GENERAL PHARMACOLOGY
PREPARED BY MR.
ABHIJIT DAS
PHARMACOLOGY
INTRODUCTION
The term "pharmacology" is derived from
two Greek words: "pharmakon" which means drug or medicine, and
"logos" which means knowledge or study. Therefore, pharmacology can
be defined as the study of drugs and their effects on living organisms.
The two main branches of pharmacology are
pharmacokinetics and pharmacodynamics.
Pharmacokinetics is
the study of how drugs are absorbed, distributed, metabolized, and excreted by
the body. This branch of pharmacology focuses on the processes that a drug
undergoes within the body, including its absorption into the bloodstream,
distribution to different organs and tissues, metabolism by the liver and other
organs, and elimination from the body. Understanding pharmacokinetics is
essential for determining the appropriate dose, frequency, and duration of drug
therapy.
Pharmacodynamics is
the study of the effects of drugs on the body. This branch of pharmacology
examines the mechanisms by which drugs produce their therapeutic or toxic
effects, including their interactions with specific receptors, enzymes, and
other molecules within the body. Understanding pharmacodynamics is essential
for optimizing drug therapy, minimizing adverse effects, and developing new
drugs that target specific disease processes.
Together, pharmacokinetics and pharmacodynamics
provide a comprehensive understanding of how drugs interact with the body,
which is essential for the safe and effective use of drugs in the prevention
and treatment of diseases.
SCOPE OF PHARMACOLOGY
The scope of pharmacology is broad and encompasses
various aspects of drug discovery, development, and usage. Some of the key
areas of study within pharmacology include:
1.
Pharmacokinetics: This is the study of
how drugs are absorbed, distributed, metabolized, and excreted by the body. It
helps to determine the optimal dosing and administration of drugs.
2.
Pharmacodynamics: This is the study of
how drugs interact with their targets, such as enzymes, receptors, and ion
channels. It helps to understand how drugs produce their therapeutic effects.
3.
Toxicology: This is the study of the
adverse effects of drugs and other chemical substances on living organisms. It
helps to ensure the safety of drugs and other chemicals.
4.
Pharmacogenetics: This is the study of
how genetic variations can affect an individual's response to drugs. It helps
to personalize drug therapy and improve treatment outcomes.
5.
Clinical Pharmacology: This is the study
of the use of drugs in humans and the effects of drugs on human health. It
involves the testing and evaluation of new drugs in clinical trials, as well as
the monitoring of drug safety and efficacy in patients.
6.
Ethnopharmacology: This is the study of
traditional medicines and their uses in different cultures. It helps to
identify potential new sources of drugs and to understand the cultural and
social contexts of drug use.
VARIOUS ROUTES OF DRUG ADMINISTRATION
There are several routes of drug administration,
each with its own advantages and disadvantages. The choice of route depends on
various factors, such as the drug's properties, the condition being treated,
and the patient's age and health status.
The routes can be broadly divided into:
·
Local/topical route
·
Systemic route
LOCAL ROUTE
Drugs may be applied on the skin
for local action as ointment, cream, gel, powder, paste etc.
Drugs may also be applied on the mucous membrane as in the eyes, ears and nose as
ointment, drops and sprays.
ADVANTAGES
1.
Precise targeting: Local administration
allows for precise targeting of the drug to the site of action, which minimizes
systemic exposure and reduces the risk of side effects.
2.
Rapid onset of action: Local
administration provides a rapid onset of action as the drug is delivered
directly to the site of action.
3.
Minimal systemic side effects: Local
administration reduces the risk of systemic side effects, as the drug is not
distributed throughout the body.
4.
Lower doses: Local administration
requires lower doses of the drug compared to systemic administration, which
reduces the risk of toxicity and side effects.
5.
Convenient: Local administration is
often more convenient than systemic administration, as it can be easily
self-administered.
DISADVANTAGES
1.
Limited scope of action: Local
administration is limited to the site of administration, which may not be
sufficient for treating certain diseases that require a systemic approach.
2.
Difficulty in reaching certain sites:
Some areas of the body may be difficult to access with local administration,
such as the brain or spinal cord, which may require systemic administration.
3.
