·Definition of a Drug:
·
Any chemical substance,
natural or man-made (usually excluding nutrients, water, or oxygen),
that - by its chemical nature - alters biological functioning when
administered and absorbed.
·Recognizing something as
a drug is usually
pretty straightforward, but how about:
·
Wine cooler?
·
Coffee?
·
Cigarettes?
·
Airplane glue?
·
Ice Cream?
·
Cough drops?
·
Soft drinks?
·
Water?
·
Candy?
·
Salt?
·
Vitamins?
·
Dietary supplements
·
Herbal or natural
remedies?
·How about when we see a
physiological or behavioral effect even though what the person took
contained no active chemicals?
·Placebo & Placebo
Effects
·
Placebo - typically an
inert (chemically inactive) substance administered like a drug
·
Placebo effect - any
psychological or physiological effect that is due to expectancy rather than chemical action
·Psychoactive Drug:
·
Any drug that affects
feelings, perceptions, thought processes, and/or behavior.
·
All psychoactive drugs
exert their effects by altering the functioning of the nervous system.
·Classifying Drugs
·
By their
availability/commercial status
·
(prescription vs
nonprescription drugs; licit vs illicit drugs)
·
By their potential for
abuse
·
(Schedules of Controlled
Substances)
·
By their typical
effects/actions
·Categories We’ll Use Most
·
Depressants
·
Stimulants
·
Narcotic Analgesics
·
Psychotherapeutics
·
Psychedelics/Hallucinogens
·
Cannabis
·
Inhalants
·Some current statistics:
·
~51% of American adults
consume alcohol
·
~29% smoke (60 million)
·
~6% use illegal drugs (14
million)
·Drug Use is Related to:
·
Over 500,000 emergency
room visits/yr
·
193,000 attempted suicides
·
208,000 related to
recreational use or dependence
·
66,000 unexpected drug
reactions
·
52,000 related to
withdrawal/detoxification
·
Over 1 million arrests/yr
·Spending Estimates:
·
49 billion/yr purchasing
illegal drugs
·
50 billion/yr on
prescription & nonprescription drugs
·
30 billion on drug
enforcement
·Deaths Attributed to Drugs
·
~25,000/yr due to illegal
drugs or drug related activities
·
~100,000/yr related to
alcohol
·
~400,000/yr related to
tobacco use
·Following a Drug
Through the Body
·
Administration – Get drug
into person.
·
Absorption - Drug gets
into bloodstream
·
Distribution - Blood
carries drug to tissues
·
Drug Action - Drug
interacts with cells
·
Termination of Effect,
Metabolism and/or Elimination
·
Study of 1,2,3, & 5= pharmacokinetics
·
Study of action = pharmacodynamics
Routes of Administration
·Oral Route
·
Easy, convenient, accepted
·
Gradual onset (5-30 min)
with 75% absorbed within 2-3 hrs; provides a longer lasting effect .
·
Reversible for a while
·
But:
Not all drugs can withstand
stomach acids, some upset stomach
·
Absorption variable
depending on stomach contents; dosing not precise
·Inhalation
·
Rapid absorption &
fastest route to brain
·
Fairly easy
·
But:
Many drugs cannot be inhaled
·
Dose
can be difficult to control
·
There
is no drug depot.
·
Inhalation via smoking
can present special risks.
·Injection (aka Parenteral)
(drug
prepared in a liquid vehicle)
·
Intravenous (IV)
·
Fast, bypasses absorption
obstacles
·
Most difficult &
risky route
·
Intramuscular
(IM)
·
Intermediate speed
depending on muscle selected (arm faster than butt)
·
Subcutaneous (SC)
·
Fairly rapid injection
route; can irritate skin
·
All give good control of
dose
Injection
Problems
l
Intravenous route most
dangerous because of risk of possible life-threatening reactions or
allergic responses
l
Risk of clots or emboli
due to particles, air bubbles
l
Must use sterile
procedures or risk infection.
l
Site of injections
deteriorates.
·Miscellaneous
·
Intranasal ; nasal sprays
·
Sublingual
·
Topical or Transdermal
·
Rectal
·
Implantable
·Routes Vary in:
·
Form of drug
·
Dose necessary due to
absorption diffs
·
Time course (latency
period, length of
effect)
·
Risks & benefits
·
Intensity of drug effects
·Some Absorption-Related
Food/Drug Interactions
·
Grapefruit juice
increases absorption of antihistamines, codeine, tranquilizers,
cardiovascular & AIDs drugs
·
Pop, fruit or veggie
juice or vitamins with iron can decrease absorption of erythromycin
·
Dairy foods or other
calcium rich items decrease absorption of tetracycline
·
Excess salt alters
lithium absorption
·Distribution
·
Bloodstream distributes
drug widely (not just to the problem area)
·
Speed with which a drug
leaves the blood and enters other tissues depends on concentration,
binding to proteins in blood, and degree to which the drug is
fat-soluble
·
Speed altered by other
drugs present
·Distribution (continued)
·
Limitations to the
distribution of some drugs:
·
the “blood-brain barrier”
restricts the entry of some substances into the brain. Psychoactive drugs are
the ones that do make it into brain.
