Pharmacology Preliminary Phase III

Reviewer  Involves use of the drugs in a vast

clinical market
 The study of the biological effects of
chemical FDA Approval

Clinical Pharmacology  The one who approve

 Is a branch of pharmacology that Brand Name

uses drug to treat prevent and
 Trade name by the pharmaceutical
diagnose disease
company
Sources of drugs
Generic Name
 Natural and Synthetics
 Original designation that t he drug
Phases of Drug Evaluation was given when the drug company
applied for the approval process
 Pre clinical trials
 Phase I Studies Chemical name
 Phase II Studies
 Reflects the chemical structure of
 Phase III Studies the drug
Pre Clinical Trials Phase IV
 A chemical that may have  Prescribers are obligated to report to
therapeutic value are tested on the FDA any untoward or
animals unexpected adverse effects
Phase I Studies associated with drugs they are using

Anti Viral Drug & Amantadine

 These studies are more tightly
controlled and performed by  Used to manage and treat with the
specially trained clinical investigator patient who have parkinsons
 Uses human volunteers to test the disease
drugs
Food drug and cosmetic act of 1938
Phase II
 Gave FDA the power to enforce
 It allows clinical investigators to try standards for testing drug toxicity
out the drug in patients who have and monitoring labeling
the disease
 That the drug is designed to treat
Kefauver-Harris Act of 1962 10 Rights

 Tightened control over the quality of  Right Drug

drugs  Right Patient
 Right Dose
1952: Durham-Humphrey Amendment ot
 Right Route
1938 Act
 Right Time
 This act distinguished between  Right Documentation
drugs, that can be sold with or  Right Assessment (including health
without prescription history)
 Right Health Teaching
1970: Controlled Substances Act  Right Evaluation (including drug
allergies)
 This act is designed to remedy the
 Right to Refuse
escalating problem of drug abuse,
included several provision 8 Rights
1983: Orphan Drugs  Right Patient
 Provided incentives for the  Right Drug
development of orphan drugs for  Right Storage
treatment of rare disease  Right Route
 Right Dose
Nurse Practice Act  Right Preparation
 Right Time
 In civil court, the nurse can be
 Right Recording
prosecuted for giving the wrong drug
or dosage, omitting a drug dose or
giving the drug by the wrong route

