The document provides an overview of general pharmacology concepts including definitions of pharmacology and drugs. It discusses the objectives of studying pharmacology and defines key terms like receptors, pharmacokinetics, pharmacodynamics, drug sources, nomenclature, dosage forms, and routes of drug administration with a focus on oral, parenteral, and other enteral routes. The document aims to introduce students to the basic concepts and principles of pharmacology.
1. College of Medicine & Health
Sciences
Pharmacology for Health
Sciences
1
Compiled by: Birhanu G.(B.Pharm)
July, 2015General Pharmacology Compiled by: Birhanu Geta
3. Objectives
@ the end of this session students will be able to:
Define what Pharmacology is?
Define what meant by drugs?
Identify source of drugs.
Differentiate Pharmacokinetics and
Pharmacodynamics.
Explain principles of Pharmacokinetics and
Pharmacodynamics.
3General Pharmacology Compiled by: Birhanu Geta
5. Derivation
Pharmacology =>
Pharmakon = Active Principle/Active
Ingredient or equivalent to drug, medicine or
poison &
Logia = study.
PHARMACOLOGY
means:
“THE SCIENCE OF DRUGS”
5General Pharmacology Compiled by: Birhanu Geta
6. DEFINITION
Pharmacology:
Is the study of substances that interact with
living systems through chemical process,
especially by binding to regulatory molecules &
activating or inhibiting normal body process.
Includes, history, source, properties,
compounding, biochemical and physiological
effects, PK and PD, therapeutic and other uses,
precautions, adverse effects, interactions and
contra-indications of drugs.
6General Pharmacology Compiled by: Birhanu Geta
7. A French word ‘Drogue’ which means dry herb.
Any substance that brings about a change in biologic
function through its chemical action.
Alters state in the body:
=>can’t create new function but alter existing
function.
Are poisons if they used irrationally.
Poisons are drugs that have almost exclusively harmful
effects. However, Paracelsus famously stated that
"the dose makes the poison,"
“Poisons in small doses are the best medicines; and
useful medicines in too large doses are poisonous.
“Every drug is a medicine but every medicine is not a drug!!!”
7General Pharmacology Compiled by: Birhanu Geta
8. Receptors
Specialized target macromolecules present on
the cell surface or intracellularly.
The biological molecule plays a regulatory role.
Drugs bind with receptors & initiate events
leading to alterations in biochemical activity of a
cell, and consequently, the function of an organ.
Some times, the drug may act through non-
specific physicochemical mechanisms.
– Osmotic properties (bulk laxatives, saline
purgatives, mannitol)
– Adsorbents (kaolin, charcoal)
8General Pharmacology Compiled by: Birhanu Geta
9. Basic Areas of Pharmacology
Pharmacokinetics (Biodisposition of drugs)
Pharmacodynamics
Pharmacokinetics: deals with absorption, distribution,
biotransformation & excretion of drugs.
Pharmacodynamics: study of biochemical &
physiological effects of drugs & their MOA.
Pharmacotherapeutics: use of drugs in prevention &
treatment of disease.
Chemotherapy: effect of drugs upon microorganisms,
parasites and neoplastic cells living & multiplying in living
organism.
Toxicology: branch of pharmacology which deals with
the undesirable effects of chemicals on living systems.
Pharmacogenomics: relationship of individual’s genetic
makeup to his/her response to specific drugs.
9General Pharmacology Compiled by: Birhanu Geta
10. History of Pharmacology
Prehistoric people recognized beneficial & toxic
effects of many plant & animal materials.
Preceding the modern era, there were attempts
to introduce rational methods into medicine.
But none were successful owing to the
dominance of systems of thought [without
experimentation & observation].
Around end of 17th century, reliance on
observation & experimentation began.
About 60yrs ago, controlled clinical trial
reintroduced; expansion of research efforts;
Drug action & receptor.
Now, the molecular mechanism of action of many
drugs is known.
10General Pharmacology Compiled by: Birhanu Geta
11. Application of pharmacology
To control speed of onset, intensity of the drug's
effect, and duration of action. Hence decide on
route of administration, the amount and frequency
of each dose, and the dosing intervals.
To identify the possible side effect, and
withdrawal symptoms of drugs and take measures
to manage.
To avoid adverse effects from drug interaction
and contraindicated drugs.
