Cp - Pneumonia(2008)

Clinical Pharmacology Rational Therapy of Community-Acquired Pneumonia 2008 Ma. Luisa D.Delacruz, M.D.

DLSU-HSI College of Medicine

Case A 64 year old female, market vendor complains of severe cough, greenish to yellowish sputum since 4 days P.E. findings: Temp.= of 39.5oC, RR=28/min, PR=110/min, BP = 130/80 (+) rhonchi, crackles

1. Define the patient’s problem Low or Minimal Risk CommunityAcquired Pneumonia • Basis: • Stable Vital Signs RR < 30 breaths/min PR <125 beats/min SBP ≥ 90 mmHg DBP ≥ 60 mmHg No or stable comorbid conditions No evidence of

1. Define the patient’s problem Low Risk Community-Acquired Pneumonia Etiologic agent: •Streptococcus

pneumoniae •Haemophilus influenzae •Chlamydophilia pneumoniae •

1. Define the patient’s problem Recommendations for definitive diagnosis: • Chest X-ray • Microbiologic studies Sputum Gram stain and culture Blood culture and sensitivity Test to document for

2. Therapeutic Objectives • To relieve symptoms • To treat the disease • To prevent complications

3. Verify Suitability of Treatment • Non-Drug Measures •Bed rest •Adequate nutrition •Hydration

3. Verify Suitability of Treatment • Drug Measures •Supportive/Symptomatic •Antipyretic •Antitussive Mucolytics •Definitive •Antimicrobial

3. Verify Suitability of Treatment • Inventory of Effective Drug

Groups for Definitive Treatment Penicillins

 Macrolides

 Sulfonamides

3. Verify Suitability of Treatment • Selecting Drugs for PFormulary Amoxicillin Co-trimoxazole Clarithromycin Cefuroxime axetil Co-Amoxiclav

3. Verify Suitability of Treatment • Efficacy •Basis (Pharmacodynamics) Antimicrobial spectrum Resistance pattern Mode of antimicrobial activity

3. Verify Suitability of Treatment • Efficacy •Basis (Pharmacokinetics) Stability in gastric acid Onset and duration of action Lipid solubility Protein binding Metabolism

Antimicrobial Resistance rates of S pneumoniae 2000

2001

2002

2003

Penicillin

18%

9%

6%

9.2%

Cotrimoxaz ole Erythromy

12%

10%

9%

9.1%

-

-

-

2.3%

cin Chloramphe

7%

3%

3%

2.9%

nicol

Source: ARSP (DOH) 1999-2003

Antimicrobial Resistance rates of H influenzae 2000

2001

2002

2003

Ampicillin

3%

6%

5%

13%

Cotrimoxaz ole Clarythrom

11%

16%

11%

18%

-

-

-

0

ycin Azithromycin

-

-

-

1.4%

Chloramphe nicol

4%

0

5%

11.8%

Source: ARSP (DOH) 1999-2003

Efficacy (Pharmacodynamics) Drugs Amoxicillin

Spectru m of activity Broad

Cotrimoxazo Broad le Clarithromy Broad cin CoBroader Amoxiclav Cefuroxime Broad axetil

Resistanc Mode of e Pattern action Mod Cidal Mod

Cidal

Low

Static

Low

Cidal

Low

Cidal

Efficacy (Pharmacodynamics) Drugs

Mechanism of Antimicrobial Action Amoxicillin Inhibition of bacterial cell wall synthesis Cotrimoxaz Inhibition of folic acid ole synthesis Clarithromy Inhibition of microbial cin protein synthesis CoInhibition of bacterial cell Amoxiclav wall synthesis Cefuroxime Inhibition of bacterial cell axetil wall synthesis

Efficacy (Pharmacokinetics) Drugs

Stability Lipid in solubili gastric ty Amoxicillin stable low acid Cotrimoxa labile mod zole Clarithrom labile low ycin Costable low Amoxiclav Cefuroxim stable low e axetil

Protein Eliminat binding ion halfilfe 18% 1 hr 45%/66 % 70% 18%/25 % 33-50%

10/11 hrs 4.8/8.7 hrs 1 hr 1-1.5 hrs

Efficacy Drugs Amoxicillin Cotrimoxazo le Clarithromyc in CoAmoxiclav Cefuroxime

Rating ++ ++ +++ ++++ ++++

3. Verify Suitability of Treatment Safety •Basis Adverse effects

Safety Drugs Amoxicillin

Adverse Reactions Hypersensitivity

Cotrimoxaz Hypersensitivity, Stevensole Johnson syndrome, GI upsets, bone marrow depression Clarithrom GI disturbances, transient ycin elevation of liver enzymes CoHypersensitivity , Diarrhea Amoxiclav Cefuroxim Hypersensitivity, GI e disturbances, Stevens-

Ratin g

++ + + ++ + ++ ++

3. Verify Suitability of Treatment • Suitability

Basis: •Ease of administration

Oral/parenteral •Compliance Frequency of administration Presence of

Suitability Drugs Amoxicillin Cotrimoxaz ole Clarithromy cin CoAmoxiclav Cefuroxime

Route of Frequenc Contraindic administra y ation tion Hypersensitiv Oral/IV TID ity Hypersensitiv ity, G6PD Oral/IV BID deficiency Hypersensitiv Oral/IV OD / BID ity Hypersensitiv Oral/IV BID/TID ity Hypersensitiv Oral/IV BID ity

Suitability Drugs

Rating

Amoxicillin

++

Cotrimoxazo le Clarithromyc in CoAmoxiclav Cefuroxime axetil

++ +++ +++ +++

3. Verify Suitability of Treatment Cost •Basis: •Cost/unit •Cost/duration of treatment

Cost Drugs Amoxicillin

Dosage 500 mg TID for 10 days

Cotrimoxazo 160/800 mg BID for 10 days le Clarithromy 500 mg BID for 10 days cin Co625 mg TID or 1 g BID for Amoxiclav 10 days Cefuroxime 500 mg BID for 10 days axetil

Cost Drugs Amoxicilli n Cotrimoxa zole Clarithro mycin CoAmoxiclav Cefuroxim e axetil

Cost per unit 6.00 per capsule 15.00 per tablet 52.60 per tablet 36.63 per tablet 82.00 per tablet

Cost of Treatment per day PhP 24.00

Rating

Php 30.00

++++ + ++++

Php 105.20

++

PhP 73.36

+++

Php 164.00

+

Most Suitable Drug Base on SANE Criteria Drugs Amoxicillin (12) Cotrimoxazole (9) Clarithromycin (11) Co-Amoxiclav (12) Cefuroxime (10)

Efficac Safety Suitabi Cost y lity

++ +++ ++

+ +++ ++ + ++ + + +++ +++ +++ +++ ++ + ++ +++ +++ +++ + ++ +++ + +++

4. Write a complete prescription Sofie Ferre Dasmarinas, Cavite 29, 2008

August

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

5. Information, Instruction, warning

☺ Need to complete treatment ☺ Report adverse events ASAP ☺ Response to treatment is

expected within 24-72 hours ☺ Fever declines within 72

hours ☺ Respiratory signs and temperature should normalize within 5 days

6. Monitor therapy ☺Compliance to medication ☺If no improvement within 24-

72 hours, need to reevaluate patient ☺Follow-up after completion of prescribed antibiotic treatment