Misfeasance

 Negligence; giving the wrong drug or

dose that results in clients death

Non-feasance

 Omission; omitting a drug dose that

results in clients death

Malfeasance

 Giving the correct drug but by the

wrong route that results in the clients
death
Pharmacology Drug and
Body
Pharmacology
 The study of the effects of chemical
substances on living tissues
Pharmacokinetics
 The study of a drug’s absorption,
distribution, metabolism and
elimination.
Pharmacodynamics
 The study of the biochemical and
physiologic actions and the effects of
drugs on the human body
Pharmaceutical phase
 The stage during which a medication
enters the body and its
pharmaceutical formulation (e.g. a
tablet) and the changes into another
form to be used (e.g. the tablet is
dissolved into solution in order to be
absorbed)
Pharmacotherapeutics
 The study of the use of drug in the
treatment of disease
Dosage
 the amount, frequency, and the
number of to be administered.
Dose
 amount of drug to be administered at
one time.
Posology
 the study of the dosage or amount of
drugs given in the treatment of
disease.
Drug
 any chemical that affects the
processes of a living organism.
Medication
 a substance administered for
diagnosis, cure, treatment and relief
or prevention of disease. It is also
called a drug.
Generic Name
 the nonpropriety name of a drug
substance. Generic names are
assigned by the United States
Adopted Name Council and are the
same regardless of manufacturer.
Brand Name
 the name given to a drug by the
manufacturer. It is also called
trademark.
Plaebo
 is a substance or treatment which is
designed to have no therapeutic
value.
Pharmaeutic phase
 the first phase of drug action
Disintegration
 is the breakdown of a tablet into
smaller particles
Dissolution
 is the dissolving of the smaller
particles in the GI fluid before
absorption
Rate limiting
 is the time it takes the drug to
disintegrate and dissolve to become
availability for the body to absorb it.
Pharmacokinetic Phase
 is the process of drug movement to
achieve drug action
Passive Absorption
 movement of the drug particle from
higher concentration to lower
concentration (diffusion)
Active Absorption
 requires a carrier such as an
enzyme or protein to move the drug
against a concentration gradient.
Pinocytosis
 it is the process by which the cells
carry drug across the membrane by
engulfing the drug particles.
Hepatic first pass (first pass effect)
 the process by which the oral drug
passes to the liver first from the
intestinal lumen to be metabolized in
its inactive form before it reaches the
systemic circulation.
Biovailability
 is the percentage of the
administered drug dose that reaches
the systemic circulation:
Distribution
 is the process by which the drug
becomes available to the boy fluids
and body tissues.
Excretion or Elimation
 The main route of drug of elimination
is through the kidneys (urine).
Pharmacodynamic Phase
 is the study of drug concentration
and its effects on the body.
Primary effect – desirable
Secondary effect – desirable or
undesirable
Onset of Action
 is the time it takes to reach the
minimum effective concentration
after the drug is administered.
Peak Action
 occurs when the drug reaches its
highest blood or plasma
concentration.
Duration of Action
 is the length of time the drug has a
pharmacologic effect.
Therapeutic Index
 estimates the margin of safety. It
should be between the MEC and the
MTC.
High Therapeutic Index
 wide margin of safety
Low Therapeutic Index
 narrow margin of safety
Therapeutic Range (Therapeutic
Window)
 drug concentration in plasma should
be between the MEC to obtain
desired drug action and the MTC to
toxic effect.
Receptor Theory
 drugs act through receptors by
binding to receptor to produce a
response or to block a response.
The better the drug fits at the
receptor site, the more biologically
active the drug is. A receptor found
on the cell. membrane are protein in
structure.
Agonists
 drugs that produce a response. E.g.
Isuproterenol (Isuprel) stimulates
beta-1 and beta-2 receptors.
Antagonist
 drugs that block a response. E.g.
Ranitidine (Zantac) blocks H2
receptors.
Nonspecific drugs
 drugs that affect various sites,
specifically the cholinergic receptor
sites.
Nonselective drugs
 drugs that affect various receptors,
specifically the alpha-1, beta-1 and
beta-2 receptors.
Peak Drug Level
 is the highest plasma concentration
of a drug at a specific time.
Through Level
 is the lowest plasma concentration
of a drug and it measures the rate at
which the drug is eliminated.
Loading Dose
 a large initial dose given to achieve
a rapid MEC in the plasma.
Side Effects
 are physiologic not related to desired
drug effects. All drugs have side
effects, desirable or undesirable.
Adverse Reactions
 are more sever than side effects,
they are range of untoward effects
(unintended and occurring at normal
doses) of a drugs that cause mild to
severe side effects, including
anaphylaxis (cardiovascular
collapse). Adverse reactions are
always undesirable.
Toxic Effects
 are likely to occur from overdosing
or drug accumulation.
Cytotoxic Reactions
 From antibodies that attack the drug
on the cell leading to cell death.
Serum Sickness
