Transes Pharmacodynamics

Pharmacology
Pharmacodynamics
→physiologic and biochemical effects of drugs and relate to a drug’s mechanism of action.
→Focuses on action and effects of drugs
→WHAT A DRUG DOES TO PATIENT
Drug action Vs. Drug effect (DRUG ACTION)

Drug action Where and how drug work
→ E.G. Action of paracetamol is to block the synthesis of endogenous substances called prostaglandins
Drug effect What drug produces in an individual
→ can be perceived and measured
→ e.g. effect of paracetamol is the reduction of fever
→They are mutually dependent
→Drug action LEADS to drug effect
→ Drug action is the initial consequences of a drug-receptor interaction
→ Drug effects is the succeeding biochemical and physiological changes
Receptor → Refers to the drug binding site in the cell or on the surface of cell which mediate the action of drug.
Physiological Vs. Pharmacological effect
Physiological Maintenance of the normal state
→ e.g. endogenous insulin regulates blood sugar levels within normal range.
Pharmacological Excess amount of a substance may produce
exaggerated nonspecific effects on the subject
→ Refers to the production of increase/decrease in function in order to treat a diseased state
→ Defined as the physiological and/or biochemical changes in the body produced by a drug in
therapeutic concentration.
→ No drug has a single pharmacological effect
→ drug usually produces several pharmacological effects.
→ e.g. exogenous insulin is administered to decrease blood sugar levels in diabetes.
Do drug create new function in living organism?
→ Drugs can only enhance or reduce the functions of which the organism is naturally capable
→Drug action is quantitative (altering only the magnitude of intensity of body function), never qualitative (changing the
nature of the function)
Drugs do not create new functions
→Drugs can speed up or slow down the following: -------Muscle contraction
-------Kidney - regulation of water and salts retained or eliminated
-------Glands - secretion (mucus, stomach acid, or insulin)
--------Nerves - transmission messages
→ Drugs cannot restore structures or functions already damaged beyond repair by the body
----heart failure, arthritis, muscular dystrophy, multiple sclerosis, Parkinson disease, and Alzheimer disease.-----
→ Some drugs can help the body repair itself
○ For example, by stopping an infection, antibiotics can allow the body to repair damage caused by the infection.
→ Some drugs can be used to replace those missing in the body
○ Some drugs are hormones, such as insulin, thyroid hormones, estrogens, or cortisol.
Every drug is a poison?
PARACELSUS
Selective Toxicity
- Difference in drug effect among diff organism…
- May be poisonous to one form of organism but not to another
- Employed I n development of antiparasitic preparation
- Neoplastic cells
Doc Garry, Clyde, Khan compiled by ericjohnperono 1

Pharmacology
- Chemotherapy- to kill infectious or parasitic living organisms (called pathogens) as well as cancers cells, which
produce disease in the host.
- Selective toxicity against microbes means killing the microbial cells but not the host's cells
BASIC MECHANISM OF DRUG ACTION
→Noncellular Mechanism
-occur Externally and involve noncellular constituents
a. Physical effects
b. Chemical reactions
c. Physicochemical mechanisms
→Physical Effect Protective, absorbent, lubricant properties of locally active agents that are applied to
cutaneous and membrane surfaces.
→Chemical React Neutralization of gastric HCL by antacids.
→Physicochemical -Alter biophysical properties of specific FLUIDS or even components of cells
→ Examples of the former include the surface-active agents or surfactants.
Detergents, antifoaming
→Modification of Exert osmotic influence across cellular membranes
composition of Mannitol, poultices
body fluids
→Cellular Mechanism
- Occur cellular level; functional constituents of the cell or biochemical reaction
a. Physicochemical & biophysical mechanisms
b. Modification of cell membrane structure & function
c. Enzyme inhibition
d. Receptor-mediated effects
Physicochemical and → alter the physicochemical or biophysical characteristics of specific components of cells.
Biophysical mech Examples
a. Inhalant anesthetics may affect the lipid matrix and the hydrophobic proteins in neuronal
membranes within the CNS.
b. Polymyxins are cationic surface active agents that disrupt membrane phospholipids.
Modification of cell → Various drugs may influence either the structure or specific functional components of cell
membrane structure membranes and thereby initiate their characteristic effects.
and function →Involve enzyme systems or receptor-mediated reaction
→ Local anesthetic binds to sodium channels in excitable membranes and prevent
depolarization
→Calcium channel blockers inhibit entry of calcium into cells
Enzyme inhibition → occur in the host animal or in invading pathogens, and can be competitive or noncompetitive,
reversible or irreversible.
Receptor-mediated Result in activation or inhibition of sequence of biochemical effects
effects → Receptors can be located on the cell membrane, in the cytosol or in the nucleus.
INTRODUCTION TO DRUG-RECEPTOR INTERACTION
→Drug action is specific
Non specific → Refers to the kind of interaction between drug molecules and plasma protein (mainly
albumin).
(no perceptible eff)
Specific → Refers to drug-receptor interaction

Pharmacology
→Free unbound drug molecules that get distributed to their site of action bind with yet another
type of molecules called drug receptors.
“lock-key”
(Perceptible drug effect)
→Drug Receptors - macromolecular component of body tissue (found on the surface or inside the cell) with which the
drug interacts to initiate its pharmacologic effects
- These are molecule to which drug has a specific affinity.
located on the cell surface membrane or within the cytoplasm.
→ ligand- drug or substance with specific affinity to receptors
→ Drug receptors have ligand-binding site (or the protein-binding site; 3D structure) and an effector site (for
message/signal transduction).
→ The term receptors are regulatory proteins in intercellular communication. But in addition to receptors, there are
other types of proteins that are targeted by drugs: enzymes, ion channels, carriers and nucleic acids.
Types of Drug Traget

RECEPTORS Reg protein, intercellular Ex.
communication Muscarinic receptors on cells of heart, smooth muscle, or
exocrine glands
Enzymes key regulatory ormetabolic processes (1) Cyclooxygenases (COX) arethe target site for NSAIDs
(2) Acetyl cholinesterase for theAChE inhibitors
(3) Dihydrofolate reductase forTMPS
Angiotensin-convertingenzyme for ACE-inhibitors
Carriers ‘membranetransport proteins’ Na+/K+/2Cl- symport inthe nephron for furosemide
Ion channels Direct interaction with ionchannels Voltage-gated Na+ channels in sensory neuronsare
Nucleic acids Nonreceptor/nonprotein targets Nucleic acids for actinomycinD
Microtubules Nonreceptor/nonprotein The anticancer drugvincristine
→ Physiological receptors receptors for endogenous regulatorycompounds such as
hormones and neurotransmitters
→ SPARE RECEPTOR maximal response is elicited by occupancy of a fraction of
the tissue receptors. NOT ALL RECEPTORS ARE NEEDED
FORMAXIMUM RESPONSE.
→known as a ‘receptor reserve’;
→Acceptor and Silent Interactions
→ Acceptors are also termed as silent receptors. Thebinding of the drug to an acceptor DOES NOT leadto a perceptible
pharmacologic effect
→ Receptors involved when a drug combines with molecules other than its receptors
→ without signal-transduction pathways, thus, binding process are not followed by a response.
→ these are chemical substances with which a drug binds NONSPECIFICALLY.
→ Plasma albumin and tissue proteins acceptors
→Drug activity
→ happens at the molecular level
→ a lock and key
→ most potent drug at a receptor will 'fit perfectly' and other drugs with similar but non-identical structure may fit less
effectively and therefore be less potent and have no effect.
→ receptor interactions (pharmacophore) generally have multiple spatial and chemical requirements for full effect.
→Different drugs in that class will have the same key structure buttherest of the structure will be different.
→ DRUG-RECEPTOR INTERACTION- when a drug molecule interacts with a drug receptor,a drug-receptor complex is
formed. This complex triggers the formation of stimulus to produce an effect.

Pharmacology
→ During the formation of a drug-receptor complex, the drug and thereceptor becomes one entity
→ receptor now being occupied by the drug is presumed to haveundergone some alteration, which is essential to drug
activity. Without this, no stimulus can be formed, and thus no drug effect may be produced.
→ Requirements for Drug Activity
Affinity → The tendency of a drug to bind with its specificreceptor.
→ Influenced by chemical structure such as size and shape (therefore, a minimal modification ofthe
drug structure may result in a major changein affinity!!!).
Intrinsic Activity or → inherent capacity of the drug to activate the receptors and thus inducing an effect (production
Efficacy ofresponse).
→ The maximal effect a drug can produce (Emax).
→Chemical Bonds Involved in Drug-Receptor Interaction
Covalent Bond → two atoms share a pair of electron
→ rare indrug interactions except in toxic situations
→ high binding energy
→ generally irreversible
→can bebroken at very high temperature or with the intervention of a catalytic enzyme
Ionic Bond → Electrostatic attraction between oppositely chargedions
→ force of attraction diminishes inversely with the square of the distance between them
→ strongest non-covalent bonds for many drugs that contain acid or amine functional groups,
ionized at physiological pH.
→ The force of attraction depends on the distance.
Hydrogen (H) Bond → Between drug molecule, surrounding water, andthe receptor
→ weaker but several H bondscan stabilize a drug-receptor interaction significantly
INTERMOLECULAR
FORCES (van der Waals
forces)
Properties of Drug-Receptor Interaction
Saturability finite number of receptors per cell or per weight of tissue.
Specificity receptor is structurally complementary with the drug ligand through a minimum of 3-point
attachment or in most cases through specific chemical structures
Reversibility binding and dissociation.
Types of drugs based on drug-receptor interaction
AGONIST → possesses affinity for a particular receptorand causes a change in the receptor that result in observable
effect
→ possesses affinity for a particular receptorand causes a change in the receptor that result in observable
effect
→FULL AGONIST
→PARTIAL AGONIST
Full Agonist →Produces a maximum response by occupying allor a

fraction of receptors.
→Higher affinity and higherintrinsic activity.
Partial Agonist (Dualist) → Produces only a submaximal response regardless of the
amount of drug applies and even
when the drug occupies allthe receptors.
→ Higher affinity but less intrinsicactivity.
ANTAGONIST → Blocks the response produced by the agonist.

