PHARMACOLOGY, Pharmacology, Toxicology
Pharmacokinetics, Pharmacodynamics and
PHARMACOLOGY = study of drugs; deals with substances
that interact with living systems through chemical processes
by binding to regulatory molecules and activating or
inhibiting body processes
TOXICOLOGY = study of poisons; deals with undesirable
effects of chemicals
THERAPEUTICS = deals with treatment
TYPES OF DRUG
1. Core or Primary Drug = drug of choice
2. Complementary or Secondary Drug = substitute or
alternative
PROPERTIES OF DRUG
1. Pharmacodynamics
2. Pharmacokinetics
3. Structure-Activity Relationship (SAR)
4. Clinical Indications
5. Drug Reaction
 Side Effect
 Adverse Side Effect
 Toxic Effect
 Addiction or Abuse = for rehabilitation;
tolerance is the first step in addiction –
increasing drug dose to produce effect
 Lethal Dose
 Under Dose = drug is ineffective
6. Contraindications (CI) For Use
7. Drug Interactions (DI)
8. Antidote = to poisoning and overdose toxicity
9. Therapeutic Dose
 Loading Dose (LD) = amount of drug to be
given; promptly raises the concentration of
drug in plasma to target concentration
LD = MD x Accumulation Factor
 Maintenance Dose (MD) = amount of drug
given to maintain a steady state of drug in the
body; just enough drug is given in each dose to
replace the drug eliminated since preceding
dose
MD = Dosing Rate x Dosing Interval
THEORIES/PRINCIPLES OF DRUG ACTION
1. Drug-Receptor Occupancy = drug must fit precisely
to the receptor; must be selective and specific to the
receptor; more acceptable
 locations of receptors may be intracellular,
extracellular, intracytoplasmic, or intranuclear
2. Spare-Receptor Theory = receptors are plenty;
maximal response elicited by agonist at a
concentration that does not result in occupancy of
full complement of available receptors; not
advantageous
 drug concentration diminishes if there are
plenty of receptors
 modify receptors to enhance the reaction of
drugs, not increase or decrease its number
TYPES OF RECEPTORS
1. Enzyme Receptor = (majority) oxidase, transferase,
phosphodiesterase, reductase, peroxidase
2. Transport or Channel Receptor = sodium-potasium
Pharmacotherapeutics
Ledo A. Torres, MD
June 16, 2010
1st shifting, Trans #1
channel, calcium channel
3. Structural Receptor = cell membrane (extracellular
receptor of insulin, intracellular receptor of
anesthetic agents), mitochondria, microfilaments,
microtubules (receptor of colchicine)
4. Chemical Mediator = regulates the function of the
cell; examples are epinephrine, acetylcholine,
dopamine, histamine, serotonin, norepinephrine
ACTIONS OF DRUG
1. Pharmacologic Action (PA)
 Non-Steroidal Inflammatory Drug (NSAID)
 Disease Modifying Anti-Rheumatic Drug
(DMAR)
 Antitussive (for cough)
 Sialagogic (anti-salivary)
 Stimulants
 Depressants
2. Therapeutic Action
 Antiviral
 Antifungal
 Antibiotic
3. Mechanism of Action (MOA)
 Ca channel blocker
 Histamine I blocker
DEGREE OF DRUG EFFECTS
1. Hyposensitivity = usual dose has no effect
 Tolerance = highest amount of drug given in
order to produce given effect
 Tachyphylaxis or Evanescent Tolerance =
common in local or general anesthetic;
diminishing tolerance to drug
 Addiction
2. Hypersensitivity = usual dose has pronounced
effects
 Allergies = increase of histamine 1 release
(vasodilator); wheal (exudation of fluids); flare
(removal of erythma after application of
pressure)
 Anaphylaxis = severe allergy
 Idiosyncracy = immunologic reaction to
certain drugs or food; genetic hypersensitivity
to drugs
PHARMACODYNAMIC QUALITY OF DRUGS = WHO and
DOH criteria that are evaluated to prove if the drug is rational
1. Potency = minimum amount of drug that produces
therapeutic effect
2. Efficacy = effectivity; ED50
3. Affinity = agonist-antagonist action
 Agonist = activate the receptor to signal as a
direct result of binding to it; has high affinity
 Antagonist = bind to receptors but do not
activate generation of signal; consequently
they interfere with the ability of an agonist to
activate the receptor; also has affinity but has