 From antibodies in the blood that
causes damage to various tissues
by depositing in the blood vessels.
Delayed Allergic Reactions
 Occurs several hours after exposure
and involves antibodies bound to
WBCs.
Dermatogical Reactions
 Rash, Hives
Superinfections
 From Drugs (antibiotics) that destroy
the normal flora.
Blood Dyscracias
 From bone marrow suppression by
antibiotics and antineoplastic drugs.
Toxicity
 Unacceptable adverse effects
Liver Injury
 having the liver exposed to first-pass
effect (fever, malaise and elevated
liver enzymes)
Renal Injury
 from excretory function of the
kidneys, some drugs are excreted
unchanged leading to damage to
renal tubules
Poisoning
 overdosage of a drug damages
multiple body systems.
Anti Infectives
Bacteria
 (Prokaryotes), are single cell
organisms lacking a true nucleus
and nucleus membrane.
Types of Gram Positive Bacteria
 Streptococcus pneumonia:
 Group A streptococci
 Group B streptococci
 Enterococci:
 Staphylococcus aureus:
Types of Gram Negative Bacteria
 Haemophilus influenza:
 Neisseria gonorrhea:
 Neisseria meningitides:
 Escherichia coli:
 Kleibsiella pneumonia:
 Pseudomonas aeruginosa:
 Bacteroides fragilis:
Spirochetes
Treponema pallidum: syphilis
Borellia burgdorferi: Lyme disease
Antibacterial/Antimicrobials
 are substances that inhibit the
growth of or kill it and other
microorganisms
Anti-bacterials Mode of Action
Bacteriostatic durgs
 inhibit the growth of bacteria
(tetracyline and sulfonamides)
Bacteria drugs
 kill the bacteria (penicillins and
cephalosporins).
Inherent resistance
 example: gram-negative bacterium
Pseudomonas aeruginosa is
resistant to Penicillin G.
Acquired resistance
 is caused by prior exposure to the
antibacterial.
Nosocomial infections
 infections acquired while the patient
is hospitalized, many of these
infections are caused by drug
resistant bacteria.
Additive effect
 is equal to the sum of two antibiotics
combined.
Potentiative effect
 occurs when an antibiotic
potentiates the effect of the second
antibiotic, increasing their
effectiveness.
Prophylaxis
 Sometimes, it is clinically useful to
use anti-infectives as a means of
prophylaxis to prevent infections
before they occur.
General adverse reactions to
Antibacterial drugs
Allergy or hypersensitivity
 Mild reactions: rash, pruritus and
hives.
Superinfection
 Secondary infection that occurs
when the normal microbial flora are
disturbed during antibiotic therapy.
Organ Toxicity
 Liver and kidneys are usually
affected.
Gastrointestinal Toxicity
 Many antibiotics have direct toxic
effects on the cells lining of the GI
tract causing N/V, stomach upset or
diarrhea
Neurotoxicity
 Some anti-infectives may damage or
interfere with the function of nerve
tissue:
Streptomycin: ototoxicity
Chloroquine: optic nerve damage
Penicillin
 interferes with bacterial cell wall
synthesis by inhibiting bacterial
enzyme, transpeptidase that is
necessary for cell division and
cellular synthesis.
Cephalosporins
 are bactericidal with action similar to
penicillin.
First Generation Cephalosporins
 effective against gram-positive
bacteria: streptococci and most
staphylococci, and gram-negative
bacteria: E. coli, Kleibsiella, Proteus,
Salmonella and Shigella.
cefazolin sodium (Ancef)
cephalexin (Keflex)
cephradine (Velosef)
Second Generation Cephalosporins
 has broader spectrum against other
gram-negative bacteria: H. influenza,
N. gonorrhea, N. meningitides,
Enterobacter.
cefaclor (Ceclor)
cefuroxime (Zinacef)
cefoxitin sodium (Mefoxin)
Third Generation Cephalosporins
 same effectiveness as 1st and 2nd
generations. Effective against gram-
negative bacteria: Pseudomonas
aeruginosa, Serratia pecies,
Acinetobacter. Less effective against
gram-positive bacteria.
ceftiaxone (Rocephin)
cefixime (Suprax)
ceftazidime (Tazicef)
Fourth Generation Cephalosporins
 similar to the 3rd generation.
Effective against: E. coli, Kleibsiella,
Proteus, Streptococci, Staphylococci
and P. aeruginosa.
cefepime (Maxipime)
Ceftaroline (Teflaro)
 shows promise in treating MRSA
and VRSA
MRSA – methicillin resistant staphylococcus
aureus
VRSA – vancomycin resistant
staphylococcus aureus
Most common S/E is GI
Pseudomembranous colitis
MRSA Infection
 including MRSA, appear as a bump
or infected area on the skin that
might be: red, swollen, painful, warm
to the touch, full of pus or other
drainage accompanied by a fever
Beta-Lactam Antibiotics
 Drug action of beta-lactam
antibiotics is the same as with
penicillin and cephalosporins.
 Beta-lactam antibiotics prevent the
formation of a new, intact cell wall
thus are most effective against
actively multiplying bacteria.
Beta-Lactamase Inhibitors
 when a broad-spectrum antibiotic
(e.g. amoxicillin) is combined with a
beta-lactamase inhibitor (e.g.
clavulanic acid), thus a new drug is
formed: amoxicillin-clavulanic acid
(Augmentin): inhibits the bacterial
beta-lactamases thus making the
antibiotic more effective and
extending its antimicrobial effect.
For oral use: amoxicillin-clavulanic acid
(Augmentin)
For parenteral use:
Ampicillin-sulbactam (Unasyn)
Piperacillin-tazobactam (Zosyn)
Ticarcillin-clavulanic acid (Timentin)
Other Beta-Lactam Antibiotics:
Aztreonam (Azactam)
Meropenem (Merren)
Imipenem-cilastin (Primaxin)