To avoid adverse effects in special populations
like geriatrics, paediatrics, pregnant and lactating
mothers.
To avoid treatment failure due to tolerance &
resistance.
To control misuse of drugs by the patient & health
professionals.
11General Pharmacology Compiled by: Birhanu Geta
12. Drugs
Drugs mostly interact with a specific molecule in
a biologic system that plays a regulatory role
[receptor].
Clinically, drugs used for:
–Diagnosis: Barium salts,
–Prevention: Vaccines, chemoprophylaxis
–Treatment: ART
–Cure: Antibiotics
–Alteration of physiological processes:
Hormones & their derivatives (insulin, GH,
contraceptives….)
–Global effect: General anesthetics
12General Pharmacology Compiled by: Birhanu Geta
13. To interact chemically with its receptor, a
drug molecule must have the appropriate:
Size (MW100-1000Dalton),
For specificity of action, the ability to move
within the body (e.g., from the site of
administration to the site of action).
Electrical charge (bonding), exception Xe.
Shape (complementary to that of the receptor
site in the same way that a key is complementary
to a lock).
– Most of drugs are chiral molecules.
Atomic composition.
13General Pharmacology Compiled by: Birhanu Geta
14. A number of useful or dangerous drugs are
inorganic elements, e.g. lithium, iron, & heavy
metals.
Many organic drugs are weak acids or bases.
– This fact has important implications for the
way they are handled by the body, because pH
differences in the various compartments of
the body may alter the degree of ionization of
such drugs.
14General Pharmacology Compiled by: Birhanu Geta
15. Source of Drugs
Drugs are obtained from various sources.
Drugs may be synthesized within the body
(hormones) or not. i.e. xenobiotics (from the
Greek xenos, meaning "stranger").
15General Pharmacology Compiled by: Birhanu Geta
16. According to sources they are:-
1.Natural drugs
A. Plants
E.g. . Digoxin from Digitalis purpurea
. Atropine from Atropa belladonna
. Quinine from Cinchona officinalis
B. Animals
E.g.. Insulin from pork/beef
. Cod liver oil from Cod fish liver.
C. Minerals: Iron, Iodine, Potassium salts.
D. Micro – organisms: Penicillin from penicillium
notatum, Chloramphenicol from Streptomyces
venezuelae (Actinomycetes).
General Pharmacology Compiled by: Birhanu Geta 16
17. 2. Synthetic drugs: prepared by chemical
synthesis in pharmaceutical laboratories.
E.g. Sulphonamides, quinolones, barbiturates.
3. Semi-synthetic drugs: prepared by chemical
modification of natural drugs.
E.g. . Ampicillin from penicillin G.
. Dihydroergotamine from ergotamine.
4. Biosynthetic drugs: prepared by cloning of
human DNA in to the bacteria like E.coli.
E.g.. Human insulin (humulin), human GH.
17General Pharmacology Compiled by: Birhanu Geta
18. Drug Nomenclature
• Existence of many names for each drug causes
lamentable & confusing situation.
• A drug has at least three types of names;
Chemical name (IUPAC) or scientific name,
Based on molecular structure of the drug
Very long, too complex to use in common practice.
International Nonproprietary/generic name,
- Given by FDA/WHO while approved, the short hand
version of chemical name.
- Recommended in RX.
Proprietary/trademark/Brand name,
- Given by the pharmaceutical company.
- Costly.
18General Pharmacology Compiled by: Birhanu Geta
20. DOSAGE FORMS (PREPARATIONS)
Dosage forms (DFs) are the means by which drug
molecules are delivered to sites of action within
the body.
The need for dosage forms:
1. Accurate dose.
2. Protection e.g. coated tablets, sealed ampules.
3. Protection from gastric juice.
4. Masking taste and odour.
5. Placement of drugs within body tissues.
6. Sustained release medication.
7. Controlled release medication.
8. Optimal drug action.
9. Insertion of drugs into body cavities (rectal,
vaginal)
10.Use of desired vehicle for insoluble drugs.