Short duration of action: Some drugs
delivered through local administration may have a short duration of action,
requiring repeated administration to maintain therapeutic effects.
4.
Irritation and tissue damage: Local
administration may cause irritation, tissue damage, or other local side
effects, particularly with prolonged use.
SYSTEMIC ROUTE
Systemic route of drug administration refers to the
delivery of drugs to the bloodstream, where they
are distributed throughout the body to exert their effects. They are of two
types such as enteral and parenteral.
ENTERAL ROUTES
Enteral routes of drug administration refer to the
delivery of drugs via the gastrointestinal tract,
including oral, sublingual, and rectal routes.
ORAL ROUTE
The oral route of drug administration is one of the
most commonly used methods of delivering drugs to the body. It involves
ingestion of the drug through the mouth, which
then travels through the gastrointestinal tract and is absorbed into the bloodstream.
This route is convenient, non-invasive, and allows for a sustained release of
the drug over time.
ADVANTAGES
·
Safest route
·
Most convenient
·
Economical
·
Self-administration is possible
·
Non-invasive route
DISADVANTAGES
1.
Variable absorption: The absorption of
drugs through the gastrointestinal tract can vary depending on factors such as
food, pH levels, and individual patient factors, leading to inconsistent and
unpredictable drug effects.
2.
First-pass metabolism: Some drugs are
metabolized by the liver before they reach the systemic circulation, reducing
their bioavailability and requiring higher doses to achieve therapeutic
effects.
3.
Gastrointestinal side effects: Oral
drugs can cause gastrointestinal side effects such as nausea, vomiting, and
diarrhea due to irritation of the digestive tract.
4.
Slow onset of action: The onset of
action for orally administered drugs can be slower compared to other routes of
administration, as the drug must travel through the digestive tract before it
can be absorbed into the bloodstream.
SUBLINGUAL ROUTE
Sublingual drug administration involves placing
medication under the tongue, where it is rapidly absorbed through the
sublingual mucosa into the bloodstream, bypassing the liver and digestive
system.
This route provides a fast onset of action and
avoids first-pass metabolism, making it suitable for drugs with poor oral
bioavailability.
Common drugs administered sublingually include
nitroglycerin for angina and buprenorphine for pain management and opioid
addiction.
ADVANTAGES
1.
Rapid onset of action: Sublingual
administration provides a rapid onset of action as the drug is absorbed
directly into the bloodstream without having to pass through the digestive
system or liver.
2.
High bioavailability: Sublingual
administration provides high bioavailability of the drug, as it bypasses
first-pass metabolism in the liver.
3.
Precise dosing: Sublingual
administration allows for precise dosing, as the drug is absorbed directly into
the bloodstream and its effects can be monitored more accurately.
4.
Patient convenience: Sublingual
administration is a convenient and non-invasive route of drug administration
that can be easily self-administered by patients.
5.
Reduced risk of gastrointestinal side
effects: Sublingual administration reduces the risk of gastrointestinal side
effects, such as nausea, vomiting, and diarrhea, that may occur with oral
administration.
DISADVANTAGES
1.
Limited drug types: Sublingual drug
administration is only suitable for a limited number of drugs. It is not
possible to administer every medication through this route.
2.
Drug taste and irritation: Some
medications can have an unpleasant taste or cause irritation when held under
the tongue. This can be uncomfortable for the patient and may discourage
compliance with the medication regimen.
3.
Dose accuracy: It can be challenging to
achieve accurate dosing with sublingual administration, as the amount of
medication that is absorbed can vary depending on factors such as the size of
the dose, the patient's saliva production, and how long they hold the
medication under their tongue.
4.
Slow onset of action: While sublingual
administration can have a faster onset of action than oral administration, it
may be slower than other routes of administration, such as intravenous
injection. This may not be suitable for medications that require rapid onset of
action.
RECTAL ROUTE
The rectal route of drug administration involves the
insertion of medication into the rectum via the anus. Suppositories
are the most common dosage form used for rectal drug delivery. They are
designed to melt or dissolve when inserted and release the medication for
absorption through the rectal mucosa.
PARENTERAL ROUTE
The parenteral route of drug administration refers
to the delivery of medication through a route other
than the gastrointestinal tract.
