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PHPY 304 General Principles Part 2

Terms in this set (43)

Drugs that don't use receptors
antacids
What is a receptor?
macromolecule whose biological function change when bound to a drug.
What is affinity?
force of attraction between drug and receptor
Dissociation constant (kd)
kd=k2/k1 the lower the value means higher affinity the drug has for receptor.
EC50
dose of drug that produces 50% of maximal response.
Emax
maximal effect of drug, measure of efficacy of drug.
Efficacy
bound drug's ability to change receptor to produce an effect
Kd
drug concentration that occupies 50% of total number of receptors at equilibrium.
Agonist
drug with affinity and intrinsic activity
Partial Agonist
has affinity but less efficacy
Antagonist
has affinity but no efficacy
Clinical significance of partial agonists
acts as antagonist in presence of agonist ex)buprenorphine
Partial agonist in presence of full agonist?
acts as an antagonist
Competitive Antagonism
presence of competitive antagonist means a higher dose of agonist is needed to have the same effect.
Non-competitive antagonism
presence of Non-competitive antagonist depresses Emax blocking agonist maximal effect
Allosteric Interaction with example
binding of ligand can affect binding/response to an agonist.
Quantal dose response curve
shows specific response in a group of individuals produced by a drug.
dose response curve
shows graded responses in a single individual produced by increasing concentration of drug
what is ED, TD, LD50?
effective, toxic and lethal
Therapeutic Index
TD50 or LD50/ED50
Therapeutic Window
difference between minimum effective concentrations for a desired and adverse response
Name 4 fundamental signal transductions mechanisms from slow to fast
1. Ion-channel receptors
2. G-protein coupled receptor systems
3. Enzymes as receptors
3. Nuclear receptors
3 major second messengers activated by GPCR's
cAMP cyclic adenosine monophos
IP3 inositol triphos
DAG diacyl glycerol
Enzyme receptor
interaction of 2 tyrosine phosphorylates it causing the activation of the enzyme. This then activates a number of other enzymes.
Examples of Ion Channel Receptors
Nicotinic acetylcholine receptor (conducts Na+ ions)
gamma aminobutyric acid conducts Cl- ions
Nuclear receptors
for steroids, retinoids and thyroid hormones.
Agonists tend to desensitize receptors
frequent stimulation of receptor causes a desensitization of receptors.
Antagonist up regulate receptors
causes a rebound effect as an increased in number of receptors affects the agonist.
Homologous desensitization
desensitization to one agonist at a receptor will desensitize other agonists at the same receptor
Heterologous desensitization
desensitization to one agonist at a recetor causes a desensitization to other agonists and receptor to produce the same response.
What was the report in USA about the study of 5381 women?
use of a drug during the first trimester of pregnancy which was an important period of organ and fetal development.
Drugs in Pregnancy classficiation
A safe
B likely safe: animals OK
C uncertain risk vs benefit
D likely unsafe risk vs benefit
X unsafe
Which trimester is the most important?
First trimester when the fetal development is most sensitive to drugs.
Explain drug transfer across placenta
drugs with mol. wt. >500D have incomplete transfer
mol. wt < 500D will transfer.
Pharmacokinetics in newborn or premature baby
variability in pharmacokinetics can be expected to be greatest when the body physiology is changing.
Enzymes during infancy
CYP2D6 and CYP2E1 expressed on first day where CYP3A4 is expressed within 1 week.
Newborns are unable to conjugate what and when?
glucuronic acid during phase 2 metabolism
Kidney function in neonates
renal elimination is reduced in neonates so dosing for drugs should be reduced to account for reduced renal clearance.
Pharmacodynamic differences in children and adults
antihistamines and barbiturates cause sedation in adults but cause hyperactivity in children due to children having increased sensitivity to sedating effects of propofol.
Physiological changes in elderly
Reduction in:
lean body mass, serum albumin, total body water
Increase in:
body fat percentage-increases volume of distribution of lipid soluble drugs
GFR decline in elderly
GFR declines after the age of 30yrs at 0.8ml/min/1.73m, decline accelerates after age 65-70
GFR of an average 85 yr old male
around 55-60 ml/min which is an approximately 50% decrease compared to age 30.
Liver function in the elderly
Hepatic blood flow and drug metabolism are reduced in elderly
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