Introduction to Drug Action and Biological Response

Health is defined as a state of optimal physical, mental and social well being and not merely the absence of disease; whereas disease is any deviation from or interruption of the normal structure or function of any organ or system of the body manifested by characteristic sign and symptoms whose etiology, pathology and prognosis, may be known or unknown.

What is a Drug?

- A drug is any substance that affects physiological function in a specific way.

- It can be any substance used in the diagnosis, prevention or treatment of disease.

Mode of Action of Drugs

1. Interaction with receptors

2. Inhibition or Activation of enzyme function.

3. Alteration of cytosoloic ion concentration by promoting or inhibiting ion entry through membrane ion channels.

The Efficacy of a Drug

The efficacy of a drug is determined by the mutual relationship between:

What the drug dose to the body = pharmacodynamics.

What the body dose to the drug = pharmacokinetics.

Pharmacodynamics

A study of what the drug does to the body. Describe where and how a drug acts on the body.

In order to produce a physiological response by binding to:

1. A particular site (Receptor or Ion channel) of cell.

2. Tissues

3. Target protein (Enzyme or Enzyme system)

e.g. When adrenaline binds to its receptor in the heart, the heart beats faster. The receptor produces an effect only when adrenaline is bound; otherwise it is functionally silent.

Receptors

1. Specific protein molecules at cell membrane.

2. Possess a binding site for a specific substance

3. Occupation of the binding-site can induce a biological response.

Biological Response

Excitation

e.g. Acetylcholine (Ach) activates the cholinergic receptors at the gastro-intestinal (GI) tract produce muscle contraction.

Inhibition

e.g. Anti-cholinergic drugs block cholinergic receptors causing muscle relaxation of the gut.

Highly specific

Receptor only bind with certain types of ligand

Certain types of ligand	Binds with
Acetylcholine	cholinergic receptor
Adrenaline	Adrenergic receptor
Morphine	Opioid receptor
Histamine	Histamine receptor

To produce a physiological response

	Full agonist	Partial agonist	Antagonists
Receptor	bind with a receptor	bind with a receptor	bind with a receptor
Activates	activates the receptor system	activates the receptor system	fail to activate
Response	maximum response	No maximum response	block the receptor
Efficacy	High efficacy	Intermediate efficacy	No efficacy at all

Efficacy

Describes the strength of a single drug-receptor complex in producing a biological response

Potency

A comparative measure of the different doses of two drugs A and B that can produce the same effect.

If drug A can produce the same effect as drug B at lower doses, then drug A is said to have a higher potency than drug B.

Depends on Reception Affinity and Efficacy
Enzyme

Another important target for drug action:

Catalyzes biological reactions

Activates metabolic processes

Produces vital substances in the cell

Drugs targeted at enzyme are called activators or inhibitors.

Pharmacokinetics

A study of what the body does to the drug. Administered drug will come across a series of events in the human body depending on the various routes of administration of the drug.

A study of the Absorption, Distribution, Metabolism and Excretion of drug in the body (ADME).

Drug Absorption

Affected by the nature and Route of Administration of the drug:

Oral, Sublingual, Parenteral, Rectal, Cutaneous/ Transdermal, Inhalation

Oral route

Advantage: Convenient, Safest and Least expensive

Affected by:

1. Drug solubility

2. Gastro-intestinal (GI) motility

3. Particle size and formulation e.g. micronised particle enteric-coating, Sustained released tablets

4. Chemical interaction with gut contents e.g. Gastric pH, Food Milk, Alcohol

5. Drug interaction e.g. Tetracycline and Calcium

6. Drug action via the oral route is slow

7. Liver metabolism (First-pass Metabolism)

First-pass Metabolism/ First-pass Effect

Most drugs are metabolized by the liver so that the amount reaching the systemic circulation is less than the amount absorbed after oral administration.

This is a detoxification mechanism of our body.

Sublingual route

1. Absorbed directly from Oral cavity into Systemic circulation without entering Portal system

2. Escape first-pass metabolism

3. Produce a faster effect

4. Suitable for drugs unstable at gastric pH e.g. insulin

5. Rapidly metabolized by the liver e.g. Nitroglycerine

Rectal route

1. Useful to a patient who is unconscious or vomiting

2. Useful for drugs required to produce a local effect e.g. Glycerine suppository

3. Absorption from the rectal mucosa is less predictable than from the small intestine

Transdermal route

1. Drugs applied to the skin surface may be absorbed slowly

2. Allow lipid-soluble drugs to be delivered lowly and continuously over many hours and days

3. May develop local irritation at the site of application

4. Only suitable for drugs given in small daily dose

Parenteral route

1. Intravenous (iv) injection is the fastest and most certain route, subcutaneous (sc) and intramuscular (im) injections also produce a faster effect than oral administration

2. Given directly into the blood stream

3. Bypasses many biological barriers

4. Can be used for drugs unstable to gastric juices e.g. Insulin, Vaccines and Gamma globulin

5. The rate of absorption depends on the site of administration and local blood flow

Inhalation route

1. Used for volatile substances and gaseous anesthetics

2. Drugs used for their effects on the lungs and bronchial tree

3. Achieve higher drug concentration

4. Minimize side effects

5. Fast onset of action

6. Bypass the liver

7. Proper use of the aerosol is important e.g. bronchodilator

Drug Distribution

After entry into the system circulation a drug will distribute between the circulating plasma and various body compartments

To be able to enter cells, a drug must cross an epithelial barrier (biological barrier) e.g. the blood brain, placenta

The equilibrium pattern of distribution between the various compartments depends on the physico-chemical properties of the drug

1. Lipophilic drugs can cross the biological barrier more readily than hydrophilic drug

2. Drugs that are strongly protein-bound stay mainly in the plasma e. g. Diazepam, Aspirin

3. Water soluble drugs are readily excreted from the body

4. Lipid-soluble drugs reach all compartments and accumulate in fat

Some drugs tend to accumulate in certain tissues and organs causing adverse effects

Drug Metabolism

The Process by which a drug is chemically altered by the body to from readily excretable products

The liver enzyme system, such as cytochrome P-450 plays a key role

The metabolites, which may be active or inactive, toxic or nontoxic, are excreted from the body.

The liver enzyme may be regarded as a detoxification system of foreign substances

The elderly people have reduced enzymatic activity, therefore require less drugs than young adults do

Drug Excretion

Drugs are eliminated from the body either unchanged or as metabolites

The kidney is the main excretory organ and most drugs leave the body in the urine

Certain drugs (e.g. aluminum) excreted from the kidney cause toxicity in patient with renal disease

Drugs may also be excreted in breast milk, sweat, tear and genital secretions

Highly volatile agents (e.g. anaesthetic) are excreted via the lungs

Entero-hepatic circulation

Some drugs (e.g. oral contraceptives) are excreted into the bile via the liver, but in most cases reabsorbed from the intestine, prolong drug action