Drug Metabolism Flashcards
What is the “goal” of drug metabolism?
To polarize the active lipoidal drug
- Polarized drugs are active or inactive?
- Polarized drugs are water soluble or insoluble?
- Unactive
- Water soluble
Which type of molecule can actively pass through a lipid bilayer, a polarized drug OR a lipoidal drug?
Lipoidal drug
What are the 3 issues in cats regarding drug metabolism?
- Sleeping beauty effect
- Cannot always convert prodrugs to active drug
- Make toxic metabolites
Most active drugs are polar or non-polar?
Non-polar
For renal elimination, a drug needs to be ____. If not, the drug is simply ____ by the kidneys.
For renal elimination, a drug needs to be water soluble. If not, the drug is simply reabsorbed by the kidneys.
To be useful, most oral drugs would be either lipoidal or polar?
Lipoidal
Which of the following are referring to PHASE I of biotransformation?
Conjugation
Small changes (Ex. Adding a hydroxyl group)
Glucuronidation
Dependence on cytochrome p450
Mediated by microsomal transferases
Initial polarization
Initial polarization
Small changes (Ex. Adding a hydroxyl group)
Dependence on cytochrome p450
Which of the following are referring to PHASE II of biotransformation?
Conjugation
Initial polarization
Small changes
Glucuronidation
Mediated by microsomal transferases
Conjugation
Mediated by microsomal transferases
Glucuronidation
Which phases does Acetaminophen use?
Phase I (hydroxylation)
Phase II (glucuronidation)
Which of the phases of biotransformation does ethanol utilize?
Phase I
(Ethanol is already water soluble prior to metabolism)
Which of the phases of biotransformation do sulfonimide antibiotics utilize?
Phase II
- What form does aspirin take after going through phase I of biotransformation?
- What form does it take after going through phase II?
- Salicylic acid
- Glycylsalicylate
What are the 4 possible outcomes of biotransformation?
- Active drug –> inactive metabolite
- Active drug –> active metabolite –> inactive metabolite
- Active drug –> toxic metabolite
- Inactive drug –> active metabolit –> inactive metabolite
Acetaminophen metabolization in cats is an example of which of the 4 outcomes of biotransformation?
Active drug –> toxic metabolite
(active drug —(phase I)—> inactive metabolite —> toxic metabolite)
Why are cats poor at metabolizing acetaminophen?
Acetaminophen is related to phytoalexins, antibiotics made by plants, and cats are poor at metabolizing plant-like materials.
Describe the first pass effect:
Some of the drug gets metabolized before reaching the systemic circulation
The first pass effect is important for which 2 types of drug administration?
Oral
&
Intraperitoneally
What are “polar-enteric” drugs?
Drugs that stay in the gut
How can one avoid the first pass effect?
- Give more orally
- Give by an alternative route
Which of the following is/are NOT an extrahepatic site of drug metabolism?
Kidneys
Lungs
Pancreas
Plasma
Brain
Skin
Nervous system
Small intestine
Pancreas
Brain
Skin
Which 2 organs are associated with the first pass effect?
Small intestine
&
Liver
What are the 3 components of the small intestine that contribute to the first pass effect?
- Bacteria
- Proteolytic digestive enzymes
- Glucuronidating enzymes
Why can insulin NOT be given orally?
Insulin is a peptide, and protein-based drugs should NOT be given orally. There are proteolytic digestive enzymes within the small intestine that would break the insulin down before it could be absorbed and utilized by the body.
How can a polarized drug exit the hepatocyte after being metabolized in the sER?
Active transport
What are 5 factors influenzing biotransformation?
(There are actually about 11 factors total)
- Age & gender
- Breed & species
- Lactation
- Hypothermia
- Liver disease (hepatopathy)
- Adipose sequestration
- Plasma protein binding
- Diet
- Other drugs
