PHARMACOLOGY: PRELIMINARIES
Romie Solacito, MLS3C
INTRODUCTION
 Pharmacology – the body of knowledge concerned
with action of chemical on biologic systems
 Drugs – any substances that brings about a change in
biologic function through its chemical actions
 Pharmacy – the science of Identification, selection,
preservation standardization, compounding, and
dispensing of medical substance.
 Pharmacodynamics – the study of the biological
therapeutic effects of drugs; what the drug does to
the body
 Pharmacokinetics – deals with the proper selection
and use of drugs for the prevention and treatment of
disease
 Toxicology – it’s the science of poison; substance
that cause harmful, dangerous or fatal symptoms in
living substance.
 Factors that influences proper dose of a drug:
o Age
o Pharmacogenetics
o Body Weight
o Body Surface Area
o Sex
o Pathologic State
o Tolerance
o Concomitant drug therapy
o Time and condition of administration
o Dosage form and route of administration
PHARMACOKINETICS
Route of Drug Administration
 Oral – Variable; affected by many factors
o Advantages: safest and most common,
convenient, and economical route of
administration
o Disadvantages: Limited absorption of some
drugs; food may affect absorption; patient
compliance is necessary; drugs nay be
metabolized before systemic adsorption.
 Intravenous – absorption not required
o Advantages: can have immediate effects; ideal if
dosed in large volumes; suitable for irritating
substances and complex mixtures; valuable in
emergency situations; dosage titration
permissible; ideal for high molecular weight
proteins and peptide drugs.
o Disadvantages: unsuitable for oily substances;
bolus injection may result in adverse effects;
most substances must be slowly injected; strictly
aseptic techniques needed
 Subcutaneous – depends on drug diluents: aqueous
solution – prompt; depot preparations – slow and
sustained
o Advantages: suitable for slow-release drugs;
ideal for some poorly soluble suspensions
o Disadvantages: Pain or necrosis if drug is
irritating; unsuitable for drugs administered
large volumes
 Intramuscular – depends on drug diluents: Aqueous
solution – prompt; depot preparation – slow and
sustained
o Advantages: Suitable if drug volume is
moderate; suitable for oily vehicles and certain
irritating substances; preferable to intravenous if
patient must self-administer
o Disadvantages: Affects certain lab tests (creatine
kinase); can be painful; can cause intramuscular
haemorrhage (precluded during anticoagulation
therapy)
 Transdermal/Patch – Slow and sustained
o Advantages: Bypasses the first-pass effect;
convenient and painless; ideal for drugs that are
lipophilic and have oral bioavailability; ideal for
drugs that are quickly eliminated from the body
o Disadvantages: Some patients are allergic to
patches, which can cause irritation; drug must be
highly lipophilic; may cause delayed delivery of
drug to pharmacological site of action; limited to
drugs that can be taken in small daily doses
 Rectal – Erratic and variable
o Advantages: partially bypasses first-pass effect;
bypasses destruction by stomach acid; ideal if
drug cause vomiting; ideal in patients who are
vomiting, or comatose
o Disadvantages: Drugs may irritate the rectal
mucosa; not a well-accepted route
 Inhalation – Systemic absorption may occur; this is
not always desirable
o Advantages: Absorption is rapid: can have
immediate effects; ideal for gases; effective for
patients with respiratory problems; dose can be
titrated; localized effect to target lungs: lower
doses used compared to that with oral or
parenteral administration; fewer systemic side
effects
 o Disadvantages: Most addictive route (drug can
be enter the brain quickly); patient may have
difficulty regulating dose; some patients may
have difficulty using inhalers
 Sublingual – Depends on the drugs: Few drugs (i.e.
