Chapter -1
GENERAL PHARMACOLOGY
A. INTRODUCTION:
a. Pharmacology : Pharmacology is a branch of science which deals with the study of drug ( history, properties ) , drug effects on body (physiological effects, mechanism of action), & body's response ( absorption, distribution, metabolism, excretion) and also uses of a drug.
Pharmacology has two major branches -
- Pharmacokinetics
- Pharmacodynamics
b. Drug: A drug is defined as any chemical substance which is used to cure, treatment, diagnose or prevent a disease.
c. Maln divisions of Pharmacology :
I. Pharmacodynamics(Drug's effects) which deals with biochemical and physiological effects of drugs and also their mechanism of action. (What the drug does to the body).
II. Pharmacokinetics (Body's response) which deals with the absorption, distribution, metabolisnı and excretion of drugs. (What the body does to the drug).
III. Therapeutics which is concerned with the use of a drug for curing diseases and relieving their symptoms.
IV. Clinical Pharmacology which is the seientific study of drugs in man. The efficacy and safety of a drug is studied in patients and healthy volunteers.
V. Chemotherapy which deals with the effects of drugs on micro- organisms and parasites which occur in a living organism, It also includes the treatment of cancer.
VI. Toxicology which deals with poisonous effects of drugs, detection of poisoning and its treatment.
B.ABSORPTION OF DRUGS
Absorption is used to described the journey of a drug travelling from the site of administration to site of action.
Drugs can pass through cell membrane by two processes. They are:
a. Passive transfer- Passive diffusion means the crossing of a pharmaceutical substance(drug) across a cell membrane from a site of administration. In this passive process that does not require energy.
I.Simple diffusion : It is a bidirectional process. Polar (water soluble) and non- polar (lipid- soluble) substances can be transported by this process. Because cell membrane made by lipid substance.
II. Filtration : Only water-soluble substances can be transported by this process. It involves passage through pores present in the cell membrane.
b. Specialised transport-
I.Active transport : It is a selective process which requires energy. Also it requires a carrier and so is called as carrier transport.
In this process drug molecules enter into the cell though protein Carrier which present in cell membrane.
II. Facilitated diffusion: It is very similar to carrier transport, but it does not require energy.
III. Pinocytosis : Proteins and macromolecules are transported by this process. It is similar to phagocytosis where cells engulf fluids from the surroundings.
Factors modifying drug absorption:
a. Physical state : Drugs in the form of liquids are well absorbed than solids. Gases are quickly absorhed through lungs.
b.Particle size : Smaller the particle size, better is the absorption of drug. If the particle size is large, the drug is slowly absorbed and hence the action is delayed.
c. Solubility : An easily soluble drug is quickly absorbed. Also drugs in the form of solutions are quickly absorbed than solids.
d. Concentration: Concentrated forms of drugs are quickly absorbed than dilute solutions.
e. Area of absorbing surface : Greater the area of absorbing surface, quicker is the absorption of a drug. For example, lungs and peritoneal cavity are large surface areas from where dnugs can be quickly absorbed.
f. Circulation to site of absorption : Increased blood flow to the area of absorption can increase the absorption of a drug. This can be achieved by massage or local application of leat. Vasoconstrictors decrease blood flow and so decrease the absorption of a drug.
g. Route of administration: This is a very important factor which determines drug absorption. Some drugs are absorbed only on parenteral administration and they fail to get absorbed on oral administration e.g. insulin. So it is necessary to carefully choose the route of adıministration of any drug.
Bioavailability:
It is defined as the quantity of the drug that is absorbed and reaches systemic circulation after administration by any route. The bioavailability is 100% after intravenous injection.
C. ROUTES OF DRUG ADMINISTRATION
Route of administration is an important factor which influences the absorption of a drug. The interval between administration and onset of action is determined by the route of administration. The interval between administration of a drug and development of response is called as Biological lag.
