Question

In: Nursing

What does it mean for a drug to be flow-limited? What type of drug is more...

  1. What does it mean for a drug to be flow-limited? What type of drug is more likely to be flow limited?
  2. How does fitness affect pharmacokinetics?
  3. How are drugs with a long half life and duration of action affected by mild exercise?
  4. How does higher intensity of exercise affect pharmacodynamics?
  5. How could exercise effect the therapeutic window?
  6. What are up and down regulation?

Solutions

Expert Solution

1. Drug metabolism mainly takes place in liver . It is the major route of elimination for wide variety of drugs

Hepatic Drug Clearance means volume of blood perfusing the liver that is cleared of drug per unit time

Factors influencing metabolism of drug in liver

There are 3 major parameters that determine drug elimination by the liver

  1. Blood flow through the liver which reflects the amount of drug delivered to the liver
  2. The fraction of amount of drug which are free and  not bound to plasma proteins
  3. The intrinsic ability of hepatic enzymes (intrinsic clearance ) to metabolize the drug in the absence of flow limitations and binding to cells or proteins in the blood

The ratio of hepatic clearance of drug to that of heapatic blood flow is called extraction ratio of the drug

According to the fraction of drug removed by the first pass through the liver , it is divided drug into 3 categories

High extraction ratio/ Flow limited drug

These drugs are rapidly cleared from the blood  by the liver within one pass. Their clearance completely depends on hepatic blood flow and binding to the blood components is not an obstacle for extraction. Hence, it is also known as non-restrictive or blood flow dependent drug or flow limited drug

Low extraction

Drugs which are not efficiently cleared by the liver and extracted incompletly form the blood

Intermediate extraction

Drug clearance depends on hepatic blood flow, intrinsic factors and free drug fractions( amount of drug bounded to plasma proteins)

Examples of Flow-limited drugs

Morphine, lidocaine,verapamil,Propranalol nitroglycerine

2.Pharmacokinetics describes the relationship between absorption,distribution,metabolism and excretion of the drugs and its effects and duration of action.

The effects of exercise on all four components are described below

Physical exercise seems to have a greater influence on absorption of drugs administered intramuscular, subcutaneous or transdermal routes than drugs administerd orally

Exercise increases rate and depth of respiration thus increases alveolar gas exchanges

Exercise increases blood flow to the muscles and lungs and thus decreases blood flow to liver and kidneys thus affecting metabolism and excretion of especially flow limited drugs such as lidocaine and nitrates

3. Half-life of a drug means duration of the action of the drug. This is the period of time required for the concentration and amount of drug in the body to be reduced to half. a drug's plasma half-life is determined by how quickly drug is eliminated from plasma

Changing position from supine to upright position can affect the distribution of the drug and if a drug has short-half life resulting in lower therapeutic range. But with long half life, concentration of drug in the plasma will be there for extended time. hence, mild exercise do not affect these drugs

4.Strenous exercise decreases blood flow to the liver and by diverting blood to lungs and muscles. this results in deactivation of flow-limited drug. Due to decreased perfusion of kidneys during exercise,renal plasma flow, urine excretion and pH are reduced during the exercise. Hence, therapeutic range of most of the drugs will be affected


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