Pharmacokinetics Flashcards
Bioavailability (F)
Will increase if the dissolution is rapid (from drug into free drug starte in blood where its AVAILABLE for use
The amount which reaches the blood UNALTERED by eg liver is bioavailable
What is the AUC, and what is it used for
Area under (the) curve measures the total drug exposure, used in measuring Absolute and relative Bioavailability
Absolute and relative bioavailebility
Absolute: availibility of drug in blood after non iv admin. iv is 1/100%, used to calculate absolute bioavailability. so when calculating compare it to how much IV is used as it will give 100%
Relative bioavailability: we compaire the bioavailability of one drug to another instead of one drug admin to iv admin
first-pass effect
Conc of drug may be greatly reduced before it reaches the bloodstream
Affects the bioavailebility - dose may need to be adjusted
Rate of distribution and blood flow
Different blood flow to different organs
1 brain, liver, kidney
2 muscle, skin
3` fat, bone
Vd - the distribution of a drug in the blood
Drugs that distribute extensively have relatively large Vd values, and vice versa.
- A very low Vd value may indicate extensive plasma protein binding of the drug.
- A very high value may indicate that the drug is extensively bound to tissue sites.
Pharmacologically inert metabolites
metabolism deactivates administered dose of parent drug and reduces effects on body
pro-drugs
an ex of Metabolites that may also be pharmacologically active, even more than the parent drug
Bioteansformation of xenobiotics
o Oxidizes the xenobiotic (phase I)
o Conjugates water-soluble groups onto the molecule (phase II).
Mainly done in the liver by redox enzymes, termed cytochrome P450 enzymes
Biotransformations on general
Phase I: no conjugations, can be active or inactive, functional gr is prod by a reaction. CYP-450!!
Phase II: conjugation resulting in lost activity. Functional gr is used to conjugate.
Enzymes inducible by drugs in cell
Only those enzymes located in the endoplasmic reticulum are inducible by drugs. Means that the only subcellular location for enzymatic activity of drugs is in the ER.
Enzymes are induced by drugs, hormones etc so they metabolise drugs
metabolic tolerance
A drug may induce its own metabolism
Glucuronyl transferase, where, what does it do?
- set of enzymes, involved in phase II reactions. - catalyzes conjugation of glucuronic acid to variety of active centers -OH, -COOH, -SH, and -NH2
In ER
Incomplete excretion
accumulation of foreign substances adversely affecting the normal metabolism.
Major site of excretion
Kidneys
Net renal excretion of drugs
- the amount of drug filtered at the glomerulus
- PLUS the amount of drug secreted by active transport mechanisms in the kidney, - MINUS the amount of drug passively reabsorbed throughout the tubule.
Zero-order elimination/kinetics
LINEAR
a constant amount of drug will be eliminated per unit time when we have taken in more drugs than the bodys` elimination mechanism has reached its limit.
First-order elimination
- Occurs when drug level is BELOW saturation point
- this is the elimination of most drugs!
- linear function of PLASMA levels!
One-compartment open model
- in central tissues
- even drug distr among tissues
- continous loss/elimination after a single administration
two-compartment model
- drug elimination in peripheral tissues
- slower!
- more common that one compartment
- has a distr phase where equilibrium is made btw peripheral and central(plasma) tissues - rapid decr, then the decr in plasma cons is more linear - only elimination phase used for calc of Vd, halftime
Bio exponential curve
Shows decr of drug level in time (plasma)
When can Repeat administration
of drug eliminated by first-order kinetics
Steady state
- Re admin of drugs to maintain a steady state.
- Often is better than larger and fewer doses.
- Approx 4-5 halftimes is needed to make a steady state.
- Its independant of the dose size, a steady state will be made either way.
Loading dose
needed when therapeutic concentration of drug in plasma must be achieved rapidly (e.g., a life-threatening situation) then the drus is administered at maintenance dose rate to
maintain drug concentration at the desired steady-state level.
How is mantinance dose rate calculated
Desired concCLmin*hours
Factors influencing drug action, that developes after repeated admin
Tolerance, dependance and allergy
Factors influencing drug action, that developes ok the first admin
Idiosyncrasy
= Individual hypersensitiveness, serious symptoms, hereditary
Types pf medication creating an allergic response
antibiotics, hormones, anticonvulsants, NSAIDs
Factors maintaining drug allergy
contamination of skin, inhalation –
contamination of airways, depot preparations, chronic diseases, atopy
Type I allergic reactions typical diseases
PQ Urticaria (hives), oedema, Rhinitis, asthmatic seizure
Histamine, prostaglandins, leukotrienes, Vasodilatation,, inflammation, Diarrhoea,), atopic dermatitis, in sever cases anaphylactic shock,
Elimination of clinical signs is rapid
Elimination Half-life (T1/2) :
- time it takes for the plasma drug concentration to be reduced by 50%.
- applies only to drugs eliminated by first-order kinetics.
- so not if dose excedes elimination capasity! = saturated, zero order