no internal affinity
 Partial Agonist/Antagonist = there is an
agonist or antagonist effect
 Full Agonist = strong, excellent, well-fitted
4. Safety = risk over benefit ratio
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 PHARMACOLOGY, Pharmacology, Toxicology
Pharmacokinetics, Pharmacodynamics and
Pharmacotherapeutics
Ledo A. Torres, MD
June 16, 2010
1st shifting, Trans #1
5. Affordability = cost
6. Necessity or Need or Suitability b. Topical
: local; administer drug at area needed
THERAPEUTIC INDEX (TI) = index of safety of drug Ex: gel, lotion, shampoo
b.1 opthalmic
TI = Toxic Dose (TD50) b.2 otic
Effective Dose (ED50) b.3 nasal
b.4 turbohaler/ inhalation
1. Wide Margin = if TI is above 10; better b.5 anus/ rectum: suppository
2. Narrow Margin = if TI is below 10; even minute c. Subcutaneous/ Parenteral
increase will produce adverse effects such as Barrier: adipose tissue which acts as fat depot;
arrythmia entry
 anesthetic drugs d. Intramuscular
 Digitalis Barrier: Adipose tissue, skeletal muscle;
 theophylline entry
 anti-epileptic drugs e. Intravenous
 barbiturates : most perfect; entry direct to blood
3. Dosage form
ANTAGONISM a. Well- absorbed
1. Competitive b. Poorly absorbed
 propanolol/norepinephrine
 atropine/acetylcholine Characteristics of drugs to be easily absorbed
2. Competitive Full 1. Lipophylic
 morphine/naloxone 2. non ionized
3. Non-competitive 3. non polar
 benzodiazepine/GABA
4. Irreversible Characteristics for excretion
 phenoxybenzamine/cathecholamines 1. water soluble
5. Chemical 2. ionized
 protamine S04/heparin 3. polar
6. Physiologic 4. pH of urine and drug must be opposing
 insulin/glucocorticoids
 acetylcholine/isoproterenol *In absorption, pH of drug and urine must be the same
*Drugs are usually weak acids and weak bases
CLINICAL DRUG TRIALS= procedure of approval of new
drugs First pass effect: drug acted is acted upon by the GI and liver
1. Animal studies Injectable drugs: has no first pass effect
2. Human studies Most oral drugs: has first pass effect
3. Patient studies
* Approving Body: BFAD DISTRIBUTION : to blood and to tissues
* If the drug is not given sanction after 20 years, it means *Concentration – amount of blood in the serum/circulation;
that the research is a failure. measured in percentage or mEq/L

GOVERNMENT AGENCIES PHARMACOKINETIC QUALITIES

1. Department of Health (DOH)
2. Bureau of Food and Drugs (BFAD)
3. Philippine National Drug Policy (PNDP)
4. National Drug Use (NDU)
5. National Drug Info Agency (NDIA)
6. National Drug Education Program (NDEP)
7. Philippine Drug Enforcement Agency (PDEA)
8. Dangerous Drug Board (DDB)
9. Pharmacovigilance- reporting and monitoring
drug reaction
PHARMACOTHERAPEUTICS = use of drug for prevention,
diagnosis and treatment
ABSORPTION
Factors for easy absorption:
1. Dosage/ Therapeutic Dose
5mg/kilo: required dose
2. Route of Administration (RoA)
a. Oral
1. Bioavailability
: fraction of unchanged drug reaching the systemic
circulation following administration; rapidity of
entry & widespread extensive distribution of drug in
the circulation
: measured in percentage
*If drug has bioavailability of
100%- excellent
75%- good
50% and below- poor
2. Bioequivalence
: same action but different pharmacokinetics
3. Plasma Protein Binding (PPB)
: binding of food or drug before absorption and
distribution; is not a major pharmacokinetic quality
nowadays; measured in percent
Proteins in blood:
a. Albumin: where drug attaches to

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 PHARMACOLOGY, Pharmacology, Toxicology
Pharmacokinetics, Pharmacodynamics and
Pharmacotherapeutics
Ledo A. Torres, MD
June 16, 2010
1st shifting, Trans #1
b. Fibrinogen: for clotting
c. Globulin: for immunity Ex: t ½ of drug is 4 hrs, multiply it to 4 (constant) =4 x 4= 16
hrs; 16hrs/2 = 8hrs. Thus, drug should be given at 8 hrs
Principles of Pharmacokinetics: interval or 3x/day
1. First Order Kinetics
: constant amount of drug circulation is measured *if drugs has a t ½ of 10hrs and above, give drug only once a
per unit time day.
