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“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.

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Presentation on theme: "“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."— Presentation transcript:

1 “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. Necro - I Need Drugs

2 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

3 Names of drugs Chemical name – using the chemical jargon, i.e. 7- chloro-1,3-dihydro-1-methyl1-5phenyl1-2H-1,4- benzodiazepin-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

4 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)

5 Dosage Use the metric system: a milligram is 1/1,000of a gram. ( a little over 28 grams in 1 ounce)

6 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)

7 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)

8 DRC continued Plot the effects on a plot Dose is reflected on the horizontal axis Effect is plotted on the vertical axis

9 The majority of clinical benefit is achieved at low doses, after which the efficacy curve begins to flatten out.

10 DRC characteristics Potency – how much is required to get a response Efficacy - maximum effect obtained Variability – individual differences in drug response

11 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

12 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

13 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

14 AN EXAMPLE OF ED-RESPONSE AND LD-RESPONSE CURVES THAT WOULD PRESENT SERIOUS TOXICITY PROBLEMS Allyn and Bacon

15 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)

16 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)

17 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)

18 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

19 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

20 Poisons continued Tetanus toxin 1 teaspoon could kill about 7 million people Sarin (nerve gas) – 0.01mg/kg

21 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)

22 Factors influencing Drug Responses some of these you listed this morning in class! Route of administrationDose Other drugs Genetics GenderAge HealthWeight BiorhythmsMood SettingTolerance ExpectancyLearning

23 Many Factors Affect Drug Response MERCK MANUAL

24 Tolerance (McKim,1987) Cross Tolerance- tolerance to one drug may diminish the effect of another drug (i.e. opiates) Behavioral tolerance/conditioned tolerance

25 Tolerance Metabolic tolerance – metabolism increase (i.e. enzyme induction to destroy the drug) Cellular or pharmacodynamic tolerance ( body makes adjustments to maintain homeostasis)

26 Tolerance Acute tolerance – i.e. alcohol- effects of alcohol are more pronounced while the BAL is rising ( Vogel-Sprott,1992)

27 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)

28 Half-life calculations Amount of drug in the body Number of half lives % eliminated % remaining

29 Examples Aspirin ca. 1 hr Morphine ca 2 hours Lithium24 hours Valiumseveral days Assuming liver and kidneys are up to par!

30 A good video on pharmacokinetics


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