Mainly two types of route drugs are administeted such as,
1.Systemic administration
A. Enteral ( means drug pass through the intenstine to systemic circulation)
● oral
● sublingual (under the toungh)
● rectal
B. Parental ( means drug pass to systemic circulation other than intensine)
●Transmucosal
●Inhalation
●Injections
◆intravenous
◆intraarterial
◆intramuscular
◆intradermal
◆subcutaneous
2. Local administration
●Skin topical
●Intra nasal
●mucosal throat,vaginal,mouth,ear
Some important notes:-
●Enteric coated pills and tablets: These are oral preparations coated with cellulose acelate or gluten. These coatings cannot be destroyed by the acid juice of the stomach. Only the alkaline imtestinal juice removes these coatings. So inactivation of the drug in the stomach is avoided. Thus a desired concentrations of the drug released in the intestine.
●Sustained release or time release preparations (Timesules, Spansules) : These are oral preparations containing various coatings. Each coating dissolves at different time intervals releasing the active drug. So the drug is released slowly for prolonged periods.
D. DISTRIBUTION OF DRUGS
After a drug is absorbed, it is distributed to various body tissues and fluids. Drugs which easily pass through cell membrane achieve wide distribution. Drugs which do not pass through cell membrane are limitcd in their distribution.
E. BIOTRANSFORMATION OF DRUGS
•Alteration of a drug in a living organism is known as 'biotransformation'.
• By this process, a drug may either be inactivated or converted into a more active compound.
• Biotransformation is sometimes called Drug metaholism or 'Detoxication'.
• Methods of biotransformation :
a. Non- synthetic reactions (Phase I reactions)
Non-synthetic reactions lead either to activation or inactivation of a drug. These reactions are further classified as:
I.Oxidation : In this reaction oxygen add with drug subsance produce reactant substance. Oxidation occurs mainly in the liver.
II. Reduction :
III. Hydrolysis :
b. Synthetic reactions (Phase Il reactions)
Synthetic reactions also called as 'cunjugation reactions' lead only to inactivation of a drug.
I. Glucuronide formation
II. Sulfate formation
III. Acetylation
IV.Methylation
V.Giycine conjugation
Factors modifying biotransformation:
a.Inhibitors Drug metabolising enzymes can be inhibited by certain drugs.
b. Stimulators : The activity of drug metabolising enzymes can be incrensed by certain drugs
c. Age: Metabolism of drugs is poor in young children because of poor development of drug metabolis ing enzymes
d. Sex: Females have less ability to metabolise drugs.
e. Species : Rabbits metabolise atropine due to the presence atropinase. Humans lack this enzyme. So atropine is toxic to humans but non -toxic to rabbits,
f.Genetic : Deficiencies in drug metabolising enzymes can be inherited
g. Body temperature : Increase in body temperature increases drug metabolism, whereas decrease in body temperature has the opposite effect.
F. EXCRETION OF DRUGS
Excretion of a drug decreases its duration of action. This in turn decreases the toxicity. Drugs may be excreted in an active or inactive form. The various routes through which drugs can be eliminated are:
1.Kidneys : Drugs may be eliminated through the kidney by:
I. Passive glonmerular filtration-most of the drugs are eliminated by this mechanism.
ii. Active tubular secretion e.g. penicillin.
iii. Passive tubular reabsorption
2. Lungs : Drugs like volatile general anaesthetics, alcohol and paraldehyde are excreted through lungs.
3. Skin : Heavy metals like arsenic and mercury are excreted through skin.
4. Intestine : Purgatives like senna and cascara are absorbed in small intestine and later get excreted in large intestine.
5. Bile : Drugs like diphenylhydantoin and phenolphthalein are excreted into small intestine through bile. These drugs may be absorbed again, carried to the liver and again excreted into small intestine through bile. This process called as 'enterohepatic circulation' prolongs the duration of action of such drugs.
6. Milk : Milk is more acidic than plasma and hence basic drugs like pethidine are eliminated through it.
7. Saliva : Drugs like iodides and metalic salts are excreted through saliva. Lead is eliminated through saliva and deposition produces black lining of teeth.
G. MECHANISMS OF DRUG ACTION
A drug may produce its effect by a number or mechanisms like combining with enzymes, cell membrane other components of a cell.
