PHARMACOKINETICS: DISTRIBUTION If really needed: Benefit must outweigh the risks

involved
Distribution is the movement of a drug to body
tissues PHARMACOKINETICS: METABOLISM
Processes by which the drug available to body fluids (Biotransformation)
& tissues
The biologic transformation of a drug into an
Affected by several factors:
inactive metabolite, a more soluble compound, or a
Blood flow ( BF = absorption)
more potent metabolite
Solubility
Liver (main organ) hepatic first pass
Protein Binding
Kidneys
- Drug component which prevents or
Lungs
regulates toxicity of medication
Plasma
- Most of the drugs that cause adverse
Intestinal mucosa
effects are highly protein bound.
Liver Enzyme Metabolism
- Free drugs elicit a response
o Phase I Biotransformation
- protein bound needs protein
Oxidation-reduction/ hydrolysis
carriers/binding sites
o Phase II Biotransformation
- Drugs will attach to protein carriers,
Conjugation reaction which makes the
those that are attached will be inactive
drug less polar and more readily
& will not cause an effect in the body. It
excreted in kidneys
will be slowly released once the free
Less polar drugs are readily excreted in
drugs are metabolized
the kidneys
- Free drugs = active;
Factors that DECREASE Metabolism:
protein bound = inactive
Cardiovascular dysfunction
- Most drugs are bound to protein to
Renal insufficiency
some extent
Starvation cells energy are used up,
- Drugs can remain free or bind to
decreased BF in GI system, peristalsis and
protein is inactive and cant exert
gastric acid activated
therapeutic effect
Obstructive Jaundice
- If more than 80% is bound to protein, it
Slow acetylator liver enzymes
is termed as highly protein bound
Erythromycin or ketoconazole drug therapy
Blood-Brain Barrier Duodenum (site of absorption)
Factors that INCREASE Metabolism
Protective system of cellular activity that keeps
Fast acetylator liver enzymes
many things away from the CNS
Barbiurates sedative, hypnotics, prevents
High lipid solubility = can cross blood brain barrier
anxiety
Water soluble = cant cross the blood brain barrier
Rifampin therapy
cells are made up of and brain is highly lipid mixture
DELAYED drug metabolism results in
Meyer Overton theory o Accumulation of drugs
Placenta & Breast Milk o Prolonged action of the effects of the drugs
Prevents sudden onset of action
Many drugs readily pass the placenta and may because some are inactive
affect the developing fetus STIMULATING drug metabolism causes
It is best not to administer any drug to a pregnant o Diminished pharmacologic effects
woman because of the possible risk to the fetus

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PHARMACOLOGIC PRINCIPLES: EXCRETION A drug cannot make a cell tissue perform a
function it was not designed to perform
Elimination of drugs from the body
Primarily occurs in the kidneys but can occur
Receptor interaction
through skin, lings, bile and feces Once a drug binds to a receptor site, it
Affected by urine acidity and kidney function elicits a response
Glomerular filtration Enzyme interaction
Passage of water and water-soluble A drug must bind to its specific receptor
components from plasma into the renal site
tubule
Drug binds to receptor and
AGONIST
Half-life (t ) there is a response
Time it takes for the amount of drug into the body Drug binds to receptor, and
to decrease to one half of the peak level it there is a diminished response
previously achieved PARTIAL AGONIST
compared with that elicited by
Important in determining the appropriate timing for the agonist
a drug dose or determining the duration of drug
effects on the body Drug binds to receptor, no
The longer the half life, the less frequent you give ANTAGONIST response
drugs) Drug prevents binding of
agonists
PHARMACODYNAMICS
Drug competes with the
Drug Actions COMPETETIVE agonist for binding to a
The cellular processes involved in the ANTAGONIST receptor. If it binds, there is no
drug and cell interaction response
Drug Effect Drug compete with different
NON-
The physiologic reaction of the body to parts of receptors and it
COMPETETIVE
the drug inactivates it so agonist has no
AGONIST
Onset response
Time it takes for the drug to elicit a
therapeutic response
Peak SELECTIVITY
Time it takes to reach its maximum Non-selective
therapeutic response Can cause multiple and widespread
Duration effects
Selective
MECHANISM OF ACTION Causes an effect to a selected receptor
site
The ways by which drugs can produce Selective Toxicity
therapeutic effects Affects specific enzyme system unique
Once the drug is at the site of action, it can to an organism or cell causing death
modify the rate (increase/decrease) at which without disrupting normal human cell
the cells or tissues function formation
S B (increase/ decrease; stimulate/block)
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PHARMACOTHERAPEUTICS Iatrogenic responses
Types of Therapies: Unintentional adverse effects that are
Acute therapy treatment-induced
Maintenance therapy Dermatologic
Supplemental therapy Renal damage
Palliative therapy Blood dyscracias ( WBC, RBC,
Prophylactic therapy platelet); Blood NADIRS
Monitoring Hepatic toxicity liver cant
Effectiveness of the drug therapy must be metabolize
evaluated Other Drug Related Effects
Familiar with the drugs
- Intended therapeutic action Teratogenic
(beneficial) Mutagenic
- Unintended but potential side Carcinogenic
effects (predictable, adverse drug
reactions)
THERAPEUTIC INDEX
Interactions may occur with other drugs or
food The ratio between a drugs therapeutic
Additive effect benefits and its toxic effects
Synergistic effect Therapeutic range (therapeutic window)
Antagonistic effect Peak and trough levels
Incompatibility Loading dose 1st large dose to
Medication misadventures immediately achieve drug concentration
Averse drug effects Side effects, adverse effects, reactions and
All are preventable toxic effects
Medication errors that result in Pharmacogenetics
patient harm Tachyphylaxis
Adverse drug reaction Placebo effect
Tolerance a decrease in response to repetitive
inherent, not preventable event occurring
drug doses
with normal therapeutic use of a drug;
some adverse drug reactions are classified Dependence reaction a physiologic or psychologic
as side effects; need for a drug
expected well-known reactions that result
Pharmacognosy
in little.
An undesirable response to drug therapy The study of natural (plant & animals) drug
Idiosyncratic sources
Hypersensitivity
Drug interactions

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