1st lecture - pharmacokinetics Flashcards
define Pharmacology
the study of the actions of drugs on the normal or pathologically altered function of the organism.
A drug is
any combination of substances that is intended for the purpose of prevention, diagnosis, treatment or alleviation of an illness or symptom of illness on a human or animal or for the restoration or alteration of functions in a human or animal.
define Pharmacokinetics
all processes that define the existence and movement of a drug in an organism:
“adbe”
1. absorption
2. distribution (metabolism)
3. biotransformation
4. excretion
What are pharmacokinetics for? (3)
helps understand the behaviour of drugs inside the organism.
helps explain undesired responses
helps find the right drug, dose, route of administration and interval for administration.
Withdrawal period?
time from last administration of drug, until the time of animal product use (meat, milk, eggs etc.).
“varoaika”
The primary use of pharmacokinetics in a clinical setting is to
calculate safe and effective drug dosage regimens for patients.
effective drug dosage regimens are generally based on
target plasma drug concentrations that are believed to be therapeutically effective.
To maintain that target concentration, what is important (2)
the dose and dosage interval are important.
Methods of Systemic administration broadly (2)
Parenteral/outside the GI tract (IV; IM; SC; inhalation)
Enteral (PO)
Methods of Local administration (4)
On the skin
On mucous membranes
Intp the udder
Into the uterus
+ Elsewhere – for instance: epidural administration
name 4 methods of parenteral administration
IV; IM; SC; inhalation
Factors impacting absorption/ impact the penetration of the membranes (4)
- drug molecule properties
- membrane properties
- pH in place of absorption
- local blood supply
drug molecule properties (5)
- Lipid solubility
- The nature (anion, cation, non ionising)
- Degree of ionisation
- pH
- Pharmaceutical form
Diffusion
the property of molecules to move from the higher concentration towards the lower concentration.
Pinocytosis
an active, energy consuming process where extracellular fluid and solutes are taken up into a cell via small vesicles / transport of liquid droplets
Phagocytosis
and give example
transport of solid particles
(e.g. immunoglobulins in milk)
Degree of dissociation indicates
how much of a drug is dissociated (broken down into ions)
/
the extent to which the dissociation occurs.
what type of molecule absorbs more easily
Non- ionised - lipid soluble
“Acid-base conflict, ionic lock” refers to what
Such as in the rumen – some drugs cannot be administered per os to ruminants; since bacteria inactivate the drug, drug can be locked in rumen, diluted.
What type of animals cannot receive systemic drugs PO?
ruminants
Exception: Specific pharmaceutical forms that stay in the rumen for a long period and release the active ingredient gradually.
pH partition
pH partition is the tendency for acids to accumulate in basic fluid compartments, and bases to accumulate in acidic compartments.
For example, in ruminants, many basic drugs tend to distribute into the rumen, resulting in distribution volumes much larger than those in monogastrics.
pH partitioning phenomenon is important in
absorption, but also in any situation where the pH of fluid compartments across a biological membrane is different.
“It will occur for a drug distributing from plasma (pH=7.4), to milk (pH=6.5-6.8), to cerebrospinal fluid (pH=7.3) or intracellular sites (pH=7.0).”
General rule: weak acid drugs (ie. aspirin) are readily absorbed from
acidic environment (from GI tract (pH 1,5) to blood (pH 7,4));
weak base drugs (ie. morphine, ketamine) are absorbed from alkaline environment and trapped in an acidic environment (very poor absorption from GI).
General rule: weak base drugs (ie. morphine, ketamine) are absorbed from
alkaline environment and trapped in an acidic environment (very poor absorption from GI).
weak acid drugs (ie. aspirin) are readily absorbed from acidic environment (from GI tract (pH 1,5) to blood (pH 7,4)).
The following 2 are prerequisites for absorption through a cell membrane:
Low molecular weight
Lipid solubility
how does Improved blood supply affect drug pharmacokinetics?
faster absorption
Bioavailability is
the fraction (%) of an administered drug that reaches the systemic circulation.