Macrolides
 are produced by a species of soil
organisms called streptomycetes.
 The antibiotics derived from these
large molecules bind to bacterial
ribosomes and thus prevent
bacterial protein synthesis.
Pharmacokinetic
 Erythromycin is sensitive to acid and
therefore maybe extensively
degraded in the stomach.
Adverse Reactions
 Abdominal discomforts and
cramping (because erythromycin
probably acts as an agonist for
motilin receptors in the stomach,
which increases strength of
contraction of muscles.
Lincosamides
 Like erythromycin, lincosamides
inhibit bacterial protein synthesis
and have both bacteriostatic and
bactericidal actions, depending on
the drug dosage.
FLUOROQUINOLONES
 Action: interfere with DNA replication
in bacteria by inhibiting enzyme DNA
gyrase, which is needed to
synthesize bacterial DNA.
TETRACYCLINES
 Block the bacterial growth by
preventing ribosomes from binding
messenger RNA, thereby preventing
the start of protein synthesis.
CHLORAMPHENICOL
 It is a very simple synthetic molecule
that inhibits the late steps in
bacterial protein synthesis.
AMINOGLYCOSIDES
 Inhibit early steps in bacterial protein
synthesis by binding to bacterial
ribosomes. Bactericidal.
SULFONAMIDES
 are one of the oldest antibacterial
agents used to treat infections.
ANTIMYCOBACTERIAL AGENTS
 resists the acids and enzymes that
usually destroy bacteria within the
macrophages.
Isoniazed (Isotamine)
 inhibits mycolic acids involved in cell
wall synthesis and blocks pyridoxine
(Vit. B6) use in a number of
intracellular enzymes. (Bactericidal)
Rifampin (Rifadin)
 inhibit DNA-dependent RNA
polymerase in sensitive organisms.
(Bactericidal effect)
pyrazinamide (Tebrazid)
 bacteriostatic or bactericidal,
depending on the site of infection
and the strain of mycobacteria.
ethambutol (Myambutol)
 bacteriostatic, most effective against
actively dividing mycobacteria, but
the precise antibacterial action is
unknown.
Streptomycin
 inhibits protein synthesis in sensitive
bacteria and in mycobacteria.
Resistance develops quickly when
the drug is used alone.
Dapson
 hemolytic anemia: symptoms:
cyanosis, shortness of breath, bluish
discoloration of the fingernails or
lips, anorexia, paleness, unusual
fatigue and weakness.
Clofazinime
 strong reddish or brownish
discoloration of body fluids.
Diarrhea, loss of appetite, nausea
and vomiting, rashes.
Dapson - CNS: headache, insomnia,
restlessness.
Carbapenems
 Inhibit cell membrane synthesis.
Oxazolidinoses
 interferes with protein synthesis on
the bacterial ribosome
Glycycyclines
 chemically-related to tetracyclines,
binds to 30s ribosomes preventing
bacterial synthesis.
Ketolides
 chemically-related to macrolide,
prevents protein synthesis.
Anti-Viral Drugs
Acute Viral Infections
 These infections often resolve
quickly and leave no latent infections
or sequelae (e.g. common colds,
influenza and Hepatitis A.)
Chronic Viral Infections
 The disease runs in a protracted
course with long periods of
  remissions and interspersed with
reappearance of a disease.
(Example: herpes infections,
Hepatitis B and hepatitis C)
Virus are acellular
 not composed of cells.
Anti-Viral Drug for HIV
 a virus that attacks specific cells but
produces a syndrome that affects
the entire body.
Reverse transcriptase (RT)
 is a viral enzyme allows this single
strand of RNA to be converted into
complementary DNA (cDNA) that is
then integrated into the host genome
by the viral enzyme called integrase.
Intergrase enzymes
 splices viral DNA into host cell DNA,
allowing entry to the cd4 nucleus,
creating pro-virus.
HIV protease
 is required to allow the viruses
released from the host cell to mature
and infect a new cell and form new
viruses.
Nucleoside Reverse Transcriptase
Inhibitors
 inhibit the action of viral reverse
transcriptase thus preventing the
synthesis of DNA and allowing the
T4 lymphocytes to increase initially.
Lactic acidosis
 (extreme weakness or tiredness;
unusual muscle pain; difficulty
breathing; stomach pain with nausea
and vomiting; feeling cold, especially
in the arms and legs)
Peripheral neuropathy:
 tingling or aching in the legs,
diminished reflexes.
Neurotoxicity:
 anxiety, headache, irritability and
sleeplessness
Non-nucleoside Reverse Transcriptase
Inhibitor
 These drug is not competitive
inhibitors of HIV RT and bind at a
different site than that occupied by
nucleoside RT inhibitors. NNRTIs
can have additive or synergistic
effects when used in combination
with nucleoside RT inhibitors as well
as protease inhibitors.
Protease Inhibitors
 Bind to the active site of HIV
protease, preventing the natural
substrate from binding. As a result,
the protease fails to separate the
HIV precursor protein into the active
enzymes the virus needs to mature
fully.
Integrase Inhibitors
 Inhibit the activity of virus-specific
enzyme integrase, needed for viral
replication.
ANTI-VIRAL DRUG FOR SYSTEMIC Anti-Fungal Drugs (Anti-
VIRAL DISEASES Mycotic)
acyclovir (Zovirax) MOA of Anti-Fungal Agents
famciclovir (Famvir) Polyene anti-fungal drug
valacyclovir (Valtrex)  target the cell wall/membrane of the
fungi.
Action: Inhibits viral cell replication.
Azole anti-fungal drug
Alfa Interferons for Systemic Viral

