Download Rating Definition

Ch 38: Introduction to
Equivalence
O Many different types of equivalence
O Two drugs may be equivalent in one category, but not
in another
© 2013-2015
Types of Equivalence
O Pharmaceutical Equivalents
O same active ingredients
O same strength
O same dosage form
O same route of administration
O may have different inactive ingredients
O may have different release mechanisms
© 2013-2015
Types of Equivalence
O Pharmaceutical Equivalent Example
O Procardia XL vs. Adalat CC
O All the similarities required but uses a different
release mechanism
© 2013-2015
Types of Equivalence
O Pharmaceutical Alternatives
O same drug moiety
O anything else may be different
O different salts or esters
O different strength
O different dosage forms
Pharmaceutical Alternatives are substitutes for treating
a specific condition, but they are NOT equivalent
© 2013-2015
Bioavailability
O Bioavailability is a measure of the rate and extent to
which the active ingredient is absorbed from a
dosage form
O For drugs that are not absorbed into the blood
stream, bioavailability is a measurement of the rate
and extent to which the active ingredient becomes
available at the intended site of action
© 2013-2015
Types of Equivalence
O Bioequivalent Drug Products
O must be Pharmaceutical Equivalents or
Pharmaceutical Alternatives, AND
O must have comparable bioavailability
O The Rate and Extent of Absorption must have no
significant differences
© 2013-2015
Types of Equivalence
O Therapeutic Equivalents
O must be pharmaceutical equivalents, AND
O must be bioequivalent
O With generic drug product selection and substitution
in the pharmacy we are concerned with therapeutic
equivalents
© 2013-2015
The Bioequivalence Study
O Used to determine if a second drug is bioequivalent
to a standard product
O Usual study includes 24 to 36 normal healthy
subjects
O A single dose of the standard drug is given and blood
levels are measured
O Then the test is repeated using the applicant drug
product
© 2013-2015
The Bioequivalence Study
O Two drugs are considered to be bioequivalent if the
results of the two samples vary by no more than
-20% /+25%
O Applicant drugs that test within less than 20% of the
standard to 25% over the standard are considered to
be bioequivalent
O For most drugs, that difference is considered to be
clinically insignificant
© 2013-2015
Therapeutic Equivalence
Rating
O In an effort to make order of bioequivalence studies,
the FDA has assumed the responsibility of
maintaining a reference of the results
O The “Orange Book”
O Approved Drug Products with Therapeutic Equivalence
Evaluations
O Uses a series of two letters to indicate equivalence
© 2013-2015
Bioequivalence Ratings
Rating
AA
AB
AN
AT
Definition
Drugs which are considered NOT to have
potential bioavailability problems – No testing
Drugs that have been shown to be
bioequivalent through testing
Equivalent solutions and powders for
aerosolization
Equivalent topical products
© 2013-2015
Bioequivalence Ratings
Rating
BC
BD
BN
BT
Definition
Non-equivalence due to PRESUMED
difference in extended release dosage
forms – No Testing
Drugs that have been shown NOT to be
bioequivalent through testing
Non-Equivalent solutions and powders for
aerosolization
Non-Equivalent topical products
© 2013-2015
DESI Drugs
O Remember that effectiveness was not a requirement
of drug approval until the 1962 Kefauver- Harris
Amendment
O The Drug Efficacy Study Implementation (DESI)
looked at 3,000 drugs approved between 1938 and
1962 and tested them for effectiveness
O Classified drugs according to their effectiveness
© 2013-2015
DESI Drugs
O When we speak of a “DESI” drug in the pharmacy, we
are referring to drugs which were found to be either
ineffective or less than effective under this study
O Insurance plans usually refuse to reimburse for DESI
drugs, for obvious reasons
© 2013-2015
Ch 39: Organ System Review