: good pharmacokinetic quality
: drug binds then unbinds to plasma protein – bound Drugs with long half life
–free- bound- free- goes to target organ (specifically a. Chloroquinine: with longest half life; given twice a
to receptors of the target tissue) to produce its week
affinity or efficacy : drug for prophylaxis and malaria
2. Second Order/ Zero Order Kinetics b. Digitoxin: t ½ of seven days
: small fraction of drug moving in circulation per unit
of time Clearance: inversely related to half life
3. Michaelis Menten
Clearance: rate of elimination
Volume of Distribution (Vd) Concn
: volume of distribution in the tissue; apparent component of Normal value: 0.7
the body that contains drug
3. Drug metabolizing microsomal enzyme system
Vd: D (amount of drug that enters the cell) (DMMES)
C ( concn in the blood) Actions in Liver:
a. Act as enzyme inducer: terminate drug action
*Vd and PPB are inversely related b. As enzyme inhibitor: enhance drug action
*Most toxic drugs are inhibitors commonly CYP3 inhibitors
METABOLISM
: changing of drug from compound to simpler one; produce a Enzymes in liver (oxidoreductase/ CYPs)
by- product or metabolite  Cytochrome P1 (CYP1): rarest (charcoal- boiled
*Physiologic process for drug absorption into system is by foods; carcinogenic)
passive diffusion, rarely by active diffusion  CYP2
 CYP3: most common
Organs of Metabolism *grape juice: inhibits liver enzyme
1. Liver – majority of oral drugs, main organ of metabolism
2. Lungs – inhaled drugs Process of Metabolism
3. Intestine – oral also Phase I
st
Rectal/enema- 1 pass effect onlu 25%  Simple hydrolysis
 Oxidation
Purpose of Metabolism  Reduction
1. DETOXIFICATION – toxic to non-toxic Phase II
2. SIMPLIFICATION – compound/complex drugs become  Methylation
simple  Acetylation
3. ACTIVATION – pro-drug into active drug
 Sulfation
4. MORE ACTIVATION – active to more active drug
ST  Glucoronidation
1 pass EFFECT - enterohepatic circulation of drug through
*Most of the drugs undergo Phase II but must also undergo
portal circulation to liver
Phase I. if not, you can expect adverse effect
- Ex. Oral – with 1st PE
st *Some drugs start with Phase II before Phase I
- IV, IM< SUBLINGUAL – no 1 PE
EXCRETION
Parameters of Metabolism
Major excretory pathways
1. First pass effect: through portal circulation
1. Biliary: through ampulla of Vater (GIT)
a. Rectal
2. Renal: through kidneys
b. Vaginal
*Bypass first pass effect:
Other excretory pathways
1. Injectable
1. Sweat: for vitamins
2. Sublingual tablet: almost similar to IV with 100%
2. Saliva: for sulfa drugs
bioavailabilty; only oral drug that has no first pass
3. Tear Glands: for Rifampicin (for meningococcemia,
effect
TB and leprosy)
3. Transdermal
4. Breast: anti thyroid drugs must not be given to
women for it may lead to fetal thyroid
2. Half- life (t ½): important for dosage scheduling ;
5. Placenta
measured in hours
t ½: Normal vol of concn (Vd)
Barriers in the body
Clearance
1. Blood- brain barrier

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 PHARMACOLOGY, Pharmacology, Toxicology
Pharmacokinetics, Pharmacodynamics and
Pharmacotherapeutics
Ledo A. Torres, MD
June 16, 2010
1st shifting, Trans #1
2. Blood- testis barrier
3. Placental barrier the drug in the body; same as in physiology
(digestion, absorption, distribution, metabolism,
Biotransformation excretion)
: occur usually between absorption into a circulation and 3. SAR (structure activity relationship)- chemical
elimantion structure of drug moiety whether the drug is a
: product of metabolism; metabolites and by products sugar, mineral, micronutrient, alkaloid, fat, etc.
