Pharmacolgical terms and antibiotics
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Transcript of Pharmacolgical terms and antibiotics
PHARMACOLGICAL TERMSAND
ANTIBIOTICSBY
IBRAHIM AL SHARABI
• Pharmacology is the study of the manner in which the function of living system is affected by chemical agents.
• Pharmacokinetics is the study of the kinetics of drug absorption, biotransformation, and excretion or the processes to which the drug is subjected in the body.
• Pharmacodynamics is the study of the biochemical and physiological effects of drugs and their mechanism of action.
PHARMACOLOGY OF ANTIMICROBIAL THERAPY
Concentrations Pharmacologic
in tissues and and toxicologic
body fluids effect
Dosing Concentrations
Regimen in Serum
Concentrations Antimicrobial
Absorption at site of infection effect Distribution
Elimination
Pharmacokinetics Pharmacodynamics
Passage of a drug from the site of administration into the blood.Absorption is affected by : 1-Physicochemicalproperties of the drug solubility ionization valency 2-Dosage form 3-Route of administration skin mucous membrane parental site 4-Area and vascularity of the absorption surface 5- Specific factors
ABSORPTION
There are four patterns for drug distribution
1-Drugs with high m. wt that present only in plasma e.g. heparin.
2-Drugs that can pass capillary wall but can not pass the cell membrane ( extracellularlly only) e.g. Na, Cl.
3-Drugs that pass freely across cell membrane with no affinity for special tissues e.g. alcohol.
4-Drugs with affinity for special tissues e.g. Iodide in the thyroid gland.
N.B. PLASMA PROTEIN BINDING
DISTRIBUTION
Chemical alteration to which a drug is undergoes within a living organism.
Hepatic enzyme activators e.g. phenobarbiton.
Hepatic enzyme inhibitors e.g. erythromycin.
BIOTRANFORMATION
Through kidneys, lungs, skin and the gut.
EXCRETION
Time (hours)
Con
cent
ratio
n
AUCAUC
MIC
PHARMACOKINETIC/PHARMACODYNAMIC PREDICTORS OF EFFICACY
Craig W. Pharmacokinetic/Pharmacodynamic Parameters: Rationale for Antibacterial Dosing of Mice and Men. Clin Infect Dis. 1998; 26:1-12.
Cmax (Peak)
Time > MIC
Area under the curve:
Parameters of Interest:
• Time > MIC
• Cmax/MIC ratio
• AUC/MIC ratio
ANTIBIOTIC
• Chemical substance produced by a microorganism which
has capacity to
inhibit growth
Kill other microorganisms.
IDEAL ANTIBIOTIC
Inhibit growth of bacteria without harming the host.
Penetrate body tissues to reach the site of infections with sufficient concentration to inhibit or kill pathogen
BACTERIOSTATIC VS. BACTERICIDAL
BACTERIOSTATIC
Arrests the growth and replication of bacteria
BACTERICIDAL
Actually kills the bacteria
HOWEVER THESE TERMS ARE NOT THE CONCERN THE FAST ELIMINATION AND CLINICAL OUTCMES ARE MOST IMPORTANT.
MIC
Seen with all beta-lactams, clindamycin, macrolides.
GOAL: optimize duration of exposure
Seen with aminoglycosides, quinolones, ketolides and amphotericin B.
GOAL: maximize concentrations
Time >MIC(time-dependent killing)
MIC
CONC. >MIC(concentration-dependent killing)
PHARMACOKINETIC/PHARMACODYNAMIC PROFILES
MIC
AUC24 /MIC(time-dependent killing)
PHARMACOKINETIC/PHARMACODYNAMIC PROFILES
tetracyclines, azithromycin.GOAL: optimize amount of drug
SPECTRUM
range of bacteria a specific drug will treat
-Narrow spectrum
Effective against a limited type/number of bacteria
Mostly gram-positive organisms
-Moderate spectrum
Generally effective against the gram-positives
Most systemic, enteric and urinary tract gram-negative pathogens
-Broad spectrum:
Effective against all prokaryotic cells except mycobacteria and pseudomonas
RESISTANCE
ABILITY OF BACTERIA TO RESIST THE EFFECTS OF THE ANTIBIOTIC
ATTRIBUTED TO– PROPERTIES OF THE DRUG– MISUSE OF ANITBIOTICS BY CONSUMERS
ANTIBIOTIC RESISTANCE RELATED TO THE SITES OF ANTIMICROBIAL ACTIVITY– ALTERED RECEPTORS FOR THE DRUG– DECREASED CONC. IN THE CELL– DESTRUCTION OR INACTIVATION OF THE DRUG
Antibiotic-resistant BacteriaAntibiotic-resistant Bacteria
INFLUX PUMP
ALTERATION OF THE TARGETS ORGANS
CLASSES OF ANTIBIOTICS
SULFONAMIDES
PENICILLINS
CEPHALSPORINS
MACROGLIDES
AMINOGLYCOSIDES
FLOUROQUINILONES
TETRACYCLINES
MISCELLANEOUS
DRAWBACKS OF THE MAIN COMPETITORS
USUAL PENICILLINSNarrow spectrum.