O Skin
O Circulatory System
O Gastro-Intestinal System
O Respiratory System
O Excretory System
© 2013-2015
The Skin
O Largest organ of the body
O Protects us from temperature
and bacteria
O Composed of several layers
O Epidermis
O Dermis
O Subcutaneous Layer
© 2013-2015
The Circulatory System
O Carries drugs throughout the
O
O
O
O
body
Heart
Arteries
Veins
Capillaries
© 2013-2015
Parts of Blood
O Red Blood Cells
O carry gases (O2 / CO2)
O White Blood Cells
O Clean up crew of the body
O Platelets
O Used in clotting process
O Bunch together to form clots
© 2013-2015
Anatomy of the Heart
O Right side –
not oxygenated
O Left side –
oxygenated
© 2013-2015
Gastro-Intestinal System
O Converts food
O Absorbs nutrients
O Replenishes water
O Removes waste
O Parenteral vs. Enternal
© 2013-2015
Nervous System
O Central Nervous System
O Brain and spinal cord
O Peripheral Nervous System
O Outward from the spinal cord
O Somatic nerves
O Sensory info in
O Out to skeletal muscle
O Autonomic nerves
O To smooth muscle
© 2013-2015
Respiratory System
O Structures
O Mechanics
O Gas Exchange
© 2013-2015
The Excretory System
O Removes Waste Products
O Regulates Fluid Retention
© 2013-2015
The Kidney
O Controls the amount of fluid
retained in the body
O Removal of waste products
© 2013-2015
Ch 40: Disease States
O Pathophysiology
O the study of the effect of a disease on normal
body functions
O “Treatment” vs. “Cure”
O a treatment causes the body function to normalize
while the underlying disease is still present
O a cure means the underlying disease is no longer
present
© 2013-2015
Risk Factors
O Many disease states are found to be more
common in individuals with certain:
O
O
O
O
habits
conditions
genetic make-up, or
traits
O These are called “Risk Factors” for the disease
© 2013-2015
Risk Factors
O Risk Factors may be controllable or uncontrollable
O What about:
- weight (obesity) ?
- gender ?
- race ?
- high cholesterol ?
- age ?
- smoking ?
- high blood pressure ?
- lack of exercise ?
© 2013-2015
Chronic Disease States &
Associated Risk Factors
O Two-thirds of all deaths in the United States are
caused by five diseases:
O Heart Disease
O Cancer
O Stroke
O Chronic Obstructive Pulmonary Disease
O Diabetes
© 2013-2015
Coronary Artery Disease
(CAD)
O Affects the arteries supplying the heart with
oxygenated blood
O CAD is caused by a constriction of these vessels by
deposits of fat, cholesterol, and plaques
O Results in a decrease in the supply of oxygen and
nutrients to the muscle tissues of the heart
© 2013-2015
Angina Pectoris
O One of the major signs of reduced oxygen delivery
O Pain that is predominantly located in the chest
and/or arm
O If the oxygen flow is not resumed in a short period of
time, death of heart tissue can occur (aka.
myocardial infarction)
© 2013-2015
Stroke
O Since the risk factors are essentially the same, CAD
and stroke are often spoken of together
O Strokes are also caused by an inadequate supply of
oxygen – this time, to the brain
O Can be caused by a blockage (~80%) or the rupture of
a blood vessel (~20%)
© 2013-2015
Risk Factors for CAD &
Stroke
O Major Risk Factors
O High blood pressure
O High blood cholesterol
O Other Risk Factors
O Diabetes
O Tobacco use
O Excess weight
O Lack of exercise
© 2013-2015
Chronic Obstructive
Pulmonary Disease (COPD)
O Covers multiple disease processes:
O chronic bronchitis
O chronic obstructive bronchitis
O emphysema
O All can cause progressive and often irreversible
damage to the lungs
We will concentrate on emphysema
© 2013-2015
Emphysema
O Irreversible destruction of the alveoli in the lungs
O Causes a loss of lung efficiency and a decrease in
the gas exchange
O Eventually causes gasping and straining for every
breathe
O Leaves the patient at risk for other diseases
O Asthma
O Pneumonia
O Bronchitis
© 2013-2015
Risk Factor for Emphysema
80% is caused by
Cigarette Smoking!
