Introduction to pharmacology Part 2 Flashcards
What is pharmacokinetics and what does it encompass?
The act of what the body does to drugs: This includes:
Absorption
Distribution
Biotransformation
Excretion
When is pharmacokinetics important?
When choosing an appropriate route of administration
What are the different types of drug entry routes?
Enteral (i.e. the oral route)
Perenteral (i.e non oral route).
Local administration
What are examples of different drug entry routes?
oral , intravenous , rectal , percutaneous, intramuscular, etc
True or False- Polar drugs are more readily penetrate through cell walls.
False - Non polar drugs more readily penetrate into cell walls.
Do most drugs exist as wholly ionised or wholly unionised?
Neither - most drugs are weak acids or bases, which can exist in ionised or unionised forms.
How can we calculate how ionised a drug is?
•The degree of ionisation is calculated from the Henderson-Hasselbalch equation:
pH= pKa + log _[A-]_
[HA]
where pka is the measure of how ionised soemthing is.
Acids follow an equilibrium equation:
HA A- + H+
thus how does changing conditions shift the side and rate of reaction?
■In an ACID ENVIRONMENT, the reaction will shift to the left, i.e. the un-ionised form
■In an ALKALINE ENVIRONMENT, the reaction will shift towards the right, i.e. the ionised form
■A weak acid in an acid solution will be mainly in its un-ionised form. However, in an alkaline solution it will be trapped in its ionised form. The result is that an acidic drug will be concentrated in a compartment with a high pH.
(acids are proton donors)
What equilibrium recation describes the ionisation of a weak base?
Basically the same reaction for weak acids but with B for base and H+ for hydrogen.
BH+ B + H+
•The degree of ionisation is represented by:
pH= pKb + log _[B]_
[BH+]
(basically the same equation for working out ionisation of an acid)
How does changing conditions of the ionisation recation of a weak base affect the side of the reaction?
BH+ B + H+
■In an ACID ENVIRONMENT, the above reaction will shift towards the left, i.e. the ionised form
■In an ALKALINE ENVIRONMENT, the reaction will shift towards the right, i.e. un-ionised form
■A basic drug in an alkaline solution will be non-ionised and have a greater ability to cross lipid membranes. However, in an acid environment it will be trapped, as it is ionised. The result is that an alkaline drug will be concentrated in a compartment with a low pH.
Why are we so concerned with pka values (a.k.a knowing how ionised a particular drug is)?
Depending on ionisation certain drugs are more likely to be absorbed by certain parts of the body.
■A weak acid e.g. Aspirin pKa= 3.5 is more likely to be absorbed from the stomach
■A weak base e.g. Pethidine pKa= 8.6 is more likely to be absorbed from the small intestine
Are conditions in the small intestine more alkali or acidic?
More alkali
As well as ionisation what other factor affects absorbtion of drugs through to tissues such as that of the small intestine?
Lipid solubility
Why are strong acids and strong bases poorly absorbed by tissues in the intestine?
■Strong bases (pK>10) and strong acids pK<3 are poorly absorbed since they are fully ionised
What other factors affect absorption of a drug?
- There are several factors which affect absorption:
- Gut motility
- Splanchnic blood flow (blood flow of the gut)
- Drug Formulation
- Physiochemical factors
- A drug taken after a meal is often more slowly absorbed since progress to the small intestine is delayed
- Drugs can be formulated specifically to delay absorption e.g. capsules, tablets with resistant coatings
Typically how long does it take a drug that is orally delivered to be absorbed?
•Typically 75% of an orally administered drug is absorbed within 1-3 hours
What is tetracycline and what scernerios is it contraindicated in and why?
It is a type of antibiotic.
It is contraindicated in pregnancy and breastfeeding as it binds to calcium stopping it being absorbed, leading to poor fetal/infant bone development.
It is also reduces the absorption of oral contraceptives ( like most antibiotics).
What is bioavailability?
