Pharmacokinetics Flashcards
What does pharmacokinetics mean?
What does the body do with the drug
Where does ADME stand for?
Absorption
Distribution
Metabolism
Excretion
Where does absorption, distribution, metabolism and excretion take place?
absorption: stomach, small intestine
distribution: bloodstream
metabolism: liver
excretion: kidneys and rhe large intestine
Name the different ways to orally (per os) by mouth swallow a drug (3)
- oral (swallowed)
- sublingual (under the tongue)
- buccal (in the cheek pouch)
Name the different types of injections (5)
- Iv intravenous
- IM intramuscular
- SC subcutaneous
- IA intraarterial
- Intrathecal (into subarachnoid space)
Name a few factors affecting drug absorption (4)
- stability to acid and enzymes
- motility of the gut (diarrhea, constipation) longer or shorter in the gut
- food in the stomach (might compete with the drug for absorption)
- degree of first-pass metabolism
What does first-pass metabolism mean?
First-pass metabolism is the process where a drug is partially broken down in the liver before it enters the bloodstream. This can reduce the amount of the drug that reaches the systemic circulation and may affect its effectiveness. Drugs with high first-pass metabolism often need higher doses or alternative administration routes to achieve therapeutic effects.
By which 2 mechanisms are drugs transported over the cell membranes?
- by a carrier
- by diffusion
How is the absorption rate determined?
concentration gradient of the unionised form of the drug across the membrane + lipid solubility of the unionised form + available r4esorption surface
The degree of drug ionisation is dependent on … (2)
- ambient pH
- Strength of acid or base (pKa value)
What does the pKa value mean?
The pKa value of a substance is like a measure of how likely it is to give away or accept a particle called a proton. Lower pKa values mean the substance is more likely to give away a proton and is a strong acid , while higher pKa values mean it’s more likely to accept one.
Why is ionisation important for drugs?
The bowl is a very acidic structure and when a drug is very acidic it cannot easily give its protons away. They do not become ionised easily
Aspirin is an acidic drug, what does this mean? low pKa
Aspirin has a pka of 3.5 and gastric juice of 3. this means that a large part of aspirin will be in the non ionised state. This means it will easily diffuse.
What happens with pethidine which is a strong base? high pKa
It will stay in the gastric content, so will not absorp easily. because it is higher then the ph of the gastric juice so a lot of ionisation takes place
Why does the lipid solubility place a role in absorption?
The amount of a drug with a high solubility that is absorbed is higher compared to a low solubility drug.
What does ph partitioning mean?
that weak acids tend to accumulate in compartments of relatively high pH, whereas weak bases do the reverse.
How can you measure the first pass effect
By measuring the bioavailability of the drug:
this is the proportion of a drug that is absorbed effectively after administration. This is (AUC oral/AUC injected)*100. AUC is area under the curve
What does bioavailability mean?
Bioavailability is like the “how much” factor for a drug—it tells us how much of the drug actually gets into the bloodstream and is able to have an effect in the body after it’s taken. If a drug has high bioavailability, a lot of it does its job; if it has low bioavailability, not as much is able to work. When you inject a drug, the bioavailability is always 100
Where does PB stand for?
It stands for proteinbound drug and it portrays the fact that a drug binds to the plasma proteins found in the vascular compartment, so the bloodstream.
Only drug molecules in their free form/ bound to a plasma protein can transfer trough the barriers
Only free molecules can transfer, drug-protein complexes are too large to cross membranes
Plasma protein binding does not affect bioavailability!
okay
What is the volume distribution? Vd
The volume distribution (Vd) of a drug is like saying how much space in the body the drug is spreading into. If the Vd is big, it’s like the drug is in a lot of places; if it’s small, the drug is more concentrated in a specific area. It helps us understand how the drug is moving around inside the body.
Lipid- insoluble drugs are mainly confined to
plasma and interstitial fluids; most do not enter the brain
What is the formula for Vd?
amount of drug in the body/ concentration in the blood
Describe what happens in the kidney with drugs?
free drug molecules enter the glomerular filtrate and are filtrated into the urine into the proximal tubule. These pass on to the tube of Henle. Then, in the distal tubule passive reabsorption takes place of lipid-soliuble un-ionized drugs. This means that the ionized, lipid-insoluble drug is excreted trough urine
How could one increase renal clearance for a base and an acid?
base: making the urine more acidic (decrease)
acid: making the urine more alkaline (increase urine pH)
What does biotransformation mean?
