Pharmacology Chapter 2

to provide a therapeutic range of a drug to an individual patient- concentrations that result in maximum benefit with least side effect

• replacing or acting as substitutes for missing chemicals
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• increasing or stimulating certain cellular activities albuterol B2 

depressing or slowing cellular activities atenolol B1 

interfering with the function of foreign cells (chemotherapeutic)

• opening or closing ion channels, activating biochemical messengers, inhibiting cellular processes, turning on a cellular function.

Receptors are most likely proteins or nucleic acids on cell wall or in cytoplasm that regulate normal cell function.  Drugs interact with receptors (binding) to produce a response.

• Agonist:  stimulates at receptor ex albuterol
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• Antagonist:  blocks at receptor ex atenolol

meds attack certain cells, such as rapidly reproducing cancer cells. Usually never happens, almost always attacks healthy cells as well. 

• way the body processes drugs and includes absorption, distribution, metabolism (biotransformation), and excretion.  

the amount of drug needed to have a therapeutic effect

extra amount of medicine initially to kick start into the critical concentration

Absorption, Distribution, Metabolism, and Excretion. Working together to achieve critical concentration. 

• drug moves from site of administration into venous or lymphatic circulation.  Affected by dosage form and route of administration and patient characteristics.  Drug transported by vascular system to site of activity.  Can stay in blood stream and be reversibly bound to protein or circulate unbound.
• Bioavalability describes how much of what is administered makes it into circulation to produce effects.

• include passive diffusion (most important), active transport (carriers that form complex with drug and carry through membrane and then dissociate),  filtration (through pores- very small)

•  Pros: easy, self administration, cheap
• Cons: takes long time, GI issues/irritation, self administration issues, choking

• Pros: Most rapid route of absorption aside from IV
• Con: may be too rapid

• Pros: faster absorption than oral
• Cons: Needles/ pain, contamination, injury, varied absorption, harder to self administer, increased expense

• Pros: fastest route, more effective in reaching tissue, accuracy
• Cons: difficult to administer/ keep/ maintain, painful, complications, expensive

• Pro: localized affect
• Cons: Incorrect technique, secondary infection, 

• Pro: easy, lower side effects, generally inexpensive, self administered, long lasting
• Cons: allergy, improper use/ understanding

• Pros: fast absorption, good for certain populations ie. Children
• Cons: uncomfortable, technique, 

nature of absorbing surface, blood flow to site, solubility of drug, ph and affect of ionization (more highly ionized less absorbable), drug concentration, dosage form

• drug movement from bloodstream to the site of action and to storage sites.  Move first into those organs with rich blood supply (heart, liver, kidney, brain) then into muscle and fat

• 1. route
• 2. tissue perfusion
• 3. how the drug is formulated
• 4. nutrition 

most drugs bound to proteins in the blood to be carried in circulation, can’t diffuse into capillaries due to size.  Drugs are variably bonded and can be released slowly or quickly which affects onset of action.  Drugs that are bound to protein are inactive.  As dissociate- free drug becomes active.  So another drug can cause loss of protein binding or low protein levels may result in more toxicity.

nonspecific

inactivated

(Biotransformation):  conversion of compounds to less toxic or nontoxic substances and prepare for excretion Liver

from gastric absorption, po meds go to portal venous system into liver where transformed by enzymes, so increased doses needed as compared to   parenteral where some of dose reaches reactive tissue before going to liver

• most important site “hepatic microsomal system” .  besides metabolizing drugs and preparing them for excretion, may actually convert an active prodrug to an active compound.
• Phase I - Alters drug to more polar and water soluble form to aid excretion.  Involves cytochrome P450 system in liver.
• Phase II is conjugation of compound to inactivate and then eliminate. (union of polar group of drug with another substance in body)
• Enzyme induction occurs when one compound increases the activity of the enzyme system.  This increased enzyme activity hastens the breakdown of other drugs that use the same pathway.

• Genetics also a fact as certain subsets of a major cytochrome system P450 may be absent or diminished in some population

•  removal of drug or its metabolites from the body
• kidneys play the major role with passive glomerular filtration, and active tubular secretion, or partial reabsorption
• occurs through skin, saliva, lungs, bile (from liver to bile to duodenum to feces), feces
• acidity of urine may  affect excretion   KIDNEY

• the amount of time it takes to go from peak drug to half the concentration of the drug  Example 500 mg->250 mg-> 125mg…
• It takes 3-5 doses to achieve a steady state

The amount of a drug or other compound in the circulation, both bound to proteins and unbound, the latter of which generally corresponds to the theraepeutically active fraction

decreased response to drug- may be due to more rapid metabolism, fewer receptors

needs drug to have normal function (can be physical psychological)

symptoms resulting from decrease in drug in dependent individual

tolerance to different drug due to chemical similarities

• 1. Weight- Most medicines when tested are tested on 140-170 lb males
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• 2. Age
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• 3. Gender
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• 4. Physiological factors- things that are occurring with that individual at the time of administration ex. hydration
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• 5. Genetic factors
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• 6. Pathologic factors- chronic illnesses
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• 7. Environmental factors- temperature, light
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• 8. Immunologic factors- allergy, hypersensitivity
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• 9. Psychological factors- placebo effect, compliance
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• 10. Drug tolerance
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• 11. Cumulative effects
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• 12. Drug Interactions- food, over the counter, other drugs