Agonist is a drug which combines with the receptor and initiates a pharmacological action.
Antagonist is a drug which combines with the receptor and blocks it without producing a pharmacological action.
H. Factors Affecting Dose:
1. Age: The age of an individual is of great significance. Children and old people need lesser amount of drug than the normal adult dose, because they are unable to excrete drugs as compare to adults.
2.Sex: Generally females require lesser dose than males because of their lesser weight and also due to the reason that they are more responsive to the effects of certain drugs than males, Drugs should be given very carefully during menstruation, pregnancy and lactation. Strong purgatives should be avoided during menstruation.
3. Body Weight: Generally recommended adult doses are based on a "nomal" body weight of 70 kg. But such a dose will be too less for a muscular person weighing 100 kg and too large for a weak person weighing about 50 kg. The calculation of doses for children on the basis of body weight is considered more dependable than that based strictly on age.
4. Route of Administration: The dose of a given drug may vary according to the dosage form and route of administration used. Drugs administered intravenously enter the blood stream directly hence require lesser dose than the subcutancous dose which in turn is smaller than the oral dose.
5. Time of Administration: Time of administration of drugs is very important. Drugs are rapidly absorbed from the empty stomach, hence an amount of drug that is effective when taken before a meal may be ineffective if administered during or after meals, On the other hand iritating drugs are better tolerated if administered after meals which will dilute the drug's concentration and reduce the gastric irritation, e.g., iron, arsenic, cod-liver oil, etc., should always be given on a full stomach.
6. Presence of Disease : Drugs are more effective in diseased conditions than normal body conditions. During fever one can tolerate high doses of antipyretics than in a nonfebrile condition. Similarly during hepatic or renal disturbances, the drugs which are metabolised in the liver or excreted through the kidneys may prove fatal.
7. Environmental Factors: Alcohol is better tolerated in cold environments than in summer. Dose of a sedative required to produce sleep during day time is much more than the dose required to produce sleep during night.
8. Emotional Factors: Females are more emotional and responsive to drugs therefore require less dose of drugs, The faith inspired by the doctor on the mind of a patient is an important factor in medication. Nervous patients require smaller doses of drugs as compared to normal patients.
9.Accumulation: When a drug is repeatedly administered for a long time, depending on its nature, it may unexpectedly accumulate in the body to produce sudden toxic symptoms. The drugs which produce such symptoms of poisoing are called cumulative drugs.
10.Synergism:
When two or more drugs are used in the combined form their action is either increased or decreased depending on the drugs used in combination When the potency or duration of action is increased, the phenomenon is called synergism. This synergism is of two types :
(a) addition When the total effect of two drugs is just equal to the sum of their individual effects, it is known as addition. (b) Potentiation When the combined effect of two drugs administered is greater than the sum of their individual effects, it is known as potentiation.
11.Antagonism: When the action of one drug is opposed by the other drug, the phenomenon is known as antagonism.
12. Habituation and Addiction
(a) Habituation When repeated use of a drug or agent leads to production of emotional or psychological dependence rather than compulsion the condition is known as habituation, e.g., use of tea, coffee, tobacco.
(b) Addiction: It is a state of psychic and physical drug dependence. Continuous use of alcobol, opium, cocaine, heroin, morphine, pethidine, LSD leads to addiction and turns the person to a wreck who becomes liability to society.
13.Idiosyncrasy
All persons do not respond alike to the same drug due to varied individual susceptibility, some may produce abnormal reaction to a drug. When an abnormal or unusual reaction is produced by a drug it is known as idiosyncrasy, e.g., few mg of aspirin may produce gastric haemorrhage and small doses of quinine may produce ringing in the ear.
14. Hypersensitivity
Hypersensitivity is an allergic reaction to a drug and is different from either the expected pharmacological response or toxic reaction to the drug. This is due to frequent or indiscriminate use of drugs like antibiotics, vitamins and especially proteinous substances. Once a person is sensitised, a minute dose of the drug will produce allergic reactions. It is of two types (i) immediate type which is serious and requires prompt injection of adrenaline othcrwise death may occur (ii) delayed type in which urticaria, skin rashes or contact dermatitis may occur.
