Drugs Flashcards
Pharmacodynamics vs pharmacokinetics?
D is what drugs does to body, K its what body does to drug (ADME)
ADME
absorption, distribution, metabolism, excretion
Therapeutic index
What is absorption?
Process of mass transfer from site of administration to blood stream (plasma). Commonly oral or IV
Distribution?
How the medication moves around the body
What is bioavailability?
Percentage of administered drug that makes it to the biophase
What is first-pass metabolism and when does it commonly occur?
Drug is metabolised before reaching bio phase so its bioavailability is less than 100%. Occurs in liver and GI tract has enzymes which can break down drug before reaching biophase
What determines extent and rate of absorption? (5)
Lipophillicity, molecule size and shape, solubility, gastric emptying time, pH in gut
What is the half life of a drug?
Time taken for drug conc. in plasma to half. Big half life = toxic and low = no therapeutic effect
How does cMax relate to drug concentration?
max conc drug reaches in plasma. High cMax = better absorption and higher bioavailability so less doses to avoid toxicity
How does cMax relate to drug concentration?
max conc drug reaches in plasma. High cMax = better absorption and higher bioavailability so less doses to avoid toxicity
What is a transcellular fluid?
Made by epithelial cells, includes CSF, peritoneal fluid
What is paracellular vs transcellular movement?
P = filtration out of capillary bed. T = transport in and out of endothelial
What is tMax
time taken to reach cMax. short means rapid onset of action, but goes away quickly so you need more doses
What method of administration would you chose if you want systemic absorption?
Oral, Rectal, Sublingual
What method of administration would you chose if you want parenteral absorption?
Intramuscular, Subcutaneous
Why is pH important in drug administration?
only unionised drug can be absorbed, so if pH is too low drug can be ionised
Why is lipophillicity of a drug important?
more lipophilic means it will transport through membranes better, but too lipophilic is bad
Which parts of the body are more protected? how?
Brain, testes, ovary, placenta. Have tight junctions so prevent capillary transport
How do free drug and plasma proteins correlate?
Plasma proteins bind to drugs and this means they’re inactive. Free drug can be absorbed and distributed.
What is vD and how does it correlate to drug duration in plasma?
vD is volume of drug available for distribution. Drugs with low vD stay in plasma longer so doesn’t go to other tissues as fast.
What is steady state?
When drug is constantly at an effective therapeutic concentration
Whats special about general anaesthetic?
It is highly lipophilic so rapidly distributes to all the tissues arrives at
What is perfusion?
passage of blood/lymph to tissue/organ
zero order kinetics
conc. of drug in body constantly decreases in a straight constant independent of concentration of drug
first order kinetics
rate of reaction is directly proportional to concentration - dependant on concentration of drugs. more time goes on, rate of drug decreases more rapidly
What are the three ways that the body protects itself from xenobiotics?
BBB,
Removal via urine or bile
Biological transformation via phase I and II
What is biotransformation?
Increasing polarity of drug so its less likely to be reapsorbed by kidney tubules
Phase I? and site?
Add functional group via oxidation, or modification of a current functional group on the drug via hydrolysis, in liver and extrahepatically
CYP450?
membrane proteins that are important phase 1 enzymes. they oxygenate the drug by adding a single oxygen atom, forming a functional hydroxyl group. this forms. handle for phase II to occur
What occurs in phase II?
Produces larger and more polar molecules by attaching hydrophilic groups. produces inactive form of drug which is usually a weak acid which has a lower chance of being reabsorbed in kidneys.
How do phase II metabolites become inactive?
They’re more likely to bind to plasma proteins so they become inactive and cant spread to other tissues
what is the significance of glucaronic acid
its an important co-factor in phase 2 metabolism for most drugs
What is warfarin?
its a drug which prevents clot formation in diseased people, and this drug is metabolised by a type of CYP450 - CYP2C9
What is clearance of drug?
Volume of plasma where drug would be completely removed per volume of time. Occurs via hepatic or renal mechanisms
How should we change drug dosage based on clearance?
If clearance is high, drug dosage should be increased as its cleared from plasma faster.
What factor allows a drug to be filtered by the kidney?
It must be present in the plasma in a free form (not bound to plasma proteins) and the kidney must be in good health, with well perfusion
How do larger molecules enter the kidney for filtration?
through transporters (protein channels)
What does transport of drug into the kidney depend on?
flow rate and free drug conc.
What factor effects reabsorption of drug in the kidneys?
if drug is too lipophilic, its more likely to be reabsorbed. this is why phase I and II metabolism occur, to make drug larger and more soluble
What makes a drug less likely to be reabsorbed?
More polar, more alkaline urine (ionises the weak-acid conjugated drug more so cant be reabsorbed)
What makes a drug less likely to be reabsorbed?
More polar, more alkaline urine (ionises the weak-acid conjugated drug more so cant be reabsorbed)