Pharmacology
→ Blocks the response produced by the agonist.
→ interacts with the receptor or other component of the effector mechanism, but antagonist is devoid of
intrinsic activity.
Competitive Antagonist → Sits on the same receptor(silent interaction) preventing
the agonist from binding
→ Completely reversible byincreasing the concentration of
the agonist.
If you increase the dose of agonist with the presence of

competitive antagonist , you will over the competitive
antagonist. So that the max efficacy of our agonist would
still be achieve
Noncompetitive Antagonist → no affinity for the same binding site in the receptor but
binds to a closely related site inthe vicinity
→irreversible or covalent bonding
→ causes a change or a sort of conformational "defect" (or
allosteric mechanism) in the receptor such that it cannot
anymore bind agonists
→not competitive
→dose response curve- if non-cop will bind to other site, it will
have allosteric change. So the agonist will not bind to its
receptor kaya nag reduce yung curve niya
→the max effect of agonist with the presence of non
competitive antagonist will be reduced even if we increase
the dose of the agonist because the binding of the non
competitive antagonist is PERMANENT(irreversible) and
this will create allosteric change.
Partial Antagonist (Dualist)
Inverse Agonists drug that acts onthe same receptor as that of an agonist,yet produces an opposite effect
Affinity and efficacy are uncoupled: a compound
can have great affinity but poor efficacy (and vice
versa).
A compound can be an agonist for one receptor
and an antagonist or inverse agonist for another

Pharmacology
receptor.
A full or partial agonist displays positive efficacy.
An antagonist displays zero efficacy.
A full of partial inverse agonist displays negative efficacy.
ability of protein to change shape.
Allostery
→Most drugs used in therapeutics are receptor antagonist and prevent the action ofnatural agonist or endogenous
ligands (NTs, hormones)
→ Some drugs may be both agonist and antagonist (e.g., butorphanol).
Lock And Key Theories - receptor is the lock, the drug is the key
OCCUPATION →“Organ Effect”
THEORY → Drug effect lasts as long as the drug sits on thereceptor.
→ Increased number of receptors occupied
= increased effect
→ Agonists have high affinity and lowdissociation constant (Kd)
RATE THEORY →‘Piano Effect”
→ Drug effect is manifested in every act of binding (only during the process of occupation)
→ There is greater effect if the drug gets to bind with more receptors.
→ Fast dissociation = greater chances tobind with other receptors = greater response
→ Agonists have high dissociation constant
(Kd); antagonists with low dissociationconstant (Kd)
Potency of the drug= refers to the dose that must be administered to produce a particular effect of given intensity
→The concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug’s maximal effect.
→It is influenced by the affinity of a drug for its receptor sites and by pharmacokinetic processes that determine drug
concentration in the immediate vicinity of its site of action
(biophase),
→Potency of a drug varies inversely with dose; the lower the dose required producing a stated response, the more potent
the drug
Potency is relative, rather than an absolute, expression of drug activity.
Relative potency
→A variant where instead of using units to describe the dose required to achieve a certain endpoint, one ends up using a
ratio of equivalent doses.
➢ i.e. Drug A is 100 times more potent than Drug B because it achieves the same effect with 1/100th of the dose
Selectivity & Specificity
Selectivity of a →The characteristic effect of the drug is produced at lower doses than those required to elicit
drug responses.
➢ Depends on its capacity to preferentially produce a particular effect.
➢ A truly selective drug produces only a single effect.
➢ Selectivity is the degree to which a drug acts on a given site relative to other sites.
➢ Relatively nonselective drugs affect many different tissues or organs.
➢ For example, atropine, a drug given to relax muscles in the GIT, may also relax muscles in the eyes
and in the respiratory tract.
➢ Relatively selective drugs, e.g. NSAIDs such as aspirin, target any area where inflammation is
present.
➢ Highly selective drugs affect mainly a single organ or system; e.g., digoxin, a drug given to manage
heart failure, affects mainly the heart, increasing its pumping efficiency
Selectivity →preference of the drug to one receptor or its subtype.

Pharmacology
→In other words, it is the ability of the drug to produce one pharmacological effect over others.
→ If a drug is selective, it will preferably bind to one receptor, but it can bind to others by increasing its
concentration.
➢ Example: verapamil normally blocks Ca-channels, but it can block Na-channels at high
concentrations.
Specificity of a →When all the effects it produced are due to single mechanism of action (single target)
drug →Rare
→ It acts at only one type of receptor but may produce multiple pharmacologic effects because of
location of receptors in various organs.
➢ Relates to the number of different mechanisms involved.

➢ Specific drug - when all the effects it produced are due to a single mechanism of action. It acts at
only one type of receptor but may produce multiple pharmacologic effects.
➢ Specific drugs: atropine (a muscarinic receptor antagonist), salbutamol (a β2-adrenoceptor

agonist), and cimetidine (an H2-receptor antagonist).
➢ By contrast, nonspecific drugs result in drug effects through several mechanisms of action;
examples: phenothiazine causes blockade of these receptors: D2-dopamine, α-adrenergic, and
muscarinic receptors.
Specificity ➢ Specificity is the ability of the drug to bind to only one receptor.
➢ Atropine is technically specific because it acts only at acetylcholine (ACh) receptors.
○ However, it is not selective because it binds to all subtypes and causes myriad
pharmacological effects
A drug may have a widespread effect throughout the body or may have a very localized or specific effect
MECHANISMS OF WIDESPREAD cardiac glycosides (digoxin) are → A relatively nonspecialized receptor
EFFECTS potent inhibitors of a fundamental serves a function common to most cells.
and vital ion transport processes →If this is a vital function, drug exposure
common to most cells; therapeutic is potentially dangerous
index is small
atropine affects gut motility, heart → Even if all effects of a drug are due to
rate and salivation, all as a result of single mechanism of action and the drug
the location of muscarinic is selective, it may produce multiple
receptors within these organs pharmacological effects because of the
location of receptors in various organs
morphine is described as an oploid → Most drugs produce multiple effects,
analgesic but it also causes although they are usually described on
respiratory depression, release of the basis of their most prominent effect.
ADH and constipation
phenothiazine tranquilizers → The effects of nonselective drugs may
produce sedation (increased rate also result from the drug having several
of dopamine turnover in brain, mechanisms of action
prevent vomiting (depress
activation of vomiting center and
chemoreceptor trigger zone),
prevent morphine-induced
excitement in cats (blockade of
central dopaminergic receptors),
reduce blood pressure (alpha-
adrenergic blockade), have an
antispasmodic effect on gut

Pharmacology
anticholinergic action) and induce
hypothermia (interference with
hypothalamic control of
temperature regulation)
MECHANISMS OF SELECTIVE AND atropine given by injection has a → Other drugs are selective by virtue of
SPECIFIC DRUG EFFECTS wide range of effects on gut and the route of administration
other organs; however, it's
→ Specialized receptors are unique to administered as an ophthalmic
specific types of cell. Therefore, the preparation its effect is confined to
effects of the drug interacting with this the eye.
type of receptor are more specific
Selectivity & Specificity [Receptors]

Selectivity of a ➢ Receptor selectivity refers to the extent to which a receptor binds with a particular drug rather than
receptor other molecules.
➢ Selectivity depends both on the receptor and on the size, shape, and bioelectrical charge of the
drug molecule.
Specificity ➢ Specificity is the measure of a receptors ability to respond to a single ligand.
(receptor) ➢ Low specificity generally results in physiological responses not targeted or intended by the drug
and side effects provide a good example.
Regulation of Receptors
Upregulation Downregulation
→Under stimulation of receptors with an agonist results in →Effect of a drug often diminishes when it is given
up-regulation due to an increase in the number of repeatedly.
receptors and a functional hypersensitivity. →It so happens when chronic or continuous stimulation of
→Also happens during chronic receptor antagonism. receptors with an agonist results in a state of long-term
desensitization.
→Hence, the number of receptors is decreased.
1. Additional receptors can be synthesized in response to 1. Continuous stimulation of cells by an agonist may result in
chronic receptor antagonism. a state of desensitization, whereby the concentration of
2. When the cell is subsequently exposed to the agonist, agonist required to produce a certain effect is increased.
more receptors are available, causing a hyperactive 2. This may occur with benzodiazepine therapy.
response or supersensitivity Downregulation of myocardial beta-receptors occurs in
cardiac failure as a result of increased sympathetic
stimulation.
➢ Upregulation (i.e., increase in the number) of receptors ➢ If β-blockers are abruptly stopped, it can cause rebound
occurs when the activity of the receptor is lower than usual hypertension because of the sudden stimulation of a large
(e.g., due to long-term administration of an antagonist). number of β adrenoreceptors.

