PHARMACOLOGY IN
REHABILITATION
Ciccone | PT 652
I. BASIC PRINCIPLES IN PHARMACOLOGY o Gov. agency that oversees testing
1.1 Drug Names
and approval
A drug is any substance that can be put into
o Responsible for drug class
the human body in concentration to alter
physiological function. Phases of Drug Testing
Pharmacotherapeutics Stage 1: Pre-clinical trials
o Consideration of pharmacology in o Lasts 1-2 years
terms of therapeutic aspects of a o Animal tests
chemical substance
Stage 2: Clinical Trial
Pharmacodynamics
o Phase 1: healthy volunteers to
o Indicates what the drug does to the
assess side effects; lasts < 1 year
body
o Phase 2: small patient sample (200-
How does it decrease pain?
300 patients) with the condition that
How does it lower BP?
the drug treats; lasts for 2 years
How does it improve motor
o Phase 3: large sample (2000-3000
function
patients), determines drug safety;
o Pharmacokinetics
lasts 3 years
What the body does to the
Stage 3: approved for marketing (for
drug
general public)
Absorption
o Phase 4: post marketing surveillance
Metabolized
Market studies
Excreted
Questionnaires
Every drug can be identified by 3 names
Surveys
o Chemical name
o Generic name – marketed as
Expedited review
generic after patent expires; drug
o A drug company can request for an
patent has finite life, once expired
expedited review if the drug has
other companies can market under
exceptional need or beneficial
the generic name
effects
Generics are equivalent if:
o May save time but drug testing must
They have the same
continue after approval
type and amount of
o Drawbacks:
active ingredient
Drug use in general
Have the same mode
population before trials are
of administration
complete
Have the same
Drug testing must continue
therapeutic effects
o Trade name
Orphan Drugs
Certain drugs are indicated for a relatively
1.2 Drug Approval & Classification
small population (e.g. <200,000 people in
FDA – responsible for approving drugs and
the USA)
marketing to the public
DAWN LAVONNE P. HASSLER PTRP, DPT, RPT | 1
, FDA arranges funding from additional Response increases as dose increases up
sources to subsidize drug development until the response plateaus, this is called
Since 1983, >300 orphan drugs approved “maximal efficacy” OR “ceiling effect”
for >80 rare diseases Dose response curve
Implications for Drug Testing Drug Potency
Drug costs Is related to the dose that causes a specific
Availability in USA vs other countries response in a specific magnitude
Failure to identify serious side effects When comparing 2 drugs, the drug that
o Testing on only 2000-3000subjects causes the response at a lower dose is said
o Side effect frequency can be low to be more potent
Potency is often misinterpreted as more
Black Box Warning “effective”
FDA’s highest warning
Was added to opioids and benzodiazepines Quantal (Cumulative) D-R Curve
regarding risk with associated use Determines dose that causes a specific
May result in profound sedation, coma, and response in a group (sample) of subject
death Used to determine dug safety
NOTE: some drugs may begin as OTC and migrate Median Effective Dose (ED50)
to prescription drugs and vice versa Dose that causes beneficial effect in half the
OTC drugs are often consumed sample
indiscriminately
Median Toxic Dose
Consumers believe that OTC products
Dose that causes toxic effect in half the
cannot have adverse effects
sample
In animal studies, also referred to as lethal
Off Label Prescribing
Prescription of a drug for a purpose not dose (LD50) where half of test animal
approved by the FDA population dies
Off brand AKA label prescribing is legal for
Therapeutic Index
physicians
TI = TD50/ED50
o The FDA cannot dictate how
The higher the TI the SAFER the drug
physicians practice medicine
Off brand process: 1.4 Pharmacokinetics
o Drug is approved for condition A A = absorption
o Find that it may be effective for D = distribution
condition B, C, D M = metabolism
o Testing by independent institutions E = excretion
for efficacy
o RCT Absorption
Off label prescribing may constitute 40-60% Drugs must typically move from site of
of ALL prescriptions administration into another tissue or central
compartment (blood stream)
1.3 Basic Concepts in Drug Therapy & Safety Absorption is related directly to the route of
Dose Response Relationship administration
No response if dose is too lo Routes of administration
Response starts to appear at a “threshold o Enteral (alimentary canal) – easy to
dose” do, less predictable absorption
2
, Oral If Vd is << 42, the drug is being retained by
Lingual the plasma
Sublingual If Vd is >> 42, the drug is being retained in
Buccal the tissue
Rectal
o Parenteral – more difficult, more Drug Storage
predictable Distribution to certain sites results in drug
All forms of injection accumulation/storage
Inhalation Primary storage sites:
Topical o Fat
Transdermal o Muscle
o Kidneys
Absorption & Bioavailability o Bone
Bioavailability is the percent of administered o Liver
dose that appears in the bloodstream o Etc.
