M&M PharmPrinciples Flashcards
Process by which drug moves from site of admin to bloodstream
Absorption
Absorption is influenced by characteristics of drugs such as
Solubility
Pka
site of absorption
dose
Fraction reaching systemic circulation is
Bioavailability
Preferentially absorbed form of the drug is
nonionized
Acidic environment favors Absorption of (AAA)
Acidic drugs
Basic environment favors ABSORPTION of
Basic drugs
This route may be limited by first pass metabolism by the liver
Oral
Routes bypasses liver and first pass metabolims
SL or buccal
Provide prolonged continuous administration
Transdermal
What is the effective barrier to all but SMALL, highly potent lipid soluble drugs
Stratum Corneum
SC and IM injection depends on what
Diffusion from the site of injection to the circulation
During SC and IM , diffusion from the site of injection to the circulation depends on what
Blood flow to the area
Carrier vehicle
Which one is absorbed faster, solution, or suspensions?
SOLUTIONS
Irritating preparations can causes
pain and tissue necrosis
IV injections and absorption
Bypasses the process of absorption because the drug is placed directly into the bloodstream
The process of circulation of a drugs in the blood throughout the body is
Distribution
Name all the highly perfused organs?
Brain Heart Liver Endocrine glands Kidneys
Less perfused organs are? what is the significance?
Fat and skin ; equillibrate more slowly because of low blood flow.
What law do drug molecule obey?
law of mass action
Explain the law of MASS ACTION that drug molecule obey? (Gradient)
When plasma concentration exceeds the concentration in tissues, drugs moves from plasma to tissue. When the plasma concentration is less than the concentration in the tissue, drugs moves from TISSUE back to PLASMA
Binds many acidic drugs what protein?
Albumin
Binds many BASIC drugs what protein
Alpha 1 acid glycoprotein (AAG)
Diseases where albumin is decreased?
Renal
Liver,
Chronic CHF
malignancies
Alpha 1 acid glycoprotein (AAG) are increased in
TRAUMA( including surgery)
Infection
MI
Chronic pain
Alpha 1 acid glycoprotein (AAG) are decreased in
Pregnancy
The apparent volume into which a drugs has been distributed is called its
Volume of distribution (Vd)
How is Vd determined?
dose divided by concentration : Vd = Dose/concentration
Most anesthetic drugs are lipophillic or hydrophillic
liphophillic
Most anesthetic drugs are liphophillic resulting in a Vd that
Exceeds total body water .
What is total body water?
~ 40 L
The Vd of fentanyl is about
350L
The Vd of propofol may exceed
5000L
The chemical alteration of a drug is the ______aka____
biotranformation; metabolism
Primary organ of metabolism
liver
The primary end products of metabolism characteristics?
INACTIVE and WATER SOLUBLE
What drugs characteristics allows excretion by the kidney?
WATER SOLUBLE
Metabolism can be divided into 2 reactions
Phase I and Phase II
What happens during phase I reaction? name them
Convert drugs into a MORE POLAR metabolites through Oxidation, reduction or HYDROLYSIS
What happens during phase II reaction? name the process involved?
Phase II couples or CONJUGATE a parent drug or a phase I metabolite with an ENDOGENOUS SUBSTRATE, to form a water-soluble metabolites that are eliminated in urine or stool.
Example of endogenous substrate that may be used by phase II reaciton
GLUCORONIC ACID
Can a phase I metabolites be excreted without undergoing PHASE II biotransformation?
YES
Can a Phase II reaction precede or occur without a phase I reaction?
YeS
Volume of plasma of blood CLEARED of drug per unit of time is
HEPATIC CLEARANCE
What is hepatic clearance?
BLOOD FLOW times the HEPATIC EXTRACTION RATIO
Clearance = Q x E
What is the hepatic extraction ratio?
Fraction of drug entering the liver that is metabolized.
If the extraction ration is 50%, what is hepatic clearance
It is half of liver blood flow.