Low penetration (low intracellular conc.).
Common resistance.
Allergic reactions.
Low patient compliance.
Most are parentral
Frequent dosing regimen
AMOXICILLIN / CLAVULANATE ( AUGMENTIN )Cost
Lack of atypical pathogens coverage .
Low intracellular concentration.
Low success rate .
Sever liver toxicity.
GI upsets.
Dosage regimen.
New resistance pattern
Affected by heat, light and humidity.
CEFUROXIME ( ZINNAT ) Cost
Lack of atypical pathogens coverage .
Low intracellular concentration.
Low success rate .
Cross allergy and cross resistance with penicillins.
AZITHROMYCIN ( ZOCIN )BACTERIOSTATIC ACTIVITY
LOWER ANTI-G +ve ACTIVITY
LOW PATIENT COMPLIANCE
FOOD INTERACTION
GI UPSETS
DELAYED ACION
LOW CLINICAL SUCCESS
VERY HIGH INTRACELLULAR LEVEL
LOW SERUM LEVEL
DIFFICULT CONTROL
FLOUROQUINOLONES
spectrum: broad coverage. effective vs. G +, G -, atypicals, and pseudomonas.
RESPIRATORY QUINOLONES (Levofloxacin): ACTIVE vs. S. Pneumo (Including penicillin-resistant forms), S. aureus (Including MRSA), H. Influ., And M. Catarrhalis (including penicillin-resistant strains).
ANTIPSEUDOMONAS QUINOLONES (Ciprofloxacin): effective vs. pseudomonas and G-ve bacteria.
NEW FLOXINS (Gati, Moxi, Gemi): Similar to respiratory quinolones but less activity vs. Pseudomonas and addition of anerobic activity
HISTORY• Erythromycin was introduced in 1952 and has remained
the prototype of the macrolides. • The limitations of erythromycin include variable
absorption, instability in gastric acid, poor tissues penetration, short elimination half life, GI irritation, and a narrow spectrum of activity.
• Modifications of the macrolide structure are designed to improve the chemical, biological and pharmacokinetic properties of erythromycin.
• Clarithromycin (KLACID) is a14-membered macrolide known as 6-O-methyl-erythromycin which overcomes all of the above limitations and introduced in 1991.
PERFECT SPECTRUM
KLACID covers almost the whole spectrum of important pathogens in RTIs (Typical as S.pneumoniae ,H.influenzae, moraxella catarrhalis, S.aureus and atypical as C.pneumoniae, M.pneumoniae, L.pneumophila) with bactericidal activities. Therefore KLACID is the ideal antibiotic to be used empirically in the treatment of CAP.
BALANCED DISTRIBUTION
• Pneumonia caused by pneumococci leads to bacteremia in about 30% of the patients. Only with sufficient serum antibiotic levels the circulating micro-organisms can be eliminated
Concentration of different antibiotics in
serum ,soft tissues and macrophagesAntibiotic Serum level Extracellular levels
Conc. in macrophages
clarithromycin + + + + + +
Roxithromycin
+ + + +
Azithromycin + + + + + +
Β-lactams + + + + ▬
EXCELLENT SAFETY PROFILE
0
2
4
6
8
10
12
14
16
6% 15%
KLACID
Amoxicillin/clavulanate
• Significantly less GI upset than amoxicillin/clavulanate
EXCELLENT PATIENT COMPLIANCE
• KLACID XL improves patients compliance so reducing the risk of resistance
010203040506070
8090
100
OD TID
NO FOOD INTERACTION
Misadministration rate
01020304050607080
90100
0% 89% 94%
KLACID
Azithromycin
Roxythromycin
HIGH CLINICAL SUCCESS RATEPharyngitis
Sinusitis
AECB
CAP
Peptic ulcer
100%
97%
99%
97%
94%
ADDITIONAL ANTI-INFLAMMATORY
AND MUCOLYTIC ACTIVITY