Chapter 2: Review of Basic Principles of Pharmacology Flashcards
What is pharmacology?
The study of drugs and their actions.
Pharmacokinetics is:
A) What the drug does to the body
B) The study of genetic attributes of an individual that lead to variable responses to drugs
C) What the body does to the drug
D) The description and analysis of the cost of drug therapy to healthcare systems and society
C. What the body does to the drug
Pharmacogenomics is:
A) What the drug does to the body
B) The study of genetic attributes of an individual that lead to variable responses to drugs
C) What the body does to the drug
D) The description and analysis of the cost of drug therapy to healthcare systems and society
B) The study of the genetic attributes of an individuals that lead to variable responses to drugs
Pharmacoeconomics are:
A) What the drug does to the body
B) The study of genetic attributes of an individual that lead to variable responses to drugs
C) What the body does to the drug
D) The description and analysis of the cost of drug therapy to healthcare systems and society
D) The description and analysis of the cost of drug therapy to healthcare systems and society
Pharmacodynamics are:
A) What the drug does to the body
B) The study of genetic attributes of an individual that lead to variable responses to drugs
C) What the body does to the drug
D) The description and analysis of the cost of drug therapy to healthcare systems and society
A) What the drug does to the body.
What are the four stages of what the body does to the drug?
Absorption
Distribution
Metabolism
Elimination
Rate of absorption determines how soon effects will begin based on:
- Route: IV, IM, PO, topical, rectal, inhaled, etc
- Characteristic of pharmaceutical preparation (e.g. immediate versus extended release).
- Amount of absorption determines intensity of effect: plasma drug levels
- Bioavailability of drug: percentage of administered dose that enters the bloodstream
Where in the body does more oral absorption occur: A) The mouth B) The stomach C) The colon D) The small intestine
D) The small intestine
Most oral absorption occurs in the small intestine (duodenum, jejunum and ileum)
Absorption is:
The movement of a drug from its site of administration into the blood.
What does it mean for a drug to have low bioavailability?
A) A high percentage of administered dose enters the bloodstream
B) A low percentage of administered dose enters the bloodstream
C) The drug was administered incorrectly
D) The drug will have a short half-life
B) A low percentage of administered dose enters the bloodstream
Because the percentage of the administered dose that does enter the bloodstream is called the bioavailability of the dosage form.
Drugs give via parenteral administration are 100% bioavailable because they are administered directly into the bloodstream.
What types of medications do NOT pass through membranes easily? A) Non-ionic (neutral) molecules B) Lipophilic molecules C) Polar molecules D) Small molecules
C) Polar molecules
Neutral, lipophilic and small molecules WILL PASS relatively easily through the plasma membrane.
Medications
MEDICATIONS that do NOT PASS through the plasma membrane easily include: polar molecules, ions, and large molecules
Distribution is:
The movement of drugs throughout the body
Factors affecting distribution include:
- Blood flow
- Lipid/water solubility
- pH (pH changes the charge of drugs depending on the pKa)
- Protein binding (Albumin; Can increase circulation, decrease metabolism and excretion; Needs to be unbound to have effect)
- Transport systems (E.G., p-glycoprotein)
What are the three ways a drug can pass across a cell membrane?
- Through channels and pores
- Via Transport systems (P-glycoprotein)
- Direct penetration of the membrane
What are the two barriers that should be considered with thinking of drug distribution?
- The Blood Brain Barrier (BBB). Capillary endothelial cells are surrounded by a sheath of glial tissue. Is impermeable to water soluble drugs and ionized drugs
- Plancental Barrier (Pregnancy). Lipid membrane that allows passage of drugs by simple diffusion. Smaller molecules cross most easily.
P-glycoprotein (P-gp) does what?
P-gp plays a part in drug distribution:
1) It is a membrane bound transport system which moves drugs from across membranes (Member of ATP binding proteins).
2) Affects the level of substrate available for absorption/elimination (If a P-gp inhibitor is given, P-gp substrate levels will rise)
Which of the following is a P-gp substrate: A) verapamil B) carvedilol C) digoxin D) ketoconazole E) B & C
E) B & C
Examples of P-gp substrates:
carvedilol
diltiazem
digoxin
verapamil and ketoconazole are P-gp inhibitors
Which of the following is a P-gp inhibitor? A) quinidine B) carvedilol C) diltiazem D) digoxin E) none of the above
A) quinidine
Other examples of P-gp inhibitors include:
verapamil
cyclosporine
ketoconazole
carvedilol, diltiazem, and digoxin are all P-gp substrates
Where are the majority of plasma proteins produced? A) Lymph tissues B) Spleen C) Liver D) Bone marrow
C ) Liver
Many plasma proteins are produced in the liver and their presence in the blood reflects liver function, nutritional status, and the effect of aging and disease. ALBUMIN is a major protein in the blood and is measured as a part of typical blood analysis.
Drug bound to plasma proteins can freely circulate in the bloodstream rather than be distributed by passive diffusion from their site of absorption, so plasma protein binding helps normalize drug concentrations in the body. Also plasma protein bound drugs can be protected from metabolism in the liver and excretion by the kidneys, which can EXTEND THE PERIOD OF TIME that drugs remain in the body.
ALBUMIN
- Most abundant and important
- Large molecule that always remains in the bloodstream
- Impacts drug distribution: if drug is bound to protein, it cannot leave the blood to get to its site of action (protein is too large) FOR EXAMPLE: phenytoin
Metabolism
Transformation of a drug by enzymes into metabolites.
It is the process of changing one chemical into another, and the process usually creates or uses energy.
What happens when a drug is metabolized?