Pharmacology
➢ For example, administration of beta-blockers ➢ Is the response of the cell to continuous exposure from a
upregulates β adrenoreceptors. ligand.
➢ Reversible process.
➢ Most membrane receptors are internalized in the receptor
mediated endocytosis.
➢ Downregulation (i.e., decrease in number) occurs due to
repeated or long-term administration of an agonist. ➢
*Desensitization of the receptor to the drug may also occur.
○ Physicochemical alteration in the receptor making it
unresponsive to the drug; this is also called
tachyphylaxis (is an acute form of tolerance).
→ The term used to describe a gradual decrease in
responsiveness to chronic drug administration (days,
months) is tolerance
Receptor regulation ➢ The homeostatic increase or decrease in receptor activity or number, in response to
activation or blockade.
➢ IMPORTANT (Downregulation): Useful in the prevention of cell damage due to the high
concentration of an agonist.
Signaling Mechanisms & Drug Action: Macromolecular Nature of Drug Receptors (doc khan)

Pharmacology
Receptors are transmembrane proteins having two functions:
→ligand binding and
→message transduction.
Transmembrane receptors include:
Type of Receptors (1) →Activation leads to some changes in metabolic process within the
Metabotropic cell.
receptors →Upon activation, a series of intracellular events is first triggered that
may also subsequently result in ion channel activation.
(2) Ionotropic →Activation directly opens or closes an ion channel for ions such as
receptors Na+, K+, or Cl- to flow.
The four super families of receptor proteins include:
(1) Ligand-gated ion channels
(2) G-protein-coupled receptors (GPCRs)
(3) Transcription Factor Receptors
(4) Receptor Tyrosine Kinase (TKR)
(1) Ligand-gated ion channels )ION CHANNEL (2) G-protein-coupled receptors (GPCRs)
INHIBITORS
*Ionotropic Receptor →Intracellular receptors regulating gene transcription.
→Activate transmembrane ion channels. They contain a →Binding ligand→activated receptors translocate to
central pore that functions as a ligandgated ion channel. nucleus→bind to DNA sequence (response elements)→
initiate transcription of specific gene(s).
Examples: nicotinic cholinergic receptor, GABAA receptor, Examples: steroid hormones, thyroid hormone, vitamin D, or
glutamate, aspartate, and glycine receptors retinoid receptors.
(3) Transcription Factor Receptors (4) Receptor Tyrosine Kinase (TKR)
*Metabotropic Receptor *Metabotropic Receptor
→Also known as seven transmembrane receptors (7TM →Another type of cell surface receptors (membrane-bound)
receptors), they transduce an extracellular signal (ligand which exert their regulatory effects by phosphorylating
binding) into an intracellular signal (G-protein activation) different effector proteins.
signal transferred to Gproteins (GP) through →Consist of extracellular binding site and intracellular
conformational alterations. portions with enzymatic activity (tyrosine kinase, serine
→GP may act directly on an ionic channel or activate an kinase).
enzyme system (adenylyl cyclase, guadenylyl cyclase, →The hormones and growth factors that act on this class of
phospholipase C, etc.) receptors are generally growth promoting and stimulate cell
release of 2nd messengers (cAMP, cGMP, IP3, etc.) which division.
ultimately permits ions to enter or leave the cell.
Examples: muscarinic acetylcholine receptor, adrenergic Examples: insulin, IGF-1, cytokines, epidermal growth factor.
receptors (alpha-1, alpha-2, beta), dopamine, histamine,
opioids, and ACTH receptors.
Signaling Mechanisms & Drug Action (doc clyde)
Several mechanisms have been identified:
1. Induction of synthesis of specific proteins by intracellular receptors that regulate gene expression (eg lipid-soluble
hormones such as corticosteroids, sex steroids, vitamin D and thyroid hormones).
2. Regulation of gated ion channels in the plasma membrane (eg, barbiturates and benzodiazepines influence chloride ion
channel function; local anesthetic agents influence sodium channel function).
3. Regulation of plasma membrane enzymes (the primary enzyme affected is adenylyl cyclase, also guanylyl cyclase)
4. Calcium entry into the cell (for hormones and neurotransmitters).
5. Accumulation of multiple intracellular second messengers (IP3 and diacylglycerol [DAG]).
6. Stimulation of plasma membrane-bound protein kinases.
→All these mechanisms are targeted in drug development.

Pharmacology
→Increased mechanisms by which drugs work enhances development of specifically targeted and rational drug
treatment.
Receptor type Examples of ligands
G protein-coupled receptors (all members of the →Adenosine receptors (adenosine (agonist), theophylline
GCPR superfamily consist of seven transmembrane (antagonist)
ahelices, an extracellular ligand binding site which →Adrenoceptors (adrenaline, noradrenaline, isoprenaline
when activated triggers conformation changes in the [agonists] phenoxybenzamine, salbutamol ([antagonists])
associated G protein on the cytoplasmic side of the →Dopamine receptors (dopamine, apomorphine [agonist]
membrane leading to decreased affinity for its bound metoclopramide (antagonist) Histamine receptors (cimetidine
guanosine diphosphate (GDP) and replacement with [antagonist]) Muscarinic acetylcholine receptors (pilocarpine
GTP in tum activating associated effector [agonist]) atropine [antagonist]) →Opioid receptors (morphine,
mechanisms, usually an enzyme or ion channel) buprenorphine agonists, naltrexone [antagonist])
→Prostanoid receptors (misoprostol [agonist]) Serotonin (5-
hydroxytryptamine or 5-HT) receptors (ergotamine [agonist]
granisetron [5-HT3 antagonist])
Ligand-gated ion channel receptors →GABA receptor (pentobarbitone, diazepam agonists]
flumazenil antagonist)
→Glutamate receptor (ketamine INMDA subtype antagonist)
→Nicotinic receptor (suxamethonium (antagonist)
→Insulin receptor (insulin agonist) biguanides (sensitizer)
→Androgen receptor, glucocorticoid
Tyrosine kinase-associated receptors receptor, mineralocorticoid receptor (aldosterone (agonist]
spironolactone antagonist), estrogen receptor, progesterone
Nuclear receptors receptor, retinoic acid receptor (isotretinoin [RARa agonist]),
thyroid hormone receptor, vitamin D receptor
Enzymes
Oxidoreductases (enzymes catalyzing the transfer of →Cyclooxygenase (acetylsalicylic acid [COX-1 inhibitor]
electrons from one molecule (oxidant hydrogen donor meloxicam (COX-2 inhibitor)
or electron acceptor to another [reductant hydrogen →Dihydrofolate reductase (methotrexate [inhibitor])
acceptor or electron donor]) →lodothyronine-5' deiodinase (propylthiouracil inhibitor)
→Lanosterol demethylase (azole antifungals (inhibitor)
→Lipoxygenase (tepoxalin (inhibitor)
→Monoamine oxidase (MAO) (selegiline (inhibitor) →Xanthine
oxidase (allopurinol (inhibitor)
Transferases (enzymes catalyze the transfer of a →DNA polymerase (aciclovir (inhibitor)
function group [For example, methyl phosphate] from →GABA transaminase (valproic acid (inhibitor) Peptidyl
one molecule [donor] to another [acceptor]) transferase (bacterial) (chloramphenicol [inhibitor)
→Reverse transcriptase (zidovudine [inhibitor)
→Tyrosine kinase
Hydrolases (enzymes catalyzing the hydrolysis of a →Angiotensin-converting enzyme (captopril (ACE inhibitor)
chemical bond) →B-Lactamase (bacterial) (clavulanic acid (inhibitor)
→Esterase (acetylcholine esterase) (organophosphates
linhibitors
Lyases (enzymes catalyzing the breaking of chemical Phosphodiesterase (caffeine (inhibitor)
bonds by processes other than hydrolysis and
oxidation)
Isomerases (enzymes catalyzing the interconversion →Carbonic anhydrase (acetazolamide inhibitor)
of isomers) →Ornithine decarboxylase (eflornithine inhibitor)
→DNA gyrase (bacterial (fluoroquinolones inhibitor)
Ligases (enzymes catalyzing formation of new →Topoisomerase II (etoposide inhibitor)
molecule from bwo separate molecules) →Δ8.7 isomerase (fungal) (amorolfin (inhibitor) →Thymidylate
synthase (fungal and mammal) (fluorouracil (inhibitor)

Pharmacology
Phosphofructokinase (protozoal) (meglumine antimoniate
inhibitor 13- B-d-glucan synthase (fungi) (caspofungin (inhibitor)
lon channels
Calcium (Ca2+) channels →L-type channels (diltazem. verapamil inhibitors) →Epithelial
Na+ channels (bupivacaine, lidocaine inhibitors)
Sodium (Na+ ) channels →Voltage-gated Na+ channels (carbamazepine, phenytoin
inhibitors)
Potassium (K+ ) channels →Epithelial K+ channel (minoxidil lopener] sulfonylureas
inhibitor)
→Mast cell Cl- channel (cromolyn sodium inhibitor)
Chloride (CI-) channels
Transport proteins
Cation-chloride cotransporter (CCC) family →Thiazide-sensitve Na Cl symporter (thiazide diuretics
[inhibitor)
→Bumetanıde-sensitve NaCl/KCl symporters (furosemide
inhibitor)
→Omeprazole (inhibitor Cardiac glycosides (inhibitors]
Proton pumps H+ /K+ -ATPase →Serotonin/Na+ symporter, dopamine/Nat symporter (tricyclic
Neurotransmitter/Na+ symporter (NSS) family antidepressants (inhibitors)
Nucleic acids →DNA and RNA alkylation (chlorambucil, cyclophosphamide)
→DNA intra-strand stabilization (cisplatin)
Ribosomes →30S subunit (bacterial) (aminoglycosides, doxycycline
inhibitors)
→50S subunit (bacterial) (chloramphenicol. clindamycin,
macrolides (inhibitors)

