Principles of the Drug Administration - Its Metabolism (Absorption) By Funom Makama

Drugs are generally employed as replacement therapy, as agonists, or as antagonists. Drugs are used as replacement for conditions in which there is deficiency or a natural substance-endogenous, e.g, hormones, or exogenous, e.g, nutrients.
Agonist drugs produce a pharmacological effect, e.g, hypotensives, analgesics. Antagonist drugs prevent the action of natural substances like anticholinergics or counteract the action of other drugs, e.g, nalorphine. Drugs produce their effect by interacting with specific receptor sites on the cell membrane. At the receptor sites the action may be positive (e.g, agonists) or opposite to those of agonists (e.g, antagonists). Initially there is physical interaction between the drug and the receptor and this drug receptor complex produces the therapeutic response.

Routes of drug administration: This may be oral, sublingual, topical or parenteral. Parenteral routes are subcutaneous, intra-muscular, intravenous, intra-arterial, intrathecal, intra-ventricular (cerebral ventricles), intra articular, intracavitary (into viscera like pleura or peritoneum or abscess cavities), and intra-amniotic.

Absorption of Drugs

The amount of drug that reaches the systemic circulation intact and is available to the target tissues for effective function is called the "bio-availability" of a drug. The rate of absorption, and the metabolic processes which tend to eliminate or inactivate the drug determine the bio-availability of the ingested drugs.

 Absorption from the gastro-intestinal tract depends upon lipid solubility, degree of ionization, and molecular weight of the drug. Low molecular weight substances and alcohol are absorbed passively, while other drugs are absorbed by active processes requiring energy, e.g, apha methyl dopa. 

Lipid-soluble drugs are absorbed easily. Since drugs have to be in solution to facilitate absorption, formulation which disintegrate rapidly, are more easily absorbed. Due to the variability of physical properties, bio-availability of the same drug may vary when administered in different formulations and therefore it is important to avoid frequent changes in formulations from time to time. 

Other factors influencing gastrointestinal absorption are the availability of surface area for absorption, motility of the gut, pH within the gut, local blood flow, and presence of other substance in the gut lumen.

Drug interactions in the gut may alter the rate and magnitude of absorption. For example, antacids reduce the absorption of Iron by changing the pH and anticholinergics reduce the absorption of other drugs due to delay in gastric emptying. Drug absorption is delayed by the presence of food. For several drugs, administration with water on an empty stomach ensures maximum absorption is erratic. In congestive heart failure venous stasis occurring in the intestines impairs absorption. Drug absorption is unpredictable in the elderly.

sublingual administration

Drugs which are better absorbed from buccal mucosa are preferably given sublingually. Some drugs like notroglycerine and isoprenaline are destroyed by the gastric acid and hence sublingual administration is ideal. Usually, the clinical effect is evident within minutes. Another advantage of sublingual administration is that, drug toxicity can be avoided by removing the drug from the mouth or swallowing it as soon as the desired effect is achieved.

Topical routes 

include the skin and the mucous membranes of the nose, rectum and lungs. Preparations for topical application include inunctions (for example, nitroglycerine), suppositories into the rectum (for example, indomethacin), nasal medications (for example, pitressin) and aerosols which are inhaled.

 Rate of absorption of topically applied drugs depends on the concentration, lipid solubility and local blood flow. Absorption is lower from Keratinized epithelium.

The size of the particle is important when drugs are applied as aerosols. Only particles, below 2 nm in size reach the alveoli.

Absorption from the respiratory epithelium is rapid and the effect is immediate. The portion deposited in the oropharynx is later swallowed and absorbed to produce mild and delayed effect. Considerable attention to details is necessary for ensuring proper administration of the aerosol.

Parenteral administration 

is resorted to when more rapid action is desired and when patient's co-operation cannot be relied upon. Local vascularity influences absorption from sites of intra-muscular or subcutaneous injections.

 Aqueous formulations are absorbed rapidly whereas oily preparations are absorbed only slowly. Local warmth and massage favour absorption.

Intramuscular injections are usually given into the deltoid, rectus abdominis or gluteal muscles.

Certain drugs like diazepam and phenytoin may be erratically absorbed, so that oral administration may be more reliable than intramuscular doses.

The subcutaneous route is to be preferred when the volume of drug is small and drug is non-irritant. The rate of absorption is slightly lower that the intramuscular route. When the peripheral circulation is insufficient, subcutaneous and intra-muscular routes are unreliable.
  
Intravenous route should be resorted to when the drug action has to be immediate, or large volumes or irritant drugs have to be given. Since the onset of action is immediate, the pharmacological effect can be adjusted by controlling the rare of intravenous infusion.

Certain drugs like digoxin take several minutes to exert their full effect even after intravenous administration.

Highly irritants drugs like nitrogen mustards can be given into a rapidly flowing rip since the drug is diluted and the venous walls are relatively resistant. Local damage to vein can be avoided by releasing the drug into more central portions of the circulation, e.g, inferior vena cava. Intra-arterial infusions are indicated when a large dose of drug has to be given in a high concentration at a particular site.

Sources:

http://EzineArticles.com/5865705

http://www.sxc.hu/photo/755991

siege auto