 Simplification : the important component of the drug's chemical
 Detoxification: conversion of toxic to non- toxic structure; example is Digitalis which contains
substances glycoside
 Activation: inactive to active form of drug 4. Clinical indications/ therapeutic uses/ drug of
choice (DOC) / rational drug use (RDU)- lactation,
TYPES OF CONCENTRATION infants, children, renal, heart, and hepatic patients
1. Area Under Curve (AUC)- measure of the extent of 5. Adverse drug reaction (ADR)- adversely affects the
bioavailability organ system; anaphylactic shock; - monitoring and
2. Steady State Concentration (SSC)- plateau effect; reporting, removed or withdraw the drug- reason for
maintenance of the treatment banning
Eg. Hematoxicity- toxicity in bone marrow causing
Rational Drug Dose Regime: t ½ aplastic anemia
Target conc. Hepatotoxicity- on liver
Nephrotoxicity- on kidney
Loading dose= Vs x TC Neurotoxocity- on nervous system
: initial dose is usually higher in dosage 6. Side effect (SE)- an unwanted effect produced by a
drug in addition to its desired therapeutic effect;
Enzyme inducers: continue using; can be relieved by rest and water;
CYPB1- Phenobarbital allergy is the most common side effect
CYP1A1- PAH/ Benzpyrene -allergy, fever, abdominal pain
CYP3A4/ CYP3A5- Glucocorticoids/ Allowable side effect- allergy, sneezing, ache
Phenytoin 7. Toxic effect (TE)= TD50 (median toxic dose) is the
dose required to produce a particular toxic effect
Enzyme Inhibitors: 8. Lethal effect (LE)- = causes death; LD50
CYP3A- Ketoconazole/ Cimetidine/ Pro Adiphen 9. Contraindications (CI)- precautions
HCl 10. Drug interaction (DI)- substance incompatibilities;
CYPF2B1- chloramphenicol example is grapefruit juice which can cause drug
interruption
Suicide Enzyme- Inhibitors : drugs- drugs interaction, food- drug interaction,
Ethinylestradiol drugs- substance, substance incompatibilities
Noreethinodrone : Can accelerate or inhibit the effect of one
Spironolactone 2 Levels of Interaction:
Fluorexene 1. PD- drugs to the body
PTU (Propyl Thiouracil) 2. PK- body to drugs
CYP3A5- single nucleotide polymorphism 11. Antidote to poisonings/ overdose toxicity
- midazolam 12. Therapeutic dose- normal amount of drug to be
Charcoal- boiled foods- CYP1A- inducers given
Grapefruit juice- CYP3A- Inhibitor toxicities a. Loading dose- amount of drug to be given
LD= maintenance dose x accumulation
THERAPEUTIC USES/ CLINICAL USES- conditions wherein factor
you use the drug b. Maintenance dose- amount of drug for
maintenance
Essential drug- core drug, primary drug MD= dosing rate x dosing interval
Complimentary drug- secondary/ alternative/ 13. Route of administration (ROA)- oral, topical/ local-
substitute; when the drug of choice is unavailable includes suppositories, or parenteral/ injectible
14. Dosage form- forms of preparations- suspension,
Therapeutic class- based on the action, classification sublingual, capsule, tablet, ointment, cream
of drug, based on organ system - Appearance of drug gives clue to its ROA

Terminologies: Pharmacodynamics- MOA/ PA on important organ system;

1. Pharmacodynamics- MOA/ PA on important organ
systems
: study of action and effect of drug on the body
 Good = therapeutic; wanted; beneficial
 Bad = toxic; unwanted; extended
2. Pharmacokinetics- A, D, M/B/ E
: how the body handles the drug; what happens to
action and effects of drugs in the body
 Pharmacologic action of drug
- Basis of classification of drug eg, as antibiotic,
antiviral
 Pharmacokinetics (A< D< M/B, and E) Action of drug

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- What happens to the drug in the
body(absorption, distribution, metabolism, and
excretion)
1. Pharmacologic action (PA)
2. MOA
3. Therapeutic categories/ classification
PHARMACODYNAMICS
