Pharmacology

Question 1

What is the therapeutic window?

Answer 1

The area between the MEC for adverse responses and the MEC for therapeutic response (desired response)

Question 2

What factors affect pharmacokinetics?

Answer 2

Age, liver/renal function, BMI

Question 3

How do most drugs interact with the plasmalemma?

Answer 3

Via surface receptors since they’re polar and cannot diffuse across

Question 4

What are most drugs conceptualized as, as far as their interactions with the cell?

Answer 4

Ligands for surface receptors

Question 5

Which kinds of drugs are lipid soluble? Water soluble?

Answer 5

Uncharged (hydrophobic)

Charged (hydrophilic)

Question 6

What is ion trapping and how does it work?

Answer 6

Ion trapping is the use of a drug’s pKa to change its charge to transport it to the desired location (like into the blood stream from the GI tract)

When pKa is greater than its environment, the charge is hydrated and it becomes nonpolar. THEN it can be transported across lipid bilayers.

(TLDR: pKa=4.4 in stomach, uncharged. Transported to blood. In blood, regains charge)

Question 7

What is a prerequisite for CNS active drugs?

Answer 7

Must be hydrophobic (due to BBB)

Question 8

What are the main uptakes for drugs from slowest to fastest?

Answer 8

Oral, Transdermal, IM, IV and intrathecal

Question 9

What is the reason oral intake is slow?

Answer 9

Has to go through first-pass metabolism (via portal circulation)

Question 10

How is bioavailability calculated?

Answer 10

F=

Quant of drug reaching system circulation
OVER
Quant of drug administered

Question 11

What route of intake has the highest bioavailability? Lowest?

Answer 11

Intravenous; oral

Question 12

What is the issue with inhalation as a route of intake?

Answer 12

Patient education and patient technique

Question 13

Where is a drug located if the Vd is 4L (equal to blood plasma volume)?

Answer 13

ALL OF IT is in the blood

Question 14

Where is a drug most likely located if the Vd is 250?

Answer 14

Extravascular spaces (muscle, tissues, adipose, etc)

Question 15

Where is a drug mostly located if the Vd is low?

Answer 15

Blood plasma (vascular compartment)

Question 16

What is the Vd of drugs that are most likely to need a loading dose?

Answer 16

High Vd may need loading dose to increase plasma levels to the therapeutic range

Question 17

Describe first order kinetics in regards to elimination of a drug?

Answer 17

drug concentration determines how much drug is eliminated (like a constant 16% elimination per half life. The plot’s slope gets smaller as more drug is eliminated)

Question 18

What are zero-order kinetics in relation to drug elimination?

Answer 18

A constant amount of drug is eliminated regardless of concentration (very linear elimination line)

Question 19

What is steady state?

Answer 19

Rate of elimination= rate of administration (takes 4-5 half lives)

maintains concentration in the blood plasma through multiple maintenance doses

Question 20

What is the formula for clearance?

Answer 20

Clearance= metabolism plus excretion, divided by the concentration of drug in plasma

Question 21

How does drug binding to proteins affect its activity?

Answer 21

Protein bound drugs (like bound to albumin in the blood) are INACTIVE

Question 22

What is protein binding’s effect on Vd?

Answer 22

More protein binding= lower Vd

Less protein binding= higher Vd

Question 23

How can disease-state modifications of proteins affect drug action?

Answer 23

Less protein= greater risk of toxicity due to incr free drug in plasma

More protein= higher conc needed for therapeutic range (not as important)

Question 24

What drugs are most susceptible to dangerous effects when protein is low?

Answer 24

Those with a low therapeutic index

Question 25

How is dosing calculated for pediatric patients?

Answer 25

Mg/kg (as compared to standard dose for adults)

More drugs are unbound (more active), average Vd for hydrophilics are higher, average Vd for lipophilics are lower

Question 26

What does alpha-1-glycoprotein bind? Albumin?

Answer 26

A1GP- basic drugs

Albumin- acidic drugs

Question 27

How is dosing for elderly patients different than adults?

Answer 27

Body composition changes drug distribution

• lower Vd for hydrophilic drugs (more in serum)
• higher Vd due to more fat stores (prolongs half life)
• acute illnesses more prevalent=more changes in plasma protein and binding

Question 28

What order of kinetics are most drugs?

Answer 28

First-order

Question 29

How is half life calculated?

Answer 29

(Ln(2))(Vd) / clearance

Question 30

Where are CP450 enzymes found?

Answer 30

Smooth ER of liver

Question 31

What are the most potent CYP enzymes for drug clearance?

Answer 31

3A4, 2D6, 2C19, 2C9, 2E1, 1A2

Question 32

How does variation factor into first-pass metabolism?

Answer 32

Some people met faster or slower than average (via induction or inhibition)

Question 33

How does induction of CYP change drug interaction?

Answer 33

Decreases response/efficacy

Question 34

What are some outcomes metabolism can have on drugs?

Answer 34

• Inactivates an active free drug
• activates an inactive free drug
• turns an active free drug into an active metabolite (incr drug effect)
• turns active drug to a toxic metabolite

Question 35

What are the phase one and two reactionsof CYP enzymes?

Answer 35

P1: redox reactions

P2: conjugation/hydrolysis actions

Question 36

What does phase 1 and 2 reactions in CYP metabolism do?

Answer 36

Increases hydrophilicity (promotes excretion)

Question 37

What are the names of the three conjugation reactions?

Answer 37

Glucuronidation, acetylation, sulfation (increases solubility in urine or bile for excretion)

Question 38

How do P450 enzymes react to aging?

Answer 38

Decreases