It also bypasses the digestive system, allowing for
more predictable absorption and bioavailability of the medication.
Parenteral route is of 3 types such as injections,
inhalation and transdermal.
ADVANTAGES
1.
Rapid onset of action: Parenteral
administration allows for rapid delivery of medication directly into the
bloodstream, bypassing the digestive system, and allowing for immediate onset
of action.
2.
Increased bioavailability: Because
parenteral administration bypasses the digestive system, medication is not
subject to first-pass metabolism, which can reduce its bioavailability. As a
result, a higher proportion of the medication reaches its target site, leading
to improved efficacy.
3.
Accurate dosing: Parenteral
administration allows for precise control of the dose of medication
administered, ensuring accurate dosing and reducing the risk of under- or
overdosing.
4.
Alternative to oral administration:
Parenteral administration is an alternative route of drug administration when
oral administration is not feasible or effective, such as in patients with
vomiting, swallowing difficulties, or gastrointestinal disorders.
5.
Suitable for poorly soluble drugs: Parenteral administration allows for the delivery of these drugs
directly into the bloodstream, improving their efficacy.
DISADVANTAGES
The parenteral route of drug administration also has
several potential disadvantages, including:
1.
Risk of infection: Parenteral
administration carries a risk of infection, as the skin is breached during
administration, and the medication is delivered directly into the bloodstream.
2.
Pain and discomfort: Some forms of
parenteral administration, such as intramuscular and subcutaneous injections,
can cause pain and discomfort at the injection site.
3.
Cost and complexity: Parenteral
administration can be more expensive and complex than oral administration.
4.
Limited self-administration: Most forms
of parenteral administration require administration by trained healthcare
professionals, limiting the ability of patients to self-administer their
medication.
5.
Risk of tissue damage: Some forms of
parenteral administration, such as intramuscular injections, carry a risk of
tissue damage or nerve injury if not administered correctly.
6.
Rapid onset of action: When medication
is administered through this route, it enters directly into the bloodstream,
bypassing the digestive system. As a result, the medication can quickly reach
its target site and produce a rapid therapeutic effect.
INJECTIONS
Injections are a common form of parenteral drug
administration that involve the use of a needle and syringe to deliver
medication into the body.
There are several types of injections used in
clinical practice, each with different indications and injection sites. Here
are some key points about the different types of injections:
1.
Intramuscular (IM) injections: These
injections are administered into the muscle tissue, typically in the deltoid,
gluteus maximus, or vastus lateralis muscles. IM injections are commonly used
for vaccines, antibiotics, and some hormonal medications.
2.
Subcutaneous (SC) injections: These
injections are administered into the fatty tissue beneath the skin, typically
in the abdomen, thigh, or upper arm. SC injections are commonly used for
insulin, heparin, and some vaccines.
3.
Intradermal (ID) injections: These
injections are administered into the dermis layer of the skin, typically on the
forearm or upper back. ID injections are commonly used for tuberculosis
screening and some allergy testing.
4.
Intravenous (IV) injections: These
injections are administered directly into a vein, typically in the arm or hand.
IV injections are commonly used for medications that require immediate onset of
action, such as anesthesia, emergency medications, and chemotherapy.
5.
Intra-articular (IA) injections: These
injections are administered directly into a joint, typically for the treatment
of inflammation or pain. IA injections are commonly used for arthritis,
tendonitis, and bursitis.
6.
Intrathecal (IT) injections: These
injections are administered directly into the cerebrospinal fluid. IT
injections are commonly used for anesthesia, chemotherapy, and treatment of
neurological disorders.
INHALATION
Inhalation is a route of drug administration that
involves the delivery of medication directly to the lungs through inhalation of
a gas or volatile liquid. Some key points about inhalation route of
administration include:
1.
Rapid onset of action: Inhalation allows
for rapid delivery of medication directly to the lungs, where it is rapidly
absorbed into the bloodstream, leading to a quick onset of action.
2. Local and systemic effects: Inhalation can provide both local and systemic effects, depending on the medication and its intended use. For example, inhalation of bronchodilators can provide local effects on the airways, while inhalation of systemic corticosteroids can provide systemic effects for the treatment of inflammation.
