1Basicprinciplesofpharm Flashcards

Question

Do protein bound molecules exert any pharmacological effects?

Answer 1

No they are not available to do so

Answer 2

-Narrow margin of safety or narrow therapeutic window Little difference between therapeutic effect and toxicity -98% protein bound -Addition of second highly protein bound drug such as aspirin competes for the protein resulting in more free drug for both warfarin and aspirin through inhibition of clearance of warfarin.

Answer 3

Yes. you have to give enough to make it work. Think of musical chairs: more kids/chair=more free drug(has an effect)

Answer 4

Passive transport: paracellular transport and diffusion Active transport: facilitated diffusion and drug transporters Ion Channels: voltage activated Na channel and ligand gated Na channel

Answer 5

-relates the amount of drug in the body to the serum concentration -determined by the physiologic volume of blood and tissues and how the drug binds in blood and tissues -used to calculate the loading dose of a drug that will immediately achieve a desired steady-state concentration gentamicin

Answer 6

Total body water and then fat

Answer 7

``` -more total body water 94%fetus 85%preemies 78% full term baby 60%adult -more extracellular fluid 50%preemies 35%4-6month 25%1year 19%adult Example: gentamicin distribution volumes of 0.48 L/kg in neonates and 0.2 L/kg in adults -decreased binding of drugs to plasma proteins: lower plasma protein concentration, binding capacity, affinity of proteins, competition ex: phenobarbital, salicylates, phenytoin -decreased body fat ```

Answer 8

- increased body fat: volume of dist. of fat soluble drugs may increase - decreased plasma albumin: increase vol of dist. of drugs that are highly protein bound

Answer 9

- decreased total body water - decreased lean body mass - ↑ body fat - decreased serum albumin - increased α1-Acid glycoprotein (↔ or ↑ by several disease states) - ↓ cardiac output

Answer 10

specific molecules in a biologic system with which drugs interact to produce changes in the function of the system

Answer 11

drugs bind to and activate the receptor in some fashion, which directly or indirectly brings about the effect

Answer 12

binds to its receptor but produces a smaller effect at full dosage than a full agonist

Answer 13

drugs, by binding to a receptor, compete with and prevent binding by other molecules

Answer 14

drugs bind to the same receptor molecule but do not prevent binding of the agonist - may enhance or inhibit the action of the agonist molecule - not overcome by increasing the dose of agonist

Answer 15

is an antagonist that cannot be overcome by increasing the agonist

Answer 16

Narcotics and Narcan

Answer 17

Look at slide 36 for diagram

Answer 18

- Unchanged—excreted as is - Changed through metabolism: - Active drug - Inactive drug

Answer 19

- Most important: liver - Kidneys important in some drugs met. - Few drugs(esters) are metabolized in many tissues(liver, blood, intestinal wall) because of the wide distribution of their enzymes

Answer 20

- convert the parent drug to a more polar (water-soluble) or more reactive product by unmasking or inserting a polar functional group such as —OH, —SH, or —NH2 - Cytochrome P450 enzyme species (eg, CYP2D and CYP3A4) that are responsible for much of drug metabolism. Many isoforms of CYP have been recognized *50% of drug reactions go through cytochrome P450: problem is that a lot of other drugs can rev it up or inhibit it

Answer 21

increase water solubility by conjugation of the drug molecule with a polar moiety such as glucuronate, acetate, or sulfate

Answer 22

An ATP-dependent transport molecule found in many epithelial and cancer cells. The transporter expels drug molecules from the cytoplasm into the extracellular space. In epithelial cells, expulsion is via the external or luminal face

Answer 23

-Usually convert the parent drug to a more polar metabolite Introduce or mask a functional group =OH, -NH₂. –SH -Usually changed to inactive May be modified or even enhanced -Polar metabolite generally more easily excreted

Answer 24

-Generic name for the group of enzymes that are responsible for most drug metabolism oxidation reactions. (Phase I) -Several P450 isozymes have been identified CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4

Answer 25

2D6 and 3A4

Answer 26

-drug which is metabolized by one of the CYP450 enzymes -Example Acetaminophen is metabolized by CYP1A2

Answer 27

-drug which can increase the activity of a CYP450 enzyme Example Smoking increases the activity of CYP1A2 What happens to acetaminophen then? decreases due to increased enzyme activity (metabolism increases) *a second drug that comes into the system and increases the activity of that particular cytochrome

Answer 28

-drug which can decrease the activity of a CYP450 enzyme Example Fluvoxamine decreases the activity of CYP1A2 What happens to acetaminophen then? Increased due to decreased enzyme activity(metabolism decreases)

Answer 29

- Increases(cyp3a4 blocks cocaine metabolism, so more cocaine stays in the body) - Cocaine is metabolized at a higher rate, is out of system faster

Answer 30

-Often the subsequent reaction (to Phase I) -Form a highly polar conjugate: Glucuronic acid (glucuronidation UDP) Sulfuric acid (sulfation SULTs) Acetic acid (Acetylation NAT) Amino acid Glutathione conjugation (GST) Glycine conjugation Methylation (TPMT, SAMe MT)

Answer 31

P-gp inhibitors include verapamil, and furanocoumarin components of grapefruit juice(not all grapefruit juices are equally potent) Important drugs that are normally expelled by P-gp (and are therefore potentially more toxic when given with a P-gp inhibitor) include digoxin, cyclosporine, and saquinavir.

Answer 32

-Drug metabolism is substantially slower in infants than in older children and adults. Example: Higher serum concentrations of morphine are required to achieve efficacy in premature infants than in adults Infants are not able to metabolize morphine adequately to its 6-glucuronide metabolite (20 times more active than morphine -Sulfation pathway is well developed in infants -Glucuronidation pathway is undeveloped in infants Example: acetaminophen metabolism by glucuronidation is impaired in infants compared with adults partly compensated for by increase through the sulfation pathway balanced to some degree because clearance of morphine quadruples between 27 and 40 weeks of postconceptional age

Answer 33

Hepatic perfusion increases: | theoretically increases the hepatic extraction of drugs

Answer 34

↓ Hepatic size ↓ Hepatic blood flow ↓ Phase I (oxidation, reduction, hydrolysis) metabolism (therefore includes the CYP450 enzymes)

Answer 35

Condition in which the average total amount of drug in the body does not change over multiple dosing cycles ie, the condition in which the rate of drug elimination equals the rate of administration

Answer 36

YES. | Linear pharmacokinetics: steady-state serum drug concentrations change proportionally with long-term daily dosing.

Answer 37

serum concentration changes more or less than expected. (does not change proportionally like in linear)

Answer 38

- Time required for serum concentrations to decrease by one-half after absorption -and distribution are complete - Determines the time required to reach steady state and the dosage interval

Answer 39

- Dependent kinetic variable because its value depends on the values of clearance and volume of distribution - Disease, age, and other variables usually alter the clearance of a drug much more than they alter its Vd

Answer 40

* Most important pharmacokinetic parameter - Determines the steady-state concentration for a given dosage rate - Determined by blood flow to the organ that metabolizes or eliminates the drug - Efficiency of the organ in extracting the drug from the bloodstream. Can increase or decrease open/close spigot analogy

Answer 41

First order: time to remove drug is a percentage: cuts down by half each half life 50-->25-->12.5 Zero order: same amount each time 50-->47.5-->45

Answer 42

