Pharmacokinetics: PK and ADME Flashcards
Pharmacokinetics deals with the ADME mnemonic which stands for?
1) Absorption
2) Distribution
3) Metabolism
4) Excretion
What are some factors that affect drug absorption?
1) Rate of dissolution (such as a tablet)
2) Surface area
3) Blood flow
4) Lipid solubility
5) pH
Which enteral route of administration produces slow, uniform absorption?
Which has limited first-pass metabolism?
Which avoids first-pass metabolism completely?
1) Oral
2) Rectal
2) Sublingual/buccal
Oral administration of drugs leads to poor absorption of particles with what properties?
Large and charged
Which parenteral route of administration bypasses barriers to absorption leading to an immediate effect and is suitable for large volumes?
Which has rapid absorption and is suitable for oily substances and suspensions?
Which is suitable for suspensions and pellets but cannot be given in large amounts?
1) Intravenous
2) Intramuscular
3) Subcutaneous
What active transport system is a major transporter of drugs out of cells?
P-glycoprotein
In what different ways can a drug be classified as polar?
1) It has a fixed charge
2) It has no net charge but has charge separation (e.g. water)
Which type of drugs cannot readily cross the cell membrane?
Polar drugs
Quaternary ammonium compounds are an example of?
Polar drugs
Weak acids and weak bases can only cross membranes in what form?
Unionized form
Why is aspirin better absorbed from stomach while amphetamines are not?
Aspirin is a weak acid so it is in its unionized form in the stomach while amphetamines are a weak base
Ka is the rate constant for?
Absorption
The salt factor (S) is less than or equal to?
1
What is bioavailability (F)?
The fraction of drug that reaches the bloodstream
What is the extracellular volume (ECV) comprised of?
Plasma volume + interstitial volume
What is the total body water (TBW) comprised of?
ECV + Intracellular volume
The gastrointestinal tract serves as transcellular reservoir for drugs that are?
1) Slowly absorbed
2) Undergoing enterohepatic circulation
A drug is only bioactive and able to exit vascular system if?
It is free and not bound by protein
What type of drugs are unable to cross the BBB unless they have a transporter?
What drugs can freely cross?
1) Ionized or polar drugs
2) Lipid-soluble drugs
Where is the primary site of biotransformation, aka metabolism?
Liver
What is the function of the liver in terms of drug metabolism?
Primarily inactivates drugs but may activate pro-drugs
The liver is crucial for the renal elimination of what drugs?
These drugs must be made more polar so that?
1) Lipophilic drugs
2) They can be trapped in the renal tubular fluid
What are the phases of drug metabolism?
1) Phase I = Oxidation, reduction, hydrolysis
2) Phase II = Conjugation
What is the goal of phase I biotransformation?
The oxidative processes involve enzymes located where?
1) Make the product more polar
2) Cytochrome P-450 system in SER
Which cytochrome enzyme is the major one involved in drug metabolism?
CYP3A
Phenobarbital, carbamazepine, ethanol, cigarette smoke are CYP inducers that have what effect?
Speeds up metabolism of any other drug metabolized by the same enzyme
Erythromycin, ketoconazole, metronidazole, and grapefruit juice are CYP inhibitors that have what effect?
Slow the metabolism of any other drug metabolized by the same enzyme
Grapefruit juice is an inhibitor of what cytochrome P450 enzyme?
In what location?
It has what effect?
1) CYP3A4 in intestinal epithelial cells
2) It increases the bioavailability of other drugs metabolized by the same enzyme
During phase II of biotransformation, what effect does conjugation have on drugs?
What are the major routes of metabolism in this phase?
1) Drugs become more water soluble, more excretable and ultimately inactive since the molecule added is highly polar
2) Glucuronidation and sulfation
In regards to conjugation, where does glucuronidation occur?
Where does sulfation occur?
1) ER
2) Cytoplasm
In regards to conjugation, while acetylation and methylation also inactivates drugs, it differs from the major routes of metabolism by?
Making the drugs less water soluble
What effect does First-pass Metabolism have on drugs?
It greatly decreases the bioavailability of orally administered drugs
What drugs are filtered during glomerular filtration?
What specifically are not filtered?
1) Small molecule drugs
2) Protein bound drugs
What drugs are involved with passive tubular reabsorption?
1) Lipid soluble drugs
2) Unionized weak acids and bases
Active tubular secretion is involved with?
In what specific location?
1) Eliminated protein-bound drugs
2) Proximal tubule
What is excretion rate?
How is it affected in first order kinetics in relation to plasma concentration?
1) The mass eliminated per unit time
2) Excretion rate increases as the plasma concentration increases
What is clearance?
How is it affected in first order kinetics in relation to plasma concentration?
1) The plasma volume from which all of the solute is removed per unit time (flow rate)
2) Clearance remains constant as plasma concentrations change
What is tachyphylaxis?
Rapid tolerance to drug
What is idiosyncrasy?
Unusual response to drug due to inherited enzyme defect
What effect does succinylcholine have on a patient that lacks plasma esterase?
Apnea of long duration
What effect does Nitrites, sulfonamides, and primaquine have on a patient that lacks NADH methemoglobin reductase?
Hereditary methemoglobinemia
What effect does Isoniazid have on a patient that has low liver acetyl transferase?
Increased toxicity from drug
What effect does Primaquine have on a patient that lacks glucose-6-phosphate dehydrogenase?
Acute intermittent porphyria
Calcium in the diet can cause precipitation of what drug in the GI tract?
Tetracylcines
St. John’s wort has what effect on CYP3A4?
Strong inducer
Tyramine in wine, cheese, aged sausage, etc., cannot be metabolized in presence of?
This leads to?
1) MAO inhibitors
2) Hyperadrenergic crisis
The actions of lithium for bipolar disorders is impacted by what ion in the diet?
Na+
Why do neonates and infants have higher free levels of protein bound drugs?
Why can drugs enter the brain?
1) Low albumin
2) BBB not developed
Why must you adjust dose downard for drugs in neonates and infants?
Because their hepatic metabolism and renal excretion are decreased compared to children and adults
How do children over 1 year of age metabolize drugs in comparison to adults?
Faster
While all drugs can cross the placenta, what type are able to cross most readily?
Lipid soluble
During zero order kinetics, how much is eliminated per unit?
How does the amount of drug eliminated compare to the drug concentration?
1) Constant amount
2) It is independent of the drug concentration
During first order kinetics, how much is eliminated per unit?
How does the amount of drug eliminated compare to the drug concentration?
1) Constant fraction
2) The mass of drug eliminated is directly related to the drug concentration
Between zero and first order kinetics, which drug elimination process is saturated?
Zero order
In first order kinetics, what happens in each half life?
How many half lives does it take for 97% of the drug to be eliminated?
1) Half of the drug is eliminated
2) 5
Kel x T1/2 = ?
Kel = First order elimination rate constant
0.693 (0.7)
The steady-state concentration is proportional to?
1) Dose/dosage interval
2) F/CL
Loading dose is needed to rapidly achieve therapeutic drug concentrations for drugs with?
Very long half-life
Rapid absorptions has what effect on peak plasma concentrations?
Higher peak