Pharmacology

Pharmacology
Drug Receptor Theories: From Occupancy Theories to the Two-State Model (doc khan’s)
(1) Occupancy Theory “The receptor-ligand interaction was described as a biomolecular interaction and
(Clark, 1923) states that: the receptor-ligand complex was considered responsible for the generation of an
effect.”
→It assumes that drug response is a linear function of drug occupancy at the
receptor level.
→But this model is limited. Remember the notion of partial agonist versus full
agonist, and the spare receptor!
Stephenson’s “The final effect of the drug is NOT directly proportional to the
Concept states number of receptor-ligand complexes but is linked to the
that: generation of the stimulus, and it is the stimulus that is
proportional to the receptor-ligand complex.”
→The efficacy of the agonist indicates its ability to generate the
stimulus.
→Remember the concept of affinity and efficacy
(2) Two-State Model of “The receptor molecule exists in two extreme conformations (active and inactive
Drug Action assumes that forms) in dynamic equilibrium. It is the conformational change of receptors from an
inactive to active state that initiates the pharmacological response.”
→This is possible by the binding of ligands to the receptor
→In the framework of this model:
(1) Agonist – is a ligand that preferentially binds to the active state of the receptor
thus shifting the equilibrium to the active state.
(1.1) Full Agonist – is selective for the active form.
(1.2) Partial Agonist – has only slightly higher affinity for the active receptor than for the inactive form.
(2) Inverse Agonist – a ligand for which a response may be observed only if there is a preexisting level of
receptor activity; decrease the response (e.g., cimetidine).
(3) Neutral competitive antagonist – has equal affinity for both conformations, does not affect equilibrium, and
will have no effect.
PHYSICAL CHEMISTRY OF DRUG-RECEPTOR INTERACTION (doc khan special)
The interaction between a drug molecule and a specific receptor is a chemical reaction consisting of:
Forward reaction The drug receptor complex formation
Reverse reaction The dissociation of the drug receptor complex
→→→The said reactions may reach a dynamic equilibrium and follows the Law of Mass Action
The Law of Mass Action States that: “The values of the equilibrium constant Kc are constant for a
particular reaction at a given temperature, whatever equilibrium
concentrations are substituted.”
a [A] + b [B] c [C] + d [D]
→Kc for a chemical reaction is obtained by this formula:
Kc = [C]c [D]d / [A]a [B]b

Pharmacology
Model of Agonism Let us consider again the drug-receptor interaction. The drug, in this section, is
referred to as the agonist [A].
Where:
[R] = concentration of empty receptors

[A] = concentration of free agonist molecules
[RA] = concentration of agonist-receptor
complex
S = stimulus
E = observed effect
k1 = the rate constant of combination
k2 = the rate constant of dissociation
PRINCIPLES OF DRUG-STRUCTURE ACTIVITY RELATIONSHIP (SAR)

→It states that: “The physiological action of a substance is due to its chemical composition and constitution
(chemical structure).”
→Simply, there is a relationship between the drug structure and drug effect.
→This can be exploited to develop drugs with a more favorable therapeutic index, fewer side effects or
shorter or longer duration of action.
• This is the foundation of medicinal chemistry both in human as well as in veterinary pharmacology.
• The principle was born more than a century ago.
• The effect of the drug is influenced by their chemical structure
• Seemingly minor alterations to a drug molecule can result in major changes in pharmacological properties
• Important Information about a specific receptor can be obtained by analyzing the structure and activity of a
series of substances structurally related to its specific agonists.
• Definitely, there is a relationship between the drug structure and drug effect.
Information about receptors
SAR is commonly employed in studying drug receptors. Important information about a specific receptor can be
obtained by analyzing the relationship between structure modification and degree of activity of a series of
substances structurally related to its specific agonists.
Basic Procedure in SAR Study (1) The biological response to a prototype or a ‘parent’ drug is specified.
(khan) (2) The chemical structure of the parent drug is sequentially modified and the
derivatives are tested for their capacity to produce specified response in the
same biologic system.
(3) The response to each of the derivatives are compared with that of the
‘parent’ as reference
The principle of structure-activity relationship is significant, for example, in the development of the drug
penicillin and its derivatives:
• Addition of an amino group to penicillin extended its spectrum for gram-negative bacteria.
→The compound is called amino penicillin and an example is ampicillin
• In 1947, an analogue is synthesized with an additional beta-hydroxy group which increases its ability to resist
hydrolysis for greater gastrointestinal absorption.
→The compound was named amoxicillin.
• Further modifications in the structure of the ‘parent’ penicillin compound have led to the availability of many
new groups or generations of antibacterial agents with differing pharmacokinetics (orally active, broader
distribution, longer acting) and microbiological (broad spectrum, beta-lactamase resistant) characteristics.
➢ Through SAR principle, drugs can be designed to be MORE EFFECTIVE and SAFER TO USE.

Pharmacology
Basic Procedure in SAR Study

➢ The "parent" drug's chemical structure is sequentially modified, and then it and its derivatives are tested one
after another for their capacity to induce the specified response in the same biological system.
➢ The list of structurally related compounds including the "parent" and derivatives is called a congeneric series.
➢ The responses to each of the congeneric series are compared with that of the "parent" as reference.
GENERIC NAME ➢ The drug’s ‘active ingredient’ that makes it work.
➢ Scientifically and internationally recognized active ingredients.
→identification of drugs and medicines by their scientifically and internationally recognized
active ingredients or by their official generic name as determined by the Bureau of Food and
Drugs of the Department of Health
NOMENCLATURE & CLASSIFICATION OF DRUGS (doc garry version)
The term drug nomenclature implies that there are several names that can be used to identify a drug
→Drugs have three different names;
1. Chemical Name:
2. Non Proprietary name
3. Proprietary name.
→Chemical
Nomenclature of drugs →Non-proprietary/ Generic name/ Approved name/ Official Name
terms
→Proprietary/ Brand name/ Trade name/ Commercial
Chemical →A chemical name is given when a new chemical entity (NCE) is developed.
→It is the name given to drug in accordance with rules of chemical nomenclature established by
International Union of Pure and Applied Chemistry.
→It is useful for chemists or technical personnel as it provides the precise arrangement of atoms and
atomic groups in the molecule.
→It is not used to identify the drug in a clinical or marketing situation.
Non-proprietary →It is a short name given to a drug that is not subject to proprietary rights. The nonproprietary name
should always be concise and meaningful. This is used in discussion and textbooks.
There are two classes of non proprietary names:

1. Approved Name
2. Official Names
APPROVED NAME: This name is given to drug by bodies like United Stats Adopted Name Council
(USAN) and British Approved Name (BAN) soon after its introduction.
This name sometime referred to as generic name however this term is used to designate a chemical
or pharmacological class of drugs such as Sulphonamide, Penicillin.
Generic/Non-Proprietary Name
• Given by USAN Council (United States Adopted Name)
Advantages
- World-wide acceptance, name remains the same in all countries.
-Usually have similar suffix in a group.
-Economical than Branded/Proprietary Medicines.
Disadvantages
-Naming of Fixed Dose combinations.

Pharmacology
Proprietary OFFICIAL NAMES: It is the name approved by the National Pharmacopeia Commission and included
in the official book i.e. Pharmacopeia.
The official name must be identical with approved name.
PROPRIETARY NAME
It is the name given to a drug by the pharmaceutical firm which sell the drug.
Thus a single drug is sold under many proprietary names by different firms.
→They are written with capital initial letter and are often further distinguished by superscript R in
circle
→Clinicians usually described drug by their proprietary names.
Example: Paracetamol
→CHEMICAL NAME: N-(4-hydroxyphenyl)acetamide,
→NON-PROPRIETARY NAME:
Approved Name: British Approved Name (BAN): paracetamol
United States Adopted Name (USAN): acetaminophen Official Name: Acetaminophen
→PROPRIETARY NAME: Panadol, Calpol, Adol
CLASSIFICATION OF DRUGS
1. Chemical Nature
2. Source
3. Target organ/Site of Action
4. Mode of Actio
5. Therapeutic Uses
6. Physiological system
7. Physical Effects
1. Chemical Nature • Chemical Nature of drug is discussed by a Chemist and
based on chemical nature we divide drugs into
→INORGANIC DRUGS

Pharmacology
----Metals and their Salts (Ferrous Sulphate, Zinc Sulphate,
Magnesium Sulphate.
----Non Metals Includes Sulphur. ORGANIC DRUGS
→ORGANIC DRUGS
----Alkaloids (atropine, Morphine, Strychnine)
----Glycosides (Digitoxin, Digoxin).
----Proteins (Insuline, Oxytocin)
----Esters, Amide, Alcohol, Glycerides.
2. Source Sources of drugs are discussed by a Pharmacologist and
Pharmacist
→Natural Source
Plants (Morphine, Atropine, Digitoxin)
Animals (Insuline, eCG)
Micro organism (Penicillin)
Mineral (Sodium Chloride)
→Synthetic Source
(Sulphonamide, Procaine).
→Semi-synthetic Source
Amoxicillin, Ampicillin, Doxycycline
→Bios-ynthetic Source
Recombinant Human erythropiotin, Recombinant
bovine somattotropine
3. Target organ/Site of Action Classification based on target organs are done by the
Physicians.
→Drugs acting on CNS (Diazepam, Phenobarbitone).
→Drugs acting on Respiratory System (Bromhexaine).
→Drugs acting on CVS (Digitoxin, Digoxin).
→Drugs acting on GIT (Omeprazole, Kaoline,
Sulphadimidine).
→Drugs acting on Urinary System (Magnesium Sulphate,
Lasix)
→Drugs acting on reproductive system (Oxytocin,
Estrogen)
4. Mode of Action Classification based on mode of action is done by Physicians
& Pharmacologists.
→Inhibitor of bacterial cell wall synthesis (penicillin)
→Inhibitor of bacterial protein synthesis (Tetracycline)
→Calcium Channel blocker (Verapamil, nifedipine)
5. Therapeutic Uses Classification based on mode of action is done by Physicians
& Pharmacologists.
→Antimicrobials/Antibacterials (Penicillin, Streptomycin,
Quinolones, Macrolides).
→Antihypertensive (Clonidine, hydralazine, Enalpril).
→Antidiarrheals (Lopramide, Kaoline).
→Antiemetics (Domperidone, Meclizine and
Metoclopramide).
6. Physiological system →Sympathomimetics (Adrenaline, Noradrenaline).
→Parasympathomimetics (Carbachol, Pilocarpine,
Neostigmine).
→Neuromuscular blockers Suxamethonium, Gallamine).
7. Physical Effects →Emollients (Lanolin, Vaseline)
→Caustics (Silver nitrate)

