Transcript psy_243_ppt_on_drug_dose-1x

“How strange would appear to be this thing that
men call pleasure! And how curiously it is related
to what is thought to be its opposite, Pain!
Wherever the one is found, the other follows up
behind.”
Plato, Phaedo, fourth century B.C.
http://www.youtube.com/watch?v=uMBozVgO77A
Necro - I Need Drugs
Terminology
• Pharmacology – science of how drugs affect
the body
• Psychopharmacology – how drugs affect the
brain and behavior
• Pharmacokinetics – basic principles of drug
absorption,distribution,metabolism and
excretion.
• Pharmacodynamics – interaction of the drug
with its receptor or other cell functions
Names of drugs
• Chemical name – using the chemical jargon, i.e. 7chloro-1,3-dihydro-1-methyl1-5phenyl1-2H-1,4benzodiazepin-2-one.
• Generic name – diazepam. Textbooks use the
generic name.
• Trade name – property of the company that sells
the drug. In this case, the trade name is Valium
PHARMACOKINETICS
• DOSAGE
use metric system
• ROUTES OF ADMINISTRATION
Injection (intravenous, intramuscular, or subcutaneous
injection)
Inhalation (smoking)
Oral administration (by mouth)
Absorption through the skin or membranes (intranasal
sniffing, sublingual absorption, rectal suppository,
transdermal patch)
Dosage
Use the metric system: a milligram is 1/1,000of
a gram. ( a little over 28 grams in 1 ounce)
Dosage continued
• Doses are therefore reported in terms if
milligrams per kilogram (kg) of body weight. A
kg is 2.2 pounds)
• LSD is the exception. Reported in micro grams
• 1 gr of LSD = 4,000 hits (McKim,1987)
Dose Response Curves
DRC
• Necessary to give a range of doses
• Range needs to cover a dose so low that there is no
detectable effect and a dose so high that increases in
dose have no further effects (McKim,1987)
DRC continued
• Plot the effects on a plot
• Dose is reflected on the horizontal axis
• Effect is plotted on the vertical axis
The majority of clinical benefit is achieved at low doses, after which the efficacy curve
begins to flatten out.
DRC characteristics
• Potency – how much is required to get a response
• Efficacy -
maximum effect obtained
• Variability – individual differences in drug response
Effectiveness of drugs
• Use ED (effective dose) and LD (lethal dose)
• Drugs’ toxicity is measured by looking at the ratio of
lethal and effective dose
EFFECTIVE DOSE (ED)
LETHAL DOSE (LD)
• The effective dose (ED) is the minimal dose
necessary to produce the intended drug effect
in a given percentage of the population under
study
• The lethal dose (LD) is the minimal dose
necessary to produce death in a given
percentage of the population under study
Effectiveness of drugs continued
• The ratio of LD50/ED50 is called the
therapeutic index
• Margin of safety – another ratio which uses
1% and 99% - the higher the ratio, the safer
the drug
AN EXAMPLE OF ED-RESPONSE AND
LD-RESPONSE CURVES THAT WOULD PRESENT
SERIOUS TOXICITY PROBLEMS
Allyn and Bacon
Examples of LD
• Nicotine - LD50 (in mice) orally is 0.23g/kg
• Caffeine – 250mg/kg in mice; 70 to 100 cups
of brewed coffee (Barnes,1973)
EXAMPLES continued
• Cocaine – depends on route of administration
• The LD50 in a 150 pound man is about 500 mg
• When it is taken intranasally,however,the
LD50 may be as low as 30 mg.(Crowley, 1987)
(Related to sudden increase in drug levels in the brain)
More examples
• Amphetamine deaths – the lethal dose ranged from
5 mg to 630 mg (O.J. Kalant,1973)
• Barbiturates – 4,000 to 6,000 mg is the estimated
lethal dose. (Moeschlin,1971)
EXAMPLES continued
• Alcohol – blood alcohol level of about 500 mg
per 100 ml – probably a lethal dose for most
people ( 25 ounces of liquor)
• LSD – 0.3 mg/kg I.V. for mice,rats, and rabbits.
It is, in the toxic sense, one of the safest drugs
known
Poisons
• Botulinum toxin A
5g – about a teaspoonful could kill a
quarter of the world’s entire current
population.
1 out of 4 persons alive today
Poisons continued
• Tetanus toxin
1 teaspoon could kill about 7 million
people
• Sarin (nerve gas) – 0.01mg/kg
Remember
• Drugs do not create any unique effects- they
merely modulate normal neuronal functioning
– they mimic or antagonize the actions of a
specific neurotransmitter.
(Julien,R.2001)
Factors influencing Drug Responses
some of these you listed this morning in class!
Route of administration
Other drugs
Gender
Health
Biorhythms
Setting
Expectancy
Dose
Genetics
Age
Weight
Mood
Tolerance
Learning
Many Factors
Affect Drug
Response
MERCK MANUAL
Tolerance
(McKim,1987)
• Cross Tolerance- tolerance to one drug may
diminish the effect of another drug (i.e.
opiates)
• Behavioral tolerance/conditioned tolerance
Tolerance
• Metabolic tolerance – metabolism increase
(i.e. enzyme induction to destroy the drug)
• Cellular or pharmacodynamic tolerance
( body makes adjustments to maintain
homeostasis)
Tolerance
• Acute tolerance – i.e. alcohol- effects of
alcohol are more pronounced while the BAL is
rising
( Vogel-Sprott,1992)
Half-life of a drug
• Time it takes for half the dose to be eliminated
from the body
• need to maintain steady-state level (i.e.
prescription medication)
Half-life calculations
Amount of drug in the body
Number of half lives
0
1
2
3
4
5
6
% eliminated
0
50
75
87.5
93.8
96.9
98.5
% remaining
100
50
25
12.5
6.2
3.1
1.6
Examples
•
•
•
•
Aspirin
Morphine
Lithium
Valium
ca. 1 hr
ca 2 hours
24 hours
several days
• Assuming liver and kidneys are up to par!
A good video on pharmacokinetics
http://www.youtube.com/watch?v=mp93nPUzHqM