Diseases  inhibit the synthesis of ergosterol

 Interferons inhibit virus replication in
infected cells and in general inhibit
cell proliferation.
Amantadines for Influenza
 Amantadines block early phases of
viral replication, but the exact
mechanism is unclear.
Anti-Hepatitis B Agents
 Inhibits reverse transcriptase in
hepatitis B virus leading to
decreased DNA Chain termination
needed for cellular wall/membrane.
Newest Anti-fungal Drug:
 inhibit the enzyme glucan
synthetase, which is involved in
synthesis of fungal cell walls.
Griseofulvin
 interferes with fungal cell mitosis.
Anti-fungal drugs are used to treat 2
types of fungal infections:
Superficial fungal infections of the skin or

Adefovir (Hepsera) mucous membrane:

Entecavir (Baraclude) tinea pedis (athlete’s foot),

S/E: GI discomfort, Hepatoxicity tinea cruris (jock itch),

Anti-Hepatitis C tinea corporis (ring worm),

Boceprevir (Victrelis) tinea capitis (ring worm of the scalp)

Simeprevir (Olysio)
Systemic fungal infections
Histoplasmosis
 is associated with soil contaminated
with chicken or bat guano.
Cryptococcosis
 may result from exposure to high
concentrations of pigeon droppings.
Cyrptococcus neoforman
 which may cause meningitis,
pulmonary disease and infections at
many other sites.
Candida species (yeast),
 are part of the normal flora of the
mouth, skin, intestine and vagina.
Candidiasis might occur as an
opportunistic infection when the
body’s defense mechanism are
impaired allowing for the overgrowth
of the fungus.
ANTI-FUNGAL: AZOLES
fluconazole (Diflucan)
itraconazole (Sporanox)
ketoconazole (Nizoral)
ACTION: Azole anti-fungal drug inhibit the
synthesis of ergosterol in the fungal cell
wall.
ADVERSE REACTION:
Ketoconazole:
 nausea, pruritus, dizziness,
nervousness, and headache;
hepatotoxicity
Fluconazole:
 nausea or diarrhea, headaches,
thrombocytopenia (unusual bleeding
and bruising) and hepatotoxicity.
Rarely, Steven- Johnson syndrome
or exfoliative skin disorders.
Itraconazole:
 less hepatotoxicity than
ketoconazole
ANTI-FUNGAL DRUG: Echinocandin
(NEW DRUG)
Caspofungin (Cancidas)
 is a new drug that inhibits an
enzyme called glucan synthase,
which plays a key role in forming the
fungal cell wall. When this enzyme is
inhibited, cell wall synthesis is
impaired, leading to damage of the
fungal cell.
Anti-Protozoal &
Anthelmintic Drugs
Malaria
 Is a serious protozoal infectious
disease transmitted by the bite of
Anopheles mosquitoes that are
infected with one of the four species
of Plasmodium that produce human
disease:
After the mosquito infects human, the

protozoan parasites undergo 2 phases:

Tissue phase

 produces no clinical symptoms in the

human

Erythrocytic phase

 invasion of the red blood cells

causes symptoms of chills, fever,
and sweating.

The incubation period is 10-35 days,

followed by flu-like symptoms.