Pharmacology
→Demulcents (Zinc Oxide, Tannic Acid).
DRUG FAMILIES
➢ These are drugs that act on specific receptors and produce the same effect but of different magnitude.
➢ Not all drugs having affinity to the same receptors belong to the same drug family because they produce
different response.
➢ [Example] A drug that is a full agonist & a full antagonist - both have affinity to the same receptor - both
belong to the same congeneric series.
➢ Drugs with similar indications (clinical uses) may not necessarily constitute a drug family.
→A Drug Family consists of drugs that act on specific receptors in certain effector systems, and produce the
same effect but of different magnitude.
→A drug that is a full agonist, and another, that is a full antagonist both has affinity to the same receptor, and
since chemical structure dictates affinity, both belong to the same congeneric series.
→Determining the family to which a new drug may belong is an important pre-requisite to SAR study.
→Some competitive antagonists having very little or no structural resemblance to agonist may exist.
→Drugs with similar indications (clinical uses) may not necessarily constitute a drug family
Naming Drug Families
• Families of agonists are often named after some typical members of the group.
• They may also be named according to their chemical structures.
• Families of antagonists may derive their names from the typical member of their corresponding
• A drug may have affinity to more than one receptor
• Furthermore, not all receptors and effectors of one kind are completely identical.
➢ Families of agonists are Adrenergic (adrenaline-like) Epinephrine, norepinephrine, isoproterenol
often named after some stimulants
typical members of the Morphine derived analgesics Morphine, hydromorphone, oxymorphone
group. Examples are→ Barbiturate anesthetics Phenobarbital, pentobarbital, primidone
➢They are also named Benzodiazepines (tranquilizer) Diazepam, clonazepam, lorazepam
according to their chemical Nitroimidazoles (antiparasitic) Metronidazole, dimetridazole, ipronidazole
structures. Salicylates (anti-inflammatory) Phenobarbital, pentobarbital, primidone
Salicylanilides (anti-flukes) Brotianide, clioxanide, oxyclozanide,
Examples are→ rafoxanide
Xanthine derivatives (nervous Aminophylline, theophylline
stimulants)
➢Families of antagonists Antihistamine (vs. histamine) Cimetidine, ranitidine, famotidine
may derive their names Anticholinergic (vs. acetylcholine) Atropine, scopolamine
from the typical member of
Adrenergic blockers (vs. Propanolol, atenolol, metoprolol, timolol
their corresponding
adrenaline)
agonists. Examples are →
● Drug families are based primarily on mechanism of action rather than on structural similarities or on clinical
uses.
● Drugs with similar indications may not necessarily constitute a drug family. Example: atropine, attapulgite &
loperamide.
PART 3
DOSE RESPONSE RELATIONSHIP (Quantifying Drug-Target Interactions) →Doc Garry
Dose Response Relationships: Quantitative Responses in the Patient → Doc Clyde
Dose Response Relationship: Quantitative Responses in the Patient (PD Models) →Doc Khan

Pharmacology
➢ The intensity of response elicited by a drug is a function of the dose administered.

➢ The relationship between dose and response may be interpreted in one of two ways through the Dose-
Response Curves
1. The GRADED-DOSE response relationship
2. The QUANTAL-DOSE response relationship
The difference is that graded dose–response relationships describe the effect on an individual, whereas quantal
relationships show the effect on a population of individuals.
1. The GRADED DOSE-response Relationship
→The intensity of drug effect (response) on an animal or any biological system is generally proportional to the
dose of the drug.
→This is because as the dose increases, more drug molecules are delivered into the receptor sites. As more
drug receptors are occupied by the drug, the greater the intensity of response
→As the dose of the drug is increased, the intensity of the response (drug effect) is increased.
→Can be measured on a continuous scale—‘Hill Model’ (e.g., body temperature, survival time, changes in blood
pressure, & hormone concentration after therapy)
➢ The relationship can be measured on a CONTINUOUS SCALE.
➢ EXAMPLES:
○ changes hormone concentration after therapy
○ progressive increases in EPI dose produce increases in CO and vasoconstriction, which lead to increases in
BP
→Graded responses can be studied in an individual; though to detect interindividual differences, group of
patients will need investigation
→Threshold dose – the lowest concentration of a drug that causes a perceptible effect.
→Graded curves – describing an individual subject.
→Can be interpreted through the Log Dose-response Curve (LDR is Sigmoidal in shape
Drug-receptor interaction and the response to drug

→The magnitude of the response is directly proportional to how many drug-receptor complexes (DR) are
formed.
→If less DR complexes are formed, there would be a weaker response, more DR formed, there would be
greater response.
→The greater the amount (or dose) of the drug made available in the biophase (immediate neighborhood of
the receptors), the greater are the chances of drug-receptor complexes being formed, and the greater will be
the magnitude of the response.
Several factors affect the amount of drug that finally gets to the receptor sites (doc khan & clyde)

Pharmacology
• The rate by which ➢ Physicochemical properties of the drug-rate of dissolution, lipid solubility
the drug is absorbed is ➢ Blood flow through the site of absorption (less blood flow, less drug absorbed)
influenced by ➢ If the amount of the drug absorbed is reduced by any of these factors, fewer drug
molecules will be able to reach the biophase. Consequently, less drug molecules will be
available to bind with the receptors
•If the entire drug is ➢ The extent and rate of distribution
absorbed, maximal ➢ The non-specific binding of drug with tissue and plasma proteins, and subsequent
response is not still liberation of the drug from these binding sites.
assured. Other factors ➢ The biotransformation or metabolism of drug in tissues and plasma
may still influence on ➢ The excretion of drug even before it reaches the biophase
how much of the drug
reach the biophase.
These include:
When the drug molecules have finally reached the biophase, the rate of combination is still influenced by the
degree of affinity of the drug to receptors.
Following the formation of drug-receptor complex, a stimulus must be formed. Its formation may be influenced
by
➢The type and condition of effector system
➢The initial drug effect (inhibitory, stimulatory, or indifferent) on the effector system
➢The local and systemic contra-regulation of the response
The magnitude of the stimulus is directly proportional to the number of occupied receptors. The formation of
stimulus results in perceptible response.
Summary*-doc khan
→Drug absorption is affected by the:
(1) physicochemical properties of the drug; and
(2) blood flow through the site of absorption.
→Other factors include:
(1) extent and rate of distribution,
(2) non-specific interactions with tissue and plasma proteins,
(3) metabolism of drug,
(4) and excretion of drug before it reaches the biophase.
Factors that affect amount of drug in the receptor sites (doc garry ppt)
Pharmacokinetic Drug is administered→ absorbed in blood → distributed to various sites but must
movement of drug reach the site where the drug needs to act→ the drug is degraded or metabolized →
excreted via (usually) urine, feces etc

Pharmacology
Factors affecting drug in receptor sites:

→ Rate of drug absorption
Rate of drug absorption → Physicochemical properties of the drug-rate of
dissolution, lipid solubility
→ Blood flow through the site of absorption (less blood
flow, less drug absorbed)
○ The flow of blood and bile to the intestine is
much greater than the flow to the stomach; thus,
absorption from the intestine is favored over that from
the stomach.
→If the amount of the drug absorbed is reduced by any
of these factors, fewer drug molecules will be able to
reach the biophase.
→Consequently, less drug molecules will be available
to bind with the receptors.
Factors modifying drug absorption
1. Lipid solubility
2. Molecular weight
3. Size of drug
1. Lipid solubility -More lipid soluble drug → more absorption
-Less lipid soluble drug → less absorption
-More water scruble drug → less absorption
2. Molecular weight -Drugs with low MW: 10-1000 ➜ more rate of absorption
-Iron-dextrose complex has high MW, so less absorption
3. Size of drug For lipid soluble drug size is not a matter but for water
soluble drug→ smaller size→more absorption
Some Information that can be Inferred from a Graded Dose-Response Relationship
→ The graded or log dose-response curve (study the figure below) can be viewed as having the following
characteristics:
(1) Potency
(2) Efficacy
(3) Slope
(4) Variation

Pharmacology
Potency The dose of the drug required to produce a given effect. Only useful to determining
the ED50 (EC50 or IC50) of a drug.
Efficacy Maximal effect produced by a drug. Efficacy is of great importance clinically, more
important than potency.
Slope Steepness at which the effect changes as a function of dose. This can vary
dramatically between agents. It is of importance in adjusting dosage in patient and in
safety of administration.
Variation All patients will respond differently.
2.The Quantal DOSE-response Relationship
→There are pharmacological responses that cannot be considered graded. These responses either occur in full
or do not occur at all (all-or-none response).
→ Cannot be considered graded; there is a stated fixed pharmacological response to which the frequency of all-
or none effect is measured—‘Fixed-effect Model’
→ Described effects are nominal (e.g., dead or alive, cured of parasites or not, appearance of unwanted effects)
“Even graded responses can be considered to be quantal if a predetermined level of the graded response is designated as
the point at which a response occurs or not.”
*doc khan*
Quantal curves – describing a population
→The resultant quantal dose-response curve follows the Gaussian or Normal Frequency Distribution Curve.
The curve shows that in any given
population, a range of doses is
necessary to achieve a single, given
effect in each of the individuals of
that population. The dose at which
50% of the individuals show the
response has been arbitrarily set to
zero. Note the numbers at the x-axis
are not true values, but standard
deviations from the mean
corresponding to ED50. Example: in
the graph, 35% of the population was
affected at a Log Dose 0, while only
→10% needed
Or the a higher
Quantal Log dose 1 to be
Log Dose-response (LDR (Curve)
affected.

