Test one: General Principles Flashcards
What is the strongest and least desirable drug binding force?
Covalent bonds–irreversible (aspirin)
What are the 3 major subdivisions of pharmacology?
Pharmacodynamics (mechanisms of drug action), pharmacokinetics, and pharmacotherapeutics
Assumptions of the occupation theory
- One molecule reversibly combines with a single receptor
- The binding is independent of other drug-receptor interactions
- The receptors are identical and equally accessible to the drug
- Only a small portion of the total drug is involved in the formation of complex with the receptor
- The biologic response is proportional to the degree of receptor occupancy and independent of time.
Exceptions to the occupation theory
some receptors have subclasses
some receptors can be desensitized
some receptors give a different response based on the type of tissue that they are in.
some receptors may require cooperative interactions of ligands before they give a response, or the amount of response is determined by how many ligands are bound to them.
What type of antagonist has affinity but not intrinsic activity?
Pharmacological antagonist (competitive/reversible or noncompetitive/irreversible)
What is the definition of an inverse agonist?
Elicits the opposite response as the agonist
What is the problem with IV route of administration?
Compliance (difficult to get an iv to take drug) and solubility (some drugs aren’t soluble); also difficult to remove from system
How does a non-competitive antagonist bind to a receptor?
Covalently–irreversibly
What is the difference between a competitive and non competitive antagonist?
Competetive shifts the dose response curve of the agonist to the right. Non-competitive will prevent the agonist from reaching the max response regardless of dose (SHIFTS RIGHT AND DOWN)
What are the 4 aspects of pharmacokinetics?
Absorption, distribution, metabolism/biotransformation, excretion
Where are weakly acidic drugs absorbed?
Stomach–environment with lower pH than its pKa to shift it to its nonpolar/lipid soluble form
Where are weakly basic drugs absorbed?
Small intestines
Chemical equivalence
Two or more drugs with equivalent amounts of the same active ingredient
What is bioavailability/bioequivalence?
Rate and extent of drug absorption, two formulations produce similar concentrations of a drug in blood and tissue (same area under curve)
Absolute bioavailability
Comparing a dosage form of bioavailability to that of iv–area under curve/dose
Relative bioavailability
Comparing two different forms of dosage
Therapeutic equivalence
Drugs that produce the same efficacy and toxicity in identical dosage forms
What are the 3 types of bio transformation?
Hepatic microsomal metabolism, hepatic non microsomal, and non hepatic metabolism
Volume of distribution (Vd)
The amount of water by which a particular dose of a drug would have been diluted to produce a given plasma concentration
Vd=Q/C, Q is quantity of drug administered and C is plasma concentration
What does a high Vd mean?
The drug is more diluted in plasma than it should be (more of it is in tissue)
What is the distribution of water in the body?
3L in plasma, 9L in interstitial fluid, 29L in intracellular fluid
How is Vd affected by liver/renal failure?
It increases due to fluid retention. Vd decreases in dehydration.
Why do highly lipid soluble drugs cause a metallic taste in the mouth?
Lipid soluble drugs have higher Vd and distribute to the saliva more easily
What are the phases in microsomal metabolism?
Phase one- nonsynthetic. Cp450 increases the polarity of the drug to make it more water soluble for eventual excretion. Typically happens via oxidation (reduction, hydrolysis, dehalogenation, and dealkylation are other options)
Phase two-synthetic: drug combines with glucuronic acid to further the polarity for excretion
What factors can affect biotransformation?
Delivery/entry in to the liver, enzyme inhibitors, enzyme inducers, age (very young or old), genetics, pathology
First pass drug biotransformation
Drug is absorbed from digestive system to enter portal system–>metabolized by liver so that only a small amount of active drug actually enters circulation. Avoid by iv administration
CYP1A1/2: substrate, inhibitor, and inducer
Substrate: acetaminophen/Tylenol
Inhibitor: cimetidine/Tagamet
Inducer: omniprazol
Enterohepatic cycling
Metabolism of drug in liver, excreted into bile into intestinal lumen, drug is reabsorbed by intestinal mucosa to reenter liver–this causes peaks and a longer half life in plasma (ie: morphine)
CYP-2A6: substrate, inhibitor, and inducer
Substrate: acetaminophen/Tylenol
Inhibitor: pilocarpine
Inducer: barbiturates
Does induction of microsomal enzymes increase or decrease acetaminophen toxicity?
Drugs that are inducers will increase its toxicity
What form of the drug is filtered into the glomerulus?
Free floating drugs–not bound to plasma protein
In what state can drug metabolites be reabsorbed?
Nonpolar
Clearance=
CL=U*V/P (amount of drug removed by kidney per unit of time)
U=urine concentration
V=urine volume
P=plasma concentration
How are clearance and distribution related?
CL= Ke*Vd, Ke= elimination rate constant
Zero order elimination kinetics
Dc/dt= Ko
Drug elimination is independent to concentration of drug; elimination is constant over time (ie:ethanol)
How is first order kinetics different than zero order?
Rate of metabolism is proportional to drug concentration. There is a constant fractional rate of metabolism dc/dt=Kc
How do you calculate half life of a first order reaction?
T1/2= 0.693/K
The single compartment model is based in what type of kinetics?
First order; body is displayed as one compartment with it’s size corresponding to Vd; helps with constructing theoretical plasma curves where dose, absorption, and elimination can be altered to see change in concentration and effect
What drugs follow the two compartment model?
Lipophilic drugs
What are the compartments in the two compartment model?
Drug initially entered into central compartment where it undergoes rapid metabolism. Drug can also be distributed to peripheral tissue/fat where it is released slowly
Tachyphylaxis
Drop in response to a drug/resistance; more of the drug is needed to achieve same response (ie: Afrin)
How do physicians account for the difference in pharmacotherapeutics with every individual?
Drugs can be titration to provide the appropriate dose to achieve max effects and minimize side effects
What factors influence therapeutic effects?
Patient factors (weight, age, pregnancy, etc), drug factors (concentration and tolerance), and drug regimen (placebo, medication error and pt noncompliance, and drug interactions)
