Drugs enter cells down concentration gradients. Passive diffusion across the cell membranes dominates the absorption and distribution of most drugs. There is further information on this area in the suggested reading. Thus, when the local pH is equal to the pKa of the drug, the drug will be 50% ionized and 50% unionized (log 1 = 0). Where B is the unionized drug and HB + is the ionized drug. Where A - is the ionized drug and HA the unionized drug. The proportions of drug in each state are calculated using the Henderson-Hasselbalch equation. Under most circumstances, the transmembrane distribution of a weak acid or base is determined by its acidic dissociation constant (pKa) and by the pH gradient across the membrane. 'Like is unionized in like', meaning that a weak acid will be most unionized in a fluid with an acidic pH and a weak base will be most unionized in a fluid with a basic pH. Unionized molecules are usually lipid soluble and can diffuse across cell membranes. Ionized molecules are usually unable to penetrate lipid cell membranes because they are hydrophilic and poorly lipid soluble. Most drugs are weak acids or bases that are present in solution as both the ionized and unionized forms. The other important factor that determines the ability of a drug to cross these biological barriers is the degree of ionization. Molecular size and shape and the solubility at the site of absorption, also directly affect the absorption of drugs. Other barriers, including multiple layers of cells (e.g., the intestinal epithelium or epidermis) exist also.īiological membranes are essentially lipid, thus the rate at which drug molecules cross these barriers is dictated primarily by their lipid solubility. All aspects of the absorption, distribution, biotransformation and elimination of drugs involve transfer across cell membranes. To have an effect drugs must enter cells or reach cell membrane receptors. Physicochemical Factors in the Transfer of Drugs Across Biological Membranesĭrugs are transported in the aqueous phase of blood plasma. Clearly this is a function of the dose given and the concentrations reached in association with the extent and rates of absorption, distribution, biotransformation and excretion. Sufficient concentrations of a drug must be present at its sites of action to produce its characteristic effects. Disease may modify the pharmacokinetic properties of drugs by altering absorption into the systemic circulation and drug disposition (distribution, metabolism and elimination). Drug therapy is based on the correlation of the effects of drugs with the physiological, biochemical, microbiological and/or immunological aspects of the disease in question. Therefore, the selectivity of a drug's effects is one of its most important characteristics. Toxicology is the field of pharmacology that deals with the adverse effects of drugs used in therapy and other non-drug chemicals.Ī drug's usefulness as a therapeutic agent is critically dependent on its ability to produce desirable effects and a tolerable level of undesirable effects. Pharmacodynamics is the study of the mechanisms of action of drugs and their biochemical and physiological effects. These factors and the dosage (route, dose and frequency) determine the drug concentration at the site of action and the intensity of a drug's effects as a function of time. The end result is determined by the physical, chemical and biochemical principles that govern the transfer and distribution of drugs across biological membranes. Pharmacokinetics is the study of absorption, distribution, biotransformation (metabolism) and excretion of drugs. The relationship between the dose of a drug given to an animal and the use of that drug in treating diseases are described by pharmacokinetics, what the body does to a drug and pharmacodynamics, what the drug does in the body (pharmacodynamics), whether it is desirable or undesirable (toxicology). The science of pharmacology includes many different fields. The study of how drugs react in living tissues and organisms is pharmacology. Unfortunately, drugs do not distribute in living organisms as though injected into balloons filled with fluid.
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