Pharmacology
The LDR is a simple way to determine

the ED50 (the effective dose, 50%).
The ED50 for an LDR is the drug dose
at which 50% of individuals will have
responded. The LDR also allows an
estimation of the concentration of
drug required to produce a response
in the entire population. Example: in
graph, at least 85% of population was
affected after a Log dose 1, and
almost everyone was affected after a
Log dose of 2
*doc clyde, garry*
Quantal dose-response (Present or absent)
→- as the dose is Increased, the number or proportion of animals exhibiting a particular, stated response is
greater.
→In an all-or-none response, an individual unit of a biological system responds to a drug dose either maximally
or not at all.
→Examples include prevention of seizures, prevention of death, and induction of parturition, prevention of
arrhythmia
Quantal dose-effect curve
Quantal effects. A set of data obtained after administration of increasing doses of a drug to a group of patients,
and observation of the minimum dose at which each patient responded with the desired outcome. The results
have been plotted as a histogram, and fit with a gaussian curve. μ = mean response; σ = standard deviation.
Some Information that can be Inferred from a Quantal Dose-response Relationship *doc khan*
(1) Median (or mean) dose
(2) Standard deviation
(3) Normal equivalent point
(1) Median (or mean) dose Corresponds to the midpoint of the curve. It is also
called effective (ED50), lethal (LD50), or toxic (TD50),
etc. depending upon the situation. It refers to the
smallest dose required to produce a stated effect in 50
per cent of the population.
(2) Standard deviation Determines the spread of the population about the
mean. In a normally distributed population the mean ±
1 SD represents 68.3% of the population, mean ± 2 SD
represents 95.5% of the population, and mean ± 3 SD
represents 9.7% of the population.

Pharmacology
(3) Normal equivalent point The percent response can be converted to NED or unit
of deviation from the mean. The resulting number is
called a probit or probability unit.
Several terms are useful when evaluating a drug dose-response curves *doc clyde and garry*
Potency is a measure of the drug concentration required to elicit
a particular effect and is related to the distance
between the response (y) axis and the EDs.
The slope of the linear past of the dose-response indicates the degree to which a change in dose results
curve in a change in effect. The steeper the slope, the greater
the change in effect with small increments of dose.
Maximum effect Corresponds to the midpoint of the curve. It is also
etc. depending upon the situation. It refers to the
smallest dose required to produce a stated effect in 50
per cent of the population.
ED50 (50% effective dose)/Median Effective Dose
ED50 (Graded dose response)
ED50 (Quantal dose response)

Dose of a drug required to produce 50% of that drug’s
maximal effect.
Dose of a drug that produces a specified all-or-none

response in 50% of a test population.
Median (or mean) Dose corresponds to the midpoint of the curve. It is also
Inhibitory (ID50), etc. depending upon the situation. It
refers to the smallest dose required to produce a stated
effect in 50 percent of the population.
Median toxic dose, TD50 ➢ The dose required to produce a particular toxic
effect in 50% of animals.
➢ Problems encountered in TD50:
○ The toxicity may develop only after years of post-
marketing data.
○ The toxicity may be completely unrelated to dose
➢ The dose required to kill 50% of a test subject

population.
➢ Some problems with LD50:
○ Pharmacokinetics change the LD50
■ Rapid administration of phenytoin may be
fatal, whereas the same dose administered slowly may
have no toxic effects whatsoever.
Drug Safety
→Some Indications of drug safety based on ED and LD

Pharmacology
1. Therapeutic Index or Therapeutic Ratio

2. Certain Safety Factor (CSF) = LD10/ED90
3. Safety Margin (SM)
1. Therapeutic Index or Therapeutic Ratio
➢ Expresses simultaneously the efficiency and toxicity of the drug.
➢ The ratio of the drug dose which produces an undesired effect and the dose which causes the desired effect
(LD50/ED50). TI = TD50 / ED50
• A measure of drug safety
• A drug with higher therapeutic index is safer than with lower therapeutic index.
• Only valid if ED50 and LD50 curves (concentration versus effect) are parallel.
• If the ED50 and LD50 curves have different shapes, the flatter the LD so curve the safer the drug, as it indicates
that, for a given change in concentration, the increase in toxicity is lower than for
• A drug with a higher therapeutic index is SAFER than with lower

therapeutic index (“measure of drug safety”). a steeper curve.
Therapeutic Index (TI)

→Sometimes called Therapeutic Ratio (TR)Related to The
→Trapeutic Window
→Sensitivity of Individual Patient
→Low Therapeutic Index
- Sensitive to Changes in Dose
→High Therapeutic Index
- Insensitive to Changes in Dose
➢ A drug with higher TI is safer than with lower TI.

➢ Only valid if ED50 and LD50 curves (concentration versus effect) are parallel.
➢ If the ED50 and LD50 curves have different shapes, the flatter the LD, the safer the drug.
➢ Theoretically, the larger the TI the safer the drug.
➢ However, if the effectiveness and lethality curves are not parallel, the TI may be misleading.
➢ It is a numeric measure of the selectivity of the drug for its desired effect.
➢ It guides the need for therapeutic level monitoring.
➢ It guides the dosing interval. ***Some drugs with a narrow therapeutic index are as follows:
★ Warfarin, lithium, digoxin, phenytoin, gentamicin, amphotericin B, 5-fluorouracil, zidovudine
Therapeutic range (window) →The range between the minimum toxic dose and the minimum therapeutic
dose. ➢ Dose range over which drug is effective and relatively non-toxic in most of the population.
2. Certain Safety Factor (CSF)
→SEM may be defined as the ratio of the TD1 and the effective dose-99 (ED99). CSF = TD1/ED99
→where TD1 is the dose that is toxic for 1% of the population and ED99 is the dose that is effective for 99% of
the population.
→The percent by which ED90 has to be increased in order to be lethal or toxic a minimum number in a
population

Pharmacology
→This is a more conservative estimate than the TI because values are derived from extremes of the respective
dose–response curves.
→ ➢ A CSF > 1 indicates that the dose effective in 99% of the population is less than the dose that would be
toxic in 1% of the population.
→If the CSF < 1, there is overlap between the maximally effective (ED99) and minimally toxic (TD1) doses.
➢ ADVANTAGE: not requiring the exposure of test subjects to doses which will cause toxicity in 50% of them.
➢ DISADVANTAGE: it may be impossible to achieve a response in 99% of the pop’ & a mild toxic effect in 1% of
the pop’n might be viewed as a trivial risk which has minimal clinical relevance.
3. Standard Safety Margin
➢ A more conservative measure of a drug’s safety than is TI and is used to relate the therapeutic effect in all
animals without the risk of producing a hazardous effect.
➢ It is the percent by which the ED99 must be increased before an LD1 is reached.
➢ SSM = [(LD1 − ED99)/ED99] × 100
○ LD1 = the dose that is lethal for 1% of the population
○ ED99 = the dose that is effective for 99% of the population
➢ SSM = [(LD1 − ED99)/ED99] × 100
➢ Assume 10 mg/kg of a drug is effective in 99% of the animal population and that a dose of 100 mg/kg will
cause toxicity in 1% of the same population.
➢ SSM = 100 - 10/10 x 100 = 900
***The dose which is effective in 99% of the population must be increased by 900% to produce a toxic effect in
1% of the population.
• The percent by which ED90 has to be increased in order to be lethal or toxic a minimum number in a
population.
SM= [LD 10 – ED90]/ED 90 X 100
DRUG INTERACTIONS (Simultaneous Actions of Two Drugs)
Drug Interactions (DI)
● DI are defined as an altered pharmacological response to one drug caused by the presence of second drug.
● The expected response may be increased or decreased as a result of the interaction.
● NATURE:
○ Pharmacokinetic interactions
○ Pharmacodynamic interactions
○ Pharmaceutic interactions
PHARMACOKINETIC Those in which plasma and/or tissue levels of a drug are altered by another drug.
PHARMACODYNAMIC those in which the action or effect of one drug is altered by a second drug.

Pharmacology
PHARMACEUTIC or drug incompatibilities result from chemical or physical reactions of drugs mixed in
vitro.
In clinical practice, drugs are often administered in combination either simultaneously or in close sequence.
Reasons for Drug Combinations in Clinical Practice:
→To optimize the beneficial effects of each drug being used.
→To reduce the toxic or adverse effect of one or both drugs.
→To terminate the action of one drug when it is no longer needed.
→To target several conditions present in a given disease state.
o Levels of Drug Interactions
(1) Molecular level
(2) Physiological level
(3) Chemical or Pharmaceutical level
Molecular level →Antagonist reaction with a receptor.
→Noncompetitive or competitive
Physiological level →When to drugs acting at different sites and by different MOA produce
opposite or the same effects.
→It involves the combined effects on the effector organ.
=Additive effects (1+1 = 2) - the effect of drug combination is equal to the
sum of the individual effects of drugs (e.g. Pen G Streptomycin)
=Antagonistic effects (1+1 = 0)
=Synergistic effects (1+1 = 3) - the effect of drug combination is greater
than the sum of the effects of the two drugs (e.g. TMPS)
=Potentiation (1+0 = 2) - one of the drugs in combination has zero or near
zero efficacy yet the combination produce a synergistic effect
Chemical or Pharmaceutical level →Occurs when drugs are combined out of the body (before administration)
→Neutralization between acids-aminoglycosides are basic; penicillins are

acidic
→Chelation of heavy metals - tetracycline chelate calcium in the gut
preventing the absorption of both; Chelation of arsenic by dimercaprol
→Adsorption of one drug by another - kaolin or attapulgite adsorbs most
drugs administered with it
Pharmacodynamic Interactions (Drug Interactions) DEEPER EXPLAINATION LANG TO HA!!!!
Examples of Physiological Interactions:
1. Additive effects
2. Synergistic effects
3. Antagonistic effects
4. Potentiation
5. Suppressive effects
** Physiological interactions between two drugs may be graphically represented in an isobole. Isobole are
curves, which represent the loci of simultaneous effects of a combination of two drugs.
Additive Effects ➢ The effect of drug combination is equal to the sum of the individual effects of
drugs.
➢ Drugs that have a similar MOA may exhibit additive effects in combination. ➢ The
end point is the algebraic sum of each drug’s action.
➢ Combination effect (C) compared with summation of individual drug effect (A + B) ○
C=A+B

