Lecture 6 (EXAM 2)

Question 1

What often determines the rate of Elimination?

Answer 1

Enzyme activity, but NOT for every drug some are eliminated by the kidney
-f.e. Metformin eliminated without being metabolized

Question 2

If enzymes decrease the effect of a drug by Elimination, how can the enzyme be deactivated?

Answer 2

Enzyme inhibition: using a drug to block the enzyme that metabolizes the therapeutic drug

Question 3

What is a risk factor for toxicity by drug overdose?

Answer 3

Age bc the liver doesn’t work as well

Same effect as Enzyme inhibition?

Question 4

What does enzyme induction mean?

Answer 4

There are more enzyme present than normal

Question 5

What could cause enzyme induction?

Answer 5

Smoking, other drugs, charcoal meat, cruciferous vegetables (broccoli, brussel sprout)

Question 6

What is the result of enzyme conduction?

Answer 6

The drugs will be metabolized faster, the elimination rate will be greater -> the curve for drug level will be lower

-Risk of reaching the subtherapeutic level

Question 7

What are Multidrug transporter?
(also affects drug level, just like enzyme inhibition and induction)

Answer 7

Protein (pumps) that moves the drug out of its working area - Efflux

Question 8

Examples of Multidrug transporters

Answer 8

-Bacteria cells
-cancer cells
-in the blood-brain barrier -> this is why there are no CNS side effects for some drugs

-(MDR - multidrug resistant transporter, P-glycoprotein, Efflux pumps, ABC cassette transporter)

Question 9

What are the hormetic effects?

Answer 9

-non-linear drug response relationship
-giving a small dose of a harmful drug with beneficial effect, giving high doses can cause harm

Question 10

Examples of hormetic effects

Answer 10

-PCB (environmental contaminants?) - experiment with mice losing weight when given small doses, and gaining weight with high doses

-cancer drugs: beneficial with small doses, harmful with high doses

-Vitamin D in Bone health

Question 11

How does the blood-brain barrier work?

Answer 11

Constriction of endothelial cells (cells that line the blood vessels)

Question 12

What are the factors determining drug access to the brain?

Answer 12

-log P (lipophilicity) the higher log P the better it crosses the BBB
-transporter (f.e. D-Glucose, amino acids)

Question 13

What is the area in the brain lacking the blood-brain barrier?

Answer 13

Area postrema
-emetic center -> monitors the blood for toxic molecules
-throwing up to protect the brain (bc no BBB)

Question 14

What are Overtones Rules?

Answer 14

Rules for substances (drugs) to cross biological barriers

1. Uncharged -> charged molecules don’t cross the barrier
2. Lipophilicity
3. Size - smaller is better
4. Shape - spherical is better

Question 15

Ficks Law of diffusion

Answer 15

Flux (J) = Rate at which a molecule crosses the barrier

J = (C1-C2) * surface area to cross * permeability of the substance / distance to move

Question 16

What are the determining factors of Flux (J)

Answer 16

-concentration gradient - the greater the gradient between two sides, the greater the driving force
-surface area - the more surface area, the better it will cross (f.e. villi in the small intestine, tubules in the kidney, alveoli in the lungs)

Question 17

What type of drugs bind to plasma proteins?

What is the most common plasma protein?

Answer 17

Lipophilic and some charged drugs
99% of absorbed drugs are bound to plasma protein

the most common plasma protein is Albumin

Question 18

Why do patients with impaired liver function suffer from edema in joints?

Answer 18

Plasma proteins are made in the liver -> Lower amounts of plasma proteins will draw fluid from tissues to the vascular system due to oncotic pressure -> Accumulation of fluid in the joints

Question 19

How does an impaired liver affect drug efficacy?

Answer 19

Fewer enzymes metabolizing the drug -> higher drug concentration -> risk of TOXICITY

Question 20

Route of Drugs to First Pass Metabolism

Answer 20

-Adsorption in the small intestine
-Transport through the hepatic portal vein to the liver
-Liver monitors blood and metabolizes the drug
-Unmetabolized drugs enter general circulation by hepatic vein

Question 21

What does the Volume of distribution indicate?

Answer 21

-measuring drug concentration after taking a drug

-The lower the drug concentration in the human body after taking the drug, the greater the distribution of the drug

Question 22

Calculate an unknown amount of liquid in a well with the known amount of dye

Question 23

Predicting the location of the distribution of a drug with the volume of distribution

Answer 23

Volume of distribution = 5L -> drug distributed in the blood
= 42L -> drug distributed in the total body water
= 70L -> drug evenly distributed throughout the body
= 500L -> drug distributed in the body fat (lipophilic drug)

Question 24

What is the Redistribution phenomenon?

Answer 24

-Applies to very lipophilic drugs (like anesthetics that needs to cross the BBB very quickly)

-the drug goes into the blood
-from the blood, it goes into the fat and accumulates there
-the drug moves from the fat back into the blood

-f.e. patients who are put into a coma during surgery, they wake up and fall asleep again, bc the drug does into the fat and back into the blood