TRANSDERMAL
The transdermal route of drug administration
involves the delivery of medication through the skin. Here are some key points
about this route of administration:
1.
Transdermal administration provides a
non-invasive, convenient, and painless method of drug delivery, with the
potential for improved patient compliance.
2.
Medication is typically delivered
through a patch or other type of delivery system that is applied directly to
the skin, allowing for sustained and controlled release of the medication over
a period of time.
3.
Transdermal administration is
particularly useful for medications that require continuous or long-term
administration, such as hormone replacement therapy, pain management, and
smoking cessation.
4.
Transdermal patches can be designed to
release medication at a constant rate, depending on the medication and the
desired therapeutic effect.
6. Some of the potential disadvantages of transdermal administration include skin irritation or allergic reactions, limited absorption of some medications due to their molecular size or properties.
DRUG ABSORPTION
Drug absorption is the process by which a drug
enters the bloodstream and becomes available for its intended action.
TYPES
There are several types of drug absorption
processes, including:
1.
Passive transport: This is the most
common type of drug absorption, in which a drug molecule moves across a cell
membrane from an area of higher concentration to an
area of lower concentration. This occurs by diffusion and is driven by
the concentration gradient of the drug.
2.
Filtration: This type of drug absorption
occurs when a water soluble drug molecule passes
through pores in the cell membrane.
3.
Active transport: This type of drug
absorption requires the use of energy (ATP) to
move a drug molecule against a concentration gradient. Active transport is
often used to move drugs from an area of low
concentration to an area of high concentration.
4.
Facilitated diffusion: This type of drug
absorption uses a carrier protein to transport
drug molecules across a cell membrane. It does not require energy and occurs
when a drug molecule moves from an area of high concentration to an area of low
concentration.
5.
Endocytosis: This type of drug
absorption occurs when a drug molecule is engulfed by
the cell membrane and brought into the cell. This process is used for large
molecules that cannot pass through the cell membrane by other means.
FACTORS AFFECTINF DRUG ABSORPTION
Several factors can affect the drug absorption
process, including:
1.
Lipophilicity: Lipophilic (fat-soluble)
drugs can cross cell membranes more easily than hydrophilic (water-soluble)
drugs.
2.
Physical state: The physical form of a
drug (e.g., solid, liquid, or gas) can affect its absorption. For example, a
liquid or gas may be absorbed more quickly than a solid.
3.
Degree of ionization: The degree of
ionization of a drug can affect its ability to cross cell membranes. Ionized
drugs are usually less lipophilic and may be less able to cross membranes.
4.
Particle size: Smaller drug particles
can be absorbed more easily than larger particles because they have a larger
surface area for contact with the absorbing membrane.
5.
pH: The pH of the environment can affect
drug absorption. For example, weakly acidic drugs are absorbed better in acidic
environments, while weakly basic drugs are absorbed better in basic
environments.
6.
Concentration of drug: The concentration
of a drug can affect its absorption. Higher concentrations may be absorbed more
slowly due to saturation of the absorbing membrane.
7.
Surface area of absorbing membrane: The
surface area available for absorption can affect drug absorption. Larger
surface areas, such as in the small intestine, are better for absorption than
smaller surface areas, such as in the stomach.
8.
Route of administration: Different
routes of administration, such as oral, intravenous, or inhalation, can affect
drug absorption due to differences in the absorbing membrane and other factors.
9.
Presence of food: Food can affect drug
absorption, either by slowing or enhancing the process. Some drugs may be
absorbed better with food, while others may be absorbed better on an empty
stomach.
Some Pharmaceutical factors can also affect drug absorption. Some
of these factors include:
1.
Disintegration: Disintegration refers to
the breakdown of a solid dosage form, such as a tablet, into smaller particles.
Disintegration is important for drug absorption because smaller particles can
be absorbed more easily than larger particles.
2.
Dissolution: Dissolution refers to the
process by which a drug dissolves in a liquid, such as gastric fluid in the
stomach. Dissolution is important for drug absorption because only dissolved
drugs can pass through the absorbing membrane.
3.
