03:04:11Z

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