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Relationship between drug concentration & pharmacological effect on body
"The dynamic response the drug has on the body"
•A protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance
-Initiates cellular response to a ligand
molecule that activates a receptor
Transduction or Transmission
–The interaction between the receptor & ligand
–changes the functioning of the cell such that a molecular signal can be transduced into a cellular message
–result in activating or inhibiting chemical that lead to effects
note: sometimes there is no transformation of the receptor, but the receptor is blocked.
Endogenous or exogenous substances that directly change cell function by binding to the receptor.
= A drug which binds to the receptor and activates it. It is a drug receptor complex which envolks a pharmacological response. Ex. Acetylcholine agonist at the end plate anectine.
Why is succs non-reversible?
binds to motor end plate
metabolized by pseudocholinesterase
worry about succs in peds
peds increased # muscarinic receptors, leading to increased bradycardia, must give atropine prior to admin

unable to assess whether the child has duchenne's (r/t milestone progression). increased risk for MH with duchenne's
A drug that binds to receptor without activating & at same time prevents an agonist from stimulating it
Competitive antagonist
Bind reversibly to receptors & can be displaced by higher concentrations of agonists
Non-competitive antagonist
Bind to receptor with such affinity that even high concentrations of an agonist can not reverse receptor blockade
Unusually  LOW  dose of drug produces its expected pharmacologic effect
allergic (sensitized) to a drug
Unusually LARGE dose of a drug for expected pharmacologic effect
•- Hypo reactivity acquired from chronic exposure to a drug
–Opioids, Barbs, ETOH - due to neuronal adaptation or cellular tolerance
–tolerance that develops ACUTELY with only a few doses of a drug

Ex. Ephedrine: indirect acting synthetic noncatecholamine alpha and beta, often people develope tachyphlaxis due to the drugs indirect affect.
Ephedrine and Tachyphylaxis
•Persistent occupancy of adrenergic receptors
•EX.  Ephedrine induced blockade of adrenergic receptors continues even after B/P has returned to pre drug levels by virtue of compensatory CV changes  (atrial stretch receptors) •Depletion of norepi stores
Other mechanisms of tolerance
–Enzyme induction - CP450- this occurs when a pt is taking a medication at home which is metabolized by a pathway, sending it into overdrive, thus other drugs which use this pathway are metabolized more rapidly. Ex. Dilantin taken at home causes vecuronium to have a faster onset and shorter duration.
–Depletion of neurotransmitters - sustained stimulation. Ex. Catecholemines in trauma patients.
–Immunity - Due to formation of antibodies
Additive Effect
–A second drug acting with the first drug will produce an effect equal to an algebraic summation

1 + 1 = 2
Demoral and Visteril
–When two drugs interact to produce an effect that is greater than the algebraic summation

1 + 1 = 3
ETOH and valium
intrathecal and IV MSO4
–Enhancement of the first drugs action by administering a second drug that has nothing to do with the first drug

0 + 2 = 3
–ND muscle relaxant + Forane
–ND + Aminoglycosides: Can occupy cholinergic receptors at the NM junction
•Immune-mediated response allergic reaction
– Exaggerated response to a foreign substance
Immune Mediated
AKA= IgE mediation always
–An antigen-antibody complex
–Stimulates the production of IgE antibodies that fix to mast cells & basophils

Mast Cell Injury
Happens with overproduction of IgE
Mast Cells release a variety of strong chemicals, including histamine, into the tissues and blood that promote allergic reactions
itching, swelling, and fluid leaking from nearby cells. +muscle spasm (bronchoconstriction)
Exposure to substance in allergic response leads to
•Release of chemical mediators:
– leukotrienes
– histamines
– kinins
–platelet-activating factor
Anaphylactoid Rxn
•Resembles anaphylaxis but is not IgE mediated
•A drug itself activates the complement system
•***Although mechanisms differ, they can be clinically indistinguishable & equally life threatening
Note: it is most frequently seen with colloid administration of hedastarch.
Tx anaphylaxis or anaphylactoid rxn
•Stop offending agent
•Maintain airway/100%
•Volume expansion/Vasopresssors •Epinephrine (less is more…)
• Wheezing - Inhaler
•H1/H2 Blockers (Both need to be blocked. So given zantac and benadryl)
What the body does to the drug
–absorption                                    -distribution                                    -metabolism                                    -excretion

Is the branch of pharmacology dedicated to the determination of the fate of the substance administered to a living organism.
Volume of distribution (VD)
–Process of reversible transfer of a drug from one compartment to another within the body
–The concentration achieved AFTER distribution is complete as a result of: –DOSE ADMINISTERED
extracellular volume ECV =
Plasma volume PV+ interstitial volume ISV
Total Body Water
–Male - 45% of Body Weight
–Female - 55% of Body Weight

This is measured by ading the ICF and ECF
-Female =35%
M&F 20%
children 40%

note: children have a higher precent of ECF, this is why there are often differnt doses for children. This and that children have immature NMJs is why they recieve a higher dose of succs.
more VD
–volume into which a drug distributes in the body at equilibrium
–BEFORE   elimination starts
meas in L or Kg/L
Measuring VD
–Vd = A/C
A=( Amount of drug at equilibrium ) or total dose
C=(  Plasma drug concentration )
the larger the Vd
the smaller the fraction in the plasma
Disease states that alter VD
–Renal failure
–Hepatic dysfunction
–Age/Body composition
–CPB Machine (Hemodilution)
Drug variables that can alter VD
–Degree of binding to plasma proteins
–Partition coefficient of the drug in fat
–Degree of binding to other tissues
–Ph of the drug in blood at physiologic (7.40) ph
1 compartment model
–Body is perceived as a SINGLE homogenous compartment
–Drug distribution after injection is assumed to be instantaneous
–The concentration can decrease only by elimination of drug from the system
-concentration decreases with time
2 compartment model

central & peripheral •IV drug administered
–Goes into Central compartment –Distributed into peripheral compartment
–Back to Central compartment to be excreted
Central Compartment
–Intravascular Fluid
–Highly perfused tissues •Heart •Brain •Lung •Kidney •Liver (splanchnic bed) •+ Endocrine organs
2 compartment model
alpha phase =?
beta phase =?
alpha= distribution
beta =elimination
name %body mass and vol blood flow
VRG 10/75
Muscle 50/19
Fat 20/6
VPG 20/1-2
1st pass effect
Oral admin
–*Principle site of absorption after oral administration is the small intestine
–From the GI tract, drug enters the portal venous system
then liver
then systemic circ
for drugs excr by liver this is the reason for the lg diff btw oral and IV doses
No 1st pass effect
Yes 1st pass effect
rectal proximal portion, but not in the lower rectum

ex. brevitol has a high first pass effect
Absorbtion is defined as...
The process by which drugs are delivered to blood in their active form
Determinants of Absorption
–Route of administration
-Transport across membranes
–Bioavailability of the drug
– Protein Binding
-Degree of ionization
5 determinants of rate of diffusion
•Drug concentration
•  Drug molecular weight
•  Diffusion surface area (note, burns have increase SA to  succs because of increased number of receptors)
• Temperature
-Diffusion distance
*Higher conc will have more rapid onset (ie larger dose) but will last longer
Carrier Mediated Active transport
–Rapid transfer of organic substances –EX.  Facilitated by glucose & amino acids
–Molecules are placed in small vesicles then it crosses the cell membrane
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