20General Pharmacology Compiled by: Birhanu Geta
21. Types of Dosage forms
According to route of administration:
Oral
Rectal
Vaginal
Parenteral
Inhaled
Topical
Ophthalmic
Otic
21General Pharmacology Compiled by: Birhanu Geta
22. Types of Dosage forms…
According to physical form of a drug;
1. Solid
a. Tablets – Conventional
- Chewable
- Sublingual
- Extended release
b. Capsules – Hard gelatin & Soft gelatin
c. Powders – Effervesent granules
- Insufflations
- Dentrifices
- Powder for injections
d. Suppositories
General Pharmacology Compiled by: Birhanu Geta 22
24. Orally (swallowed)
Through Mucus Membranes
– Oral Mucosa (e.g. sublingual)
– Nasal Mucosa (e.g. insufflated)
Topical/Transdermal
(through skin)
Rectally (suppository)
According to on set of action
Slow Absorption
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26. Medication Administration
– Right Medication
– Right Dosage
– Right Time
– Right Route
– Right Patient
– Right Documentation
26General Pharmacology Compiled by: Birhanu Geta
27. Routes of Drug administration
Is the path by which a drug, fluid, poison
or other substance is brought into contact
with the body.
27
General Pharmacology Compiled by: Birhanu Geta
28. Commonly Used Routes of Drug Administration
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IV = intravenous;
IM = intramuscular;
SC = subcutaneous.
29. Factors governing choice of Route
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29
Drug characteristics
Ease of administration
Site of action
Onset of action
Duration of action
Quantity of drug administered
Liver and kidney diseases
30. General Pharmacology Compiled by: BirhanuGeta 30
Enteral Routes
Enteral - drug placed directly in the GI tract:
–sublingual - placed under the tongue
–Oral - swallowing (p.o., per os)
–Rectal - absorption through the rectum
31. Oral Route
General Pharmacology Compiled by: BirhanuGeta 31
ADVANTAGES
Safe
Convenient
Economical
Usually good absorption
Can be self
administered
DISADVANTAGES
Slow absorption slow
action
Irritable and unpalatable
drugs
Un co-operative &
unconscious pts.
Some drugs destroyed
First-pass effect
32. Sublingual Route
General Pharmacology Compiled by: Birhanu Geta 32
ADVANTAGES
Economical
Quick termination
First-pass avoided
Drug absorption is quick
Can be self administered
DISADVANTAGES
Unpalatable & bitter drugs
Irritation of oral mucosa
Large quantities not given
Few drugs are absorbed
33. Rectal Route
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ADVANTAGES
Used in children
Little or no first pass effect
Used in vomiting/unconsciuos
Higher concentrations rapidly
achieved
DISADVANTAGES
Inconvenient
Absorption is slow and erratic
Irritation or inflammation of
rectal mucosa can occur
Vaginal Routes
Drug may be administered locally in the vagina in
the form of pessaries.
E.g. Antifungal vaginal pessaries
34. General Pharmacology Compiled by: BirhanuGeta 34
First-pass Effect
The first-pass effect is the term used for the
hepatic metabolism of a pharmacological agent
when it is absorbed from the gut and delivered to
the liver via the portal circulation.
The greater the first-pass effect, the less the
agent will reach the systemic circulation when the
agent is administered orally.
35. General Pharmacology Compiled by: BirhanuGeta 35
First-pass Effect cont’d…
Magnitude of first pass hepatic effect:
Extraction ratio (ER)
ER = CL liver/Q
Where, Q is hepatic blood flow (usually about 90 L per
hour for 70 kg adult).
Systemic drug bioavailability (F) may be
determined from the extent of absorption (f) &
the extraction ratio (ER),
F = f x (1-ER)
38. Administration of drugs by the Parenteral
Route
General Pharmacology Compiled by: BirhanuGeta 38
Needle insertion for
parenteral drug:
A. Intradermal
injection @15⁰.
B. Subcutaneous
injection @45⁰.
C. Intramuscular
injection @90⁰.
D. Intravenous
injection
39. Intravascular (IV)
General Pharmacology Compiled by: BirhanuGeta 39
1. Absorption phase is bypassed (100% BA)
2. Precise, accurate and almost immediate onset of
action.
3. Large quantities can be given, fairly pain free
4. Greater risk of adverse effects
a. High concentration attained rapidly
b. Risk of embolism and cannot be recalled by
strategies such as emesis or by binding to
activated charcoal
5. IV is the most common parenteral route for
drugs that are not absorbed orally.
