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Specific drug effects vs. Non-specific drug effects
- Specific drug effects: effects based on the physical and biochemical interactions of a drug with a target site in living tissue
- Nonspecific drug effects: those that are not based on the chemical activity of a drug-receptor interaction but on certain unique characteristics of the individual
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Therapeutic effects
The intended/desired physical/behavioral effects
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Side effects
Unintended drug effects that may be mild or may be dangerous
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Drug action vs. drug effect
- Drug action: the specific molecular changes produced by a drug when it binds to a particular target site/receptor
- Drug effects: more widespread alterations in physiological or psychological functions; not necessarily in the same site as the drug action
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Placebo and double-blind experiments
You know this
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Bioavailability
Concentration of a drug in the blood that is free to bind at specific target sites
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Pharmacokinetics
- Factors that contribute to the administration, absorption, distribution, binding, inactivation, and excretion of a drug
- How the body reacts to the drug
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How the body reacts to the drug
Pharmacokinetics
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Pharmacodynamics
- Study of the physiological and biochemical interactions of a drug with the target tissue responsible for the drug's effects
- What the drug does to the body; includes the drug's mechanism of action
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What the drug does to the body
Pharmacodynamics
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4 factors of pharmacokinetics (according to lecture):
- Absorption
- Distribution
- Metabolism
- Elimination
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5 factors of pharmacokinetics (according to book):
- Routes of administration
- Absorption and distribution
- Binding
- Inactivation
- Excretion
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Drug inactivation
Biotransformation
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Methods of drug administration
- Oral (PO)
- Intravenous (IV)
- Intramuscular (IM)
- Subcutaneous (SC)
- Inhalation
- Topical
- Transdermal (skin patches)
- Epidural (directly into CSF)
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First-pass metabolism
When the liver metabolized some of a drug before it can circulate through the body; occurs particularly with orally administered drugs
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Advantages/disadvantages or oral administration:
- Advantages: safe; self-administered; economical; no needle-related complications
- Disadvantages: slow and variable absorption; subject to first-pass metabolism; less predictable blood levels
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Advantages/disadvantages of IV administration:
- A: Most rapid; most accurate blood concentration
- D: Overdose danger; cannot be readily reversed; requires sterile needles and medical technique
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Adv./Disadv. of IM administration:
- A: slow and even absorption
- D: localized irritation at injection site; needs sterile equipment
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Adv./Disadv. of SC administration:
- A: Slow and prolonged absorption
- D: Variable absorption depending on blood flow
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Adv./Disadv. of inhalation:
- A: Large absorption surface; rapid onset; no injection equipment
- D: Irritation of nasal passages; small inhaled particles may damage lungs
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Adv./Disadv. of topical administration:
- A: Localized actions and effects; easy self-administration
- D: May be absorbed into general circulation
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Adv./Disadv. of transdermal administration:
- A: Controlled and prolonged absorption
- D: Local irritation; useful only for lipid soluble drugs
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Adv./Disadv. of epidural administration
- A: Bypasses blood-brain barrier; rapid effect in CNS
- D: Not reversible; needs trained anesthesiologist; possible nerve damage
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Drug depots
Inactive sites where drugs accumulate
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Depot binding
The binding of a drug to inactive sites; it is reversible
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First-order kinetics
Exponential elimination of drugs from the bloodstream
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Zero-order kinetics
Constant, linear rate of drug removal from the body, regardless of drug concentration in blood
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Half-life
The amount of time required for removal of 50% of a drug
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Phase I biotransformation reactions
- Frequently carried out through the P450 system
- Nonsynthetic modification
- Often is oxidation (usually by addition of a hydroxyl)
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Phase II biotransformation reactions
- Synthetic reactions
- Combination (conjugation) with some molecule such as glucuronide, sulfate, or methyl groups
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Phase I and phase II reactions of phenobarbital, aspirin, morphine, and diazepam
- Phernobarbital -----> Hydroxyphenobarbital (phase I)
- Asprin ---(I)----> Salicylic acid ----(II)----> Salicyclic glucuronide
- Morphine ----(II)----> Morphine-6-glucuronide
- Diazepam ---(I)---> Desmethyldiazepam ---(I)---> Oxazepam ---(II)---> Oxazepam-glucuronide
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P450 Induction/Inhibition
- Induction ---> More P450; increased rate of biotransformation; lower blood level; reduced biological effect
- Inhibition ---> Less P450; less biotransformation; higher blood level; larger biological effect
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ED50
- 50% effective dose
- The dose that produces half the maximum response
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TD50
- 50% toxic dose
- The dose at which 50% of the population experience a particular toxic effect
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Therapeutic index
TD50 / ED50
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Additive effects vs. Potentiation in drug interactions
- Additive effects: two drugs interact and the outcome equals the sum of the two individual effects
- Potentiation: two drugs interact and it produces effects that are greater than the sum of the two individual effects
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Pharmacokinetic steady state
When the intake of a drug is in equlibrium with its elimination
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How many half-lives does it typically take to reach steady state?
4-5 half-lives
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Volume of distribution
- The volume a drug would have to occupy to provide the same concentration as it currently is in blood plasma
- Higher VOD = more drug stored in fat and tissue rather than blood = lower concentration in blood
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Clearance
- The volume of plasma that is cleared of a drug per unit time
- Includes direct excretion as well as biotransformation
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Half life equation:
Half life is proportional to VOD/clearance
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Steady state concentration equation:
- SS concentration = F x (dose/time)(1/clearance)
- F is a constant
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When you age, what happens to clearance and VOD?
Clearance decreases and VOD increases
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