Pharmacology of Phentermine

Pharmacology of Phentermine

Phentermine
Indication	For the treatment and management of obesity.
Pharmacodynamics	Phentermine is indicated in the management of exogenous obesity as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction. Phentermine hydrochloride is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance have been demonstrated with all drugs of this class in which these phenomena have been looked for.
Mechanism of action	Phentermine is an amphetamine that stimulates neurons to release or maintain high levels of a particular group of neurotransmitters known as catecholamines; these include dopamine and norepinephrine. High levels of these catecholamines tend to suppress hunger signals and appetite. The drug seems to inhibit reuptake of noradrenaline, dopamine, and seratonin through inhibition or reversal of the reuptake transporters. It may also inhibit MAO enzymes leaving more neurotransmitter available at the synapse.Phentermine (through catecholamine elevation) may also indirectly affect leptin levels in the brain. It is theorized that phentermine can raise levels of leptin which signal satiety. It is also theorized that increased levels of the catecholamines are partially responsible for halting another chemical messenger known as neuropeptide Y. This peptide initiates eating, decreases energy expenditure, and increases fat storage.
Absorption	Phentermine is rapidly absorbed after oral ingestion.
Volume of distribution	Not Available
Protein binding	Approximately 96.3%
Metabolism	Hepatic.
Route of elimination	Not Available
Half life	16 to 31 hours
Clearance	Not Available
Toxicity	LD50 is adult monkeys is 15 to 20 mg/kg. Symptoms of overdose include delirium, mania, self-injury, marked hypertension, tachycardia, arrhythmia, hyperpyrexia, convulsion, coma, and circulatory collapse.

Pharmacokinetic Phase

Pharmacokinetic Phase
Pharmacokinetics refers to activities within the body after a drug is administered. These activities include absorption, distribution, metabolism, and excretion (ADME). Another pharmacokinetic component is the half-life of the drug. Half-life is a measure of the rate at which drugs are removed from the body.

Following are phases of pharmacokinetics

1. Absorption
2. Distribution
3. Metabolism
4. Excretion
5. Half-Life

Half-Life

Half-life refers to the time required for the body to eliminate 50% of the drug. Knowledge of the half-life of a drug is important in planning the frequency of dosing. For example, drugs with a short half-life (2–4 hours) need to be administered frequently, whereas a drug with a long half-life (21–24 hours) requires less frequent dosing. It takes five to six half-lives to eliminate approximately 98% of a drug from the body. Although half-life is fairly stable, patients with liver or kidney disease may have problems excreting a drug. Difficulty in excreting a drug increases the half-life and increases the risk of toxicity. For example, digoxin (Lanoxin) has a long half-life (36 hours) and requires once-daily dosing. However, aspirin has a short half-life and requires frequent dosing. Older patients or patients with impaired kidney or liver function require frequent diagnostic tests measuring renal or hepatic function.

Excretion

The elimination of drugs from the body is called excretion. After the liver renders drugs inactive, the kidney excretes the inactive compounds from the body. Also, some drugs are excreted unchanged by the kidney without liver involvement. Patients with kidney disease may require a dosage reduction and careful monitoring of kidney function. Children have immature kidney function and may require dosage reduction and kidney function tests. Similarly, older adults have diminished kidney function and require careful monitoring and lower dosages. Other drugs are eliminated by sweat, breast milk, breath, or by the gastrointestinal tract in the feces.

Metabolism

Metabolism, also called biotransformation, is the process by which a drug is converted by the liver to inactive compounds through a series of chemical reactions. Patients with liver disease may require lower dosages of a drug detoxified by the liver, or the primary care provider may select a drug that does not undergo a biotransformation by the liver. Frequent liver function texts are necessary when liver disease is present. The kidneys, lungs, plasma, and intestinal mucosa also aid in the metabolism of drugs

Distribution

The systemic circulation distributes drugs to various body tissues or target sites. Drugs interact with specific receptors (see Fig.) during distribution. Some drugs travel by binding to protein (albumin) in the blood. Drugs bound to protein are pharmacologically inactive. Only when the protein molecules release the drug can the drug diffuse into the tissues, interact with receptors, and produce a therapeutic effect.

Drug-receptor interactions

As the drug circulates in the blood, a certain blood level must be maintained for the drugs to be effective. When the blood level decreases below the therapeutic level, the drug will not produce the desired effect. Should the blood level increase significantly over the therapeutic level, toxic symptoms develop. Specific therapeutic blood levels are discussed in the subsequent chapters when applicable.

Absorption

Absorption follows administration and is the process by which a drug is made available for use in the body. It occurs after dissolution of a solid form of the drug or after the administration of a liquid or parenteral drug. In this process the drug particles within the gastrointestinal tract are moved into the body fluids. This movement can be accomplished in several ways: active absorption, passive absorption, and pinocytosis. In active absorption a carrier molecule such as a protein or enzyme actively moves the drug across the membrane. Passive absorption occurs by diffusion (movement from a higher concentration to a lower concentration). In pinocytosis cells engulf the drug particle causing movement across the cell.

As the body transfers the drug from the body fluids to the tissue sites, absorption into the body tissues occurs. Several factors influence the rate of absorption, including the route of administration, the solubility of the drug, and the presence of certain body conditions. Drugs are most rapidly absorbed when given by the intravenous route, followed by the intramuscular route, the subcutaneous route, and lastly, the oral route. Some drugs are more soluble and
thus are absorbed more rapidly than others. For example, water-soluble drugs are readily absorbed into the systemic circulation. Bodily conditions, such as the development of lipodystrophy (atrophy of the subcutaneous tissue) from repeated subcutaneous injections, inhibit absorption of a drug given in the site of lipodystrophy.