Why is there no such thing as a standard dose?
Because each patient is different and takes up medicine at different rates (absorbance rates, metabolic rate and elimination rates from kidneys)
What is pharmacokinetics and what is pharmacodynamics?
Pharmacokinetics is what the body does to the drug (How the drugs gets to the active site, how long it stays there and when it leaves)
Pharmacodynamics is what the drugs do to the body and the relationship between concentration intensity/nature of the effect
What issues affect drug efficacy?
Patient compliance
Medication errors
Absorption rates/ammount
Distrobution
Biotransformation
Excretion
Passive diffusion
Active transport
Tissue responsiveness
effects of other drugs
What is the theraputic range?
The difference between the minimum effective concentration of a drug and its minimum toxic concentration
It is used to determine if monitoring is neccesary
E.g penicillins have a large window, antihypertensives have a reasonable window and anti-cancer drugs have a narrow window
What is bioavaliability?
How well a drug is absorbed and reaches its site of action
What factors affect abosption orally?
Stability in GI tract
Extent abosrbed into the blood
Extent of hepatic drug metabolism
How does protein binding affect drug action?
More binding reduces the free drug ammount and vice versa.
Administering multiple drugs can use the same proteins
Certain diseases can reduce protein ammounts
How do some drugs transform to be excreted?
They get metabolised to be more hydrophilic to be excreted in the urine in phase 1 and phase 2 reactions
What factors effect drug metabolism?
Reduces:
Liver disease
Old age
Drug interactions
Inhibitors
Increased:
Liver enzyme induction
What factors affect drug excretion?
Reduced:
Kidney disease
Cardiovascular disease
Drug interactions
Increased:
Kidney disease
Drug interactions
Under what circumstances is Theraputic drug monitoring valid and when isn’t it?
Valid:
Difficult to measure pharmacological action
Poor correlation between dose and effect
Good correleation between plasma level and effect
Narrow theraputic range
Uneccessary:
Non-individualised doses
Pharmalocial effects can be clinically quarantines
Plasma conc is not linnked to intensity
Concentration-effect relationship is not know (antidepressants)
What drugs usually requrie TDM?
Phenytoin -epilepsy anticonvulsant (monitored when starting therapy or when something changes with the condition)
Theophylline
Digoxin - atrial fib treatment (monitoring done when poor response to treatment or toxicity is detected)
Lithium - treatment of manic depressive illness (monitoring important when starting treatment, when compliance is an issue and when taking other drugs)
Valproate
Gentamicin
Cabamezepine
Cyclosporin
How is Theraputic drug monitoring carried out?
Samples collected from patients at specific times (before next dose and after drug has entered elimiation phase)
What are biomarkers?
Things such as enzymes, proteins, hormones ect that arise in response to disease
What is enzymology?
Measurment of ennzyme activity in samples.
Used to identify tissue damage, extent of diseases, obstruction, infection and inflammation.
What are the two types of enzyme assays?
Kinetic fixed time - a tthe end point after a fixed period of time
Kinetic continuous monitoring - graph of absorbance against time to find the rate using the slope
What is aspartate amino transferase (AST) measured for?
It is measured via kinetic continuous monitoring as a test of liver function
It is also a coupled reaction so a rate can be determined for one reaction (loss of NADH as NADH absorbs at 340nm but NAD+ doesn’t) and this corrolates to the reaction related to liver function
What are isoenzymes?
Enzymes with different amino acid composition but catalyse the same reaction.
Tend to be tissue specific therefore better for clincial use
What is Lactate dehydrogenase and what is it a biomarker for?
There are 5 isoenzymes for it
LDH 1 can be used as a cardiac biomarker but also has a high activity in hemolysis of red blood cells so should be used alongside other cardiac biomarkers.
LDH5 is responsible for the reaction of pyruvate to lactate and LDH1 does the reverse reaction with 2-4 doing responsible for the intermdiate points
In liver damage a spike in LDH 4 is present compared to normal
In MI more 1 and less 3 is present
In muscle damage more 5 is present
However it takes longer to be produced after an MI so is less useful as a biomarker than others such as creatine kinase
What is creatine kinase and what is it a biomarker for?
It is the enzyme that catalyses creatine and ATP into phosphocreatine
It has 3 isoenzymes due to it having 2 subunits
The ratio of CK-MB to CK-MM is larger in cardiac than skeletal muscle so it is good to use CK-MB as a biomarker.
It is released from MI, surgery, injections, muscle disease, renal failiure and prolgoned exercise
It is highest around 24 hours after an MI and has up to a 3 hour lag phase before it starts increasing after an event
What are troponins biomarkers for?
Troponins come in two types I and T
Gold standard biochemical test
Heart specific biomarker (MI)
Highest sensitivity
Remains elavated for up to 7 days after event
What is myogloin used as a biomarker for?
Biomarker for MI for 0-4 hours after
Binds oxygen in cardiac and skeletal muscle but difficult to determine tissue of origin
Useless after 12 hours.
