In a large majority of cases drugs or medicinal agents are usually prescribed for treatment of diseases. A disease implies that a structural or functional abnormality is occurring in the body: cells, tissues, organs or biological systems. The objectives of drug therapy include: (a) curative by removing or sustained correction of the abnormality of disease (b) palliative by alleviating the symptoms of disease or the patient’s suffering and (c) prophylactic by preventing the complications of the disease or of the co-administered drugs.
To be effective, the administered drug must reach its target(s) or sites where disease is occurring: in a sufficient concentration, and remain there for a sufficient duration. Drug administration is done to achieve this purpose. Administration of drugs may be broadly categorized as: (a) local administration when the drug is administered directly to the intended site or target, possible when the target is readily accessible. Examples include topical (eye drops, skin ointments and lotions), intra-articular injections into joints etc., and (b) systemic administration whereby drug is administered to reach the systemic circulation via which it is transported to the target site(s). This is done because the target is not readily accessible e.g. the viscera or lying deep inside the body.
Drugs are taken orally as either local administration or systemic administration. As local administration, the drug is not significantly absorbed, and acts locally inside the lumen or on the mucosa of the gut. Examples include (i) direct acting gastric antacids such as Magnesium hydroxide and Aluminum hydroxide, (ii) Neomycin for sterilizing the gut before surgery and (iii) acarbose to prevent absorption of carbohydrates ( See MJCMP Vol No ) and or list at to prevent absorption of fat. Being poorly absorbed, locally administered drugs produce very little or no systemic side effects.
Taken as systemic administration, the drug first reaches the stomach where it becomes soluble by the action of gastric juices. However, for most drugs very little or none is absorbed from the stomach since the gastric mucosa is not equipped for absorption but primarily for secretion. To be absorbed, the drug must reach the small intestines whose mucosae are equipped for both secretion and absorption (villi). For the drug to reach the small intestines, it must pass the pylorus or functional gastro-duodenal “valve”. This valve opens under two conditions: either when the acidity of the gastric contents is reduced sufficiently (e.g. by direct gastric antacids), or when the pyloric antrum of the stomach is distended. Drinking a sufficient volume of a non-acidic beverage, even plain water would accomplish both of these conditions.
Actual absorption of the drug from the intestinal mucosa may occur by: (i) passive diffusion whereby drug molecules travel passively form a higher concentration (gut lumen) to a lower concentration (blood stream), and is dependent solely on the concentration gradient; passive absorption stops when this gradient is lost through absorption and passive absorption is not complete or (ii) active transport. Here, absorption occurs against concentration gradient and energy is required to do so. It may even involve “carriers” which carry the drug molecules across the cell membranes. Complete absorption (100%) may be possible with active transport.
Absorption necessitates the passage of drug molecules across cell membranes. It has been found that only the un-ionized or uncharged molecules can do so, being fat soluble. Otherwise, the drug molecules must be small enough to pass the pores in the cell membrane, e.g. aspirin. Based on their chemical structure and/or formulation, some drugs are well absorbed and some poorly absorbed from the gut.
Drugs absorbed from the gut first pass through the hepatic portal system in the liver. Here, some of the drugs may be metabolized into inactive metabolites, called “first pass hepatic extraction”. The fraction of the administered drug reaching the systemic circulation as unchanged or active form represents the “oral bioavailability” and is dependent on the liver function. Hence, in the elderly or when the liver function is compromised, oral bioavailability is increased. First pass extraction does not occur in drugs that are not metabolized as a means of termination of drug action.
Optimal drug effect occurs only when a sufficient plasma drug concentration is achieved through absorption, called the “target concentration”. When a drug is administered according to a “single dose kinetics” i.e. dosage interval wider than one-and-half times the drug’s half-life, a “peak” concentration is achieved with each single dose. When the drug is administered according to “multiple dose kinetics” i.e. dosage interval less than one-and-half times the drug’s half-life, accumulation occurs with each subsequent dose and plasma drug level increases accordingly until a “steady state concentration” is achieved.
One of the factors that impede intestinal absorption of drugs is the intra-luminal interaction between co-administered drugs or between food and drug whereby drug molecules become insoluble or competition occurs for absorbing mechanisms. Taking the drug together with a large meal may hamper or restrict the effect of many drugs. To avoid this, drug taking is generally recommended one hour before or two hours after meals (to allow for gastric emptying).
Systemic administration of drugs by the oral route has many advantages:
(i) The technique needs no special apparatus and is simple
(ii) Several drugs can be taken simultaneously or one drug several times a day
(iii) Useful for long-term treatment e.g. months or years
(iv) Adverse reactions can be remedied more readily
However, there are some disadvantages of the oral administration:
(i) Onset of drug action is slow, so not suitable for emergencies
(ii) Bioavailability is unpredictable, being dependent on the liver function
(iii) Cannot be used in unconscious or un-cooperative patients, severe vomiting
(iv) Over dosage is possible, intentionally or by accident
From the above it may be suggested that in case of drugs taken orally for systemic effect, onset may be quickened by taking the correct dosage together with an adequate volume of water or some beverage. This would hasten the drug reaching the small intestines where absorption occurs.
Prof Win Maw
MBBS, MMedSc (Rgn); PhD (London)
PhD (Hon) (Ygn)