When drug is administered per os, the bioavailability may be influenced by
the fullness of the gastrointestinal tract; differences between animal species.
the primary site for most drug absorption is
the small intestine
The drug moves from the stomach and small intestine to the
liver via the portal circulation
Pharmacokinetics:
some drug additives increase what
absorption,
some inhibit absorption.
3 important points in regard to Absorption from subcutaneous tissue and muscle
- Blood supply in the site of administration
- Aqueous solutions absorb faster, oleaginous solutions absorb slower (fat soluble)
- Prolonged effect via this route because absorption takes time
Oleaginous Solutions are
oh-lee-aj-i-nuss
fat soluble solutions
forms of drug for Absorption from the lungs (3)
Gases, aerosols, vapours
What stage follows the absorption stage
Distribution stage follows, except in case of administration into the blood vessel
(in that case no absorption occurs because its literally already in the blood)
Factors impacting distribution (4)
- Binding of the drug with the blood plasma proteins and formed blood elements
- Physical-chemical drug properties
- Blood supply of the organ
- Tissue affinity
where is the effective portion of drug in the blood
The free fraction achieves the effect, the bound fraction is not free to bind target tissues if its bound to a transport protein.
Tissue affinity in the context of pharmacology is
Specific sensitivity of tissues with respect to certain medication.
Tissue affinity/specific sensitivity of Aminoglycosides (a group of ab)
kidneys
Tissue affinity/specific sensitivity of Tetracyclines
bones, including teeth
capable of destroying bones in young animals so long courses should be avoided in growing animals.
Volume of distribution refers to
the theoretical volume that the total amount of administered drug would have to occupy to provide the same concentration as it currently is in blood plasma.
The volume of distribution (Vd) is a pharmacokinetic parameter representing an individual drug’s propensity to either remain in the plasma or redistribute to other tissue compartments.
what compounds can penetrate the blood-brain barrier
small enough nonionized lipid-soluble compounds
ie. small polar molecules like glucose
Before elimination, what takes place
Biotransformation – transformation of the drug into metabolites through chemical reactions
Elimination includes what two processes?
biotransformation and excretion
Biotransformation mainly occurs in ?
And to a lesser extent in (4)?
It mainly occurs in the liver,
to a lesser extent also in the intestines, kidneys, lungs, blood plasma.
The primary liver enzymes that participate in biotransformation are the following:
oxidases, reductases, transferases.
What does the following describe:
The drug that passes through the liver then goes into the gall bladder and it may be absorbed back from the gall bladder or the intestinal tract, getting back into the liver through the hepatic portal vein.
Enterohepatic circulation (recycling)
explain secondary peak in plasma concentration
Compounds that are excreted into bile may have a prolonged stay in the body because of continuous opportunity for intestinal reabsorbtion via the enterohepatic circulation.
explain First-pass metabolism
The degree of metabolic breakdown of an orally administered drug that occurs in the intestine or liver before it reaches the systemic circulation.
It is also known as the first-pass effect and results in a reduction in the concentration of the drug.
Excretion usually occurs through (3)
1) the kidneys
2) the intestines via feces
3) the lungs
In addition, possible through: mucous membranes & glands
(sweat glands, sebaceous glands, mammary glands, biliary excretion)
explain organ clearance
the volume of blood or plasma that an individual organ clears over a unit of time
explain total clearance
the volume of blood or plasma that an organism clears over a unit of time,
= “the sum of organ clearances”
Thus, total body clearance is equal to the sum clearance of the substance by each organ.
explain Half-life, T1/2
the period of time over which the concentration of a drug is reduced by 50% in the blood.
Half-life depends on (3)
the animal species,
the particular nature of the tissue,
the method of administration.
the aim of Interspecies extrapolations of pharmacokinetics is
to predict drug activity or toxicity in a new species not previously studied.
2 difficulties with Interspecies extrapolations of pharmacokinetics
- a drug’s pharmacokinetic profile does not extrapolate without ajusting for species characteristics
- the pharmacodynamic response may be very different across species
difference between pharmacokinetics and pharmacodynamics?
pharmacokinetics is the movement of drugs through the body, whereas pharmacodynamics is the body’s biological response to drugs.