Formulation: The formulation of a drug
can affect its absorption. For example, a sustained-release formulation may be
absorbed more slowly than an immediate-release formulation.
BIOAVAILABILITY
Bioavailability refers to the proportion of a drug
that reaches the systemic circulation after administration. It is a measure of
the extent and rate of drug absorption. Bioavailability is an important
consideration in drug development and administration, as it affects the
efficacy and safety of a drug.
FACTORS AFFECTING BIOAVAILABILITY
There are several factors that can affect the bioavailability
of a drug, including:
1.
Route of administration: Different
routes of administration can have different bioavailabilities. For example,
oral administration can have lower bioavailability due to the first-pass effect
in the liver, while intravenous administration has 100% bioavailability.
2.
Dosage form: Different dosage forms,
such as tablets, capsules, or liquids, can have different bioavailabilities due
to differences in disintegration, dissolution, or absorption rates.
3.
Drug solubility: The solubility of a
drug can affect its bioavailability, as only dissolved drugs can pass through
the absorbing membrane.
4.
Particle size: The particle size of a
drug can affect its bioavailability, as smaller particles can be absorbed more
easily than larger particles.
5.
Food and drink: The presence of food and
drink can affect the bioavailability of some drugs, either by enhancing or
reducing absorption.
6.
GI motility: The rate of gastric
emptying and intestinal motility can affect the bioavailability of orally
administered drugs.
7.
Liver function: The liver can metabolize
drugs before they reach the systemic circulation, affecting their
bioavailability.
8.
Drug interactions: Co-administration of
other drugs can affect the bioavailability of a drug by affecting its
absorption, metabolism, or elimination.
DRUG DISTRIBUTION
Drug distribution refers to the movement of a drug
from the bloodstream to the desired tissues and organs in the body.
FACTORS AFFECTING DRUG DISTRIBUTION
1.
Blood flow to different organs: Blood
flow to different organs can impact drug distribution. Organs with high blood
flow, such as the heart and liver, tend to receive a larger proportion of the
drug compared to organs with lower blood flow.
2.
Binding to plasma proteins: Drugs that
bind strongly to plasma proteins may remain in the bloodstream for longer
periods, reducing their distribution to tissues.
3.
Metabolism and excretion: The rate at
which a drug is metabolized and excreted from the body can also impact
distribution. If a drug is rapidly metabolized or excreted, it may have limited
time to distribute to target tissues.
4.
Presence of barriers: Biological
barriers such as the blood-brain barrier can limit the distribution of certain
drugs to specific tissues or organs.
5.
Lipid solubility: Drugs that are highly
lipid-soluble tend to distribute more readily into tissues with high lipid
content, such as the brain.
6.
Molecular size: Larger molecules may
have more difficulty passing through cellular barriers, such as the blood-brain
barrier, which can impact their distribution to certain tissues.
BIOTRANSFORMATION OF DRUGS
Biotransformation, also known as drug metabolism,
refers to the process by which the body chemically alters drugs to make them
more easily eliminated from the body. Biotransformation primarily takes place
in the liver, although other organs such as
the kidneys, lungs, and intestines can also contribute.
There are two main phases of biotransformation: Phase I and Phase II.
PHASE I
Phase 1 reactions are all about making a drug more
hydrophilic. These reactions involve introduction or unmasking of a polar
functional group so in phase 1 we are going to see oxidation, reduction,
hydrolysis, cyclization and decyclization.
OXIDATION
The enzyme system which oxidizes the drug is called
‘cytochrome P-450 system’. This reaction involves addition of oxygen/negatively
charged radical or removal of hydrogen/positively charged radical.
Types of oxidation: Microsomal oxidation and
NON-microsomal oxidation.
Microsomal Oxidation-
Catalyzed by enzymes present in the microsome of liver
·
Hydroxylation – addition of hydroxyl
group. Ex – phenytoin will be converted to hydroxyl phenytoin
·
Dealkylation – removal of alkyl group.
Ex – codein will be converted to morphine
·
S-Oxidation – addition of sulfoxide
group. Ex- Cimentidine will be converted to cimentidine sulfoxide
Non-microsomal Oxidation-
catalyzed by enzymes present in the endoplasmic reticulum of liver. Barbiturates,
imipramine, phenothiazines, imipramine, ibuprofen, paracetamol etc are oxidized
in this way.