Transformed into a molecule that is:
- -More easily excreted
- -Usually becomes more water soluble (less lipid soluble)
- -Increased or decreased therapeutic action
- -Increased or decreased toxicity
True or False: Phase I Metabolism reactions are called synthetic reactions and involve adding something to the drug to synthesize a new compound.
False: Phase I Metabolism reactions are called NON-synthetic reactions and involve oxidation, reduction, and hydrolysis (Cytochrome P450 {CYP 450} system)
What are prodrugs?
A) A drug before it is approved by the FDA.
B) People who support the use of medications.
C) Compounds that are excreted quickly.
D) Drugs that rely on metabolism to become active.
D) Drugs that rely on metabolism to become active.
True or False: Phase II Metabolism reactions are called synthetic or conjugation reactions because drug molecules are metabolized and something is added to the drug to synthesize a new compound
True. Metabolites are linked, or conjugated, to highly polar molecules such as glucuronic acid, glycine, sulfate, or acetate by specific enzymes.
True or False:
Conjugation to drug molecules in Phase II Metabolism reactions makes metabolites more water soluble and easier to excrete by the kidneys.
True: Metabolites are more water soluble and more easily secreted by the kidneys, so the presence or activity of these enzymes can influence the pattern of drug activity and duration of action for drugs.
Which of the following is a change in ADME associated with the elderly? A) Increased acid secretion B) Decrease in lean body mass C) Increased hepatic blood flow D) Increased renal function
B) Decrease in lean body mass
Cytochrome P450 (CYP450) enzymes are primarily found in which organ: A) The heart B) The kidney C)The liver D)The brain
C) The Liver
Account for 70-80% of the enzymes involved in drug metabolism
Examples:
CYP3A4 – 50% of drug metabolism
CYP2D6 – 25% of drug metabolism
*Selective serotonin reuptake inhibitors (SSRIs), Tricyclic antidepressants (TCAs), Beta blockers, codeine
CYP2C9
*Warfarin, antiepileptic drugs (phenytoin), glipizide
Some Prodrug examples:
L-DOPA=> dopamine
Codeine(CYP2D6)=> morphine
Hydrocodone (CYP2D6)=> hydromorphone
Meperidine (CYP2B6, 2C19, 3A4)=>normeperidine (toxic and has a long half-life of 14-21 hours in patients with normal renal function…must be careful with administration of this).
Excretion
The process in which drugs are transferred from inside the body to outside the body.
First Pass Metabolism refers to what?
Metabolism by the liver following oral if administration is called first-pass metabolism and is important in determining whether a drug can be orally administered
- -Some drugs can be completely inactivated on first pass if liver is able to metabolize
- -For this reason some medications cannot be given orally (E.G., nitroglycerin)
What is the primary organ of excretion for most drugs: A) The colon B) The liver C) The lung D) The kidney
D) The kidney
The kidney is the primary organ of excretion for most drugs.
The strategy of the kidney is to allow removal of a large volume of plasma and then to take back the substances that the body needs.
What is the glomerular filtration rate (gfr)?
It is a measurement of renal function. It measures the amount of blood flow through the glomeruli in the kidneys per minute.
Name the primary organs for drug elimination
Kidneys, lungs, biliary system, and intestines.
Any individual drug may rely on one or more of these sites for elimination or on a different site, such as skin excretion or excretion into saliva or breastmilk.
In excretion what is “ion tapping”?
Acidification of the urine creates an “ion tapping” situation that favors the excretion of basic drugs and metabolites, whereas basic urine encourages the excretion of acidic drugs and metabolites.
Other than the kidney and liver where else can drugs be excreted?
Drugs can diffuse out of the body at various sites, and although these excretion sites are typically not major, they can be important for forensic and clinical reasons.
- Pulmonary excretion can excrete any volatile material present in the body. Pulmonary excretion is important for an aesthetic gases such as nitrous oxide and helps rid body of alcohol by breathing off ethanol.
- Drugs can be excreted through the skin, although this is often a minor route of elimination. Additionally, drugs can be excreted out through the sweat in saliva.
- Drugs can also be excreted into the breast-milk of nursing mothers.
True or False?
Competitive inhibitors bind to the same site as the substrate.
True
What is the ratio of the LD50 to the ED50 called? A) Efficacy B) Potency C) Toxic Dose D) Therapeutic Index
D) Therapeutic Index
Simvastatin is metabolized to its inactive metabolite in part by CYP3A4. Diltiazem is an inhibitor of CYP3A4. Which of the following is most likely to happen if simvastatin and diltiazem are taken together?
a) Increased concentration of simvastatin
b) Increased concentration of diltiazem
c) Decreased concentration of simvastatin
d) Decreased concentration of diltiazem
A) Increased concentration of simvastatin
Approximately how many half-lives does it take for a medication to reach steady state?
a) 7
b) 6
c) 5
d) 4
C) 5
CYP2C9 is involved in the metabolism of warfarin. If a SNP leads to a mutation in the gene for CYP2C9 which results in the patient being a poor metabolizer, how will the patient respond to warfarin?
a) Increased response
b) Decreased response
c) No change in response
d) Either B or C
A) Increased response
Rationale
Which of the following costs is correctly matched to its type of cost?
a) Cost of valsartan – direct nonmedical cost
b) Cost of driving to get lab tests done – direct medical cost
c) Cost of losing job due to illness – direct nonmedical cost
d) Cost of pain from amputation – intangible cost
D) Cost of pain from amputation-intangible cost
Rationale:
A) Medication costs are DIRECT MEDICAL COST
B) Transportation costs are DIRECT NON-MEDICAL COST
C) Cost of losing a job due to illness is an INDIRECT MEDICAL COST
(see p. 132)
