Pharmacology Exam Ib

• Blood profusion of various organs
• Binding of drug to proteins in blood
• The nature of capillaries
• Mechanisms of drug transport with in the target organ

• Brain
• Kidney
• Liver
• Lungs

• Skeleton
• Fat

Skeletal muscle

• Albumin
• Alpha 1 acid glycoproteins

• 50% of proteins in plasma
• affinity to bind weak acid drugs

• Affinity for weak base drugs
• much less abundant than albumin

• better drug delivery
• kidney
• liver

• Poor drug delivery
• Brain

• Conductive = drug travels well
• Non-conductive = drug will not travel well

• free drug in organs
• Free drug in circulation is in equillibrium with drug in organs

• Lowered proteins in the body
• Lower binding of weak acid drugs to albumin
• Increased free drug concentration in circulation
• More drug distribution

lowered proteins

• Bind albumin
• Compete with weak acid drug for binding
• May result in a higher free drug concentration if fatty acid has a higher affinity for albumin than drug

• Decreased plasma albumin
• Increased Alpha 1 Acid Glycoproteins
• Decreased body water
• Decreased lean body mass

more weak acid drug distribution

lower distribution of weak base drugs

less opportunity for drug to disperse resulting in higher drug concentrations in the body.

• increased fat
• lipid soluble drugs hide in fat

• Alteration in chemical structure of a drug
• Enzymatic or non-enzymatic

• Make the drug less lipid soluble and more water soluble
• Promote excretion

• Pharmacological activation
• Pharmacological inactivation
• Toxification
• Detoxification
• A combination of any of the above

• Prodrug -> Drug
• Not the most common

Most drugs are rendered inactive when they are metabolized.

body changes a harmless entity into a harmful entity

most common

Major organ of metabolism

• Major cells of metabolism in the liver
• Nucleus
• Mitochondria
• Endoplasmic Reticulum
• Cytosol

Endoplasmic Reticulum

• First wave of reactions to which the drug is subject
• Drugs may bypass phase 1 and go directly to phase 2
• Reduction
• Hydrolysis
• Dehalogenation
• Oxidation

• Side chain hydroxylation
• Aromatic hydroxylation
• O-Dealkylation
• N-Dealkylation
• S-Dealkylation
• Sulfoxidation

Enzymes present in every other cell compartment

• Further metabolism
• Increase solubility
• Decrease lipid solubility
• Synthetic Reactions
• Conjugation Reactions