■bioavailability refers to the fraction of the dose that proceeds unaltered from the site of administration and becomes available at the site of action
- basically percentage of drug that actually reaches the target site in the form you want it in.
What is bioavailability largely dependant on?
■Bioavailability is to a large extent dependent on the rate of absorption
As well as rate of absorption what other factors affect bioavailability?
First pass metabolism
What is first past metabolism?
■First pass metabolism represents the breakdown of a drug by biotransformation via enzymes this can be within the gut wall or liver before it reaches the plasma compartment.
Basically the start point at which drugs start to be broken down or acted upon
What factors affect distribution of a drug?
■Following absorption, distribution of a drug is frequently not uniform, due to:
■physicochemical properties of the drug
■differences in blood flow between tissues - i.e. if a tissue is more vascular it will recieve more of the drug through the blood supply
■degree of “leakiness’ of the blood vessels within a particular tissue
■A drug may have an affinity for a particular tissue component e.g. melanin or fat.
■Plasma protein binding is another important variable
Why does plasma protein binding affect drug distribution?
Essnetially whist the drug is travelling around in the blood it starts binding to the proetin in the blood lasma, reducing bioavailability as the drug is getting caught up with the protein rather than reaching the intended target site.
Does plasma proetin binding also affect drug elimination?
Yes
What are the protein components of blood plasma?
Albumin, beta-globin and alpha acid glycoprotein
Which type of drugs does albumin typically bind to hindering its distribution?
Albumin binds to mainly acidic drugs e.g. warfarin and non-steroidal anti-inflammatory drugs (NSAID).
Which type of drugs does beta-globin and alpha glycoprotein typically bind to hindering its distribution?
■ß-globin and a acid glycoprotein, bind mainly basic drugs e.g. propanolol
Why are non polar drugs poorly eliminated from the kidney?
They tend to get reabsorbed by cells in the tubules whilst being eliminated
How does elimination of drugs from the body occur?
■The elimination of drugs from the body occurs by metabolism ( also known as biotransformation) and excretion
What is metabolism of drugs?
■Metabolism involves the enzymatic conversion of the drug into another chemical entity
What are the two stages of drug metabolism called and what is the point of them?
■Drug metabolism (occurring predominantly in the liver) involves two types of chemical transformation, which are termed phase I and phase II reactions
■The purpose is to make the drug more polar (hydrophilic) to hasten its secretion by the kidneys
Phase I reactions involve adding or unmasking a functional group e.g. –OH, -NH2, -SH.
■Phase II processes (often termed conjungation) involve the attachment of a substituent group e.g. glucuronyl, acetyl, methyl or sulphate. These reactions make the drug more polar so that it can be excreted by the kidneys
What are examples of routes of excretion of a drug?
■Most drugs leave the body in the urine either unchanged or as polar metabolites
■Other drugs are secreted into bile via the liver followed by loss of the drug via the faeces
What affects the rate of excretion of drugs?
■The rate of renal clearance is variable: some drugs are lost in a single transit whilst others are cleared more slowly
Why do we need to be careful about prescribing drugs that do not undergo biotransformation and for whom do we need to be more careful?
■For those drugs that are excreted without biotransformation, drug action can only be terminated by renal elimination. These drugs therefore need to be prescribed with special care in the elderly and in those with altered renal function
What factors affect drug metabolism?
■Some drugs increase the activity of drug metabolizing enzymes e.g. barbiturates
■Other drugs inhibit drug metabolizing enzymes e.g. erythromycin, ethanol
^ thus we need to be careful of different drugs interacting with eachother.
■Genetic polymorphisms lead to inter-individual variation in drug metabolism a.k.a everyone is different and the way their bodies absorb drugs is different
■Age: neonates may have an immature drug metabolizing mechanism. The elderly may have impaired hepatic metabolism of drugs and also show an impaired glomerular filtration rate reducing renal clearance.
What is the intrathecal administration of drugs?
Adinistration into the spinal chord