Theories/ Principles of drug action
1. Drug- receptor occupancy
- Drug must fit precisely to the receptor, must be
selective and specific to the receptor
- Location of receptors:
o Extracellular
o Intracellular
o Intracytoplasmic
o Intranuclear
Characteristics of Receptors:
A. Specificity- very specific, stereospecific
B. Selectivity- highly selective
Antagonist- borrows the mechanism of agonist, borrow
receptor
Agonist- has its own receptor, strong affinity too receptor,
increasing the activity of the drug
Effectivity- efficacy
2. Spare receptor theory
- Certain number of receptors are more than the
normal
- Maximal response elicited by agonist at a
concentration that doesn’t result in occupancy
of full complement of available receptors
Increase number of receptor will not enhance the activity and
affinity of the drug
The affinity remains to the specific receptor
The concentration of the drug is diminished when the
receptors are increased, lowers the efficacy of drug
Drug receptors/ sites- usually CM, but through secondary
messengers (CGMP, CMAP, Ca2+, ITP, adenyl cyclase) also
nucleus
Types of Drug Receptor Sites
1. Enzyme receptors- oxidase, transferase
2. Transport receptors/ channel receptors- for
transport process, eg. Na+, K+
3. Regulatory receptors- mediates action of
endogenous chemical signals; autonomic and
endocrine regulators, substance release through
different cell endings
- Neurotransmitters, chemical mediators, Ach,
dopamine, GABA, serotonin, epinephrine,
histamine, norepinephrine
4. Structural Receptors- due to structure of cells
- Cell membrane:c extracellular receptor of
insulin; intracellular receptor of anesthetic
agents
- Also mitochondria, microfilaments,
microtubules
- Nuclear receptors- has 2nd messengers such as
cAMP, cGMP, IP3, Calcium
Pharmacodynamic effect of drugs
1. Good- wanted, expected, beneficial, therapeutic
- Patient is relieved from signs and symptoms
2. Bad- unwanted (ADR/ toxic/ addiction/ lethal/ side)
PHARMACOLOGY, Pharmacology, Toxicology
Pharmacokinetics, Pharmacodynamics and
Pharmacotherapeutics
Ledo A. Torres, MD
June 16, 2010
1st shifting, Trans #1
Unwanted/ Unintended/ extended effects of drugs:
1. Side Effect (SE)
2. ADR
3. Toxic effects- TD50, toxicotherapeutics
4. Lethal effect- LD50
5. Addiction/ Abuse- know the antidote and
management; withdraw from rehab
Degree of drug effects:
1. Hyposensitivity effect
- Tolerance- highest amount of drug given in
order to produce the given effect
- Responsiveness to drugs decreases as a result
from continued administration
- Needs increased dose to produce the desired
pharmacologic effect
- Tachyphylaxis/ evanescent/ tolerance- rapidly
diminishing effect after administration eg. Local
anesthesia which undergo hydrolysis
- Effect of Tolerance- steps toward addiction
- 1. Habitual 2. Dependence 3. Addiction
2. Hypersensitivity effect
- Allergy
- Simple or low dose leading to allergic reaction
(d/t release of histamine 1 from mast cells and
basophils
s/sx of allergy:
1. Reddening and vasodilation
2. Heat
3. Wheal formation
4. Flare- whitening of the reddened area after
the removal of applied pressure
Severe allergy- eg. Injectible causes anaphylactic shock,
collapse, circulatory failure
Genetic- immunologic type of allergy- idiosyncrasy; food
(lobster and seafoods)
Clinical Drug Trials (CDT)- procedure for approval of new
drugs
a. experimental- animal level
b. clinical- volunteer
c. Hospital- patients with known disease
4 PHASES
Phase 1 – NONBLIND or “OPEN”-
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 PHARMACOLOGY, Pharmacology, Toxicology
Pharmacokinetics, Pharmacodynamics and
Pharmacotherapeutics
Ledo A. Torres, MD
June 16, 2010
1st shifting, Trans #1
- both the subjects and the investigators know what is
being given.
