cp - pneumonia(2008)

Clinical PharmacologyClinical PharmacologyRational Therapy of Community-Rational Therapy of Community-

Acquired PneumoniaAcquired Pneumonia20082008

Ma. Luisa D.Delacruz, M.D.Ma. Luisa D.Delacruz, M.D.DLSU-HSI College of MedicineDLSU-HSI College of Medicine

CaseCase• A 64 year old female, market vendor A 64 year old female, market vendor

complains of severe cough, greenish to complains of severe cough, greenish to yellowish sputum since 4 daysyellowish sputum since 4 days

• P.E. findings:P.E. findings: Temp.= of 39.5Temp.= of 39.5ooC, RR=28/min, C, RR=28/min, PR=110/min, BP = 130/80 PR=110/min, BP = 130/80

(+) rhonchi, crackles(+) rhonchi, crackles

1. Define the patient’s problem1. Define the patient’s problem

Low or Minimal Risk Community-Acquired Low or Minimal Risk Community-Acquired PneumoniaPneumonia• Basis:Basis:

• Stable Vital SignsStable Vital SignsRR < 30 breaths/minRR < 30 breaths/min

PR <125 beats/minPR <125 beats/minSBP ≥ 90 mmHgSBP ≥ 90 mmHg

DBP ≥ 60 mmHgDBP ≥ 60 mmHg• No or stable comorbid conditionsNo or stable comorbid conditions• No evidence of extrapulmonary sepsisNo evidence of extrapulmonary sepsis


Low Risk Community-Acquired PneumoniaLow Risk Community-Acquired PneumoniaEtiologic agent:Etiologic agent:

• Streptococcus pneumoniaeStreptococcus pneumoniae• Haemophilus influenzaeHaemophilus influenzae• Chlamydophilia pneumoniaeChlamydophilia pneumoniae• Mycoplasma pneumoniaeMycoplasma pneumoniae• Moraxella catarrhalisMoraxella catarrhalis


Recommendations for definitive diagnosis:Recommendations for definitive diagnosis:• Chest X-rayChest X-ray• Microbiologic studiesMicrobiologic studies

• Sputum Gram stain and culture Sputum Gram stain and culture • Blood culture and sensitivityBlood culture and sensitivity• Test to document for Test to document for atypicalatypical agentsagents in in

hospitalized patientshospitalized patients

2. Therapeutic Objectives2. Therapeutic Objectives

• To relieve symptomsTo relieve symptoms• To treat the diseaseTo treat the disease• To prevent complicationsTo prevent complications

3. Verify Suitability of Treatment3. Verify Suitability of Treatment

• Non-Drug MeasuresNon-Drug Measures• Bed restBed rest• Adequate nutritionAdequate nutrition• HydrationHydration


• Drug MeasuresDrug Measures• Supportive/SymptomaticSupportive/Symptomatic

• AntipyreticAntipyretic• Antitussive - Mucolytics Antitussive - Mucolytics

• DefinitiveDefinitive• Antimicrobial Antimicrobial


• Inventory of Effective Drug Groups for Inventory of Effective Drug Groups for Definitive TreatmentDefinitive Treatment

• PenicillinsPenicillins • MacrolidesMacrolides • SulfonamidesSulfonamides • -lactam+-lactam+-lactamase inhibitor-lactamase inhibitor • Second Generation CephalosporinsSecond Generation Cephalosporins


• Selecting Drugs for P-FormularySelecting Drugs for P-FormularyAmoxicillinAmoxicillinCo-trimoxazoleCo-trimoxazoleClarithromycin Clarithromycin Cefuroxime axetilCefuroxime axetilCo-AmoxiclavCo-Amoxiclav


• EfficacyEfficacy• Basis (Pharmacodynamics)Basis (Pharmacodynamics)

Antimicrobial spectrumAntimicrobial spectrumResistance patternResistance patternMode of antimicrobial activity Mode of antimicrobial activity Mechanism of antimicrobial Mechanism of antimicrobial actionaction


• EfficacyEfficacy• Basis (Pharmacokinetics)Basis (Pharmacokinetics)

Stability in gastric acid Stability in gastric acid Onset and duration of actionOnset and duration of actionLipid solubilityLipid solubilityProtein bindingProtein bindingMetabolismMetabolismExcretionExcretion

Antimicrobial Resistance rates of S pneumoniaeAntimicrobial Resistance rates of S pneumoniae

20002000 20012001 20022002 20032003

PenicillinPenicillin 18%18% 9%9% 6%6% 9.2%9.2%

CotrimoxazoleCotrimoxazole 12%12% 10%10% 9%9% 9.1%9.1%

ErythromycinErythromycin -- -- -- 2.3%2.3%

ChloramphenicolChloramphenicol 7%7% 3%3% 3%3% 2.9%2.9%

Source: ARSP (DOH) 1999-2003

Antimicrobial Resistance rates of H influenzaeAntimicrobial Resistance rates of H influenzae