15. Tolerance
When a drug administered in an ordinary dose fails to produce the normal therapeutic effect and requires large dose of the drug to produce the normal effect. The unusual resistance thus produced is known as tolerance, e.g., smokers can tolerate nicotine, alcoholics can tolerate large doses of alcohol, rabbits can tolerate large doses of atropine due to quick destruction of the drug by enzyme atropine estrase present in their blood.
16.Tachyphylaxis
It is also known as acute tolerance. It is observed in certain drugs that when they are administered repeatedly at very short intervals the cell receptors get blocked up and pharmacological response to that particular drug is decreased. By increasing the dose this decreased response cannot be reversed. But if the administration of the drug is stopped for a long time and administered again after being discontinued then the initial effect of the drug can be reobserved. This condition is known as tachyphylaxis. Drugs like ephedrine, amphetamine, cocaine, and nitrites behave in this way.
Short Questions & Answers
1.Who is known as father of pharmacology ?
(a) Oswald Schmiedeberg
(b) J langley
(c) Rudolf Buchheim
(d) Paul Ehrlich
2.From which of the following routes, bioavailability of the drug is likely to be 100%
(a) subcutaneous
(b) Intravenous
(c) Intramuscular
(d) Intradermal
3.Essential drug is-
( a ) Drugs that has been developed specifically to treat a rare medical condition.
( b ) Those drugs that satisfy the health care needs of the majority of the population
( c ) Those drugs that satisfy the health care needs of at least 50 % of the population
( d ) Drug that is to be used with in first hour of the acute attack of the disease
4.Pharmacokinetics includes study of all except
(a) Absorption
(b) Distribution
(c) Adverse effects
(d) Excretion
5. Pharmacodynamics includes
(a) Drug elimination
b) Drug excretion
(c) Drug absorption
(d) Mechanism of action
6.Most important mechanism of drug transport across cell membrane -
(a) Filtration
(b) Active transport
(c) Passive diffusion
(d) Facilitated diffusion
7.Acidic drug is more ionized at
(a) Alkaline
(b) Acidic pH
(c) Neutral pH
(d) None
8.About acidic drug true is
(a) Best absorbed in acidic medium
(b) Best absorbed in alkaline medium
(c) Not absorbed in acidic medium
(d) Binds to alpha glycoprotein
9.Route of administration of drug depend on
(a) Physical and chemical properties
(b) Site of desired action
(c) The time course of the action
(d) All of the above
10.Sublingual route is used for:
(a) Enhancing the drug action
(b) Reducing the toxic effect of the drug
(c) By passing the first pass metabolism of drug
(d) None of the above
11.Large volume of fluids are administered
(a) Intramuscular route
(b) Subcutancous route
(c) Intravenous route
(d) None of the above
12.Oily injection is preferably given by:
(a) Subcutaneous route
(b) Intramuscular
(c) Intravenous route
(d) None of the above
13.For rapid and intense action, which of these parenteral route is used :
(a) Subcutaneous
(b) Intramuscular
(c) Intravenous
(d) All of these
14.Absorption of drug depend on :
(a) Particle size
(b) Solubility
(c) pH
(d) All of the above
15.Transport of drug against concentration gradient take place by :
(a) Active transport
(b) Passive transport
(c) Filtration
(d) All of the above
16. Any chemical substance which is used to cure, treatment, diagnose or prevent a disease called as_____________.
17.The interval between administration of a drug and development of response is called as ____________.
18. _________or ____________are used to prepare enteric coated pills.
19.Which barrier helps to drug pass into central nervous system ( CNS ).
20. Which barrier helps to drug pass into foetal circulation.
21.BBB present between.
22.BPB present between.
23.Which type of drugs pass into CNS.
24.Which type of drugs pass into foetal circulation.
25.Pharmacology is .. .....
