Lecture 6 (EXAM 2) Flashcards
(24 cards)
What often determines the rate of Elimination?
Enzyme activity, but NOT for every drug some are eliminated by the kidney
-f.e. Metformin eliminated without being metabolized
If enzymes decrease the effect of a drug by Elimination, how can the enzyme be deactivated?
Enzyme inhibition: using a drug to block the enzyme that metabolizes the therapeutic drug
What is a risk factor for toxicity by drug overdose?
Age bc the liver doesn’t work as well
Same effect as Enzyme inhibition?
What does enzyme induction mean?
There are more enzyme present than normal
What could cause enzyme induction?
Smoking, other drugs, charcoal meat, cruciferous vegetables (broccoli, brussel sprout)
What is the result of enzyme conduction?
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
What are Multidrug transporter?
(also affects drug level, just like enzyme inhibition and induction)
Protein (pumps) that moves the drug out of its working area - Efflux
Examples of Multidrug transporters
-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)
What are the hormetic effects?
-non-linear drug response relationship
-giving a small dose of a harmful drug with beneficial effect, giving high doses can cause harm
Examples of hormetic effects
-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
How does the blood-brain barrier work?
Constriction of endothelial cells (cells that line the blood vessels)
What are the factors determining drug access to the brain?
-log P (lipophilicity) the higher log P the better it crosses the BBB
-transporter (f.e. D-Glucose, amino acids)
What is the area in the brain lacking the blood-brain barrier?
Area postrema
-emetic center -> monitors the blood for toxic molecules
-throwing up to protect the brain (bc no BBB)
What are Overtones Rules?
Rules for substances (drugs) to cross biological barriers
- Uncharged -> charged molecules don’t cross the barrier
- Lipophilicity
- Size - smaller is better
- Shape - spherical is better
Ficks Law of diffusion
Flux (J) = Rate at which a molecule crosses the barrier
J = (C1-C2) * surface area to cross * permeability of the substance / distance to move
What are the determining factors of Flux (J)
-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)
What type of drugs bind to plasma proteins?
What is the most common plasma protein?
Lipophilic and some charged drugs
99% of absorbed drugs are bound to plasma protein
the most common plasma protein is Albumin
Why do patients with impaired liver function suffer from edema in joints?
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
How does an impaired liver affect drug efficacy?
Fewer enzymes metabolizing the drug -> higher drug concentration -> risk of TOXICITY
Route of Drugs to First Pass Metabolism
-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
What does the Volume of distribution indicate?
-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
Calculate an unknown amount of liquid in a well with the known amount of dye
Predicting the location of the distribution of a drug with the volume of distribution
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)
What is the Redistribution phenomenon?
-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
