definitions pharmacokinetics –the process by which a drug is administered, absorbed, distributed,...
Post on 21-Dec-2015
219 views
TRANSCRIPT
![Page 1: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/1.jpg)
Definitions
• Pharmacokinetics– The process by which a drug is administered,
absorbed, distributed, bound, inactivated, metabolized and eliminated by the body
• Pharmacodynamics– The interactions of a drug and the receptors responsible
for its action in the body and CNS
![Page 2: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/2.jpg)
Drug Administration
• Orally (swallowed)
• through Mucus Membranes– Oral Mucosa (e.g. sublingual)
– Nasal Mucosa (e.g. insufflated)
• Rectally (suppository)
![Page 3: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/3.jpg)
Drug Administration (cont.)
• Parenterally (injection)– Intravenous (IV)
– Intramuscular (IM)
– Subcutaneous (SC)
– Intraperitoneal (IP)
• Inhaled (through lungs)
![Page 4: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/4.jpg)
Drug Administration (cont.)
• Topical/Transdermal (through skin)
• Directly into CNS– Intracranial or intracerebral (into brain
tissue)
– Intracerebroventricular (into brain ventricles)
![Page 5: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/5.jpg)
Drug Administration Summary
• Pharmacokinetics relates to bioavailability– The fraction of an
administered dose of a drug that reaches the blood stream
• How quickly a drug reaches its site of action relates to “addictiveness.”
![Page 6: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/6.jpg)
Distribution: Solubility
• Water-soluble– Ionized (have electrical charge)
– Crosses through pores in capillaries, but not cell membranes
– The extent of ionization of a drug is expresses as the pKa of the drug
• Lipid(fat)-soluble– Non-ionized (no electrical charge)
– Crosses pores, cell membranes, blood-brain-barrier
![Page 7: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/7.jpg)
![Page 8: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/8.jpg)
Distribution: Blood Brain Barrier
![Page 9: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/9.jpg)
![Page 10: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/10.jpg)
Depot Binding
• Drugs bind to “depot sites” or “silent receptors”
• Deposits slow elimination, can increase drug detection window
![Page 11: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/11.jpg)
Metabolism & Elimination
• Kidneys– Traps water-soluble
compounds for elimination via urine
• Liver– Enzymes transform drugs
into more water-soluble metabolites
![Page 12: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/12.jpg)
Metabolism and Elimination (cont.)
• Half-lives and Kinetics– Half-life:
• Plasma half-life: Time it takes for plasma concentration of a drug to drop by 50%.
• Whole body half-life: Time it takes to eliminate half of the body content of a drug.
– Factors affecting half-life• age
• renal excretion
• liver metabolism
• protein binding
![Page 13: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/13.jpg)
First order kinetics
A constant fraction of drug is eliminated per unit of time.
When drug concentration is high, rate of disappearanceis high.
![Page 14: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/14.jpg)
Zero order kinetics
Rate of elimination is constant.
Rate of elimination is independent of drug concentration.
Constant amount eliminated per unit of time.
Example: Alcohol
![Page 15: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/15.jpg)
The Dose-Response Curve
• X-axis = Dose
• Y-axis = Response, measured as either– magnitude of response in individual
– number/percentage of individuals responding at a given level
![Page 16: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/16.jpg)
Therapeutic Index
• ED50 = dose at which 50% population shows response
• LD50 =dose at which 50% population dies
• TI = LD50/ED50, an indication of safety of a drug (higher is better)
![Page 17: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/17.jpg)
Potency
• Relative strength of response for a given dose– accessability, affinity, and efficacy
• D-R curve shifts left with greater potency
![Page 18: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/18.jpg)
Efficacy(% of maximal change elicited)
• Maximum possible effect
• Indicated by peak of D-R curve
![Page 19: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/19.jpg)
Tolerance(desensitization)
• Decreased response to same dose with repeated exposure
• or more drug needed to achieve same effect
• Right-ward shift of D-R curve
• Sometimes occurs in an acute dose (e.g. alcohol)
• Can develop across drugs (cross-tolerance)
• Caused by compensatory mechanisms that oppose the effects of the drug
![Page 20: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/20.jpg)
Tolerance
• Physical – User requires more of the drug to achieve the same
effect, and the same amount will produce a lesser effect.
• Psychological– As the user becomes familiar with the drug’s effects,
s/he learns tricks to hide or counteract the effects.
• Metabolic– The user is able to break down and/or excrete the drug
more quickly due to repeated exposure.
![Page 21: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/21.jpg)
Sensitization
• Increased response to same dose with repeated exposure
• or less drug needed to achieve same effect
• Left-ward shift in D-R curve
• Sometimes occurs in an acute dose (e.g. amphetamine)
• Can develop across drugs (cross-sensitization)
![Page 22: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/22.jpg)
Mechanisms of Tolerance and Sensitization
• Pharmacokinetic– changes in drug availability at site of action; metabolic changes
• Pharmacodynamic– changes in drug-receptor interaction (G-protein uncoupling; down
regulation)
• Conditioning– automatic physiological change in response to cues
• Motivational– change in organism’s behavior to attenuate/increase effect
![Page 23: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/23.jpg)
Pharmacodynamics
• Receptor– target/site of drug action (e.g. genetically-coded proteins embedded
in neural membrane, cytoplasm, nucleus)– Lock and key model
• Drug acts as key, receptor as lock, combination yields response
![Page 24: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/24.jpg)
Pharmacodynamics continued
• Affinity– propensity of a drug to bind with a receptor
• Selectivity– specific affinity for certain receptors (vs. others)
![Page 25: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/25.jpg)
Agonism and Antagonism
Agonists facilitate receptor response
Antagonists inhibit receptor response
(direct ant/agonists)
![Page 26: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/26.jpg)
Agonists
• Full Agonist
• Partial Agonist
• Direct/Competitive Agonist
• Indirect/Noncompetitive Agonist
![Page 27: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/27.jpg)
Antagonists
• Direct/Competitive Antagonist
• Indirect/Noncompetitive Antagonist
• Inverse Agonist
![Page 28: Definitions Pharmacokinetics –The process by which a drug is administered, absorbed, distributed, bound, inactivated, metabolized and eliminated by the](https://reader036.vdocument.in/reader036/viewer/2022062407/56649d645503460f94a46d6b/html5/thumbnails/28.jpg)
Important implications ofdrug-receptor interaction
• drugs can potentially alter rate of any bodily/brain function
• drugs cannot impart entirely new functions to cells
• drugs do not create effects, only modify ongoing ones
• drugs can allow for effects outside of normal physiological range