40. Intramuscular Route(IM)
General Pharmacology Compiled by: BirhanuGeta 40
Advantages
Absorption reasonably
uniform
Rapid onset of action for
drugs in aqueous solution.
Mild irritants can be given
Repository and slow release
preparations
First pass avoided
Gastric factors can be
avoided
Disadvantages
Only up to 10ml drug given
Local pain and abscess
Expensive
Infection
Nerve damage
41. General Pharmacology Compiled by: BirhanuGeta 41
Subcutaneous route(SC)
1. Slow and constant absorption
2. Absorption is limited by blood flow, affected if
circulatory problems exist
3. Concurrent administration of vasoconstrictor will
slow absorption
42. Inhalation
1. Aerosols (gaseous & volatile agents)-lungs
2. Rapid onset of action due to rapid access to
circulation
A. Large surface area
B. Thin membranes separates alveoli from
circulation
C. High blood flow
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43. General Pharmacology Compiled by: BirhanuGeta 43
Inhalation cont’d
Respiratory system. Except for IN, risk hypoxia.
Intranasal (snorting) Snuff, cocaine may be partly oral via
post-nasal dripping. Fairly fast to brain, local damage to
septum. Some of the volatile gases also appear to cross
nasal membranes.
Smoke (Solids in air suspension, vapors) absorbed across
lung alveoli: Nicotine, opium, THC, freebase and crack
cocaine, crystal meth.Particles or vapors dissolve in lung
fluids, then diffuse. Longer action than volatile gases.
Tissue damage from particles, tars, CO.
Volatile gases: Some anaesthetics (nitrous oxide, ether).
Lung-based transfer may get drug to brain in as little as
five seconds.
44. General Pharmacology Compiled by: BirhanuGeta 44
Topical
Mucosal membranes (eye drops, nasal drops,
antiseptic, sunscreen, callous removal etc.)
Skin
A. Dermal - rubbing in of oil or ointment (local
action)
B. Transdermal - absorption of drug through
skin (systemic action)
i. Stable blood levels
ii. No first pass metabolism
iii. Drug must be potent or patch
becomes to large
46. General Pharmacology Compiled by: BirhanuGeta 46
Time-release preparations
Oral - controlled-release, timed-release,
sustained-release
Designed to produce slow, uniform
absorption for 8 hours or longer.
Better compliance, maintain effect over
night, eliminate extreme peaks and troughs.
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Time-release preparations
Depot or reservoir preparations
Parental administration (except IV), may be
prolonged by using insoluble salts or
suspensions in non-aqueous vehicles.
Example: Implantable contraceptives.
48. The ROA is determined by:
Physical characteristics of the drug,
Speed which the drug is absorbed and/or released,
The need to bypass hepatic metabolism and achieve
high conc. at particular sites
Important
Info
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49. No single method of drug administration is ideal for all
drugs in all circumstances !!!!!!!!!!!!!!!
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50. Pharmacokinetics (The life cycle of a Drug)
Pharmacokinetics:
– Pharmakon: drug
– Kinesis: motion
Action of body on drug/ how body handles drugs
Pharmacokinetics: ADME
Four pharmacokinetic properties determine the
onset, intensity & duration of drug action.
Using knowledge of pharmacokinetic parameters;
clinicians can design optimal drug regimens;
including the route of administration, dose,
frequency & duration of treatment.
50General Pharmacology Compiled by: Birhanu Geta
51. Absorption
Absorption is the process by which a drug enters
the bloodstream without being chemically altered
or
The movement of a drug from its site of
application into the blood or lymphatic system
How drugs transfer form site of administration?
1. Filtration [aqueous diffusion]-passage of drugs
through aqueous pores.
Size should be less than size of pore
Has to be water soluble.
E.g. Na+, glucose, caffeine.
51General Pharmacology Compiled by: Birhanu Geta
52. 2. Diffusion: drugs supposed to pass membrane.
Drugs must be lipid soluble.
High partition coefficient high absorption.
3. Carrier mediated absorption
a. Facilitated diffusion
- Passive but facilitated.
E.g. levodopa & amino acid into brain.
b. Active transport
- Use ATP & carrier proteins.
- Against the concentration gradient.
E.g. levodopa & methyldopa from the gut.
52General Pharmacology Compiled by: Birhanu Geta
53. 4. Phagocytosis & pinocytosis
- Process by which large molecules are engulfed by
the cell membrane forming a vesicle & releases
them intracellularly.
