Individual Drug Response

PRESCRIBED

DOSE

ADMINISTEREDDOSE

CONCENTRATIONAT LOCUSOF ACTION

INTENSITYOF EFFECT

Dosis standa

r

Efek Toksik

(Pasien C)

Efek Subterapi

(Pasien A)

Efek Terapi (Pasien B)

Kegagalan Terapi

Optimal

Dose of drug administered

Drug Concentration in sytemic ciculation

Drug Concentrationat. SOA

Phamacologic effect

Mengapa Terjadi Perbedaan Efek Pada Dosis Mengapa Terjadi Perbedaan Efek Pada Dosis Standar ?Standar ?

- Optimal-

Faktor Farmakodinamik

Faktor Farmakokinetik (Absorbsi, distribusi,

metabolisme, eleminasi)

Kepatuhan Pasien

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. Physiological conditions 2. Pathological conditions 3. Genetic factors 4. Drug interactions 5. Development of tolerance 6. Placebo effects 7. Environmental factors 8. 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– SkillfullyIncrease patient compliance

II. INTERNAL FACTORS1. 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