Study of Drugs actions
Study of Drug structures
Study of Structural activity relationship
None of them
26. Drug is..
Any substance for diagnosis, prevention cure
Used to explore pathological states for benefit
Both of them
None of them
27.Pharmacodynamics is ..
What Drug does to body
What body does to drug
ADME of drug
All of them
28.Pharmacokinetics is ...
What Drug does to body
What body does to drug
About effect and MOA of drug
All of them
29.Therapeutics is ..
Pharmacology knowledge application in prevention
Pharmacology knowledge application in treatment
Both of them
None of them
30.Study of adverse effect of drug given in large dose is ..
Toxicology
Chemotherapy
Oncology
Mycology
31. Effect of drug on microorganism and parasite is...
Toxicology
Chemotherapy
Oncology
Mycology
32.Clinical Pharmacology is ..
Scientific study of drugs in humans
Pharmacodynamic and Pharmacokinetics investigation
Scientific study in healthy volunteer and patient
All of them
33. Drugs used in rare diseases are....
Orphan drugs
Antibiotics
Antivirals
Analgesics
34. First pass metabolism occurs in
Brain
Liver
Kidney
All of them
35.......... route avoid First pass metabolism
Sublingual
Injectables
Rectal
All of them
36. Distribution of drug in body fluids compartments occurs after
Absorption
Metabolism
Excretion
All of them
37..............is not a biological barrier
Placenta
BBB
Cell membranes
Renal tubule
38. Metabolic transformation includes...
Oxidation, Reduction and Hydrolysis
Conjugation
Both of them
None of them
39. Prodrug is ...
An inactive drug
Must be metabolised in body
Converted to active form
All of them
40................ Are the factors modifying drug action
Age and Sex
Genetics
Pathological state
All of them
41.One drug altering pharmacological effect of another when given concurrently is ..
Drug interaction
Drug tolerance
Tachyphylaxis
None of them
42........ is a substance that binds to the receptors without directly altering their functions
Antagonist
Agonist
Partial agonist
None of them
43. A competitive antagonist is a substance that
Binds to the nonspecific sites of tissue
Binds to one receptor subtype as an agonist and to another as an antagonist
Interacts with receptors and produces submaximal effect
Binds to the same receptor site and progressively inhibits the agonist response
44. Idiosyncratic reaction of a drug ...
Can be due to genetic variation
Can't be attributed to drug allergy
Is different from usual effect
All of them
45. Agonist .
Has affinity to receptor
Has the Intrinsic activity
Both of them
None of them
46.Ratio of LD 50 : ED 50 is...
Toxicity index
Therapeutic index
Environment index
Safety index
Answer
1.aOswald Schmiedeberg
2.b Intravenous
3.c Those drugs that satisfy the health care needs of at least 50 % of the population
4.c Adverse effects
5.d Mechanism of action
6. Passive diffusion
7.Alkaline
Implication of ionization Acidic drugs ionize more at alkaline pH.Basic drugs ionize more at acidic pH.
8.b Best absorbed in acidic medium
9.d All of the above
10.c By passing the first pass metabolism of drug
11.c Intravenous route
12.b Intramuscular
13.c Intravenous
14.d All of the above
15.a Active transport
16. Drug
17. Biological lag
18.cellulose acelate or gluten
19. Blood Brain Barrier (BBB)
20. Blood Placental Barrier (BPB)
21. Plasma & extracellular surface of brain
22. Maternal & foetal circulation
23. Lipid soluble & non-ionised drugs
24.Lipid soluble & non-ionised drugs
25. Study of Drugs actions
26. Any substance for diagnosis, prevention cure
27.What Drug does to body
28.What body does to drug
29.Both of them
30.Toxicology
31. Chemotherapy
32. All of them
33. Orphan drugs
34. Liver
35.All of them
36. Absorption
37. Renal tubule
38. Both of them
39. All of them
40. All of them
41. Drug interaction
42.Antagonist
43. Binds to the same receptor site and progressively inhibits the agonist response
44. All of them
45. Both of them
46. Therapeutic index
Therapeutic index: It is defined as the ratio of median lethal dose to median effective dose.
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