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1 Liver Dysfunction Liver is the primary site of drug metabolism Conditions like cirrhosis, hepatitis, fatty liver reduce enzyme activity Result: Slower drug metabolism Prolonged half-life Dose reduction required 2 Renal Impairment Kidneys eliminate drugs and metabolites Reduced GFR leads to drug accumulation Result: Increased plasma concentration Higher risk of toxicity Dose adjustment or increased dosing interval 3 Endocrine Disorders Hypothyroidism drug metabolism Hyperthyroidism drug metabolism Result: Dose modification based on metabolic rate 4 Electrolyte & AcidBase Imbalance Changes in pH affect drug ionization and distribution Result: Altered drug action Unpredictable response Clinical Significance Ignoring metabolic disturbances can turn a therapeutic dose into a toxic dose