Pharmacodynamics and Pharmacokinetics are both concerned with the response of drugs on the body. Pharmacodynamics is concerned with the effect of a drug on the body. It has to do with the relationship between the dosage and the molecular mechanisms of the drug activity. Pharmacokinetics is concerned with the effect of the body on the drugs. It has to do with drug metabolism, transport, absorption and elimination.
The body influences how the drug is distributed within the body, and this influence is due to the rates of drug intake in the body's tissues; and the rate of which the drug is eliminated from the body. Pharmacokinetics, then is devoted to the development of mathematical models, that are designed to study the three activities of drug intake and its relationship with the body. These models are then used to predict the outcomes of different dosages of drug concentrations in the body with respect to time. These models are difficult to construct for any specific drugs because of the complications that can be introduced through the interactions of the compound, (the drug make up) the organism and the presence of the disease.
The underline concept of pharmacokinetics is to consider the simple situation of the introduction of the drug in the body, and the elimination of this drug from the body over time. The three processes involved are biotransformation, absorption or bioavailability, distribution, and excretion. The biotransformation and excretion of drugs are concerned with the passing of medication across cell membranes. For the process to be effective we have to be concerned with the properties of molecules and membranes that influences this process.
In biotransformation two products are of importance, the composition of the drug and the structure of the cells.
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Drug Absorption and Bio-Availability
The rate at which a drug leaves the site where it enters the body is called absorption. Bio- availability is concerned with the availability of the administered drug at the needed site. Many factors affect the bioavailability and absorption of drugs in the body.
Site of Absorption
If the drug enters the body through the mouth and is absorbed in the stomach and the intestines, then the drug is metabolized in the liver, and excreted in the bile. In this situation some of the drug will be diverted before it reaches the circulatory system and can be distributed to the needed site.
Drug Solubility
Drugs given in a water solution are more easily absorbed than drugs in oily solution, suspension or solid form. Drugs that are water soluble mixes readily at the site of absorption than those that are given in solid form. The absorption of drugs given in solid form will depend on the rate at which it dissolves. The local conditions at the site of absorption also alter solubility, some drugs are insoluble in acidic conditions.
The concentration of drugs also influences its rate of absorption. Drugs that are delivered in solution of high concentration are absorbed more rapidly than the drugs that are administered in solution of low concentration.
The circulation at site of administration
The circulation at the site of administration also affects the absorption of drugs. Increased blood flow enhances the chance of greater absorption rates are compared to areas of decreased blood flow. Increased blood flow can be brought about by the application of heat or by massaging the site.
The surface area
The area of the site at which the drug is given affects the rate of absorption. Drugs will be absorbed more rapidly from large surface areas. The absorbing surface is also determined by the route of administration.
The Route of Administration
Oral administration
Oral administration is the most common choice, and is considered the safest and most convenient. There are disadvantages to this route of administration. These include:
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- The incapability to absorb some drugs because of their physical characteristics
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- Irritation to the mucosa membrane of the mouth
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- Destruction of some drugs by the digestive system
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- The irregularities in absorption or propulsion when food is present
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- Metabolization by the enzymes of the intestines or the liver before they reach the circulation system.
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- Cooperation on the part of the patient
Parenteral Injections
This form of administration is vital to drugs that need to be absorbed in active form. Bio-availability is usually more rapid, and the dosage can therefore is more suitable if the patient is uncooperative, or if treatment is needed in an emergency situation. The disadvantages are that pain may accompany the injection, the injection may be given in a vascular, or the injection may be given when it is not necessary. It is also difficult to self medicate.
Sublingual Administration
Absorption from the oral mucosa has special significance for certain drugs. Drugs such as nitroglycerin is absorbed quite rapidly. Only a few molecules need to be absorbed for the drug to be effective. The drainage from the mouth goes to the superior vena cava, therefore the drug is protected from metabolism by the liver.
Rectal Administration
The rectal route is preferred if the oral ingestion causes vomiting or if the patient is unconscious. Most of the drug that is absorbed from the rectum will bypass the liver. The disadvantage of the rectal absorption is that absorption of the drug is often irregular and incomplete, and some drugs can cause irritation of the rectal mucosa.
Drug Distribution
After the drug is absorbed, or injected in the body it needs to be distributed into the interstitical and cellular fluids. Drug distribution consist of physiological factors and physiochemical properties. The heart, liver, kidney, brain, and fused organs receive most of the drug during the first minutes after absorption. The muscles, the skin, and fat have a slower rate of absorption.
Drug distribution is affected by:
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a) Blood flow
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b) The rate at which drug diffuse into the issue
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c) Drug binding to plasma protein
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d) The accumulation of drugs in tissues in high concentration.
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e) The function of the patient's age, gender, and body composition.
The volume of drug distribution relates the amount of drug in the body to the concentration of drug in the blood plasma based on the type of fluid measured.
Volume = Amount of drug in the body / Concentration. To calculate the distribution of drugs, the body is considered as a one compartment model (like a box). All drugs is administered into the central compartment and the distribution of the drug is instantaneous throughout the volume. Simplified the amount of drug eliminated per unit of time depends on the amount of drug in the body's compartment. The equation C= (d/V) - exp(kt) is used to calculate the decline of a drug introduced in the body (compartment). K is the rate of constant elimination.
The half life of the drug is the time it takes for the drug's concentration in the body to be reduced by 50%. This half life can be used to determine how to administer successive dosages of the drug. It has been shown that half life of a drug is the function of both clearance, and volume of distribution. Therefore a formula for half life can be adjusted to t1/2 = 0.693. (v/cl).
Biotransformation of Drugs
This is the process that permits rapid passage of the drugs across cellular membranes. The enzyme systems that are responsible for the biotransformation of many drugs are located in the liver. Fewer are also present in other organs such as the kidney, lungs, and gastrointestinal lining.
There two phases involved in biotransformation.
Phase 1: The drug is converted to a more polar metabolite by oxidation, reduction or hydrolysis. Phase II: The drug is coupled with metabolites, with sulfate acetate or with an amino acid. These actions occur concurrently or consecutively so that the original drug is converted to several metabolites. These actions usually take place in the liver.
Excretion of Drugs
The excretion of drugs has to do with how drugs are eliminated from the body either unchanged or as metabolites. The excretory organs eliminate polar compounds more efficiently than substances with high lipid solubility. Drugs that are not lipid soluble are not eliminated unless they are metabolized to polar compounds. The kidney is the organ the is responsible for the elimination of drugs, however some drugs are eliminated through the feces, the breast milk, the lungs, through the sweat glands, saliva and the tears.
Renal Excretion
This excretion of drugs in the urine involve three processes
a) Glomerular filtration
b) Active tubular secretion
c) Passive tubular re- absorption
Biliary and Fecal Excretion
The metabolites of drugs formed in the liver are excreted into the intestinal tract in the bile. Some of the metabolites may be reabsorbed into the blood and then is excreted in the urine.
Pulmonary Excretion
Pulmonary excretion is responsible for the elimination of anesthetic gases and vapors, and small quantities of some other drugs.
Excretion from Other Routes
Drug is also excreted from the sweat glands and the tears in small amounts. Drugs is excreted from the mouth through the saliva where it is swallowed. The saliva provides another place where drug concentration can be obtained.. Drug is also excreted in the breast milk. Milk is more acidic than plasma therefore certain drugs will enter the breast milk in small amounts. Certain drugs are also excreted through the skin and hair follicles.