E.g. protein, toxin
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54. Summary of transport across a membrane
54General Pharmacology Compiled by: Birhanu Geta
55. Drug absorption
• Transfer of a drug from its site of
administration to the bloodstream.
• The rate and efficiency of absorption depend on
the route of administration.
– For IV delivery, absorption is complete; that
is, the total dose of drug reaches the systemic
circulation.
– Drug delivery by other routes may result in
only partial absorption and, thus, lower
bioavailability.
55General Pharmacology Compiled by: Birhanu Geta
56. Factors affecting GI absorption
PH of media & pKa of the drug
Area of absorbing surface
Particle size of the drug
Formulation
Gut motility
GIT blood flow
Gastric secretion
Drug interaction
56General Pharmacology Compiled by: Birhanu Geta
57. A drug must be in solution to be absorbed, since
most drugs are either weak acids or weak bases,
pH affects their solubility and hence absorption.
Weak bases are absorbed more rapidly from the
intestine than stomach.
Small intestine is the major absorption site
because:
–It has large surface area (microvilli
200M2)
–There is good blood supply (1L blood/min
compared to 150mL/min stomach)
–Permeability to drugs is greater
57General Pharmacology Compiled by: Birhanu Geta
58. Bioavailability (F)
• Fraction of administered drug that reaches the
systemic circulation in a chemically unchanged
form.
– Amount of drug available in the circulation/site
of action
– It is expressed in percentage
– It is 100% for drugs given IV.
• For example, if 100 mg of a drug is administered
orally and 70 mg of this drug are absorbed
unchanged, the bioavailability is 0.7 or 70%.
Factors affecting bioavailability
– Extent of absorption
– First pass effect
58General Pharmacology Compiled by: Birhanu Geta
60. Drug distribution
Reversible movement of drug from bloodstream
to interstitium (extracellular fluid) and/or cells.
Factors affecting drug distribution
1. Plasma protein binding
– Albumin [acidic & hydrophobic drugs]
– -glycoprotein [basic drugs]
2. Tissue uptake of drugs/tissue binding
-Adipose tissue [DDT]
-Bone [TTC]
-Liver [chloroquine]
-Thyroid gland [iodine]
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62. Drug metabolism
Enzymatically mediated alteration in drug
structure.
Transforms lipophilic drugs into more polar
readily excretable products.
Liver - major site for drug metabolism, but
specific drugs may undergo biotransformation in
other tissues, such as the kidney and the
intestines.
Note: Some agents are initially administered as
inactive compounds (pro-drugs) and must be
metabolized to their active forms.
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63. Inducers
The cytochrome P450 enzymes are an important
target for pharmacokinetic drug interactions.
Certain drugs, most notably phenobarbital,
rifampin, and carbamazepine, are capable of
increasing the synthesis of one or more CYP
isozymes.
This results in increased biotransformations of
drugs.
1. Decreased plasma drug concentrations.
2. Decreased drug activity if metabolite is
inactive.
3. Increased drug activity if metabolite is
active.
4. Decreased therapeutic drug effect. 63General Pharmacology Compiled by: Birhanu Geta
64. Inhibitors
Inhibition of CYP isozyme activity is also an
important source of drug interactions that leads to
serious adverse effects.
The most common form of inhibition is through
competition for the same isozyme.
For example, omeprazole is a potent inhibitor of
three of the CYP isozymes responsible for
warfarin metabolism.
If the two drugs are taken together, plasma
concentrations of warfarin increase, which leads to
greater inhibition of coagulation and risk of
hemorrhage and other serious bleeding reactions.
CYP inhibitors are erythromycin, cimetidine,
ketoconazole, and ritonavir, because they each
inhibit several CYP isozymes. 64General Pharmacology Compiled by: Birhanu Geta
65. Inhibition of drug metabolism may lead to;
- Increased plasma levels over time with long-term
medications.
- Prolonged pharmacological drug effect.
- Increased drug-induced toxicities.
Microsomal enzyme inducers
Phenobarbitone
Phenytoin
Rifampicin
Carbamazepine
Sulphonamides
St. John’s Wort
Cigarette smoking
Microsomal enzyme inhibitors
Isoniazid
Disulfiram
Cimetidine
Allopurinol
Chloramphenicol
Erythromycin
Metronidazole
Grape fruit juice
65General Pharmacology Compiled by: Birhanu Geta
66. First-Pass Effect: significant metabolic
inactivation of some drugs by the liver following
oral administration.