o Example: if 100 mg taken orally and
Primary problems:
50 mg appear in the bloodstream, o Local tissue damage
this dug is 50% bioavailable
o Redistribution – “leaks”
This is only applicable to drugs taken orally
or via transdermal patch Metabolism
Active form of drug is changed chemically to
Absorption & the First Pass Effect
an inactive or less active by product or
If a drug is administered orally
metabolite
Absorbed from GIT goes to liver via hepatic
Often creates a more polar water-soluble
portal vein
metabolite that can by kidneys
Some of the drug is often destroyed during
o Non-polar drugs are much more
this “first pass” through the liver
difficult to excrete and are usually
First pass effect can be extensive drugs (ex:
reabsorbed into the body
nitroglycerin)
Also referred to as biotransformation
It is important to know the percentage of a
Primary site of metabolism = LIVER
drug that will not survive the first pass effect
o Other sites:
Distribution Lungs
Drugs typically cross membranes and Kidneys
tissues to reach a target site GIT
Distribution is affected by the following: Skin
o Administration route Enzymes metabolize drug via:
o Psychochemical properties of the o Phase I reactions – oxidation (most
drug binding to plasma proteins common), reduction, hydrolysis
o Various “barriers” and “carriers” o Phase II reactions – conjugation
(adds a second molecule to phase I
Volume of Distribution (Vd) by products)
Vd = amount of drug administered / Active metabolites – some metabolites can
concentration in plasma continue to exert effects and side effects for
Vd is then compared to 42 (the amount of prolonged periods
body water in liters)
If Vd is approx. 42, this means equal
distribution of the drug throughout the body Excretion
3
, Primary site = kidneys Is the most common way to assess how
o Other sites = lungs & GIT long drug effects will last
o Minor sites = sweat, saliva, breast 1st order kinetics – 50% of the drug is
milk eliminated in each half lifetime period
Kidneys usually excrete metabolites after
biotransformation in liver and other organs Dosing Schedule
NOTE: approximately 25-30% of excreted drugs Drugs given continuously (IV drips &
are intact Patches) can contain and maintain a fairly
Urine pH can also affect excretion vs stable level of drug in the blood stream
reabsorption Drugs given intermittently will cause peaks
and troughs in plasma levels
Golden Rule of Pharmacology Some drugs may have
The more directly you administer a drug g to sustained/extended/controlled release
a tissue that needs it, the better the effect, preparations to reduce peaks and troughs
using less drugs, often with less side effect Peaks and troughs – important to be aware
of peaks and troughs of both beneficial and
1.5 Pharmacokinetic Variables side effects
Assessing drug elimination
o Clearance – the rate at which the Factors Affecting Normal Pharmacokinetics
drug can be removed completely Disease
from the body Age
Can be measured in one Genetics
organ (ex: CL hepatic) Gender
Can be the sum of all organs Body composition
(CLsystemic = CLhepatic + Diet
CLkidney + etc.) Other chemicals
Clearance depends on 2 key variables Physical factors
o Blood flow to the organs (Q)
Pharmacokinetics Implications for Rehab
o Extraction ratio – the concentration
Timing of rehab sessions with peaks and
entering organ minus concentration
troughs
leaving divided by concentration
o Effects of oral drugs tend to peak at
entering
30-60 mins after administration
CLorgan = ((Cin-Cout)/Cin)
Effects on physical factors
Clinical Relevance of Clearance
absorption/distribution
Drugs will be cleared best if an organ has o Increased by heat, exercise, and
high blood flow (Q) and good extraction massage
ratio o Decreased by cold
Any disease or illness that affects an
organ’s blood flow or extraction ratio will
impair its ability to clear drugs! II. MANAGEMENT OF PAIN AND INFLAMMATION
2.1 Opioids
Decreased CL will prolong a medication’s
Opioids (narcotics)
effects and side effects
o They do not necessarily remove
Half-Life painful sensation will alter pain
Amount of time required for 50% of the perception
active form of the drug to be eliminated o Used in moderate to severe pain
o Indicated in:
4
REHABILITATION
Ciccone | PT 652
I. BASIC PRINCIPLES IN PHARMACOLOGY o Gov. agency that oversees testing
1.1 Drug Names
and approval
A drug is any substance that can be put into
o Responsible for drug class
the human body in concentration to alter
physiological function. Phases of Drug Testing
Pharmacotherapeutics Stage 1: Pre-clinical trials
o Consideration of pharmacology in o Lasts 1-2 years
terms of therapeutic aspects of a o Animal tests
chemical substance
Stage 2: Clinical Trial
Pharmacodynamics
o Phase 1: healthy volunteers to
o Indicates what the drug does to the
assess side effects; lasts < 1 year
body
o Phase 2: small patient sample (200-
How does it decrease pain?
