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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
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