Basic Principles Flashcards
____ actions of a drug on the body
Pharmacodynamics
___ actions of the body on the drug
Pharmacokinetics
Arrange to according to decreasing strength
Covalent, Hydrophobic, Electrostatic bonds
- Covalent
- Electrostatic
- Hydrophobic bonding
[Type of diffusion]
passive movement of non-protein bound drugs
Aqueous diffusion
[Type of diffusion]
affected by the drug concentration and charge
Aqueous diffusion
[Type of diffusion]
governed by Fick’s Law of Diffusion
Aqueous diffusion, Lipid Diffusion
[Type of diffusion]
movement of drugs through lipid membranes from ECF to the ICF
lipid diffusion
[Type of diffusion]
most important limiting factor for permeation
Lipid diffusion
[Type of diffusion]
important for the diffusion of weak acids and weak bases
Lipid diffusion
[Type of diffusion]
for drugs that do not readily cross through membranes; transported across barriers by mechanisms that carry similar endogenous substances
transport by special carriers
[Type of diffusion]
not governed by Fick’s law of diffusion is capacity-limited
transport by special carriers
[Type of diffusion]
vitamin B12 bound to intrinsic factor is a type of _____
endocytosis
pinocytosis
[Type of diffusion]
iron bound to transferrin
endocytosis and pinocytosis
[Water/Lipid Solubility of Drugs]
____ is directly proportional to electrostatic charge
directly proportiona
[Water/Lipid Solubility of Drugs]
ionized and polar drugs _____ (water/lipid soluble)
water soluble
[Water/Lipid Solubility of Drugs]
this is associated with an increased clearance
water soluble
[Water/Lipid Solubility of Drugs]
inversely proportional to electrostatic charge
inversely proportional
What are the 3 dependent factors for permeation?
- Solubility
- Concentration gradient
- Surface area and vascularity
[Water/Lipid Solubility of Drugs]
unprotonated weak acid
more water-soluble, better clearance
[Water/Lipid Solubility of Drugs]
protonated weak acid
more lipid soluble, more likely to cross biological membranes
[Water/Lipid Solubility of Drugs]
unprotonated weak base
more lipid soluble, cross biological membrane
[Water/Lipid Solubility of Drugs]
protonated weak base
more water soluble, better clearance
[Absorption/Excretion]
if a compound is placed in a solution above its pKa
this favors? (Absorption/excretion)
favors absorption
Above its pKa, unprotonated form predominates, which favors absorption
[Absorption/Excretion]
if a compound is s placed in a solution below its pKa
this favors? (Absorption/excretion)
favors excretion
Below its pKa, protonated form predominates, which favors absorption
[Absorption/Excretion]
if a weak base is placed in an acidic environment?
this favors? (Absorption/excretion)
favors excretion
Again, basic drugs are excreted in an acidic environment
[Absorption/Excretion]
if an acidic compound is placed in an alkalitic environment
this favors? (Absorption/excretion)
favors excretion
What are the 3 major factors that affect drug absorption>
- Route of administration
- Blood flow
- Concentration
[Route of drug administration]
highest first pass effect?
oral route
[Route of drug administration]
potentially more dangerous
IV route
[Route of drug administration]
bypasses first pass effect
IV
IM
SQ
Buccal/Sublingual
[Route of drug administration]
anticoagulants cant be given by this route
IM
[Route of drug administration]
IM injection to buttocks is safest at
superolateral
[Route of drug administration]
inferomedial buttock IM injection can result to this complication
sciatica
[Route of drug administration]
superomedial buttock IM injection is associated with this gait
gluteus medius gait
[Route of drug administration]
Offers direct absoprtion to systemic venous circulation, bypasses the FPE
Buccal/Sublingual
[Route of drug administration]
trace the route of the drug via the sublingual route before reaching the heart
lingual, IJV, Brachiocephalic, SVC, RA
[Route of drug administration]
partial avoidance of the FPE, used for large amounts of drugs with unpleasant tase
Racta
[Route of drug administration]
offers delivery closes to target
inhalational
[Drug distribution]
What are the factors that affect drug distribution?
- Size of the organ
- Blood flow
- Solubility
- Protein binding
[Drug distribution]
Basic drugs are bound to these proteins ____
orosomucoid and alpha 1 acid glycoprotein
[Drug distribution]
acidic drugs are bound to this protein
albumin
Drug with the lowest molecular weight, can cross BBB
lithium
Drug that is water soluble, but can cross the BBB because it has a low molecular weight
ethanol
the duration of drug action is determined by?
- dose administered
2. rate of elimination following last dose
[Drug elimination]
rate of elimination is proportionate to the concentration
first order
[Drug elimination]
rate of elimination is constant regardless of concentration
Zero-order
What drugs display zero order elimination kinetics?
- Warfarin
- Heparin
- Aspirin
- Tolbutamide
- Phenytoid
- Ethanol
- Theophylline
What are the characteristics of a receptor?
- Selective in their ligand-binding
- modifiable
- most are proteins
[Graded dose-response relationship]
___ concentration required to bind 50% of the receptors
Kd
[Graded dose-response relationship]
A ____ kd is associated with greater affinity for its receptor
smaller Kd
[Graded dose-response relationship]
____ is the maximal effect achievable with increasing concentration of a drug
Emax
[Graded dose-response relationship]
____ concentration of drug wherein half of the maximal effect is achieved
EC50
[Graded dose-response relationship]
___ maximum percentage of receptors with increasing concentration of a drug/maximal number of receptors boudn
Bmax
[Type of dose response curve]
response of a particular receptor-effector mechanism measured against increasing drug concentration
dose response
[Type of dose response curve]
fraction of the population that response at each dose against the log of the dose administered
quantal dose-reponse curve
[Type of dose response curve]
Efficacy and potency are derived from this curve
graded dose-response curve
[Type of dose response curve]
Median effective, median toxic, median lethal doses are derived from this curve
quantal dose-response curve
What is the formula to determine the therapeutic index?
TI = TD50/ED50
___ refers to the dose range between the most effective dose and the most toxic dose
Therapeutic index
___ refers to the amount of drug needed to produce a given effect
potency
___ is determined by the affinity of the receptor for the drug (efficacy/potency)
potency
Noncompetitive antagonist causes ____ shift of the DRC
downward
competitive antagonist causes _____ shift of DRC
right shift
_____ continuous activation may lead to depletion of essential substrates
tolerance
____ responsiveness diminishes rapidly after administration of a drug; frequent or continuous exposure to agonist results in short-term diminution of the receptor
tachyplaxis
[Volume of distribution]
a low Vd distributes in?
blood
[Volume of distribution]
a high Vd distributes in?
tissues
___ most important pharmacokinetic parameter to be considered in defining rational steady state during dosage regimen
clearance1
Steady state is achieved after how many half-lives?
4-5
___ are also called mixed function enzyme
Cyt P450
____ is a standard in vitro test for mutagenicity
Ames test
____ is an in vivo mutagenicity test carried out in mice
dominant lethal test
[Clinical trial]
____ preclinical data collected up to time ofsubmission
investigation
[Clinical trial]
____ request for approval of general marketing of the agent for prescription use
new drug application
[Clinical trial]
evaluation of the dose-response relationship and pharmakokinetics among normal human volunteers (20-100 volunteers)
Phase 1 Trial
[Clinical trial]
in phase 1 trial of a cancer drug, how many volunteer patients are needed
20-50
[Clinical trial]
100-200 patients with target disease, done in hospital ward
phase 2
[Clinical trial]
1000-5000 patients; double-blind crossover design
phase 3
[Clinical trial]
post marketing surveillance
phase 4