- Drugs absorbed from the GI tract enter the
portal circulation and are carried to the liver
before entering the systemic circulation.
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67. Drug excretion
Removal of a drug from the body occurs via a
number of routes.
The major routes of excretion include renal
excretion, hepatobiliary excretion & pulmonary
excretion.
The minor routes of excretion are saliva, sweat,
tears, breast milk, vaginal fluid & hair.
The rate of excretion influences the duration of
action of drugs.
If the drug is excreted slowly, the concentration
of drug in the body is maintained and the effects
of the drug will continue for longer period.
67General Pharmacology Compiled by: Birhanu Geta
68. Routes of drug excretion
a. Renal excretion
For water soluble and non volatile drugs.
The three principal processes that determine the
urinary excretion of a drug.
– Glomerular filtration
– Active tubular secretion
– Passive tubular reabsorption
The function of glumerular filtration and active
tubular secretion is to remove drug out of the
body, while tubular reabsorption retain the drug.
68General Pharmacology Compiled by: Birhanu Geta
69. b. Hepatobiliary Excretion
The conjugated drugs are excreted by
hepatocytes in the liver.
After excretion of drugs through bile to the
intestine; certain amount of drug is reabsorbed
in to the portal vein leading to an entrohepatic
cycling which can prolong the action of drug.
E.g. Chloramphenicol, estrogen.
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70. c. Gastro intestinal excretion
When a drug is administered orally, part of the
drug is not absorbed and excreted in the faeces.
The drug which do not undergo enterohepatic
cycling after excretion in to the bile are
subsequently passed with stool.
E.g. Aluminum hydroxide changes the stool
color in to white, Ferrous sulphate darkens it
and Rifampicine gives orange red colour to the
stool.
70General Pharmacology Compiled by: Birhanu Geta
71. d. Pulmonary excretion
Many inhalation anesthetics and alcohol are
excreted through the lungs.
e. Sweat
E.g. Rifampcine, metalloids like arsenic are
excreted in to the sweat.
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72. f. Mammary excretion
Many drugs are excreted in to breast milk.
Lactating mothers should be cautious about the
intake of these drugs because they may enter in
to baby through milk and produce harmful
effects in the baby.
E.g. Ampicillin, Aspirin, Chlorodizepoxide,
Streptomycin.
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73. Pharmacodynamics
Pharmacodynamics include:
Mechanism of actions of the drug.
How does a drug act in the body?
Effects of the drug: both beneficial &
harmful effects.
What does a drug do in the body
73General Pharmacology Compiled by: Birhanu Geta
74. Pharmacodynamics…
Mechanisms of drug action
It is of two types:
A. Receptor mediated mechanism
Receptors- targets of drug action.
May present either on the cell surface or
inside the cell.
D + R → DR → Biological effect
Where; D=Drug, R=Receptor, DR=Drug Receptor Complex
B. Non-receptor mechanisms
Simple physical or chemical reaction.
E.g. Antacids: neutralization reaction.
74General Pharmacology Compiled by: Birhanu Geta
75. Types of Receptors
Regulatory proteins
For endogenous regulatory ligands – particularly
hormones, growth factors, and neurotransmitters.
E.g. Insulin receptors-insulin
Enzymes
Receptors that are inhibited by binding with a drug.
E.g. Cyclooxygenase – Aspirin
Transport proteins: Na+/K+ ATPase- Digoxin
Structural proteins: Tubulin- colchicine
Genetic materials: Rifampcin- RNA polymerase
Ion channels: Na, Ca, K, channel blockers.
75General Pharmacology Compiled by: Birhanu Geta
76. Models of D-R interaction…
Lock & key
Drug acts as key, receptor as lock, combination
yields response.
Induced-fit models
Dynamic & flexible interaction.
76General Pharmacology Compiled by: Birhanu Geta
77. Implications of drug-receptor interaction
Drugs can potentially alter rate of any function
in the body.
Drugs cannot impart entirely new functions to
cells.
Drugs do not create effects, only modify
ongoing ones.
Drugs can allow for effects outside of normal
physiological range.