nitroglycerin) have rapid, direct systemic adsorption;
most drugs erratically or incompletely absorbed
o Advantages: Bypasses first-pass effect; bypasses
destruction by stomach acid; drug stability
maintained because the pH of saliva relatively
neutral; may cause immediate pharmacological
effects
e. Expression of P-glycoprotein
o Disadvantages: Limited to certain types of drugs;
f. Route of administration
limited to drugs that can be taken in small doses;
may lose part of the drug dose if swallowed

Transport Processes – mechanism of drug movement

across cell membrane

1. Passive Transport/Diffusion – most dominant;

movement of particles from higher concentration to
lower concentration; non-energy requiring; factors
affecting the processes: surface area, concentration,
thickness, and diffusion coefficient (permeability) – g. Bioavailability – measure the rate and extent of
particle size and liposolubility drug entry into the systemic circulation. Two
2. Carrier-Mediated Transport – Utilize carrier proteins methods of determining Bioavailability:
features: selectivity, subject to  Cumulative Urinary Excretion
competition/inhibition and saturability. Types:  Drug Plasma Concentration: uses time data,
a. Facilitated Diffusion – along a concentrated and most commonly used
gradient h. Factors that influence bioavailability:
b. Active Transport – energy requiring
 First-pass hepatic metabolism
c. Convective Transport – solvent-drag movement
 Solubility of drug
3. Endocytosis/Picocytosis/Exocytosis – Cell drinking,
 Chemical instability
vesicle mediated, not requiring to be in aqueous
 Nature of the drug formulation
solution, energy requiring, and ADEK
2. Distribution – the process of drug movement from
Drug Pathway the systemic circulation to the different body
compartments and into the site of Action
1. Absorption – rate and extent of drug entry into the
a. Affected by two physiologic parameters
systemic circulation. Factors influencing absorption
 Cardiac output – volume pumped by the heart
a. Effects of pH on drug absorption
per minute
b. Blood flow to the absorption site
 Regional blood flow – fraction of cardinal
c. Total surface area available for absorption
output
d. Contact time at the absorption surface
b. Two distribution parameters:
 High Gastric Emptying Time, Low Gastric
 Protein binding – binding of drugs to plasma
Emptying Rate = Low Rate of Absorption
proteins and tissues
 Binding to plasma proteins
 Binding to tissues proteins
 Volume of distribution – hypothetical volume
of the body fluid necessary to dissolve a given
 dose of drug or amount of drug to a  Hepato-biliary Excretion
concentration equal to the plasma  Pulmonary Excretion
(Application: estimated loading dose)
3. Metabolism – Sites: Liver (major), intestine, blood Dose-Time Relationship
plasma (esterases), and kidneys (dihydropeptidases)  Half Life – the time taken for the concentration of
a. Exceptions: drug in the blood or plasma to decline to half of
 Prodrug – inactive drug introduce to the body original value or the amount of drug in the body to
to make active. be reduced by 50%.
 Allopurinol – Alloxanthine  Loading Dose – one or series of doses that may be
 Enalapril – Enalaprilat given at the onset of therapy with the aim of
 Chloramphenicol palmitate – achieving the target concentration rapidly.
Chloramphenicol  Maintenance Dose – the rate of drug administration
 Active metabolites is adjusted such that the rate of input equals to rate
 Benzodiazepine Diazepam – Oxazepam loss
 Toxic Metabolites
 Paracetamol – NAPQI (Hepatotoxicity)/N- PHARMADYNAMICS
acetyl-p-benzoquinone Imine General Mechanism of Drug Action
b. Objective: to make the drug polar, inactive,
 Receptor (i.e. antagonist, agonist)
excretable form
 Physical (i.e. sunblock)
c. First Pass Metabolism – initial metabolism that
 Chemical (i.e. hyperacidity)
happens before the drug reaches the systemic
 Physiological (i.e. antibiotic, dimercaprol)
circulation
d. Enzyme Inducers – stimulate expression of Receptor - Like a dynamite
metabolizing enzymes
 If drug is prodrug? efficacy and toxicity  Single Transduction:
o The drug – receptor complex
 If the parent drug is active with inactive
o Receptor State
metabolite? Efficacy
o Major Receptor Families
 If with toxic metabolite? Toxicity
A. Ligand – Gated Ion Channels (i.e cholinergic nicotinic
e. Enzyme Inhibitors – Reduce expression of
receptor)
metabolizing enzymes
B. G Protein – Coupled Receptors (i.e. Beta
f. Genetic Polymorphism – genetic differences in
adenoreceptors)
expression of enzymes
C. Enzyme – Linked Receptors (i.e. Insulin Receptors)
g. Categories for enzyme expression:
D. Intracellular Receptors (i.e. Steroid Receptors)
 Extensive Metabolizers – produce
normal/adequate amount of enzymes Dose Response Relationship
 Ultra-Rapid Metabolizers – produce more than
 Graded dose – response relations
the normal amount of enzymes
o Potency – measure of the amount of drug
 Poor Metabolizers – Produces less than the
necessary to produce an effect of a given
normal amount of enzymes
magnitude.
