Pharmacodynamics Flashcards
Drug actions
Stimulate or inhibit normal cellular functions
Cannot add functions
Drug binding to drug targets
Weak: reversible
H bond, ionic, hydrophobic bond
Few are covalent
Drug selectivity
Size, shape, and charge of a drug determine whether it binds to a particular receptor
Drugs for ion channels
Altering the conductance of ion channels
Eg:
Local anesthetics: diffuse inside to the cytoplasm, bind to specific binding site on channel, close it
Sedative-hypnotics for anxiety
Antiepileptics
Drugs for GPCR
60% of prescription
Eg:
Albuterol: bata2-agonist, for asthma
Propranolol: beta-antagonist, for hypertension
Drugs for enzyme-linked receptors
Insulin receptor
EGFR
Anticancer drug
Gain-of function mutations in these tyrosine kinase R can lead to cancer
Important in cell growth and differentiation
Eg:
Imatinib: for leukemia
Members of nuclear R superfamily
Steroid hormones
Thyroid hormones
Vitamin D
Drugs targeting enzymes
Inhibit enzyme activity
Eg:
Aspirin
Ibuprofen
Omeprazole
Drugs targeting transporters
Target nt transporter for psychiatric disorders
Eg:
Antidepressant drugs: blocking serotonin reuptake
Drugs targeting structural proteins
Bind to tubulin, prevent polymerization, arrest cells in metaphase
Drugs not binding to receptors
Antacids: neutralize gastric acid
2 types of dose-response relationships
Graded
Quantal
Graded dose-response curves
E=Emax*C/(C+EC50)
Hyperbolic
Receptor binding of drugs
B=Bmax*C/(C+KD)
KD:concentration of drug required to occupy half of the receptors
Affinity: measure the strength of drug-receptor complex
Graded dose-response curves
Drug effect agains log of C
Sigmoid curve
Compare the value of eE50 and KD
KD is larger than EC50
Because an agonist does not have to occupy all receptors to evoke a full response
Spare receptors
Indicating that there is signal amplification
EC50 in whole animal experiments
Is ED50 = log of drug dose since cannot measure drug concentration
Efficacy
Magnitude of the response a drug produces
=Emax
Potency
C of the amount of drug necessary to produce an effect of a given magnitude
Measured by EC50
Agonist
Bind and activate R
Has affinity and efficacy
Antagonist
Inhibit agonist
Has affinity but no efficacy
Bind and do nothing
Receptor antagonism
Competitive
Noncompetitive
Nonreceptor antagonism
Physiological
Chemical
Reversible competitive antagonist
EC50 increase
Same Emax
Irreversible competitive antagonism
Reduced Emax
Same plot as allosteric
Noncompetitive antagonism
Allosteric
Reduced Emax
Physiological antagonism
1 drug opposes another drug, thru different receptors
Eg:
Epinephrine vs histamine
Chemical antagonism
Reacts chemically with an agonist to form an inactive product
Eg:
Protamine + charged
Counteracts heparin, anticoagulant - charged
Partial agonist
Produce lower Emax than full agonist
Competitive antagonist to full agonist
Inverse agonist
Reverse the constitutive activity of R
Therapeutic index
TI=TD50/ED50
Or LD50/ED50
Safe drug: large LD small ED
Therapeutic window
Min effective C and min toxic C
