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Drug
Any chemical that affects living processes
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Pharmacology
The study of drugs and their interactions with living systems
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Clinical pharmacology
The study of drugs in humans
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Pharmacotherapeutics/therapeutics
The use of drugs to diagnose, prevent,or treat disease or to prevent pregnancy
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Properties of an Ideal Drug
- • Effectiveness (1)
- • Safety (2)
- • Selectivity (3)
- • Reversible action
- •Predictability
- •Ease of administration
- • Minimal drug interactions
- • Low cost
- • Chemical stability
- • Possession of a simple generic name
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Generic VS Trade
• Same dose
• Inert ingredients can differ
• Preparation can differ
• Therefore absorption rate (onset) can differ
• Bioequivalent-equal time to onset
– Bioavailability
• ability to reach the circulation from
the site of administration.
• Cost-varies-but is usually considerable
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Pharmacogenomics
•study of how genes affect individual drug responses
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Toxidromes
•a group of signs and symptoms and/or characteristic effects associated with exposure to a particular substance or class of substances.
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Drug Schedules (control of drugs)
- 1-no use in US• heroin, mescaline, LSD– (highest potential for abuse)
- 2-5-progressively less potential for abuse
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Intensity of Drug Responses
• Factors influencing drug response
- –Administration
- –Pharmacokinetics
- –Pharmacodynamics
- –Individual variations
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Administration
- Route
- Parenteral
- Enteral
- Topical
- Timing
- Dosage
- ComplianceErrors
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Pharmacokinetics
• Absorption
– Get in
• Distribution
– Get around
• Metabolism
– Get to work
• Excretion
– Get out
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Drug absorption &movement into blood (factors affecting drug absorption)
- •Rate of dissolution–faster is better
- •Surface area–more is better
- •Blood flow–high is good
- • Lipid solubility–high solubility more absorbed
- • pH partitioning
- –Ion trapping
- –environment promotes ionization
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drug distribution alters in response to changes in what blood component
altered plasma pH.
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Drug distribution
- movement through the body
- • Blood flow to tissue
- • Exiting the vascular system-cap bed
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The blood-brain barrier (bbb)
- –only lipid soluble or direct transport mechanism
- • Placental drug transfer-not a barrier
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3 ways by which drugs cross cell membranes
- (1)Direct penetration
- Most common
- Lipid-soluble
- (2)Channels & Pores
- Very small Activate a receptor
- (3)Transport Systems
- Specific structure
- P-glycoprotein Trans-membrane protein that transports drugs out
- Decreases absorption and drug access to tissues
- Liver, kidney, placenta,intestine, brain
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receptor
any functional macromolecule in a cell to which a drug binds to produce its effects
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the four main receptor families
- Cell membrane–embedded enzyme receptor
- Ligand-gated ion channels
- G protein-Coupled Receptor
- Transcription factors
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Cell membrane–embedded enzyme receptor
- Most common
- Send signal through the cell membrane
- Activate internal enzyme systems
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Ligand-gated ion channels
Specific protein needed to open ion channel
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G-protein coupled receptor
- Drug activates receptor
- Receptor activates G-protein
- G-protein activates internal mechanism
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Transcription factors
On DNA of nucleus-regulate protein synthesis
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Biotransformation
Drug metabolism
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Drug metabolism/biotransformation
Enzymatic alteration of drug structure (useable)
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primary site of drug metabolism
Liver
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Hepatic microsomal enzyme system
- P450 system (cytochrome P450)
- 12 related enzyme families
- CYP1, CYP2, CPY3-metabolize drugs
- Others metabolize endogenous compounds
- Fatty acids, steroid hormone
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Actions of P450
- – Inactivate a drug
- – Increase therapeutic action
- – Activate prodrugs
- – Accelerate renal excretion
- – Increase or decrease toxicity
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First-pass effect
– Deactivation by the liver after GI absorption
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Special considerations in drug metabolism
- • First-pass effect
- – Deactivation by the liver after GI absorption
- • Induction of drug-metabolizing enzymes
- – Some drugs cause an increased production of drug metabolizing enzymes in the liver
- • Increase self-metabolism (and of other drugs)
- • Nutritional status
- • malnourished decreases liver enzymes
- • Competition between drugs
- • same metabolic path compete for metabolism
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Drug Half Life
- – Time for drug levels to decrease by 50% • Morphine-half life 3 hours
- • 5 half-life rule
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– Loading dose
• drugs with short half life get large initial doses to reach therapeutic range
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Maintenance dose
• small doses to maintain therapeutic range
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Pharmacodynamics:
The impact of drugs on the body at the action site
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Dose-response relationships
size of the dose controls the response
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Maximal efficacy
- largest response the drug can produce regardless of dose
- Dopamine 20 mcg/kg/min
- Levophed 25 mcg/min
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Relative potency
- -dose of drug required to produce an effect
- MSO4- 4 mgs (more potent)
- Meperidine 50mgs
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Agonist
- molecules that activate receptors
- mimic the action of endogenous molecules
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Antagonist
-prevents receptor activation
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Competitive
-binds reversibly by highest concentration
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Noncompetitive
-binds irreversibly
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Partial agonist-(partial antagonist)
- achieves less than the effect of an agonist,
- but can compete for agonist sites pentazocine/meperidine(talwin/demerol)
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Minimum effective concentration (MEC)
- • Level below which effect will not occur
- doses
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– Toxic concentration
-causes harm–
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Therapeutic range-between MEC & Toxic
• Therapeutic effects, no toxicity
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– Maintaining therapeutic range
- • Peak and trough
- • Timing of doses
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Excretion: drug removal
• Glomerular filtration
–Non-protein bound drugs are removed
• Passive reabsorption
– Lipid soluble drugs move back into the
blood
• Active Transport
– Pumps remove drugs from blood to the
urine
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