20002000 20012001 20022002 20032003

AmpicillinAmpicillin 3%3% 6%6% 5%5% 13%13%

CotrimoxazoleCotrimoxazole 11%11% 16%16% 11%11% 18%18%

ClarythromycinClarythromycin -- -- -- 00

AzithromycinAzithromycin -- -- -- 1.4%1.4%

ChloramphenicolChloramphenicol 4%4% 00 5%5% 11.8%11.8%

Source: ARSP (DOH) 1999-2003

Efficacy Efficacy (Pharmacodynamics)(Pharmacodynamics)

DrugsDrugs Spectrum of Spectrum of activityactivity

Resistance Resistance PatternPattern

Mode ofMode ofactionaction

AmoxicillinAmoxicillin BroadBroad ModMod CidalCidal

CotrimoxazoleCotrimoxazole BroadBroad ModMod CidalCidal

ClarithromycinClarithromycin BroadBroad LowLow StaticStatic

Co-AmoxiclavCo-Amoxiclav BroaderBroader LowLow CidalCidal

Cefuroxime axetilCefuroxime axetil BroadBroad LowLow CidalCidal

Efficacy Efficacy (Pharmacodynamics)(Pharmacodynamics)

DrugsDrugs Mechanism of Antimicrobial ActionMechanism of Antimicrobial Action

AmoxicillinAmoxicillin Inhibition of bacterial cell wall synthesisInhibition of bacterial cell wall synthesis

CotrimoxazoleCotrimoxazole Inhibition of folic acid synthesisInhibition of folic acid synthesis

ClarithromycinClarithromycin Inhibition of microbial protein synthesisInhibition of microbial protein synthesis

Co-AmoxiclavCo-Amoxiclav Inhibition of bacterial cell wall synthesisInhibition of bacterial cell wall synthesis

Cefuroxime Cefuroxime axetilaxetil

Inhibition of bacterial cell wall synthesisInhibition of bacterial cell wall synthesis

Efficacy Efficacy (Pharmacokinetics)(Pharmacokinetics)

DrugsDrugs Stability in Stability in gastric acidgastric acid

Lipid Lipid solubilitysolubility

Protein Protein binding binding

Elimination Elimination half-ilfe half-ilfe

AmoxicillinAmoxicillin stablestable lowlow 18%18% 1 hr1 hr

CotrimoxazoleCotrimoxazole labilelabile modmod 45%/66%45%/66% 10/11 hrs10/11 hrs

ClarithromycinClarithromycin labilelabile lowlow 70%70% 4.8/8.7 hrs4.8/8.7 hrs

Co-AmoxiclavCo-Amoxiclav stablestable lowlow 18%/25%18%/25% 1 hr1 hr

Cefuroxime Cefuroxime axetilaxetil stablestable lowlow 33-50%33-50% 1-1.5 hrs1-1.5 hrs

EfficacyEfficacy

DrugsDrugs RatingRating

AmoxicillinAmoxicillin ++++

CotrimoxazoleCotrimoxazole ++++

ClarithromycinClarithromycin ++++++

Co-AmoxiclavCo-Amoxiclav ++++++++

CefuroximeCefuroxime ++++++++


SafetySafety• BasisBasis

Adverse effectsAdverse effects

SafetySafety

DrugsDrugs Adverse ReactionsAdverse Reactions RatingRating

AmoxicillinAmoxicillin HypersensitivityHypersensitivity ++++++

CotrimoxazoleCotrimoxazole Hypersensitivity, Stevens-Johnson Hypersensitivity, Stevens-Johnson syndrome, GI upsets, bone marrow syndrome, GI upsets, bone marrow

depressiondepression

++

ClarithromycinClarithromycin GI disturbances, transient elevation GI disturbances, transient elevation of liver enzymesof liver enzymes

++++++

Co-AmoxiclavCo-Amoxiclav Hypersensitivity , DiarrheaHypersensitivity , Diarrhea ++++

CefuroximeCefuroxime Hypersensitivity, GI disturbances, Hypersensitivity, GI disturbances, Stevens-Johnson syndromeStevens-Johnson syndrome

++++


• SuitabilitySuitabilityBasis:Basis:

• Ease of administrationEase of administrationOral/parenteralOral/parenteral

• ComplianceComplianceFrequency of administrationFrequency of administration

• Presence of contraindicationsPresence of contraindications

SuitabilitySuitability

DrugsDrugs Route of Route of administrationadministration FrequencyFrequency ContraindicationContraindication