The only hope is to quit smoking before
the damage becomes too great
© 2013-2015
Diabetes
O Affects the proper use and storage of glucose in the
body
O Often develops without any tell-tale signs
O There are two types of diabetes
© 2013-2015
Normal Glucose Reaction
O Increased blood glucose level (after a meal)
O Body signals special cells in the pancreas
O Insulin is released into the bloodstream
O Insulin signals the cells to open special channels in
the cell wall for glucose entry
O Lowers blood glucose level to the normal level
© 2013-2015
Type 1 Diabetes
(~10%)
O In Type 1 diabetes, little or no insulin is produced by
the cells in the pancreas
O When the body triggers insulin release, there is not
enough for the desired effect
O Treatment – inject additional insulin into the body
© 2013-2015
Type 2 Diabetes
(~90%)
O With Type 2 diabetes, either there is not enough
insulin produced or the receptors where the insulin
works are not functioning adequately and the
glucose channel in the cells do not get opened
O Usual Treatment – oral medications that stimulate
additional release of insulin or increase receptor
sensitivity
© 2013-2015
Risk Factors for Diabetes
O Family History
O higher if close family member has diabetes
O Weight
O about 80% of Type 2 are over weight
O Inactivity
O the less you exercise, the greater the risk
O Age
O after 45 y/o the risk of Type 2 increases greatly
O Race
O Type 1 is higher in Caucasian, Europeans
O Type 2 is higher in African Americans, Hispanics, and
American Indians
© 2013-2015
Ch 41: Introduction to
Pharmacology
O In this session we will look at how drugs exert their
effect on the body and some of the most common
drug classes used today
O While it is impossible to cover a full semester
pharmacology class in this program, we will highlight
the important facts on these medications
O First, some definitions…
© 2013-2015
“Pharmacology”
O The fancy definition
O the study of substances that interact with living
systems through a chemical process, by binding to
regulatory molecules which activate or inhibit a normal
body process
O The short definition
O the study of the drug’s actions on the body
© 2013-2015
“Toxicology”
O The branch of pharmacology that deals with the
undesirable effects of drugs
© 2013-2015
“Drug”
O Chemicals that are administered to achieve a
beneficial therapeutic effect on some process within
the patient, or for their toxic effect on a parasite
within the patient
© 2013-2015
“Receptor Site”
O The spot where the drug binds to have it’s effect
© 2013-2015
“Bond”
O The manner in which two chemicals adhere to each
other
O May be very weak to very strong
© 2013-2015
“Agonist”
O A drug that causes a biological action to occur
© 2013-2015
“Antagonist”
O A drug that blocks a naturally occurring body
chemical from reaching its receptor site
O It stops the natural chemical from initiating a body
response
© 2013-2015
“Dose”
O The amount of drug administered
© 2013-2015
“Potency”
O Concerns the amount
of drug necessary to
produce the desired
effect
O The more drug needed,
the lower the potency
and vice versa
Relative Potency
© 2013-2015
“Maximal Efficacy”
O The maximum
response possible
from a drug
O A point where giving
more drug does not
increase the desired
effect further
© 2013-2015
How Drugs Work
O Physical Properties of the Drug
O Bonding to Receptors
O Drug Action at the Receptors
O Dosage and Potency
© 2013-2015
Physical Properties of the
Drug
In order to be biologically active, a
drug must have:
O the right chemical structure and
size
O the correct chemical bond
activity
O the correct shape
THINK OF THE DRUG AND RECEPTOR AS A LOCK AND KEY
© 2013-2015
Correct Chemical Structure &
Size
O The drug must have a part of itself that fits into the
receptor site exactly
O The rest of the drug molecule can have effects on
how easily the drug can bond with the receptor
© 2013-2015
Correct Bonding Properties
O Must bond in the right manner
O not too strong or too weak of a bond
O Covalent Bonds
O strong bonds
O may even be irreversible
O Electrostatic Bonds
O can be very weak as in van der Waal’s forces