Biotransformation with drugs is like the body’s way of changing or breaking down the medicine to make it easier to remove. It’s like giving the drug a makeover so it can leave the body more easily after doing its job.
Which 2 organs are primarly responsible for the elimination of drugs?
Biotransformation in the liver
and excretion in the kidney
Bio transformation is not the same as inactivation and/or detoxification
okay
What happens with diazepam during biotransformation
It will form 2 biologically active metabolites named oxazepam, temazepam.
Name what happens with the enterohepatic recirculation during biotransformation
contraceptive hormones are attacked inside the gut by the microbiome bacteria and create different metabolites
What happens during the biotransformation of paracetamol?
If too much paracetamol is administered, phase 1 biotransformation will take over the control instead of phase 2 and this will lead to a highly toxic metabolites which will damage liver cells and overall death
The rate of drug disposition is most likely to be impaired in the very young and the very old, why?
The very young have more water so it has an easier uptake
The very old have less muscle, so it is harder to uptake the drug
when you have obesity, the half life is increased
Drug doses should be modified if the patient has a disease that impairs the function of organs with an important role in drug metabolism and/or excretion, name 2
- liver
- kidney
What does the elimination rate determine?
It determines the length of time a known amount of drug remains in the body and, thereby, its duration of action
What does first-order kinetics mean?
First-order kinetics is like a simple rule for how the body handles drugs—it means the body breaks down or gets rid of a constant fraction of the drug over time, like consistently taking little bites out of it. So, if you start with a lot of the drug, you’ll have less and less of it at a predictable rate. it’s rate is proportional to the drug concentration
What does zero-order kinetics mean?
Zero-order kinetics is like saying the body is working at full capacity to get rid of a certain amount of drug, no matter how much is there. It’s like having a maximum speed for removing the medicine, so even if you have more of it, it still disappears at the same steady rate.
What is the difference between first-order and zero-order kinetics?
First-order kinetics is like eating a slice of pizza one bite at a time, where the body removes a consistent percentage of the drug over time. On the other hand, zero-order kinetics is like having a maximum speed limit for eating pizza—you eat at a fixed rate, and even if there’s more pizza, you can’t eat it any faster.
What are idiosyncratic reactions? and name an example
diosyncratic reactions are like unexpected surprises the body sometimes has to medicines where a person reacts in an unusual or uncommon way that’s not easy to predict.
e.g. agranulocytosis inflicted by clozapine
Name the different forms of toxicity (4)
- hepatotoxicity (liver due to drug metabolites)
- nephrotoxicity (kidneys, high concentration accumalates in the urine)
- mutagenesis and carcinogenesis (DNA damage)
- teratogenesis (structural damage to fetus, first 3 months of pregnancy)
Name an example of type 1 hypersensitivity and explain
it is the immediate-type hypersensitivity and an example is penicillin
Name an example of a type 2 hypersensitvity and explain
type 2 is antibody-dependent cellular cytotoxicity and an example is cefotetan
Name an example of a type 3 reaction and explain
immune-complex reaction and an example is mitomycin C
Name an example of a type 4 hypersensitivity reaction and explain
it is a delayed-type hypersensitivity and an example is sulfamethoxazole
What is tachyphylaxis?
repeated administration of the same dose of a drug results in a reduced effect of the drug over time. a quick tolerance is developed
What is desensitization?
decreased ability of a receptor to respond to stimulation by a drug or ligand (takes more time to become desensitized compared to rapid tachyphylaxis)
What is the difference between homologous and heterologous desensitization?
Homologous is a decreased response at a single type of receptor
heterologous is a decreased response at two or more types of receptors
What is down-regulation?
Repeated or persistent drug-receptor interaction results in the removal of the receptor from sites where subsequent drug-receptor interactions could take place.
What is the therapeutic range?
TD50-ED50
What is the TD50?
It tells us the dose at which a drug is toxic for half of the people who take it
What is the ED50?
it’s the amount that works just right for half of the people who take it. So, if you give this dose to a group, about half of them will get the desired effect.
What is the safety index?
TD1:ED99,