-Animal testing; effects of drugs as a function of dosage
are established in a small number (25-100) of healthy
volunteers.
Phase 2 – SINGLE-BLIND DESIGN with PLACEBO
- drug is studied for the first time in patients with the
target disease to determine its efficacy (“proof of
concept”) (100-200 pxs)
Phase 3 – DOUBLE-BLIND and crossover techniques are
used. To every guy that has said, "You're beautiful."
-thousands of patients are tested to establish safety and To every guy that has said, "Sex CAN wait."
efficacy To every guy that was never too busy to drive across town to
Phase 4 – POST-MARKETING SURVEILLANCE (Generics) see her.
- Monitoring the safety of the new drugs under actual To every guy that gives flowers and a card.
conditions of use in large number of patients. To every guy who has given her flowers just because.
To every guy that said he would die for her.
ENZYME INDUCERS ENXYME INHIBITORS To every guy that really would.
CYP2B1 – Phenobarbital CYP3- KETOCONAZOLE, To every guy that did what she wanted to do.
CIMETIDINE, HCL, pro- To every guy that cried in front of her.
adiphen To every guy that she cried in front of.
To every guy that holds hands with her.
CYP1A1-PAH/benzopyrene CYP2B1- chlorampenicol,
To every guy that hugs her when she's sad.
secobarbital To every guy that hugs her for no reason at all.
CYP3A4/CYP3A5 – To every guy who would give their jacket up for her.
glucocorticoids/phenytoin To every guy that calls or sends SMS to make sure she got
CYP2E1- INH/ethanol home safe.
To every guy that would sit and wait for her for hours just
to see her for ten minutes.
To every guy that would give his seat up.
Kathy, Fiel, Vincent, Chiqui To every guy that just wants to cuddle.
To every guy that reassured her that she was beautiful no
matter what.
To every guy who told his secrets to her.
To every guy that tried to show how much he cared through
every word and every breath.
To every guy that thought maybe this could be the one.
To every guy that believed in her dreams.
To every guy that would have done anything so she could
achieve them.
To every guy that never laughed at her when she told him
her dreams.
Every woman was once a little girl. And every little girl holds To every guy that walked her to her house.
in her heart her most precious dreams. She longs to be To every guy that gave his heart.
swept up into a romance, to play an irreplaceable role in a To every guy who prays that she is happy even if he is not
great adventure, to be the Beauty of the story. Those desires with her.
are far more than child’s play. They are the secret to the To every guy who is willing to wait for years just to prove
feminine heart. his love for her.
To every guy who still prioritizes God instead of making the
- Captivating girl as the sun of his life.
John & Stasi Eldredge

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PHARMACOLOGY, Pharmacology, Toxicology
Pharmacokinetics, Pharmacodynamics and
Pharmacotherapeutics
Ledo A. Torres, MD
June 16, 2010
1st shifting, Trans #1

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