Pharmacology - chapter 1 - Pharmacokinetics Flashcards
what four pharmacokinetic properties determine the speed of onset of a drug?
Absorption - drug absorption from the site of administration
Distribution - drug leave blood stream and enter ECF and ICF
Metabolism - biotransformation by liver or other tissues
Elimination - by urine, bile or feces
Pharmacokinetics =
What the body does to a drug
what are the two ways of enteral drug administration, and what are their benefits?
Swallowed or sublingual.
The benefits are that they are safe, cheap, convenient and common
enteric coated preparations vs. extended-release preparatioins?
Enteric-coated - chemical envelope that protects from stomach acid, but is absorbed in upper intestine.
Extended-release - medication does not have to be taken as often. Longer duration.
The three major parenteral routes are?
IV, IM and SC
IV injection. Pro’s & Con’s?
Pro - rapid effect and maximum degree of control. Almost emmidiate systemic delivery.
Con - cannot be recalled. Introduce bacteria and infective particles. May precipitate blood constituents, induce hemolysis.
IM injections, two different types?
aqueous soulutions - rapid absorption.
depot preparations - slow absortion due to nonaqueous vechile(polyethylene glycol)
SC injection, two characteristics?
Require absorption via simple diffusion. Minimizes risk of hemolysis or thromobosis associated with IV.
Six “less common”routes of administration?
Oral inhalation, nasal inhalation, intrathecal/intraventricular, topical, transdermal & rectal
what is drug absorption?
the transfer of a drug from its site of administration into the bloodstream
name four mechanisms of drug absorption in the GI tract?
passive diffusion(most common)
faciliitated diffusion
active transport
endocytosis and exocytosis
name five factors that influence drug absorption?
pH - most drugs are either weak acids or weak bases
Blood flow to absorption site - intestine favored over stomack
Total surface area available for absorption - again intestines
Contact time at absorption surface - e.g. transport and food influence.
Expression of P-glycoprotein
what is P-glycoprotein, and what is its function in different tissues?
P-glycoprotein is a multidrug membrane transporter protein that transport various molecules, including drugs, across membranes.
Liver - transport drugs into bile
Kidney - pump drugs into urine
Placenta - transport drugs back into maternal blood
Intestines - transport drugs into intestinal lumen, reducing absorption.
Brain capillaries - pump drug into blood, limiting drug access to brain.
what is bioavilability?
Fraction of administered drug that reaches the systemic circulation.
By definition this is 100% for drugs that are delivered intravenously.
Four factors that influence bioavailability?
1 First-pass hepatic metabolism
2 Solubility of drug - should be largely hydrophobic with aqueous some solunility
3 Chemical stability - e.g. penicilin G is unstable in the gastric juices
4 Nature of the drug formulation - size, salt form, crystal polymorphisms, enteric coatings and the presence of binders & dispersing agents.
bioequivalence vs therapeutical equivalence, co jest the difference?
bioequivalence - two related drug preparations show similar bioavailability and similar time to achieve peak blood concentrations
therapeutical equivalence - two similar products are pharmaceutically equivalent with similar clinical and safety profiles.
What is drug distribution?
the process by which a drug reversibly leaves the blood stream and enters the interstitium and then the cells of tissues.
Name five facors that influece drug distribution? Come on nah!
1 cariac output
2 blood flow(brain, kidney & liver recieve the most blødd)
3 capillary permeability( spleen and liver have fenestrated capillaries whereas the brain got the BBB)
4 the tissue volume
5 binding of drugs to plasma proteins and tissues( albumin, lipids, proteins, nucleic acids etc.)
Three major routes of drug metabolism?
1 hepatic metabolism
2 elimination in bile
3 elimination in urine
Kinetics of metabolism:
The two main types: name them and their differences.
First-order kinetics: more enzyme precent than free drug, therefore the rate of drug metabolism is directly proportional to the concentration of free drug.
Zero-order kinetics: enzyme is saturated by high free drug concentration. E.g aspirin, ethanol and phenytoin, where does are large.
Two general sets of drug metabolism?
Phase I: convert lipophilic molecules into more polar molecules by introducing or unmasking a polar functional group, such as -OH or -NH2. This is most frequently done på P450 system
Phase II: Conjugation reactions that convert too lipophilic metabolites into sufficiently polar molecules that can be excreted.
Four major P450 isozymes?
CYP3A4/5
CYP2D6
CYP2C8/9
CYP1A2
P450 and grapefruit??
bergamottin, dihydroxybergamotin and paradicin-A, found in grapefruit juice, inhibit CYP3A4/5. Thus, drugs such as nifedipine, clarythroycin and simvastatin, which are metabolized by this system, persist in greater amount in the blood. This can potentially increase the drugs therapeutic and/or toxic effects.
Drug clearance by the kidney:
Name the three processes.
1 glomerular filtration
2 proximal active tubular secretion
3 distal passive tubular absorption
What is ion trapping?
making a drug polar by changing the pH of the urine, this traps the molecule in the renal tubule where it is excreted. Weak acids can be eliminated by alkalinization of the urine, whereas weak bases can be eliminated by acidification of the urine.
Liver and kidney… name four other routes by which drugs can be cleared
bile, intestines, the lungs and milk in nursing mommas
CL total =
CLhepatic + CLrenal + CLpulmonary + CLother
3 clinical situations where half life is increased and 3 where it is decreased?
Increased: low renal plasma flow or hepatic blood flow, decreased bility to etract drug from plasma(renal failure), decreased metabolism
Decreased: increased hepatic blood flow, decreased protein binding, increased metabolism
How long does it usually take a drug to reach the steady state(state where drugs is absorbed and excreted at the same rate)?
Approx 4 x half life
Vd = ?
drug in body:drug in plasma ratio
Drug clearance =?
ratio of the rate of elimination: concetration in plasma
What is first-pass effect?
the elimination of a drug that occurs after administration but before it reaches the systemic circulation.
What is steady state?
condition where the total amount of drug in the body does not change over multiple dosing.
rate of drug input = rate of elimination
What is extraction?
The fraction of drug in the plasma that is removed by an organ as the drug passes through that organ.