77General Pharmacology Compiled by: Birhanu Geta
78. Three aspects of drug receptor function
1. Receptors determine the quantitative
relation between drug concentration and
response.
This is based on receptor’s affinity to bind
and it’s abundance in target cells.
2. Receptors (as complex molecules) function
as regulatory proteins and components of
chemical signaling mechanisms that
provide targets for important drugs.
3. Receptors determine the therapeutic and
toxic effects of drugs in patients.
78General Pharmacology Compiled by: Birhanu Geta
79. Dose response relationship
Dose: amount of a drug required to produce
desired response in an individual.
Dosage: the amount, frequency and duration
of therapy.
Potency: measure of how much a drug is
required to elicit a given response. The lower
the dose, the more potent is the drug.
Efficacy: the intrinsic ability of the drug to
produce an effect at the receptor.
Maximal efficacy: largest effect that a drug
can produce. 79General Pharmacology Compiled by: Birhanu Geta
80. Dose response relationship...
Drug response depends on:
Affinity of drug for receptor.
Intrinsic activity (degree to which a drug is
able to induce intrinsic effects).
80General Pharmacology Compiled by: Birhanu Geta
81. Agonism and Antagonism
Agonists facilitate
receptor response.
Antagonists inhibit
receptor response.
81
(Direct Ant/agonists)
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82. Types of drug-receptor interactions
Agonist drugs: bind to and activate the receptor
which directly or indirectly brings about the
effect.
Some agonists inhibit their binding molecules
to terminate the action of endogenous
agonists.
E.g. slowing the destruction of endogenous
acetylcholine by using acetyl cholinesterase
inhibitors.
Antagonist drugs: bind to a receptor to prevent
binding of other molecules, but lack intrinsic
activity.
E.g. Atropine decrease acetylcholine effects.82General Pharmacology Compiled by: Birhanu Geta
83. Types of drug-receptor interactions…
Partial agonist drugs: acts as agonist or
antagonist depending on the circumstance, have
affinity but have lowered maximal efficacy.
E.g. Pindolol can act as an antagonist if a “full
agonist” like Isoproterenol is present.
Inverse agonist: is a ligand which produces an
effect opposite to that of the agonist by
occupying the same receptor.
E.g. metoprolol in some tissues.
83General Pharmacology Compiled by: Birhanu Geta
84. Full agonist- A drug with high positive efficacy & produce the
system maximal response.
Partial agonist- maximal response to the ligand is below the system
maximal response.
Antagonists- no efficacy or such a low level of efficacy with no
visible response.
Inverse agonist- A ligand with negative efficacy can reduce the
basal response. 84General Pharmacology Compiled by: Birhanu Geta
85. Graded dose–response relations
As the concentration of a drug increases, its
pharmacologic effect also gradually increases
until all the receptors are occupied (the
maximum effect).
It is used to determine affinity, potency,
efficacy and characteristics of antagonists.
General Pharmacology Compiled by: Birhanu Geta 85
86. Potency
Is relative strength of response for a given dose.
Effective concentration (EC50) is the concentration of an
agonist needed to elicit half of the maximum biological
response of the agonist.
The potency of an agonist is inversely related to
its EC50 value.
D-R curve shifts left with greater potency.
86General Pharmacology Compiled by: Birhanu Geta
87. Efficacy
Maximum possible effect
relative to other agents.
Indicated by peak of D-R
curve.
Full agonist = 100%
Partial agonist = 50%
Antagonist = 0%
Inverse agonist = -100%
87General Pharmacology Compiled by: Birhanu Geta
88. Quantal(cumulative) dose response r/ship:
Is between the dose of the drug and the
proportion of a population that responds to it.
For any individual, the effect either occurs or it
does not (‘all’ or ‘none’).
Are useful for determining doses to which most
of the population responds; ED50%, TD50%,
LD50%, TI(r/ship b/n dose & toxicity) & inter
subject variability in drug responses.
They do not predict idiosyncratic reactions and
hypersensitivity.
General Pharmacology Compiled by: Birhanu Geta 88
89. Therapeutic index
Median Lethal Dose (LD50): dose which would
be expected to kill one half of a study
population.
Median Effective Dose (ED50): dose which
produces a desired response in 50% of the
test population.
