Pharmacokinetics Flashcards
Define pharmacokinetic
This is the study of drug disposition and focuses on the changes in the drug plasma concentration.
The plasma drug concentration of any drug will change.its will either rise or fall depending on which processes.
A. Absorption
B. Distribution
C.elimation
- metabolism)
-excretion)
Which processes makes up biotransformation
Metabolism and excretion
What is metabolism
This is the breaking down of the parent drug Into one or more metabolites.Mostly done by liver
The excretion of the parent drug or metabolites is done by what.
It’s primarily done by the kidney
What is absorption
This is the passage of drug molecules from the site of administration into the systemic circulation
Absorption applies to all routes expect for two routes . name those routes giving reasons why
- The topical route.
This is because drugs administered topically are directly applied on the target tissue. - The lV route
This is because drugs administered through the IV route are directly delivered into the circulation.
Orally administered drugs have been found to face a greater barrier than the parenteral route True/ False
True
Absorption is dependent on three major forms of transport.which are….
Passive diffusion
Active transport
Facilitated diffusion
By which processe are most drugs absorbed
Passive diffusion across the biological barrier
How is passive diffusion across a biological barrier achieved .
It’s accomplished either through lipid diffusion or aqueous diffusion
What is lipid diffusion
This involves the dissolving of a drug in the lipid components of the cell membrane.
What is the important facilitator for the process of lipid diffusion.
Lipid solubility
What is aqueous diffusion
This involves the absorption of the drug molecules through the aqueous pores of the cell membrane.
Aqueous diffusion is restricted by ……….of drugs and thus many drugs are too large to be absorbed by this process.
Molecular weight
State Ficks law
This states that the rate of absorption is proportional to the concentration gradient across the barrier and the surface area available available for absorption at the site.
What is active transport
This is a process that requires a carrier molecule and energy provided through the high energy phosphate bond of adenosine triphosphate (ATP)
Give an example of a drug that can be transported against the concentration gradient.
5- fluouracil an antineoplastic drug
What is facilitated diffusion
This is a process that needs a carrier molecule but no energy is needed.
Which process cannot transport drugs against concentration gradient but diffusion is enhanced when the carrier molecule is absent.
Facilitated diffusion
Which process Can transport drugs against the concentration gradient
Active transport
Cephalosporines like cephalexin undergo facilitated diffusion by …………in ………
- oligopeptide transport protein..in intestinal epithelial tissues
Generally ,many drugs exist as acids or bases , both existing as either…
Ionized form or non ionized from
The non ionized form of drugs are sufficiently soluble in membrane lipid to cross the cell membranes and the ratio of the concentration of the ionized to the non ionized at a particular site influences what.
The rate of absorption
In the stomach with a pH of 1 what will happen in terms of non ionized form of weak acids and ionized weak bases.
Both of them will dominant but weak acids will be more readily absorbed than weak bases.
We’re are weak bases mostly absorbed
In the intestines with pH of 7
Weak acids can also be readily absorbed from the intestines than from the stomach despite their greater ionization because
Because of the increased surface area
What is the use of the Henderson - Hasselbalch equation
It’s useful for estimating the PH of a buffer solution and finding the equilibrium PH in an acid -base reaction
What do the weak acids (HA) donate and what do the weak bases accept
The weak acids donate a proton (H+) to form anion (A-) while weak bases accept a proton to form cations
How are drugs distributed to the body organs and tissues into the interstitial fluid and cells
Through circulation and diffusion
A good number of drugs are not uniformly distributed throughout total body water.other drugs are restricted to the extracellular fluid or……..
Plasma concentration
Drugs with……… easily diffuse into cells through membranes
Sufficient lipid solubility
Drugs can also be actually transported into cells eg ….
Drugs transportation into hepatic cells were they may undergo biotransformation
Drugs distribution is some way opposed by a number of ATp driven efflux pumps known as ..
ABC transporters ( ABC being an acronym of ATP binding cassette)
The most notable or widely studied ABC is the p- Glycoprotein(pgp) also called….
Permeability Glycoprotein.
Which is expressed on the luminal side of intestines, brain capillaries.
What do phg excludes from various tissues act as
They act as a detoxifying mechanism but can lead to therapeutic challenges like the exclusion of cancer drugs from tumours which can cause chemotherapeutic drug resistance
Drugs like………..inhibit pgp and hence help in increasing tissue levels of these drugs and thereby augmenting their pharmacological effects
Amiodarone , erythromycin, propranolol
Organ blood flow is one of the factors that affect drug distribution which tissues experience the rapid drug distribution and thus enabling a rapid onset of action
High perfused tissues like the brain, heart,liver and kidney
Which tissues experience a low drug distribution.