300 patients) with the condition that
How does it lower BP?
the drug treats; lasts for 2 years
How does it improve motor
o Phase 3: large sample (2000-3000
function
patients), determines drug safety;
o Pharmacokinetics
lasts 3 years
What the body does to the
Stage 3: approved for marketing (for
drug
general public)
Absorption
o Phase 4: post marketing surveillance
Metabolized
Market studies
Excreted
Questionnaires
Every drug can be identified by 3 names
Surveys
o Chemical name
o Generic name – marketed as
Expedited review
generic after patent expires; drug
o A drug company can request for an
patent has finite life, once expired
expedited review if the drug has
other companies can market under
exceptional need or beneficial
the generic name
effects
Generics are equivalent if:
o May save time but drug testing must
They have the same
continue after approval
type and amount of
o Drawbacks:
active ingredient
Drug use in general
Have the same mode
population before trials are
of administration
complete
Have the same
Drug testing must continue
therapeutic effects
o Trade name
Orphan Drugs
Certain drugs are indicated for a relatively
1.2 Drug Approval & Classification
small population (e.g. <200,000 people in
FDA – responsible for approving drugs and
the USA)
marketing to the public
DAWN LAVONNE P. HASSLER PTRP, DPT, RPT | 1
, FDA arranges funding from additional Response increases as dose increases up
sources to subsidize drug development until the response plateaus, this is called
Since 1983, >300 orphan drugs approved “maximal efficacy” OR “ceiling effect”
for >80 rare diseases Dose response curve
Implications for Drug Testing Drug Potency
Drug costs Is related to the dose that causes a specific
Availability in USA vs other countries response in a specific magnitude
Failure to identify serious side effects When comparing 2 drugs, the drug that
o Testing on only 2000-3000subjects causes the response at a lower dose is said
o Side effect frequency can be low to be more potent
Potency is often misinterpreted as more
Black Box Warning “effective”
FDA’s highest warning
Was added to opioids and benzodiazepines Quantal (Cumulative) D-R Curve
regarding risk with associated use Determines dose that causes a specific
May result in profound sedation, coma, and response in a group (sample) of subject
death Used to determine dug safety
NOTE: some drugs may begin as OTC and migrate Median Effective Dose (ED50)
to prescription drugs and vice versa Dose that causes beneficial effect in half the
OTC drugs are often consumed sample
indiscriminately
Median Toxic Dose
Consumers believe that OTC products
Dose that causes toxic effect in half the
cannot have adverse effects
sample
In animal studies, also referred to as lethal
Off Label Prescribing
Prescription of a drug for a purpose not dose (LD50) where half of test animal
approved by the FDA population dies
Off brand AKA label prescribing is legal for
Therapeutic Index
physicians
TI = TD50/ED50
o The FDA cannot dictate how
The higher the TI the SAFER the drug
physicians practice medicine
Off brand process: 1.4 Pharmacokinetics
o Drug is approved for condition A A = absorption
o Find that it may be effective for D = distribution
condition B, C, D M = metabolism
o Testing by independent institutions E = excretion
for efficacy
o RCT Absorption
Off label prescribing may constitute 40-60% Drugs must typically move from site of
of ALL prescriptions administration into another tissue or central
compartment (blood stream)
1.3 Basic Concepts in Drug Therapy & Safety Absorption is related directly to the route of
Dose Response Relationship administration
No response if dose is too lo Routes of administration
Response starts to appear at a “threshold o Enteral (alimentary canal) – easy to
dose” do, less predictable absorption
2
, Oral If Vd is << 42, the drug is being retained by
Lingual the plasma
Sublingual If Vd is >> 42, the drug is being retained in
Buccal the tissue
Rectal
o Parenteral – more difficult, more Drug Storage
predictable Distribution to certain sites results in drug
All forms of injection accumulation/storage
Inhalation Primary storage sites:
Topical o Fat
Transdermal o Muscle
o Kidneys
Absorption & Bioavailability o Bone
Bioavailability is the percent of administered o Liver
dose that appears in the bloodstream o Etc.