Therapeutic Index: gives a rough idea about the
potential effectiveness and safety of the drug in humans.
Therapeutic Index (TI) = LD50/ED50
The smaller the TI, the less safer the drug is.
Margin of safety=LD1/ED99.
89General Pharmacology Compiled by: Birhanu Geta
91. Factors modifying the dosage & action of drugs
1. Age
2. Sex
3. Body weight
4. Genetics
5. Drug tolerance
6. Drug intolerance
7. Disease states
91General Pharmacology Compiled by: Birhanu Geta
92. Drug- Drug interactions
Consequences of Drug- Drug Interactions
1. Intensification of effects: increased therapeutic
or adverse effects.
Additive Drug Effects (Summation): 1 + 1 = 2.
Most frequently seen when two drugs possess similar intrinsic
activity.
E.g. sedative-hypnotic type drugs (i.e., barbiturates, alcohol,
benzodiazepines (diazepam, etc.) administered in combination
will produce additive effects resulting in over-sedation.
Synergism - the effect of two drugs in combination is greater
than the sum of the drugs administered alone (1 + 1 > 2).
E.g. Aminoglycosides with penicillins.
Potentiation – one substance alone does not have effect
but when added to another chemical, it becomes
effective. (1 + 0 > 1).
92General Pharmacology Compiled by: Birhanu Geta
93. 2. Reduction of effects – inhibit drug effects;
Either beneficial or detrimental.
Antagonism: it occurs when the effect of one drug
is diminished by another drug.(1+1<1).
Types of antagonism;
Chemical antagonism or inactivation
Physiological (functional) antagonism
Pharmacologic or Receptor antagonism
Pharmacokinetic/Dispositional antagonism
93General Pharmacology Compiled by: Birhanu Geta
94. Basic mechanisms of Drug- Drug interactions
Direct chemical or physical interaction - can occur
with drugs mixed together.
Pharmacokinetic interaction – can alter all four
processes.
Absorption – increase or decrease (e.g., PH, laxative,
changes in blood flow).
Distribution – competition for protein binding or changes in
extra cellular PH.
Metabolism - induction of drug metabolizing enzymes,
inhibition of metabolizing, and competition of metabolism.
Excretion - altered renal excretion (e.g. filtration,
reabsorption, and secretion).
Pharmacodynamic interaction
Interactions at same receptor – almost always
inhibitory.
Interactions resulting from actions at separate sites
(if drugs influence same physiologic process).
94General Pharmacology Compiled by: Birhanu Geta
95. Drug- Food interactions
Impact of Food on Drug Absorption
– Decreasing rate and/or extent of absorption
– Some foods can increase extent of drug
absorption.
Impact of Food on Drug metabolism
– The grapefruit juice effect (can inhibit
metabolism of certain drugs increased drug
levels).
Impact of Food on Drug Toxicity
– MAOIs with tyramine
– Caffeine with theophylline
Impact of Food on Drug Action
– Vitamin K with warfarin. 95General Pharmacology Compiled by: Birhanu Geta
96. Adverse drug reactions (ADRs)
Any undesired response to a drug.
Can range in intensity from annoying to life
threatening.
Types of adverse drug reactions
Side Effects: unavoidable secondary drug effect
produced at therapeutic drugs doses.
E.g. 1. Drowsiness that often accompanies the use of
antihistamines
2. Gastric bleeding that can be produced by low
therapeutic doses of aspirin.
Toxicities: an adverse drug reaction caused by
excessive levels of drug.
E.g. Coma caused by overdose with morphine.
Allergic reactions:
– Prior sensitization of the immune system.
– Re- exposure to that drug can bring on an allergic response.
E.g. Penicillin allergy
96General Pharmacology Compiled by: Birhanu Geta
97. ADRs...
Idiosyncratic effects: an unusual drug response
resulting from a genetic predisposition.
Physical dependence: a state in which the body
has adapted to prolonged drug exposure in such a way
that if drug use is discontinued abstinence syndrome
will result.
Develop during long-term use of certain drugs (e.g. Opoids,
barbiturates etc)
Carcinogenic effects: ability of certain
mediations /chemicals to cause cancer.
Although a number of carcinogenic compounds have
been identified, very few of these are employed
therapeutically.
Teratogenic Effects: drug- induced birth defect.
97General Pharmacology Compiled by: Birhanu Geta