Individual Drug Response

PRESCRIBED DOSE ADMINISTERED DOSE

CONCENTRATION AT LOCUS OF ACTION

INTENSITY OF EFFECT

Efek Subterapi (Pasien A) Efek Terapi (Pasien B)

Kegagalan Terapi

Dosis standar

Optimal

Efek Toksik (Pasien C)

Mengapa Terjadi Perbedaan Efek Pada Dosis Standar ?

Dose of drug administered
Kepatuhan Pasien

Drug Concentration in sytemic ciculation

Faktor Farmakokinetik (Absorbsi, distribusi, metabolisme, eleminasi) Faktor Farmakodinamik

Drug Concentration at. SOA

Phamacologic effect

- Optimal-

I. EXTERNAL FACTORS

Patient compliance
Temporary Easy to correct without alter dose of drug or the regimen

Medication errors

II. INTERNAL FACTORS (Drug-body interaction)

A. Pharmacokinetic factors
Drug level at the receptor

B. Pharmacodynamic factors
Responses of the body to the drugs

II. INTERNAL FACTORS

1. 2. 3. 4. 5. 6. 7. 8.

Physiological conditions Pathological conditions Genetic factors Drug interactions Development of tolerance Placebo effects Environmental factors Biological rhythmic.

I.EXTERNAL FACTORS Patient compliance Factors

1. Diseases
Without symptom Chronic diseases Diseases which is needs preventive therapy Decreases patient compliance

I.EXTERNAL FACTORS Patient compliance Factors

2. Drugs/therapy
Multiple drugs Complex regimen dose The tablet is difficult to be swollen or bad tasty Adverse drug reactions Decreases patient compliance

I.EXTERNAL FACTORS Patient compliance Factors

3. Patient
Very old/ very young Low intellectuality Psychiatric problem

4. Doctor
Optimistic Skillfully Increase patient compliance

II. INTERNAL FACTORS 1. Condition of Physiological Factors

A. Neonates and Premature Infants

Lower biotransformation function of lever Low plasma protein binding capacity Undeveloped blood-brain barrier Low excretion function of kidney High receptor sensitivity

II. INTERNAL FACTORS 1.Condition of Physiological Factors

B. Elderly person
Deceasing of metabolic capacity Decreasing of plasma protein capacity Decreasing of excretion functions of kidney Increasing of receptor sensitivity

II. INTERNAL FACTORS 2. Condition of Pathophysiological Factors

GIT: alter absorption of drugs Lever dysfunctions:

Plasma protein binding capacity Circulation to the lever Metabolic capacity

Congestive heart failure: clearance of lidocaine

II. INTERNAL FACTORS 2. Condition of Pathophysiological Factors

Pulmonary diseases: decreases circulation to lever and kidney Kidney diseases: decreasing of drugs clearance Hypo and Hyperthyroids
Bioavailability (riboflavin) Biotransformation (Propilthiourasil) Renal excretion (digoxin)

II. INTERNAL FACTORS 2. Condition of Pathophysiological Factors

Pregnancy
Decreasing plasma protein binding capacity (phenytoine) Increasing renal excretion Alter of metabolism

Diseases which are alter the receptor sensitivity

Myasthenia gravis Parkinson's

II. INTERNAL FACTOR 3. Genetic Factors

Contribute in pharmacological activity differences (qualitative and quantitative) Quantitative :

Metabolic capacity (INH-slow/fast acetylators)

Qualitative :
Drugs which are have specific toxicity in persons with abnormal genetic factors (exp. G6PD)

II. INTERNAL FACTOR 4. Drug Interaction

II. INTERNAL FACTOR

5. Development of tolerance

Tolerance: decreasing pharmacological effect in repeated dose (exp. CNS depressants, opioid, organic nitrite May appear cross-tolerance among drugs which have the same receptor Pharmacokinetic tolerances: induce metabolism Pharmacodynamic tolerances: cellular adaptations (exp. Chronic uses of opioids, barbiturates, ethanol, organic nitrite)

II. INTERNAL FACTOR 6. Placebo Effects

Net effect = pharmacological + placebo effect placebo effect may different interindividual and intraindividual (intraindividual in different time)

II. INTERNAL FACTOR 7. Environmental Factors

Alcohol and smoking are suspected interfere drug responses Cigarette is containing polycyclic hydrocarbon may increasing metabolism of specific drugs (exp. Theophylline) Alcohol may alter responses of some drugs
Acute : Inhibition of drug biotransformation Chronic: Induce of drug biotransformation

II. INTERNAL FACTOR 8. Biological Rhythmic

chronofarmacology Circadian Circasesten Circatrigintan Circanual