``` -Primary: Kidney -Others: Lungs Skin GI Biliary Salivary Mammary ```

Answer 43

- Renal disease or reduced cardiac output often reduces the clearance of drugs that depend on renal function. - Alteration of clearance by liver disease is less common but may also occur. - Impairment of hepatic clearance occurs (for high extraction drugs) when liver blood flow is reduced, as in heart failure, and in severe cirrhosis and other forms of liver failure.

Answer 44

- Total filtration rates of functioning nephrons of kidney - GFR cannot be measured directly - Variables: gender, age, weight, and race - Used for the detection, severity, and treatment of kidney disease

Answer 45

-Efficiency of renal excretion is determined by: glomerular filtration tubular secretion tubular reabsorption -Processes may not develop fully for several weeks to 1 year after birth

Answer 46

-Maternal plasma volume, cardiac output, and glomerular filtration increase by 30% to 50% or higher: potentially lowering the concentration of renally cleared drugs -Higher levels of estrogen and progesterone alter liver enzyme activity: increase the elimination of some drugs but result in accumulation of others

Answer 47

``` ↓ GFR ↓ Renal blood flow ↓ Filtration fraction ↓ Tubular secretory function ↓ Renal mass ```

Answer 48

-Modification of Diet in Renal Disease (MDRD) equation Estimates GFR adjusted for BSA More accurate than ----Cockroft-Gault Used by most laboratories as eGFR Cockroft-Gault equation Uses body weight Is the standard for drug dosing

Answer 49

``` Age Gender Weight Ethnic background Concurrent disease states Other drug therapy ```

Answer 50

-Deals with the effects of drugs on biologic systems Potency denotes the amount of drug needed to produce a given effect Efficacy is the greatest effect (Emax) an agonist can produce if the dose is taken to the highest tolerated level partial agonists have lower maximal efficacy than full agonists

Answer 51

measure of dose required to produce a response | slide 76

Answer 52

Maximal response a drug can produce | slide 77 figure

1Basicprinciplesofpharm Flashcards

(76 cards)