Less perfused tissues like the skin, bones and skeletal muscles
Almost all drugs are reversibly bound to plasma proteins primarily albumin while others are what…
Lipoprotein, glycoprotein and B-globulins
The extent of binding depends on what
Drugs affinity for the protein binding site which ranges from 10 -99% of the plasma concentration
Plasma protein binding is saturable and a drug can be displaced by another drug with what
Higher affinity for such sites
Molecular size is one of the factors that affect drug distribution . what kind of drugs does it affect and give an example.
It’s affects the distribution of extremely large molecules eg antic
What is drug biotransformation or metabolism
This is an enzyme catalyzed conversation of drugs to their metabolites
Biotransformation mostly takes place in the liver but the metabolizing enzymes are also found were
They are also found in other tissues like the gut , brain, kidney, lungs and skin
Which two processes are responsible for the decline of plasma drug concentration over time
Biotransformation and excretion
Which process are involved I. Drug elimination
Biotransformation and excretion
Define clearance
Is a measure of the rate of elimination of the drug
What is the role of drug biotransformation
The fundamental role is to inactive drugs and other foreign compounds that Can harm the body
It’s also acts as the natural detoxifying process
Why is it that drug metabolites are usually excreted by the kidney s
Because drug metabolites are usually more water soluble than their parent drugs
Note some drug metabolites are are active while others are inactive
What is conjunction
This is the process by which drugs undergo attachment to polar groups
Note a general rule suggest that most of these conjugated drugs are inactive expect with a few exceptions
Give an example of a active drug that can be converted to their active metabolites
Sedatives drugs like deazepam
How do drugs absorbed through the gut reach the liver
It’s reaches the liver through the hepatic portal vein before entering the systemic circulation.
What type of reaction does phase l include or involve
It’s involves oxidative, hydrolytic, deamination and reductive reactions
What is a prodrug
Theses are pharmaceutically formulated inactive compounds which are biotransformed into active metabolites.
Drug biotransformation is dividend into two phrases each carried out by unique sets of metabolic enzymes these phases are what
Phase l and phase II
In which phase is drugs metabolites mostly active and in which phase is drug mostly inactive.
In phase I drug metabolites are pharmacologically active and mostly in phase ll drug metabolites are inactive.
Which phase l reaction of biotransformation is catalyzed by enzymes isolated by the microsomal fraction of the liver
Oxidative reaction
What happens at phase l
In phase l ezymetic reactions create or unmask a chemical group required for phase for phase l l
What is the microsomal cytoplasm p450 ( Cyp) mono- oxygenase system
This is a family of enzymes that catalyzes the biotransformation of drugs with a wide range of chemical structure
Give an example of a prodrug
Enalapril
CYP exist in different families as what
CYP1,CYP2, CYP3 which are likely related by gene duplication
How is each family divided
It’s divided into subfamilies with a related homologous protein sequence of which CYP3A catalyzes more than half of microsomal drug oxidation
There are a number of drugs that affect the metabolism of drugs by either….
Inducing or inhibiting the CyP enzymes
What do CYP450 enzyme inducers do
They cause the increase in the enzyme secretion
What happens when the CYP inducers are given concomitantly with another drug whose metabolism is dependent on the CYP enzyme.
The other drug is metabolized at an increased rate.which may affect the therapeutic effect because of the reduced bioavailability of the other drug
Give examples of cyp enzyme inducers
Rifampicin, phenobarbitone, carbamazepine, phenytoin (RPPC)
What do CYP450 enzyme inhibitors do
They cause the reduction in the secretion of the enzyme
What happens when the secretion of enzymes is reduced
It’s leads to the accumulation of the other drug whose metabolism is dependent on the CYP enzyme because of reduced clearance.which will eventually lead to toxicity
Give examples of cyp enzyme inhibitors
Erythromycin, ciprofloxacin, cimetidine .
Alcohol is metabolized to aldehyde by what…
Alcohol dehydrogenase
Caffeine and theophylline a bronchodilator are metabolized by what enzyme
Xanthine oxidase
Amides and esters are hydrolyzed by a variety of enzymes including
Cholinesterase which inactivate choline esters
A drug esmolol is used for what
The treatment of tachycardia
Which vasodilator undergoes reductive hydrolysis catalyzed by glutathione organic nitrate reductase
Nitroglycerine
Chloramphenicol,an antimicrobial agent is metabolized by what
By nitro reductase with also an involvement of CYP enzymes
Which reaction is less common compared to oxidative and hydrolytic reactions
Reductive reactions