AmoxicillinAmoxicillin Oral/IVOral/IV TIDTID HypersensitivityHypersensitivity

CotrimoxazoleCotrimoxazole Oral/IVOral/IV BIDBID Hypersensitivity, Hypersensitivity, G6PD deficiencyG6PD deficiency

ClarithromycinClarithromycin Oral/IVOral/IV OD / BIDOD / BID HypersensitivityHypersensitivity

Co-AmoxiclavCo-Amoxiclav Oral/IVOral/IV BID/TIDBID/TID HypersensitivityHypersensitivity

CefuroximeCefuroxime Oral/IVOral/IV BIDBID HypersensitivityHypersensitivity

SuitabilitySuitability

DrugsDrugs RatingRating

AmoxicillinAmoxicillin ++++

CotrimoxazoleCotrimoxazole ++++

ClarithromycinClarithromycin ++++++

Co-AmoxiclavCo-Amoxiclav ++++++

Cefuroxime axetilCefuroxime axetil ++++++


CostCost• Basis:Basis:

• Cost/unitCost/unit• Cost/duration of treatmentCost/duration of treatment

CostCost

DrugsDrugs DosageDosage

AmoxicillinAmoxicillin 500 mg TID for 10 days500 mg TID for 10 days

CotrimoxazoleCotrimoxazole 160/800 mg BID for 10 days 160/800 mg BID for 10 days

ClarithromycinClarithromycin 500 mg BID for 10 days500 mg BID for 10 days

Co-AmoxiclavCo-Amoxiclav 625 mg TID or 1 g BID for 10 days625 mg TID or 1 g BID for 10 days

Cefuroxime axetilCefuroxime axetil 500 mg BID for 10 days500 mg BID for 10 days

Cost Cost DrugsDrugs Cost per unitCost per unit Cost of Treatment Cost of Treatment

per dayper dayRatingRating

AmoxicillinAmoxicillin 6.00 per capsule 6.00 per capsule PhP 24.00PhP 24.00 ++++++++++

CotrimoxazoleCotrimoxazole 15.00 per tablet15.00 per tablet Php 30.00Php 30.00 ++++++++

ClarithromycinClarithromycin 52.60 per tablet52.60 per tablet Php 105.20Php 105.20 ++++

Co-AmoxiclavCo-Amoxiclav 36.63 per tablet36.63 per tablet PhP 73.36PhP 73.36 ++++++

Cefuroxime Cefuroxime axetilaxetil

82.00 per tablet82.00 per tablet Php 164.00Php 164.00 ++

Most Suitable Drug Base on SANE CriteriaMost Suitable Drug Base on SANE Criteria

DrugsDrugs EfficacyEfficacy Safety Safety SuitabilitySuitability CostCost

Amoxicillin Amoxicillin (12)(12) ++++ ++++++ ++++ ++++++++++

Cotrimoxazole Cotrimoxazole (9)(9) ++++ ++ ++++ ++++++++

Clarithromycin Clarithromycin (11)(11) ++++++ ++++++ ++++++ ++++

Co-Amoxiclav Co-Amoxiclav (12)(12) ++++++++ ++++ ++++++ ++++++Cefuroxime Cefuroxime (10)(10) ++++++++ ++++ ++++++ ++

4. Write a complete prescription4. Write a complete prescription

Sofie FerreSofie FerreDasmarinas, CaviteDasmarinas, Cavite August 29, 2008 August 29, 2008

Co-Amoxiclav Tablet Co-Amoxiclav Tablet 625 mg625 mgDispense no. 30Dispense no. 30Sig: Take one tablet every 8 hours round the clockSig: Take one tablet every 8 hours round the clock for 10 days.for 10 days.

Ma. Luisa D. Delacruz. MDMa. Luisa D. Delacruz. MDLicense no. 049339License no. 049339PTR no. 7211851PTR no. 7211851

5. Information, Instruction, warning5. Information, Instruction, warning ☺ Need to complete treatmentNeed to complete treatment☺ Report adverse events ASAPReport adverse events ASAP☺ Response to treatment is expected within Response to treatment is expected within

24-72 hours24-72 hours☺ Fever declines within 72 hoursFever declines within 72 hours☺ Respiratory signs and temperature Respiratory signs and temperature

should normalize within 5 daysshould normalize within 5 days

6. Monitor therapy6. Monitor therapy

☺Compliance to medicationCompliance to medication☺If no improvement within 24-72 hours, If no improvement within 24-72 hours,

need to reevaluate patientneed to reevaluate patient☺Follow-up after completion of prescribed Follow-up after completion of prescribed

antibiotic treatmentantibiotic treatment

cp - pneumonia(2008)

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