·
the “placental barrier”
excludes some large molecule chemicals but does NOT exclude
psychoactive drugs.
·Why Drug Effects End
·
*Drug may be metabolized
by liver, then removed by kidney
·
Drug may be removed by
kidney
·
Drug may be redistributed
to body fat
·
Some drugs may leave in
feces or other bodily fluids (milk, sweat, breath)
·
Some molecules may be
broken down at site of action (receptor
sites in CNS) or before they are even absorbed
·Some Food-Drug
Interactions Where Food Affects Drug Elimination
·
Grapefruit juice
interferes with metabolism of a wide range of drugs by affecting CYP
enzymes
·
Broccoli and similar
veggies counteract blood thinner coumadin
·
Licorice is dangerous
when using heart med Lanoxin (hyperadditive effect)
·The “Half-Life” of a Drug
·
The half-life of a drug
is the time it takes for half the dose to be eliminated from the body.
·
A drug’s effects may be
longer and more intense if liver and/or kidney are not functioning up
to par.
·
Knowing half life is important for understanding time course of
drug and how often to administer it to achieve steady-state levels.
·Sample Half-Lives
·
Aspirin
1+/- .5 hrs
·
Morphine
2 +/- .5 hrs
·
Tetracycline 4 +/- 1.5
hrs
·
Haldol
12
+/- 6 hrs
·
Lithium
24
+/- 6 hrs
·
Phenobarbital >30 hrs
·
Valium
several
days
Meet the Families
Cytochrome P450
Families
l
Enzymes found in liver
& a little in GI tract
l
Break down or detoxify
lots of chemicals
l
Different subfamilies
handle different drugs
The Subfamilies
l
CYP 3
- metabolizes about 50-55% of all known drugs; CYP 2 – 45-50%;
CYP 1 - 5%
l
Anything that affects
these enzymes will alter drug metabolism (e.g. grapefruit juice)
l
Some drugs alter these
enzymes (Tegretol increases them, Prozac decreases them)
l
Our genes determine our
individual levels
·Dose
·
Most drugs we discuss
have doses expressed in milligrams (mg.) (thousandths of a gram)
·
Exceptions: LSD (50-150 micrograms (millionths)); fentanyl
(.05 mg-.10mg)
·Dose
·
That many drugs are sold
in just a few dosages belies the fact that there is wide individual
variability in drug response. We do not all have the same absorption,
distribution, drug action, or elimination and shouldn’t be surprised
that we respond differently !
·The Dose-Effect or
Dose-Response Curve
·
Graphic representation
relating the amount of drug administered to the response produced
·
Response may be
represented as intensity of response OR as % of population responding
·Potency vs Effectiveness
·
Potency – the amount of
drug required to produce a particular effect
·
Effectiveness – the
maximum effect obtainable from a particular drug
·Comparing Curves - Be
Sure You Understand Dose-Response Graphs
·Sample Contents of a
Coated Tablet:
·
5 mg active drug
·
30 mg sugars
·
6 mg cornstarch
·
9 mg miscellaneous
·
10 mg coating
With such a composition, would it be very useful to come up with a more
potent drug (say one that only required 2 mg active drug)?
·Drug Interactions
·
Additive/potentiating/synergistic
interactions
·
Antagonistic interactions
·
Altered side effects,
time course
·
The presence of another
drug may alter absorption, distribution, metabolism, elimination, or
receptor interactions.
·Some examples:
·
Tagamet, Zantac, birth
control pills, or erythromycin can
increase effects of benzodiazepines like Xanax
·
Smoking can decrease the
effectiveness of a wide range of medications
·
Taking antacids can
affect the absorption of lots of drugs
·
Taking alcohol and
aspirin increases stomach upset
·Tolerance:
·
Tolerance:
progressively decreasing drug effects due to regular, repeated
administration. In order to experience the
original degree of drug response the individual must increase their
dose.
·Time-Related Tolerance
Terms
·
Acute tolerance or
tachyphylaxis – rapid tolerance which develops during a single drug use
period (e.g. during an evening)
·
Protracted tolerance -
tolerance which occurs over the course of 2 or more drug use occasions
·
Reverse tolerance or
sensitization - increased response with repeated use
·Mechanisms by Which
Tolerance Occurs:
·
Metabolic or
dispositional tolerance (increased liver metabolism of drug)
·
Cellular adaptation or
tissue tolerance or pharmacodynamic tolerance (cells at drug’s site of
action adapt to the presence of drug)
·
Behavioral
conditioning/tolerance (learning and conditioning lead to decreased
drug effects)
Example of
Behavioral Conditioning
·
Measure tolerance of
Group A getting drug 10 times in same situation vs tolerance of Group B
getting same drug in 10 diff. situations.