4. Elimination (Output) – Final loss of drug from the
o Efficacy – the magnitude of response of a drug
body; elimination = metabolism + excretion.
causes when it interacts with a receptor;
a. Minor:
dependent on the number of drug-receptor
 Gastrointestinal Excretion
complexes formed and the intrinsic activity of
 Skin – through sweat
the drug.
 Mammary Excretion
o Intrinsic Activity - its ability to activate the
b. Major:
receptor and cause a cellular response
 Renal excretion – renal excretion processes
 Filtration
 Tubular Secretion
 o NOTE: Efficacy is a more clinically useful  Enzyme induction – during metabolism is
characteristic that the drug potency, since a drug accelerated and is cause of therapeutic
with greater efficacy is more therapeutically b. failure. (i.e. of enzyme inducers:
 Effect of Drug Concentration on Receptor Binding phenobarbital, phenytoin, carbamazepine,
rifampicin, and St. John’s Wort)
Drug + Receptor = Drug Receptor Complex – Biologic
 Enzyme Inhibition – by this biotrans of drugs
effect
is delayed and is cause of increased
The Relationship of Drug Binding to Pharmacology intensity, and sometimes toxicity. (i.e.
Effect cimetidine, Flucazole, Erythromycin,
Ketoconazole, grapefruit juice.)
 The magnitude of the response is proportional o Interaction during Excretion – some drugs
to the amount of receptors bound or occupied interact with others of the site of excretion;
 The Emax occurs when all receptors are bound probenecid and penecilin interaction
 The binding of the drug to the receptor exhibits  Pharmacodynamics
no cooperativity o Drug Synergism
Intrinsic Activity  Additive Effects – equivalent to the
summation of their individual
1. Full Agonist – mimic endogenous substances; drug pharmacological action A + B = AB
binds to a receptor and produces a biological  Potentiation Effects – the net effect of
response that mimics the response to the two drugs used together is greater than
endogenous ligand. the sum of individual effects AB > A + B
2. Partial Agonist – cannot produce the same o Drug Antagonism – opposing actions of two
maximum efficacy as a full agonist drugs on the same physiological system
3. Inverse Agonist – reverse the activity of receptor, o Importance of drug antagonism
and exert the opposite pharmacological effect of  Correcting adverse effects of drugs
agonist.  Treating drug poisoning
4. Antagonists – binds to a receptor with high affinity  Predicting drug combinations which
but possess zero intrinsic activity; can decrease the reduce drug efficacy.
effect of an agonist when present by blocking the o Types of Antagonism
drug’s ability to bind to the receptor; bind allosteric  Based on bond formation:
site to change the structure  Reversible
Drug Interaction  Irreversible
 Based on surmountability:
 Drug Incompatibility – Serious loss of potency that  Competitive
occurs between an infusion fluid and a drug that is  Non-Competitive
added to it  Based on mechanism:
 Pharmaceutical – drug in compatibility – serious loss  Pharmacologic Antagonism
of potency that occurs between an infusion fluid and  Physiologic Antagonism
a drug that is added to it.  Chemical Antagonism
 Pharmacokinetics
o Interaction drug absorption – drug may interact
in the gastrointestinal tract resulting in either
decreased or increased absorption
o Interaction during distribution – a drug which is
extensively bound to plasma protein can be
displaced from its sites by another drug or
displacement from other tissue binding sites.
o Interaction during Biotransformation: