Chapter 3: Different Receptors

• All tissues are involved to some extent in metabolism

• A drug needs to be changed from a lipid form to be eliminated. • Metabolism of a drug follows either phase 1 or phase 2

Questions

1. The study of absorption, distribution and elimination is called a. Pharmacodynamics b. Drug tolerance c. Pharmacokinetics d. Drug efficacy

The answer is c, pharmacokinetics

2. Pharmacokinetics refers to the relationship of a drug a. Dose to dose concentration in blood plasma b. Dose to drug at the receptor site c. Concentrations to drug effect d. Dose to drug effect

The answer is a, dose to dose concentration in blood plasma

3. We measure drug levels in the plasma because it is the same as the body tissues. a. True b. False

The answer is a, true

4. Which of the following is true about cell membranes? a. Cell membranes are basically impervious to water b. A drug can be transported across a membrane in an active fashion c. Central nervous system membranes are more impervious to allow cerebral spinal fluid in d. The ionized form of a drug is most likely to cross

The answer is b, a drug can be transported across a cell membrane in an active fashion

5. Which of the following drug delivery methods gives the quickest access to the blood stream

a. Oral b. Subcutaneous c. Sublingual d. Intramuscular

The answer is c, sublingual

6. Intrathecal drug deliver suited for drugs that need to reach the a. Liver b. Pancreas c. Lungs d. Brain

The answer is d, brain

7. The interosseous drug delivery method is used for difficult IV sticks a. True b. False

The answer is a, true

8. Drug distribution is affected by a. Cardiac output b. Decreased blood flow to an organ c. The percentage of cardiac output received d. All of the above

The answer is d, all of the above

9. What does the formula “amount of drug given divided by the concentration” represent? a. Creatinine clearance b. Cardiac index c. Drug receptor efficacy d. Volume of Distribution

The answer is d, volume of distribution

coupled receptors. Two important second messengers from G coupled receptors are cyclic AMP and calcium.

Transmembrane receptors include in their domain insulin receptors, receptors responsible for innate immunity, growth factors and those for tumor necrosis factor. Growth factor receptors, when activated, increase cell survival and in some cells lead to proliferation. The activation of growth factors leads to a protein kinase process called the mitogen activated protein kinase pathway. This is a major factor in the stimulation of a cell nucleus. Drugs involved with these receptors include insulin and several anti-leukemic drugs.

Figure 2 describes transmembrane receptors of different types:

Figure 2

The aspect of immunity related to transmembrane receptors has them classified as toll-like receptors. These toll like receptors have a high density in hematopoietic cells. Pathogens activate these receptors, leading to an inflammatory reaction against them. Tumor necrosis factor works in a fashion like a toll receptor.

Included in the transmembrane receptor class are the natriuretic peptide receptors. There are three of these, atrial natriuretic peptide, brain natriuretic peptide and C type natriuretic peptide. The actions of these peptides are to decrease blood pressure, reduce cardiac enlargement and stimulate growth of the long bones. Atrial peptide is stored in granular form and released due to increased intravascular volume. C type peptide and brain peptide are formed on the spot and respond to growth factors and stressed vascular cells. The cell responds to the peptide stimulation by increasing intercellular cyclic GMP. Cyclic GMP in turn stimulates phosphodiesterase’s and protein kinase.

Figure 4 shows the different parts of the renin angiotensin system:

Figure 4

When the regulation of the RAAS pathway become pathologic the body pays a high price. Renin may be involved in over half of the cases of essential hypertension. Low renin hypertension is found more often in older patients, African-Americans and type 2 diabetics. The role of RAAS in congestive heart failure is significant. The reduced vascular volume in congestive heart failure leads to increased levels of renin and subsequently increases aldosterone. This will increase the afterload on the heart, decreasing the heart’s function further. Abnormal levels of angiotensin converting enzyme or abnormal angiotensin receptors may also cause hypertensive conditions.

After the initial clarification of the role of RAAS inthe body,drugs were targeted at the system through renin blockers. This was short lived due to the inability of the drugs to be formulated as an oral drug. The search for blockers continued on to ACE inhibitors and angiotensin receptor blockers.

Conclusion

Many drugs affect the renin/angiotensin aldosterone system (RAAS). A clear knowledge of howthese hormonesare connectedisneeded tousedrugsthattarget them.At the head of anephron is the glomerulus. Alongside the glomerulus are juxtaglomerular cells. This cell release renin.