Pharmacology
➢1+1=2
➢ aka SUMMATION
➢ Example: when 2 bacteriostatic antibiotics agents with the same MOA are used
BENEFICIAL OUTCOME:
➢ ASPIRIN + ACETAMINOPHEN
○ Acetaminophen lacks anti-inflammatory action but adds to the antipyretic and
analgesic effect of aspirin.
HARMFUL OUTCOME:
➢ MACROLIDES + QUINOLONES
○ Both antibiotic groups have the potential of inducing heart arrhythmia.
Synergistic Effects ➢ Drug combinations that produce a therapeutic or toxic effect, which is greater than
the sum of each drug’s action, are termed synergistic.
➢1+1=3
➢ The effect of drug combination is greater than the sum of the effects of the two
drugs.
EXAMPLES (concurrent use of):

➢ PENICILLIN + STREPTOMYCIN
○ When 2 bactericidal antibiotics are used in combination.
○ One of the drugs must show at least 4-fold increase in antibacterial activities
(or decrease MIC to ¼) for synergism.
➢ SULFONAMIDE + TRIMETHOPRIM
○ A sulfonamide and an inhibitor of dihydrofolate reductase (trimethoprim,
ormetroprim) potentiate the antibacterial effect of the sulfonamide.
➢ FUROSEMIDE + AMINOGLYCOSIDE
○ A furosemide and an aminoglycoside antibiotic may potentiate the
nephrotoxic effect of the aminoglycoside.
➢ FUROSEMIDE + DIGITALIS
○ A furosemide and a digitalis may potentiate the inotropic effect of the
digitalis. Furosemide can induce hypokalemia.
BENEFICIAL OUTCOME:
➢ ASPIRIN + ACETAMINOPHEN
○ Penicillins are bactericidal through bacterial cell destruction, which also
enhances aminoglycoside transport into cell and its bactericidal effect.
Grouping of antibiotics by bactericidal and bacteriostatic categories

Bacteriostatic Bactericidal
Tetracyclines Penicillins
Erythromycin Cephalosporins
Clarithromycin Metronidazole
Azithromycin Ciprofloxacin
Clindamycin Aminoglycosides
Sulfonamides

Pharmacology
Antagonistic Effects ➢ One drug cancels or blocks effects of another.

➢ Specific antagonists are available to be used therapeutically to block agonist
activity.
➢ The antagonistic effects could be pharmacological or physiological.
➢1+1=0
EXAMPLE:
➢ Bacteriostatic + Bactericidal Antimicrobials
○ Usually, bacteriostatic agents are antagonistic to bactericidal agents.
○ e.g. , chloramphenicol has been shown to antagonize the bactericidal activities
of penicillin in the treatment of pneumococcal meningitis.
➢ A miotic druĀ and an H1-antihistamine
○ Most H1-antihistamines have the side effect of blocking muscarinic receptors
to evoke mydriasis, which will antagonize the effect of a miotic drug (physiological
antagonism).
Pupil
Miosis - parasympathetic nervous system
Mydriasis - sympathetic nervous system
Miotics - Pilocarpine. →Physostigmine→ Constriction of pupil (vasoconstriction)

Mydriatics - Atropine→Scopolamine → Dilation (vasodilation)
Agents Affecting Pupil Size

→MIOSIS (COPS)
Cholinergics, clonidine, carbamates
Opioids, organophosphates
Phenothiazines (antipsychotics), pilocarpine, pontine hemorrhage
Sedative-hypnotics
→MYDRIASIS (SAW)
Sympathomimetics
Anticholinergics
Withdrawal syndromes
MIOTIC DRUGS
• Drugs that constrict the pupil.
A - Parasympathomimetics:
1. Direct acting :
e.g. pilocarbine, carbachol & bethanecol.
2. Indirect acting :
e.g. physostigmine.

Pharmacology
EXAMPLE:
➢ An α-adrenerĀic aĀonist (e.Ā., EPI, PE) and a phenothiazine tranquilizer (e.Ā., ACP
or CPZ) .
○ A phenothiazine can block α-adrenergic receptors to antagonize the effects of
an α-adrenergic agonist (pharmacological antagonism).
➢ An α-adrenerĀic aĀonist (e.Ā., EPI, PE) and a phenothiazine tranquilizer (e.Ā., ACP
or CPZ) .
○ Blockade of the α-adrenergic action of epinephrine may produce hypotension
by unmasking the β-adrenergic action of epinephrine. This effect is known as
epinephrine reversal.
➢ TETRACYCLINE & a β-LACTAM ANTIBIOTIC
○ A β-lactam antibiotic works most effectively in rapidly growing bacteria.
○ Tetracycline inhibits bacterial growth, thereby reducing the antibacterial effect
of a β-lactam (physiological antagonism)
BENEFICIAL OUTCOME:
➢ OPIATES + NALOXONE
○ Naloxone as the opioid receptor blocker reverses the opiate effect in acute
poisoning, i.e., respiratory depression
➢ COPPER + PENICILLAMINE
○ Penicillamine binds copper and reduces its harmful effect during copper
poisoning.
HARMFUL OUTCOME:
➢ WARFARIN + VITAMIN K
○ Supplementary vitamin K disturbs the anticoagulation state maintained by
warfarin.
○ This can lead to suboptimal or failure of anticoagulation therapy.
Suppressive ➢ Hyper-antagonistic cases in which the addition of one drug on top of another
Interactions actually increases growth—a surprising effect, given that both drugs alone inhibit
growth.
Pharmaceutic Interactions (Drug Interactions)
Drug ➢ Physical and/or chemical incompatibility between drugs is common and may result in
Incompatibilities inactivation or increased toxicity.
➢ Drugs should never be mixed in a syringe or added to parenteral solutions unless the
components are known to be compatible.
➢ Visual indicators of incompatibilities such as cloudiness or precipitation may or may
not be evident.
Physical ➢ Usually manifested as insolubility.
Incompatibilities ➢ EXAMPLES:
○ A macrocyclic lactone diluted in water or aqueous solution will form precipitate
(propylene glycol should be used as a diluent).
○ Amphotericin B is insoluble in water, but can be dissolved in sodium
deoxycholate.

Pharmacology
Chemical ➢ EXAMPLES:
Incompatibilities ○ pH
■ The stability of many drugs in solution is pH dependent.
■ Alkaline solutions (sulfonamides, aminophylline, or barbiturates) are incompatible
with acidic solutions (penicillin G, cephalosporins, xylazine HCl, ketamine HCl, etc.) or
alkaloid salts such as atropine sulfate.
○ Oxidation-reduction
■ Redox reactions may result in loss of drug potency.
■ Tetracyclines are oxidized by riboflavin; phenothiazine tranquilizers are oxidized by
ferric salts.
○ Complex formation
■ Multivalent cations may form insoluble complexes with anionic drugs.
■ Examples: Ca2+ reacts with NaHCO3, tetracyclines, cephalosporins, barbiturates,
fluoroquinolones, penicillins, furosemide, and the following NSAIDS: aspirin,
phenylbutazone, meclofenamic acid, flunixin, ketoprofen, carprofen, and etodolac.
Factors Modifying Drug Action (Drug Interactions)
SPECIES ➢ Attributed to differences in either pharmacological processes (absorption,
distribution, biotransformation, and excretion) or in the pharmacodynamic sensitivity of
specific tissue receptor.
Anatomical & Differences among the GI tracts can influence the disposition of drugs administered PO.
Functional
Differences
Presence of body Highly lipid-soluble drugs may accumulate in body
fats
Placental passage of ○ Species with less intimate placentation (epitheliochorial) tend to exclude drugs from
drugs the fetus more than those with more intimate placentations (endotheliochorial,
hemochorial, or hemoendotheliochorial).
Urinary pH ○ Urinary pH variations
■ ruminants, 7-8
■ horses and pigs-7
■ carnivores, 5-6.5
Genetic factors ○ Genetic or breed characteristics may alter the susceptibility of animals.
■ Doberman Pinschers are predisposed to the extrapyramidal side effects of opioids.
■ Some Boxer dogs have pronounced side effects with acepromazine.
AGE ○ Toxicity as a result of therapy in neonates (up to 1 month) is common.
○ The BBB is poorly developed in fetus and the newborn in some species.
○ Absence oÿ enzymes
■ Sulfonamides, nitrofurans, methylene blue, acetylsalicylic acid, and the
phenothiazines may produce methemoglobinemia in the newborn due to deficiency of
methemoglobin reductase in the fetal RBC.
■ Increased permeability of the small intestine following birth - absorption of drugs
retained in the intestine.
■ Percentage of body weight is high; volume of ECF is greater than the ICF.
○ Hypoproteinemia is common in neonates - increases the amount of drug available to
diffuse into the tissues.
○ Deficiency of hepatic microsomal enzyme function during the first week leads to
prolong tissue levels and toxic effects if adult regimen are followed.