O or stronger as in ionic bonds
© 2013-2015
Drug Actions at the
Receptor
O Agonist
O “turns on” the action at the receptor
O causes a body action to occur
O Antagonist
O “turns off” the action at the receptor
O stops a normal body chemical from binding to the
receptor
O can be “competitive” or “non-competitive”
© 2013-2015
Competitive Antagonists
O The effect is temporary and
lasts only as long as the drug
is bound to the receptor
O The concentration of the drug
is a major determinant of the
action of the drug
O A good example is the child’s
game “musical chairs”
© 2013-2015
Non-Competitive
Antagonists
O aka, Irreversible Antagonists
O The drug binds permanently to the receptor
O The action continues even after the blood levels of
drug are insignificant
O The effect will last until the cell makes a new
receptor site
© 2013-2015
Pharmacological Classes of
Medication
O Drugs can be classified by where their effects take
place, by their mechanism or action, or by their
chemical structure
O Most times their chemical structure will give us clues
as to their location and mechanism of action
© 2013-2015
Ch 42: Drugs Used in Cardiac
Conditions
O Hypertension
O Angina
O Heart Failure
O Hyperlipidemia
O Blood Clotting Disorders
© 2013-2015
Hypertension Overview
O Blood pressure readings are a series of two numbers
(ie, 120/80)
O Systolic blood pressure
O the highest pressure achieved
O occurs when the heart finishes the ventricular
contraction
O Diastolic blood pressure
O the lowest pressure
O occurs right before the heart begins its contraction
© 2013-2015
Hypertension Overview
O Remember blood pressure is a dynamic value
O You can not make decisions based on a single blood
pressure reading
O Blood pressure treatment should be initiated or
modified in response to a series of blood pressure
checks
© 2013-2015
Complications of
Hypertension
O Stroke
O Heart disease
O Heart attack
O Kidney damage
O Other problems
Symptoms often present themselves only after
damage has occurred, leading to hypertension being
called the “Silent Killer”
© 2013-2015
How can we treat HTN?
O Think in terms of plumbing
O lessen the force of the
“pump”
O lower the amount of fluid in
the system
O increase the diameter of the
“pipes”
© 2013-2015
Diuretics
O Mechanism of Action (MOA) – Decrease re-
absorption of sodium and potassium causing more
fluid to be eliminated by the kidneys. Initially they
lower the volume of fluid in the blood vessels. Over
the long term other mechanisms are involved.
O Three main types:
O thiazides
O loop
O potassium sparing
O Major side effect – potassium depletion
© 2013-2015
Thiazide Diuretics
O Place of Action – distal tubule of the kidney
O Common thiazide diuretics
O hydrochlorothiazide
O indapamide
O metolazone
O chlorthalidone
© 2013-2015
Loop Diuretics
O Place of Action – Loop of Henley in the kidney
O Common loop diuretics
O furosemide
O bumetanide
O torsemide
LOOP SPECIFIC SIDE EFFECT – Ototoxicity at
high doses
© 2013-2015
Beta Adrenergic Blockers
O MOA – Decrease the rate and force of the
heartbeat by blocking the messages the body
sends to the heart
O Problem with Beta Blockers – there are beta
receptors in other areas of the body
O Who should not receive beta blockers?
O Asthmatics – blocks beta receptors in the
lungs
O Diabetics - blocks the tell-tale signs of
hypoglycemia
© 2013-2015
Beta Adrenergic Blockers
O Non-specific
O propranolol
O nadolol
O pindolol
O Beta 1 specific
O atenolol
O metoprolol
O bisoprolol
O sotalol
Note the “–olol” suffix
© 2013-2015
The Renin-Angiotensin System
O One of the body’s systems that constricts blood
vessels when activated
Angiotensin I  Angiotensin II  Receptor Binding
Angiotensin I is not a potent vasoconstrictor
O Angiotensin I is converted to angiotensin II by Angiotensin
Converting Enzyme (ACE)
Angiotensin II IS a potent vasoconstrictor if allowed to
bind to it’s receptors
© 2013-2015
ACE Iinhibitors
Angiotensin IX
 Angiotensin II  Receptor Binding
O Blocks the conversion of angiotensin I 
angiotensin II
O Major side effect – cough
O Who should never receive ACE Inhibitors?
