pharmaco

Any chemical that affects living processes

The study of drugs and their interactions with living systems

The study of drugs in humans

The use of drugs to diagnose, prevent,or treat disease or to prevent pregnancy

• • 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

• 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

•study of how genes affect individual drug responses

•a group of signs and symptoms and/or characteristic effects associated with exposure to a particular substance or class of substances.

• 1-no use in US• heroin, mescaline, LSD– (highest potential for abuse)
• 2-5-progressively less potential for abuse

• –Administration
• –Pharmacokinetics
• –Pharmacodynamics
• –Individual variations

• Route
•     Parenteral 
•     Enteral
•     Topical
• Timing
• Dosage
• ComplianceErrors

• Absorption

– Get in

• Distribution

– Get around

• Metabolism

– Get to work

• Excretion

– Get out

• •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

altered plasma pH.

• movement through the body
• • Blood flow to tissue
• • Exiting the vascular system-cap bed

• –only lipid soluble or direct transport mechanism
• • Placental drug transfer-not a barrier

• (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

any functional macromolecule in a cell to which a drug binds to produce its effects

• Cell membrane–embedded enzyme receptor
• Ligand-gated ion channels
• G protein-Coupled Receptor
• Transcription factors

• Most common
• Send signal through the cell membrane
• Activate internal enzyme systems

Specific protein needed to open ion channel

• Drug activates receptor
• Receptor activates G-protein
• G-protein activates internal mechanism

On DNA of nucleus-regulate protein synthesis

Drug metabolism

Enzymatic alteration of drug structure (useable)

Liver

• P450 system (cytochrome P450)
• 12 related enzyme families
• CYP1, CYP2, CPY3-metabolize drugs
• Others metabolize endogenous compounds
•    Fatty acids, steroid hormone

• – Inactivate a drug
• – Increase therapeutic action
• – Activate prodrugs
• – Accelerate renal excretion
• – Increase or decrease toxicity

– Deactivation by the liver after GI absorption

• • 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

• – Time for drug levels to decrease by 50% • Morphine-half life 3 hours
• • 5 half-life rule

• drugs with short half life get large initial doses to reach therapeutic range

• small doses to maintain therapeutic range

The impact of drugs on the body at the action site

size of the dose controls the response

• largest response the drug can produce regardless of dose
•  Dopamine 20 mcg/kg/min
•  Levophed 25 mcg/min

• -dose of drug required to produce an effect
• MSO4- 4 mgs (more potent)
• Meperidine 50mgs

• molecules that activate receptors
• mimic the action of endogenous molecules

-prevents receptor activation

-binds reversibly by highest concentration

-binds irreversibly

• achieves less than the effect of an agonist,
• but can compete for agonist sites pentazocine/meperidine(talwin/demerol)

• • Level below which effect will not occur
• doses

-causes harm–

• Therapeutic effects, no toxicity

• • Peak and trough
• • Timing of doses

• 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