Group A shows more tolerance due to
learned counter-reaction or compensatory mechanisms.
·Physical or Physiological
Dependency:
·
Body has physiologically
adapted to, and (to a certain extent) compensated for the regular
presence of the drug.
·
Adaptation/compensation
processes result in tolerance (having to increase your dose to achieve
the same degree of effect) and may produce withdrawal symptoms when
drug levels drop.
·Cross-Tolerance &
Cross-Dependence
·
When tolerance to a drug
develops
it often extends to other (usually chemically related) drugs
although they have not
been used.
·
When physical dependence
occurs, other chemically-related drugs can “satisfy” that dependency
& prevent withdrawal
·Psychological Dependency:
·
Emotional or
psychological reliance on the reinforcing effects of the drug.
·
Drug-taking behavior is
reinforced by the positive feelings or escape the drug provides,
leading to a well-learned behavioral habit difficult to extinguish.
·
Trying to break this
habit leads to craving the missing reinforcement and desire to return
to the more comfortable drug-taking behavior pattern.
.
·Drug Names
·
Chemical name
·
Generic name – official,
nonproprietary
·
Brand name(s) – owned by
a company
·
Street names
·Examples:
·
sodium
5-ethyl-5-(1-methyl butyl)barbiturate
·
sodium pentobarbital
·
Nembutal
·
bluebirds
·Which name is which?
·
Benedryl
·
2-(diphenyl
methoxy)-N,N-dimethylamine HCl
·
allergy pills*
·
diphenhydramine
·Generic vs Brand Name
Drugs
·
Are they equivalent?
·
Are generic substitutions
fair to brand-name companies?
·
Will generic availability
decrease drug development research?
·Side-Effects of Drugs
·
All drugs produce
multiple effects.
·
“Side-effects” are
effects not sought by the user.
·
One person’s desired
effect may be another person’s “side effect”.
·
Side effects may be mild
or disturbing or even dangerous.
·
Serious side-effects are
often called “adverse reactions”.
·
Every drug has some
side-effects that are quite common & others that occur more rarely.
·Some Adverse Reactions: Hypersensitivity
·
An allergic response to a
drug after it has been given more than once. May cause rash, swelling,
fever, or, in the worst cases, anaphylactic shock. Anaphylaxis is a
life-threatening medical emergency.
·Signs of anaphylaxis:
·
tingling lips and mouth
·
flushing of face, body
·
itchy eyes, nose, face
·
eyes and face swelling
·
hives
·
wheezing
·
diarrhea, nausea
·
Symptoms rapidly progress
to:
·
weakness,dizziness
·
throat swelling closed
·
low blood pressure
·
loss of consciousness
·
possible
death
·Some Adverse Reactions: Idiosyncratic Response
·
Rare, unpredictable,
highly individual response to a drug. The user may be at the extremes
of the dose-response curve or may exhibit unusual physiological or
behavioral responses to the drug.
·Risks With Street Drugs
·
Actual drug composition
unknown
·
Dose variable and unknown
·
Possibly harmful
diluents/contaminants
·
Abuse
liability
·Signs of Drug Distress
·
slowed respiration (16-20
inhalations/min is normal)
·
cyanosis
·
fast (>140), slow
(<50), or irregular pulse
·
high temperature
·
loss of consciousness
·
extreme behavioral change
(agitated, aggressive, suicidal)
·Factors Influencing Drug
Response
·
Route
·
Dose
·
Tolerance
·
Other Drugs
·
Genetics
·
Gender
·
Age
·
Health
·
Weight
·
Biorhythms
·
Mood
·
Setting
·
Baseline behavior
·
Expectancy
·
Learning
·A Few Examples:
·
Genetic diffs in initial
sensitivity.
·
Women respond more
strongly than men to equivalent doses of alcohol
·
Asians require lower
doses of tranquilizers and antipsychotics. Also handle caffeine and
alcohol differently.
·
Blacks require higher
doses of BP meds
·
The elderly often require
lower doses.
·Basic Nervous System
·
All
psychoactive drugs change nervous system functioning. Even
non-psychoactive drugs often produce their “side-effects” by affecting
the peripheral parts of the nervous system.
·Best Known
Neurotransmitters
·
Acetylcholine (ACh)
·
Norepinephrine (NE)
·
Dopamine DA)
·
Serotonin or
5-Hydroxytryptamine (5HT)
·
GABA
·
Endorphin
Glutamate
Receptor
Specificity
l
Each transmitter binds
only to its receptors, but there are multiple types of receptors for
each.
Eliminating
Neurotransmitter
l
Transmitter must be
removed from synapse after its release
l
Most neurotransmitters
are recycled thru a process called “reuptake”.
l
Less often an enzyme
breaks down transmitter into inactive components.
·Acetylcholine (ACh)
·