REDUCTION
This reaction involves removal of oxygen or addition
of hydrogen. Warfarin, halothane, chloramphenicol etc. are reduced.
HYDROLYSIS
Hydrolysis is any chemical reaction in which a
molecule of water breaks one or more chemical bonds. Ex- aspirin, procaine,
lidocaine etc. are hydrolyzed.
CYCLIZATION
Formation of a ring structure from a straight chain
compound. Ex- proguanil.
DECYCLIZATION
Opening up of ring structure of the cyclic drug
molecule. Ex- phenytoin, barbiturates etc.
PHASE II
Phase II biotransformation reactions involve the
conjugation of a drug molecule with a polar substance to increase its water
solubility and facilitate its elimination from the body. Some common types of
Phase II reactions include:
1.
Glucuronide conjugation: Addition of a
glucuronic acid molecule to the drug molecule, typically via the
UDP-glucuronosyltransferase (UGT) enzymes. This can lead to the formation of a
glucuronide metabolite, which is highly water-soluble and readily excreted in
the urine. An example of a drug that undergoes glucuronide conjugation is
morphine.
2.
Acetylation: Addition of an acetyl group
to the drug molecule, typically via the N-acetyltransferase (NAT) enzymes. This
can lead to the formation of an acetylated metabolite, which is more
water-soluble than the parent drug. An example of a drug that undergoes
acetylation is isoniazid.
3.
Methylation: Addition of a methyl group
to the drug molecule, typically via the catechol-O-methyltransferase (COMT) or
thiopurine S-methyltransferase (TPMT) enzymes. This can lead to the formation
of a methylated metabolite, which is more water-soluble than the parent drug.
An example of a drug that undergoes methylation is epinephrine.
4.
Sulfate conjugation: Addition of a
sulfate group to the drug molecule, typically via the sulfotransferase enzymes.
This can lead to the formation of a sulfate metabolite, which is highly
water-soluble and readily excreted in the urine. An example of a drug that
undergoes sulfate conjugation is acetaminophen.
5.
Glycine conjugation: Addition of a
glycine molecule to the drug molecule, typically via the
glycine-N-acyltransferase (GLYAT) enzyme. This can lead to the formation of a
glycine conjugate metabolite, which is more water-soluble than the parent drug.
An example of a drug that undergoes glycine conjugation is benzoic acid.
FACTORS INFLUENCING DRUG METABOLISM
1.
Genetics: Genetic factors play a
significant role in determining an individual's ability to metabolize drugs.
Variations in genes that code for drug-metabolizing enzymes can result in
faster or slower metabolism of drugs.
2.
Age: Age-related changes in the liver
and kidney functions affect drug metabolism. Children and elderly people may
have a slower drug metabolism rate than adults.
3.
Gender: Gender differences can also
influence drug metabolism. For example, females have lower levels of cytochrome
P450 enzymes, which are responsible for metabolizing many drugs.
4.
Diet: The type and quantity of food
consumed can affect drug metabolism. Certain foods and supplements can inhibit
or induce drug-metabolizing enzymes, resulting in altered drug metabolism.
5.
Disease state: Certain medical
conditions such as liver disease, kidney disease, and metabolic disorders can
affect drug metabolism. These conditions can alter enzyme levels and function,
leading to changes in drug metabolism.
6.
Environmental factors: Exposure to
environmental toxins such as cigarette smoke, air pollution, and industrial
chemicals can affect drug metabolism. These toxins can induce or inhibit
drug-metabolizing enzymes, leading to altered drug metabolism.
7.
Drug interactions: When two or more
drugs are taken together, they can interact with each other, affecting drug
metabolism. Some drugs can inhibit or induce drug-metabolizing enzymes,
resulting in altered drug metabolism.
EXCRETION OF DRUGS
Excretion of drugs refers to the process by which
the body eliminates drugs or their metabolites from the body. It involves the
removal of drugs and their metabolites from the bloodstream, followed by their
elimination through urine, feces, sweat, breath, or other bodily fluids or
tissues.
