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FACTORS THAT CHANGE DRUG ACTION FACTORS AFFECTING DRUG ACTIONS RELATED TO THE DRUG *PHYSICOCEHEMICAL PROPERTIES OF DRUG *PHARMACEUTICAL DOSAGE FORMS *PHARMACODYNAMİC PROPERTIES *DRUG INTERACTIONS RELATED TO THE PATIENT *AGE (Pregnancy, lactation, pediatric and geriatric populations) *SEX *GENETIC FACTORS *HEPATIC AND RENAL DISEASES *OTHER PATHOLOGICAL CONDITIONS *COMPLIANCE EFFECT OF AGE Newborn and babies have increased gastric emptying time Intestinal peristaltism is slow and irregular Gastric acid secretion is slow and irregular, gastric juice is neutral(acid sensitive oral penicillins have high systemic bioavailability) Since the skin is thin, absorption of drugs from skin in newborn and babies is increased EFFECT OF AGE Distribution In newborn and babies plasma protein binding is lower BBB is not developed well in the newborn Metabolism In the newborn metabolising enzymes are not sufficiently Developed (Gray baby syndrome) Elimination In newborn and babies, glomerular filtration rate and tubular Secretion are also insufficient. Doses of drugs such as penicillins and aminoglycosides need to be regulated. CALCULATION OF DOSE There are several formulas: Pediatric dose = [(4x Age + 20)/72] x adult dose Ausberger Formula Pediatric dose = (Weight/72) x adult dose Clark formula Pediatric dose = (Body area (m2)/1.8) x adult dose OLD PEOPLE In older people PK of drugs change. After age 25, every year functions of organisms related to drug action decline. Stomach acid secretion decreases, gastic emptying time increases, absorption surface declines (Abs rate↓) Distribution The ratio of lipid tissue to muscle tissue increases in older people. Volume of distribution of lipid soluble drugs ↑. Blood flow to tissues decreases and distribution takes longer. Plasma albumin level ↓. Highly albumin bound drugs free fraction increase and their effects ↑. Metabolism Efficiency of oxidation of CYP enzymes ↓(more in men) First pass effect decreases (Propranolol’s elimination ↓) Glucurunidation is not very much effected Elimination Glomerular filtration and tubular secretion ↓. Receptor number and sensitivity ↓. ReceptorGprotein-enzyme coupling efficiency ↓, cAMPdependent kinase efficiency ↓. Effects of several drugs increase in older people Hypnotic drugs (1/2 dose) Anxiolytic drugs (1/2 dose) Morphine, meperidine Phenothiazines and neuroleptic drugs extrapyramidal effects, hypotension Anticholinergic drugs Thiazides hypokalemia Sufonylureas hypoglycemia DISEASE PRESENT Shock, chf blood flow to tissues ↓ and absorption after parenteral and GI administration decreases. However blood flow from elimination organs also ↓ and they balance each other. Kidney diseases, decrease in renal clearance effects ionized and polar drugs.Gentamycin’s hl increases to 30-60 h compared to 2h. Drug choice in diseases: renal vs hepatic! FEMALE VS MALE Females metabolize antiepileptic drugs faster. Males are less susceptible to tricyclic antidepressants. CYP enzymes sensitivity decrease in old age......... Side effects of neuroleptics tardive dyskinesia and succinylcholines myalgia are observed more frequently in women. Administration route effects drug bioavailability Oral Paranteral Local Circadian rythm Slow acetylation of isoniazid is an example of autosomal recessive inheritance. G-6-phosphate-deficient hemolysis is an example of X-linked inheritance. In slow acetylators isoniazid causes neuropathies. Plasma cholinesterase activity distribution in the population Sleep apnea after succinylcholine occurs for prolonged periods of time in people who have a defective plasma cholinesterase In G6PD deficient people due to reduced amount of GSH, primaquine nitrofurantoin and fava beans cause hemolysis.