Pharmacology
Drug Actions not Involving Receptors

Nonspecific action
and cell membrane
perturbation: 1. Osmotic agents Mannitol (osmotic diuretic), Mg sulfate (Epsom salt) and Na
sulfate (Glauber’s salt) which are bulk cathartics.
2. Acids and bases Mg hydroxide (antacid), ascorbic acid and ammonium chloride
(urine acidifiers).
3. Change in cell detergents, oxidizing agents, lidocaine (block sodium channels),
membrane nifedipine (block calcium channel), and bretylium (block
permeability potassium channel).
4. Oxidizing agents
and anesthetics
Drugs acting with
small molecules and
Ethylenediaminetetra antidote for lead poisoning.
ions
cetic acid (EDTA)
Penicillamine remove copper from tissues
Dimercaprol/British chelates heavy metals like arsenic, gold, and mercury.
antiLewisite (BAL)
Deferoxamine antidote for iron toxicity.
Drugs incorporating
into Sulfonamides drug replaces a normal metabolite in the synthesis of an
macromolecules imitating PABA important compound resulting in a biologically inactive
(Counterfeit compound.
incorporation)
Sir Garry Handout ppt

PHARMACOKINETICS
→ Concered with the study and characterization
of the time course of drug ADME
→ how these effects relate to a drug's
MECHANISM OF ACTION.
→ focuses on the action and effects
→ focuses on the action and effects
Drug Action vs Drug Effect

Drug Action WHERE & HOW the drug works
Kapoy nako.

1. With regards to the pharmacologic effects of catecholamines, which of the following is TRUE:
→Norepinephrine and epinephrine are potent constrictors of blood vessels in skin and mucous
membranes
2. Regarding the clinical uses of beta-adrenergic blockers, which statement is TRUE:
→ Control cardiac dysrhythmias
3. A 5-10 mcg/kg dose of Acetylcholine produces a brief but rapid fall in blood pressure. Why?
→Decrease peripheral resistance due to its vasodilatory effect
4. The following are reversible cholinesterase inhibitors EXCEPT

→Malathion
5. Regarding cholinergic receptors, which of the following is TRUE:

→Muscarinic receptors are metabotropic receptors
6. Which of the following statements is TRUE:*

→Carbachol can cause myometrial contractions
7. A carabao was wandering around the farm and was able to accidentally 2/2 drink a substance spilled
from an unlabelled bottle. Few hours later, the carabao was observed to be experiencing increased
Salivation, Lacrimation, Urination, Diarrhea, Gl distress and Emesis (SLUDGE). It was later found out
that the farmer was applying a pesticide, parathion, on his crops. Which of the following is the best
drug that can effectively treat the toxicologic condition?
→Atrophine
8. Endogenous catecholamines include the following except:

→Isoproterenol
9. Regarding adrenergic receptors and their catecholamine agonist preference, which of the following
is FALSE"
→ Norepinephrine is the most potent beta receptor agonist
10. Pupillary dilation caused by norepinephrine and epinephrine is thru the activation of what
adrenergic receptor/s?"
→Alpha receptors
11. Which of the following statements is TRUE:
The CNS is composed of the brain and its ligaments
The PNS is composed of the sympathetic and parasympathetic branches
Reflex kick when the knee is tapped by a hammer is a function of the ANS
The Autonomic Nervous System (ANS) controls all the involuntary functions of the body
12. Atropine is routinely used as a pre-anesthetic agent because:
→It decreases salivary and bronchial secretions during anesthesia
13. Regarding the clinical use of catecholamines, which of the following is FALSE:
→Epinephrine is not indicated in treating cardiac arrest and atrioventricular blocks
14. Which of the following does not belong to the group: "
Sympatomimetic
Adrinergic
Parasympatolytic
Sympatolytic
15. Atropine has pronounced Nicotinic receptor blockade activity."

→False
16. Phenylephrine, or less commonly phenylpropanolamine, is a component 2/2 of over-the-counter flu

medications. These agents exert vasopressor effects on the blood vessels of the nasal mucosae thus
lessening the production and secretion of mucous discharges (rhinorrhea). "
→True
17. Which of the following statements is FALSE:"

The preganglionic nerves of parasympathetic innervations are long
The preganglionic nerves of sympathetic innervations are short
The postganglionic nerves of sympathetic innervations are long
The postganglionic nerves of parasympathetic innervations are long
18. In the gastrointestinal tract, the sympathetic nervous system has the following effect EXCEPT:
→Increased peristalsis
19. Epinephrine has a diabetogenic (able to increase blood glucose) effect. * 2/2
→True
20. Regarding Amphetamine sulfate, which of the following is FALSE:

→Immediately after consumption, humans experience decreased alertness, depressed mental
states and dysphoria
21. Nicotinic receptors are found in all of the following altes EXCEPT:
→Heart muscle
22. Muscarinic receptors are found in the following, EXCEPT:

→Postganglionic neurons of parasympathetic nerves
23. What is the term specifically used to describe an Acetylcholine-like effect on effector cells?
→Parasympatomimetic
24. Sympathetic peripheral nerves originate from the CNS:
→Thoracolumbar
25. Regarding adrenergic receptors, which of the following is TRUE:

→Beta 1 receptors are prevalent in the heart where they exert positive inotropic, chronotropic and
dromotropic effects.
26. The following are pharmacologic effects of Atropine EXCEPT:

Tachycardia
Treatment of intestinal spasms and hypermotility via relaxation of GI smooth muscles
Urine retention due to inhibition of bladder muscle tone
→Pronounced CNS depression
27. Beta 2 receptor blockade results in bronchodilation, hence most antiasthma medications exert its
effect via this MOA. Which of the following is NOT a Beta 2 receptor agonist?
→Propranolol
28. Paympathetic peripheral nerves originate from branches _______of the CNS:
→Craniosacral
29. The following are alpha-adrenergic blockers EXCEPT:

→Xylazine
30. Nicotinic receptors are found in all of the following sites EXCEPT:
Autonomic ganglia of both sympathetic and parasympathetic ANS branches
Adrenal medullary chromafin cells
Neuromuscular junctions
→Heart muscle
31. Regarding naturally occurring cholinomimetic alkaloids, which of the following statements is FALSE:
Pilocarpine is primarily used in veterinary medicine as a pupillary dilator
Muscarine is derived from a poisonous mushroom
Arecoline, from the betel nut, is used as purgative against tapeworms
→Colic and excessive diarrhea are not associated with toxic doses of these drugs
32. In the sympathetic innervation of sweat glands, the postganglionic neuron secrete_____ which
interact with its________ receptors of the effector gland cells."
→Acetylcholine; Muscarinic
33. Which is NOT an effect of Epinephrine-Alpha 1 receptor binding:

→Miosis

Transes Pharmacodynamics

Uploaded by

Copyright:

Available Formats

Transes Pharmacodynamics

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Transes Pharmacodynamics

Uploaded by

Copyright:

Available Formats

Pharmacology

Drug action Vs. Drug effect (DRUG ACTION)

Doc Garry, Clyde, Khan compiled by ericjohnperono 1

Doc Garry, Clyde, Khan compiled by ericjohnperono 2

Types of Drug Traget

Doc Garry, Clyde, Khan compiled by ericjohnperono 3

Full Agonist →Produces a maximum response by occupying allor a

Doc Garry, Clyde, Khan compiled by ericjohnperono 4

If you increase the dose of agonist with the presence of

Doc Garry, Clyde, Khan compiled by ericjohnperono 5

Doc Garry, Clyde, Khan compiled by ericjohnperono 6

➢ Relates to the number of different mechanisms involved.

➢ Specific drugs: atropine (a muscarinic receptor antagonist), salbutamol (a β2-adrenoceptor

Doc Garry, Clyde, Khan compiled by ericjohnperono 7

Selectivity & Specificity [Receptors]

Doc Garry, Clyde, Khan compiled by ericjohnperono 8

Doc Garry, Clyde, Khan compiled by ericjohnperono 9

Doc Garry, Clyde, Khan compiled by ericjohnperono 10

Doc Garry, Clyde, Khan compiled by ericjohnperono 11

Doc Garry, Clyde, Khan compiled by ericjohnperono 12

Doc Garry, Clyde, Khan compiled by ericjohnperono 13

Doc Garry, Clyde, Khan compiled by ericjohnperono 14

[R] = concentration of empty receptors

PRINCIPLES OF DRUG-STRUCTURE ACTIVITY RELATIONSHIP (SAR)

Doc Garry, Clyde, Khan compiled by ericjohnperono 15

Basic Procedure in SAR Study

There are two classes of non proprietary names:

Doc Garry, Clyde, Khan compiled by ericjohnperono 16

Doc Garry, Clyde, Khan compiled by ericjohnperono 17

Doc Garry, Clyde, Khan compiled by ericjohnperono 18

Doc Garry, Clyde, Khan compiled by ericjohnperono 19

➢ The intensity of response elicited by a drug is a function of the dose administered.

Drug-receptor interaction and the response to drug

Doc Garry, Clyde, Khan compiled by ericjohnperono 20

Doc Garry, Clyde, Khan compiled by ericjohnperono 21

Factors affecting drug in receptor sites:

Doc Garry, Clyde, Khan compiled by ericjohnperono 22

Doc Garry, Clyde, Khan compiled by ericjohnperono 23

The LDR is a simple way to determine

Doc Garry, Clyde, Khan compiled by ericjohnperono 24

ED50 (Graded dose response)

ED50 (Quantal dose response)

Dose of a drug that produces a specified all-or-none

➢ The dose required to kill 50% of a test subject

Doc Garry, Clyde, Khan compiled by ericjohnperono 25

1. Therapeutic Index or Therapeutic Ratio

• A drug with a higher therapeutic index is SAFER than with lower

Therapeutic Index (TI)

➢ A drug with higher TI is safer than with lower TI.

Doc Garry, Clyde, Khan compiled by ericjohnperono 26

Doc Garry, Clyde, Khan compiled by ericjohnperono 27

→Neutralization between acids-aminoglycosides are basic; penicillins are

Doc Garry, Clyde, Khan compiled by ericjohnperono 28

EXAMPLES (concurrent use of):

Grouping of antibiotics by bactericidal and bacteriostatic categories

Doc Garry, Clyde, Khan compiled by ericjohnperono 29

Antagonistic Effects ➢ One drug cancels or blocks effects of another.

Miotics - Pilocarpine. →Physostigmine→ Constriction of pupil (vasoconstriction)

Agents Affecting Pupil Size