ROUTES OF DRUG EXCRETION
- Renal:
through the kidneys into the urine
- Biliary:
into the bile, which is then eliminated through feces
- Pulmonary:
through the lungs into the breath
- Sweat
and Saliva: through sweat glands and salivary glands
- Mammary:
through breast milk
- Others:
such as hair, nails, and skin.
GENERAL MECHANISM OF DRUG ACTION
Drugs can exert their action in the body through
various mechanisms, including:
1.
Receptor binding: Drugs can bind to
specific receptors on the surface or inside cells, leading to changes in
cellular activity or signaling pathways.
2.
Enzyme inhibition: Drugs can inhibit the
activity of enzymes, which are responsible for various metabolic and
biochemical reactions in the body.
3.
Ion channel modulation: Drugs can
modulate the activity of ion channels, which control the flow of ions across
cell membranes, leading to changes in cellular excitability.
4.
Transporter inhibition or activation:
Drugs can inhibit or activate transporters that are responsible for the uptake
or efflux of molecules in cells.
5.
Physical or chemical interactions: Drugs
can interact with other molecules in the body through physical or chemical
mechanisms.
PRINCIPLES OF DRUG ACTION
Drugs don’t impart new functions to any system,
organ or cell; they only alter the pace of ongoing activity. The basic types of
drug action are stimulation, depression, irritation, replacement, and cytotoxic
action.
1. STIMULATION
·
It refers to selective enhancement of
the level of activity of specialized cells.
·
Ex- Adrenaline stimulates heart,
caffeine stimulates CNS
2. DEPRESSION
·
It means depression of activity of
specialized cells.
·
Ex- Barbiturates depress CNS, Quinidine
depress heart
3. IRRITATION
·
Mild irritation may stimulate associated
function.
·
Ex- bitters increase salivary and
gastric secretion.
4. REPLACEMENT
·
This means use of natural metabolites or
their derivatives in deficiency states.
·
Ex- Insulin in diabetes mellitus, Iron
in anaemia.
5. CYTOTOXIC
ACTIONS
·
This means selective cytotoxic action
for invading parasites or cancer cells.
·
Drugs destroy those toxic cells without
affecting the host cells.
·
Ex- Penicillin
FACTORS MODIFYING DRUG ACTION
1.
Route of administration: The route of administration
can affect the rate and extent of drug absorption and distribution. A drug may
have entirely different uses through different routes.
Ex- Magnesium sulfate
when given orally causes purgation but when given intravenously it produces hypotension.
2.
Cumulation: Repeated administration of a
drug can lead to accumulation in the body, which can affect drug action and
toxicity.
Ex- prolonged use of
chloroquine causes retinal damage.
3.
Age: Age-related changes in body
composition, organ function, and metabolism can affect drug action and
toxicity.
4.
Gender: Gender differences in body weight,
hormone levels, and enzyme activity can affect drug action and toxicity.
5.
Body weight: Body weight can affect drug
dosing and distribution, which can affect drug action and toxicity.
6.
Genetic factors: Genetic variations in
drug-metabolizing enzymes and drug targets can affect drug action and toxicity.
7.
Presence of food: Food can affect drug
absorption and metabolism, which can affect drug action and toxicity.
8.
Disease: Disease can affect drug
absorption, metabolism, and excretion, which can affect drug action and
toxicity.
9.
Metabolism: The rate and extent of drug
metabolism can affect drug action and toxicity.
10.
Race: Genetic and environmental
differences among races can affect drug metabolism and drug action.
11.
Rate of absorption: The rate of drug
absorption can affect drug action and toxicity.
12.
Psychological factors: Psychological
factors, such as placebo effect and, nocebo effect can affect drug action.
13.
Time of drug administration: The timing
of drug administration can affect drug action and toxicity. Example-
Hypnotics taken at night and in quiet atmosphere may work more easily.
14.
Effect of other drugs: The concurrent
use of multiple drugs can affect drug action and toxicity.
15.
Tolerance: Repeated use of a drug can
lead to tolerance, which can affect drug action and efficacy. Example-
When Morphine or Alcohol is used for a long time, larger and larger doses must
be taken to produce the same effect.