Principal organ of excretion
Kidneys
Kidneys: explain what happens with ionized and unionized fraction of the drug?
Ionized fraction of Drug EXCRETED IN URINE
NONionized fraction of drugs get REABSORBED in the RENAL TUBULES
What part of kidney are nonionized drugs absorbed at
RENAL tubules.
The rate of elimination of a drug from kidney excretion is the
Renal clearance
Renal clearance formula
Clearance = Q x E (renal extraction ratio)
What is enterohepatic circulation?
DRUG excreted into the bile and THEN REABSORBED in the intestine
Multi-compartment models provide
Mathematical framework to relate drugs dose to a drug concentration overtime
2 compartment drug model phases
Distribution or ALPHA phase
Elimination or BETA phase
Explain the distribution or alpha phase
After an initial bolus , there is a RAPID drop in concentration over the first few minutes as drugs quickly DIFFUSES into PERIPHERAL compartments
2 compartment graph explanation
x-axis
Y-axis
SHAPE
X-axis is the –> TIME after dose
y-axis is the –> PLASMA Concentration
STEEP drop then slow downward slope
Explain the Elimination or beta phase
Continued drop in concentration but LESS STEEP decline in plasma concentration
What is pharmacodynamics
How drugs affects the body
Concepts of pharmacokinetics are
ADME Absorption Distribution Metabolism Excretion
Concepts of PHARMACODYNAMICS are (PET)
POTENCY
EFFICACY
Therapeutic window
What does the dose response curve explain?
relationship between drug dose and pharmacologic effect
The shape of drug dose and pharmacological effect is
SIGMOIDAL in a log scale.
The sigmoidal shape of the dose response curve means that
a certain amount of drug must be present before there is any measurable physiologic response.
The left side of the dose response curve is flat until
the drug concentration reaches a minimum threshold.
The right side of the dose response curve is flat until
reflecting the MAXIMUM physiological response of the body.
What is the therapeutic window defined as
Difference between the concentration associated with a desired therapeutic effect and the concentration associated with a toxic drug response.
Therapeutic index is
Toxic concentration / therapeutic coencentration
What are drug receptors usually made of
Usually macromolecules typically proteins that bind a drug and mediate the drug response.
Bind a drug
Agonist
Reverses the effects of the agonist
Antagonist
Occurs when the ANTAGONIST competes with THE AGONISTS for the binding site , each displacing the other.
COMPETITIVE ANTAGONISM
WHEN the ANTAGONISTS through COVALENT BINDING or another process PERMANENTLY impaired the drug’s access to the receptor?
NONCOMPETITIVE ANTAGONISM
Drugs effect is governed by what?
FRACTION of receptors occupied
Fraction of receptors occupied is based on
concentration of drug
Concentration of a receptor
AFFINITY of drug to the receptor.
What is the RECEPTOR occupancy importance
the first step in mediating the drug effect.
Binding of a drug to a receptor can trigger MULTIPLE STEPS including
opening or closing of ion channel
activating of a G protein
activating an intracellular kinase
Interaction directly with a cellular structure, binding directly to DNA
Prolonged binding and activation of a receptor may lead to (PROLONGED AGONIST)
HYPO reactivity (desensitization) and TOLERANCE
If the binding of Endogenous ligand is chronically blocked, receptors may proliferate, resulting in (PROLONGED ANTAGONIST)
HYPERREACTIVITY and INCREASED SENSITIVITY.
Beta-blockers cause subtype-specific upregulation such that nonselective beta-blockers increase the density of both.
beta1- and beta2-adrenoceptors whereas beta1-selective antagonists upregulate only beta1-adrenoceptors
Chornic BETA blockers, As a consequence of increased sympathetic tone, cardiac beta-receptors are down-regulated in the
failing ventricle and dilated cardiomyopathy.
However, in the presence of acute myocardial ischemia there is rapid upregulation of beta-receptors in the presence of _____________which forms the basis of beta blockade therapy for treatment of ACS.
elevated circulating catecholamines,