O Pregnant women
ACE inhibitors cause serious injury or death to the
fetus
© 2013-2015
ACE Inhibitors
O Common ACE inhibitors
O lisinopril
O captopril
O enalapril
O ramipril
O fosinopril
O benazepril
Note the “–pril” suffix
© 2013-2015
Angiotensin Receptor Blockers
X
Angiotensin I  Angiotensin II  Receptor Binding
O Block the binding of Angiotensin II to its receptor
O Can be denoted both as ARB (Angiotensin
Receptor Blocker) or ARA (Angiotensin Receptor
Antagonist)
O No side effect of cough
O Same contraindication with pregnant women
© 2013-2015
Common ARB’s
O Common ARA’s
O losartan
O valsartan
O candesartan
O eprosartan
O telmisartan
O irbesartan
Note the “–sartan” suffix
© 2013-2015
Calcium Channel Blockers
O In order for muscle fibers to contract, there must be
a flow of calcium into and out of the cells
O There are special “channels” where this flow occurs
O Calcium channel blockers block these channels
© 2013-2015
Calcium Channel Blockers
O MOA #1 – Blocks the flow of calcium into vascular
smooth muscle (blood vessels)
O MOA #2 – Decreases the force of the heartbeat by
decreasing the transmission of electrical impulses on
the heart muscle
Different calcium channel blockers vary in their
ability to accomplish MOA #1 and #2
© 2013-2015
Calcium Channel Blockers
O Common Calcium Channel Blockers
O
O
O
O
O
O
O
verapamil
diltiazem
nifedipine
amlodipine
isradipine
felodipine
nicardipine
Note the “–dipine” suffix on several
© 2013-2015
Alpha Adrenergic Blockers
O MOA – Block alpha receptors on vascular smooth
muscle that induce vasoconstriction
O Concern with alpha blocker – Prazosin  First Dose
Syncope
© 2013-2015
Alpha Adrenergic Blockers
O Common Alpha Blockers
O prazosin
O terazosin
O doxazosin
Note the “–azosin” suffix
© 2013-2015
Angina
O Chest pain- “crushing feeling on the chest” caused by
lack of oxygen to the heart muscle
O Caused by a disruption in the blood flow of the heart
O Treatment efforts directed at restoring the blood flow
and accompanying oxygen
O Three main classes of anti-anginal drugs
O nitrates
O beta blockers
O calcium channel blockers
© 2013-2015
Nitrates
O Available in topical patches, ointment, oral tablets,
and sublingual tablets
O Sublingual NTG is used to treat acute chest pain
O Other forms are used to prevent chest pain
O Important considerations with sublingual NTG:
O Should be kept in their glass bottle or an approved
container – never in prescription bottles
O Should be kept out of excessive heat
O Dissolved under the tongue
O Usual dose is 1 at onset of pain, then one every 5
minutes if pain persists. If no relief after 3 tabs 
© 2013-2015
GET TO ER!
Heart Failure
O Condition where the heart can no longer pump a
sufficient amount of blood to the body
O Commonly called Congestive Heart Failure (CHF)
O Inotropic Medications are used in conjunction with
some of the previous drug classes we have already
covered
O Common inotropic drugs:
O digoxin
O dobutamine
© 2013-2015
Hyperlipidemia
O Condition of abnormally high cholesterol and/or
triglyceride levels in the body
O Aim is to decrease the lipids in the bloodstream
O Common Drugs Classes
O bile acid sequestrants
O niacin
O fibric acid derivatives
O HMG-Co A reductase inhibitors (statins)
© 2013-2015
Blood Clotting Disorders
O Clots may form in blood vessels throughout the body, depleting
tissues of necessary oxygen and nutrients
O Clots may even break off from their original location and travel
to a vessel that they can no longer pass through (stroke or
pulmonary embolism)
O Anticoagulants work in two ways
O Work in the liver to prevent the formation of clotting factors that
are necessary in the formation of the clot
O By directly affecting clot formation and expansion
O Common Anticoagulant Drugs
O heparin
O warfarin
O rivaroxban
O apixaban
O dabigatran
© 2013-2015
Questions?
© 2013-2015
Assignments Due Next
Week
O Class Eight Homework Worksheet
O Study Drug Flash Cards # 141-160
NEXT WEEK IS OUR THIRD SECTION TEST!
Covers Chapters 33 thru 39
NO MATH QUESTIONS
© 2013-2015
Math Test Number Two
15 Questions
45 Minute Time Limit
No Talking Please!
© 2013-2015