Pharmacodynamics l Pharmacology MCQs for dental students

 Pharmacodynamics: Mechanismsof Drug Action l Pharmacology  MCQs

 Pharmacodynamics

• Pharmacodynamics (Gr. Pharmacon: drug; dynamics: power): In short, it covers all the aspects relating to ‘what the drug does to the body’. It is the study of drugs—their mechanism of action, pharmacological actions and adverse effects.

Types of Drug Action

1. Stimulation: 

• Some drugs act by increasing the activity of specialized cells, e.g. adrenaline stimulates the heart resulting in an increase in heart rate and force of contraction.

2. Depression: 

• Some drugs act by decreasing the activity of specialized cells, e.g. alcohol, barbiturates, general anaesthetics, etc. depress the central nervous system.

3. Irritation:

• Certain agents on topical application can cause irritation of the skin and adjacent tissues. When an agent on application to the skin relieves deep-seated pain, it is known as counterirritant (e.g. eucalyptus oil, methyl salicylate, etc.). They are useful in sprains, joint pain, myalgia, etc.

4. Replacement: 

• When there is a deficiency of endogenous substances, they can be replaced by drugs, e.g. insulin in diabetes mellitus, thyroxine in cretinism and myxedema, etc.

5. Cytotoxic: 

• Drugs are selectively toxic for the infecting organism/cancer cells, e.g. antibiotics/ anticancer drugs.

 

Mechanism of Drug Action

 

Non receptor-mediated Mechanisms

1. By physical action:

a. Osmosis:

• Some drugs act by exerting an osmotic effect, e.g. 20% mannitol in cerebral oedema and acute congestive glaucoma.

b. Adsorption:

Activated charcoal adsorbs toxins; hence it is used in the treatment of drug poisoning.

• c. Demulcent:
• Cough syrup produces a soothing effect in pharyngitis by coating the inflammed mucosa.

d. Radioactivity: 

• Radioactive isotopes emit rays and destroy the tissues, e.g. 131 I in hyperthyroidism.

2. By chemical action:

• Antacids are weak bases; hence they neutralize acid in the stomach in peptic ulcer.
• Metals like iron, copper, mercury, etc. are eliminated from the body with the help of chelating agents. They trap the metals in their ring structure and form water-soluble complexes, which are rapidly excreted from the body. For example , dimercaprol (BAL) in arsenic poisoning, desferrioxamine in iron poisoning, D-penicillamine in copper poisoning.

3. Through enzymes:

• Some drugs act either by activating or inhibiting the enzyme activity.

a. Drug action via enzyme inhibition:

• Angiotensin-converting-enzyme inhibitors (ACEI) such as captopril, enalapril, etc. act by inhibiting angiotensin converting enzyme (ACE) and are used in the treatment of hypertension, congestive cardiac failure, etc.

4. Through ion channels:

• Some drugs directly bind to ion channels and alter the flow of ions, e.g. local anaesthetics block sodium channels in neuronal membrane to produce local anaesthesia.

5. Through antibody production: 

• Vaccines produce their effect by stimulating the formation of antibodies, e.g. vaccines against tuberculosis (BCG), oral polio vaccine, etc

6. Transporters:

•  Some drugs produce their effect by binding to transporters. Selective serotonin reuptake inhibitors (SSRIs) --- bind to 5-HT transporter --- block 5-HT reuptake into neurons ------antidepressant effect.

7. Others: 

• Anticancer drugs like cyclophosphamide produce their effect by binding to nucleic acids.

 

 

Receptor-mediated Mechanisms

• Receptors are macromolecules present either on the cell surface, cytoplasm or in the nucleus with which the drug binds and interacts to produce cellular changes.
• For example, adrenergic receptors (α and β), cholinergic receptors (muscarinic and nicotinic), opioid receptors, etc.

1. Affinity : The ability of the drug to get bound to the receptor is known as affinity.
2. Intrinsic activity: The ability of the drug to produce pharmacological action after combining with the receptor is known as intrinsic activity of the drug.
3. Agonist: A drug that is capable of producing pharmacological action after binding to the receptor is called an agonist.
4. Agonist has high affinity + high intrinsic activity (e.g. morphine and adrenaline).
5. Competitive antagonist: A drug that binds to receptors but is not capable of producing pharmacological action is called an antagonist.
6. Antagonist has high affinity without intrinsic activity (e.g. naloxone and atropine). It produces receptor blockade.
7. Partial agonist: A drug that binds to the receptor but produces an effect less than that of an agonist is called partial agonist.
8. Partial agonist has affinity + less intrinsic activity (e.g. pindolol and buprenorphine).
9. Inverse agonist: It has full affinity towards the receptor but produces effect opposite to that of an agonist. For example, benzodiazepines produce antianxiety and anticonvulsant effects by interacting with its receptors; but β-carbolines act as inverse agonist at benzodiazepine receptor, and produce anxiety and convulsions.

Receptor Families

1.  Ligand-gated ion channels (inotropic receptors).
2.  G-protein-coupled receptors (metabotropic receptors).
3.  Enzymatic receptors.
4.  Receptor regulating gene expression (transcription factors) or the nuclear receptor