o Example: if 100 mg taken orally and
Primary problems:
50 mg appear in the bloodstream, o Local tissue damage
this dug is 50% bioavailable
o Redistribution – “leaks”
This is only applicable to drugs taken orally
or via transdermal patch Metabolism
Active form of drug is changed chemically to
Absorption & the First Pass Effect
an inactive or less active by product or
If a drug is administered orally
metabolite
Absorbed from GIT goes to liver via hepatic
Often creates a more polar water-soluble
portal vein
metabolite that can by kidneys
Some of the drug is often destroyed during
o Non-polar drugs are much more
this “first pass” through the liver
difficult to excrete and are usually
First pass effect can be extensive drugs (ex:
reabsorbed into the body
nitroglycerin)
Also referred to as biotransformation
It is important to know the percentage of a
Primary site of metabolism = LIVER
drug that will not survive the first pass effect
o Other sites:
Distribution Lungs
Drugs typically cross membranes and Kidneys
tissues to reach a target site GIT
Distribution is affected by the following: Skin
o Administration route Enzymes metabolize drug via:
o Psychochemical properties of the o Phase I reactions – oxidation (most
drug binding to plasma proteins common), reduction, hydrolysis
o Various “barriers” and “carriers” o Phase II reactions – conjugation
(adds a second molecule to phase I
Volume of Distribution (Vd) by products)
Vd = amount of drug administered / Active metabolites – some metabolites can
concentration in plasma continue to exert effects and side effects for
Vd is then compared to 42 (the amount of prolonged periods
body water in liters)
If Vd is approx. 42, this means equal
distribution of the drug throughout the body Excretion
3
, Primary site = kidneys Is the most common way to assess how
o Other sites = lungs & GIT long drug effects will last
o Minor sites = sweat, saliva, breast 1st order kinetics – 50% of the drug is
milk eliminated in each half lifetime period
Kidneys usually excrete metabolites after
biotransformation in liver and other organs Dosing Schedule
NOTE: approximately 25-30% of excreted drugs Drugs given continuously (IV drips &
are intact Patches) can contain and maintain a fairly
Urine pH can also affect excretion vs stable level of drug in the blood stream
reabsorption Drugs given intermittently will cause peaks
and troughs in plasma levels
Golden Rule of Pharmacology Some drugs may have
The more directly you administer a drug g to sustained/extended/controlled release
a tissue that needs it, the better the effect, preparations to reduce peaks and troughs
using less drugs, often with less side effect Peaks and troughs – important to be aware
of peaks and troughs of both beneficial and
1.5 Pharmacokinetic Variables side effects
Assessing drug elimination
o Clearance – the rate at which the Factors Affecting Normal Pharmacokinetics
drug can be removed completely Disease
from the body Age
Can be measured in one Genetics
organ (ex: CL hepatic) Gender
Can be the sum of all organs Body composition
(CLsystemic = CLhepatic + Diet
CLkidney + etc.) Other chemicals
Clearance depends on 2 key variables Physical factors
o Blood flow to the organs (Q)
Pharmacokinetics Implications for Rehab
o Extraction ratio – the concentration
Timing of rehab sessions with peaks and
entering organ minus concentration
troughs
leaving divided by concentration
o Effects of oral drugs tend to peak at
entering
30-60 mins after administration
CLorgan = ((Cin-Cout)/Cin)
Effects on physical factors
Clinical Relevance of Clearance
absorption/distribution
Drugs will be cleared best if an organ has o Increased by heat, exercise, and
high blood flow (Q) and good extraction massage
ratio o Decreased by cold
Any disease or illness that affects an
organ’s blood flow or extraction ratio will
impair its ability to clear drugs! II. MANAGEMENT OF PAIN AND INFLAMMATION
2.1 Opioids
Decreased CL will prolong a medication’s
Opioids (narcotics)
effects and side effects
o They do not necessarily remove
Half-Life painful sensation will alter pain
Amount of time required for 50% of the perception
active form of the drug to be eliminated o Used in moderate to severe pain
o Indicated in:
4
