9 Pharmacokinetics Flashcards by a m

What is pharmacodynamics?

what the drug does to the body

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Describe the principles of drug formulation

solid (tablet) or liquid

2. if solid, solubility and acid stability in stomach must be considered

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What is patient compliance?

e.g. once daily dosage (easier to remember)

important the patient takes the drug as required

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Describe the site of administration including the use of different sites of administration

focal: eye, skin, inhalation etc.
systemic:
enteral: sublingual (under the tongue), oral, rectal
parenteral: subcutaneous (under the skin), intramuscular, intravenous, inhalation, transdermal (‘patch’ stuck on skin, delivered across skin)

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What is oral bioavailability?

the proportion of a dose given orally (or by any other route other than IV) that reaches the systemic circulation in an unchanged form

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What are factors that can affect bioavailability?

amount (depends on GI absorption and 1st pass metabolism)
gut absorption altered by food, disease
rate of availability: depends on pharmaceutical factors and rate of gut absorption

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How is amount measured in bioavailability?

measured by area under curve of blood drug level VS time PLOT

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How is rate measured in bioavailability?

measured by peak height and rate of rise of drug level in blood

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What is therapeutic ratio?

maximum tolerated dose (LD50) : minimum effective dose (LE50)

LD50/LE50 (divide)
tolerated/effective

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What is first pass metabolism?

blood from the gut reaches the LIVER by portal system, where the liver could metabolise the drug BEFORE it gets to the SYSTEMIC circulation (e.g. lignocaine, opiates, propranolol, glyceryl trinitrate)

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What is 1st pass metabolism avoided by?

parenteral route

2. sublingual or rectal route (enteral)

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What is pharmacokinetics?

what the body does to a drug

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What is volume of distribution?

the theoretical volume into which a drug has distributed assuming that this occurred instantaneously
(amount given / plasma conc. at time ‘0’)

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What happens when drugs bind to plasma proteins?

protein binding interactions could occur

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Which is the level of drug that exerts an effect? When are they important? Examples?

free level of drug NOT total level
important when: 1. drug is highly BOUND to albumin (>90%)
2. drug has small volume of distribution
3. drugs has a low therapeutic index 
e.g. warfarin + tolbutamide

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What is the therapeutic index?

can also be called therapeutic ratio

when the amount of therapeutic agent that causes therapeutic effect VS amount that causes toxic effects

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What is volume of distribution?

(Vd)
theoretical volume required to contain total amount of an administered drug at the same concentration that is observed in the blood plasma

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What is object drug and which class of drugs is it?

class I drug
drugs used at a dose which is much lower than the number of albumin binding sites

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What is precipitant drug? which class is it?

class II drug
precipitant drug is used at a dose which is GREATER than the number of available binding sites

What are examples of object drugs - precipitant drug

warfarin - sulphonamides, aspirin, phenytoin
tolbutamide - sulphonamides, aspirin
phenytoin - valproate

What is the protein binding interaction of drugs leading to toxicity?

when a patient is taking an object drug, then takes a precipitant drug, then the precipitant drug will lead to higher free levels of object drug, leading to a higher risk of toxicity

What is first order kinetics?

when the rate of decline of a plasma drug level is proportional to drug level.
half life can be determined

When does first order kinetics occur?

when a drug is metabolised by enzymes that obey Michaelis Menten kinetics and the drug is used at a concentration LOWER than Km

less drugs each time eliminated

When is zero order kinetics used?

drug metabolised by enzyme obey MMk
drug used at a concentration much GREATER than Km
[C] > Km

What is zero order kinetics?

when the rate of decline of plasma drug level is CONSTANT

When is steady state reached?

in drug administration, steady state will be reached within 5 1/2 lives of that drug

How is an immediate effect reached?

through a loading dose

What are the 2 ways that drug is eliminated in the body?

1. metabolism (e.g. by liver) | 2. excretion (e.g. by kidney)

What are the 2 phases of liver metabolism?

Phase I - oxidation, reduction, hydrolysis | Phase II - Conjugation (glucuronide, acetyl, methyl, sulphate)

Describe what happens in phase I of liver metabolism

carried out by mixed function oxidases in liver 1. consists of NADPH cytochrome P450 reductase, cytochrome P450 in liver microsomes, low substrate specificity, affinity for lipid soluble drugs 2. enzymes are inducible (by substrate), and inhibitable (can't be blocked) (competitive, non-competitive)

What are examples of enzyme inducer and the drugs they affect?

Phenobarbitone - warfarin, phenytoin Rifampicin - oral contraceptive Cigarettes - Theophylline

What is an example of enzyme inhibitor and the drug it is affected?

cimetidine - warfarin, diazepam

Drug interactions with Warfarin (blood clotting) are especially important. What are potentiators of warfarin action? (enhance warfarin)

1. alcohol - inhibits metabolism 2. aspirin, sulphonamides, phenytoin - displacement from plasma proteins 3. broad spectrum antibiotics - reduced vit. K synthesis by bacteria in gut 4. aspirin - reduced platelet function

Drug interactions with Warfarin are especially important. | What are inhibitors of warfarin action?

Barbiturates, rifampicin - induces liver metabolising enzymes (breakdown blood-clotting proteins synthesised in the liver?)

In liver disease, what are drugs that have a low therapeutic ratio?

1. cellular dysfunction - warfarin, phenytoin, theophylline 2. portasystemic shunts - opiates, propranolol (ß) 3. Reduced blood flow - opiates, propranolol, lignocaine 4. reduced albumin - affects drug binding to plasma proteins

Describe the how kidney can excrete drugs

only free unbound drug is filtered through glomerular tuft | drugs can be actively secreted by the tubule (e.g. penicillin)

What determines how much of the drug is excreted in the urine pH?

urine pH can determine how much of the drug is excreted weak acids (e.g. aspirin) makes urine alkaline: making drug ionised, so less tubular absorption, because charged drug stays in the tubule lumen (less drug absorbed because charged ions are v difficult to cross the tubule border, so needs a drug close to urine pH to be absorbed) further away from urine pH, more excreted

How much of a weak base drug will be excreted by the kidneys? give an example

e.g. amphetamine acid urine INCREASES excretion for a weak base drug (pH different) as the acid urine will ionise the weak base, making the charged drug stay in the tubule lumen

What happens in renal disease if the drug or active metabolite is excreted as its main route of elimination?

the 1/2 life (T1/2) is prolonged | therefore, lower the maintenance dose

What happens every time the dose is changed?

it takes 5 1/2 lives to reach a new equilibrium

When will the loading dose change?

when the volume of distribution changes e.g. digoxin

How does the protein binding of drug alter in renal disease?

if the drug / active metabolite is excreted as its main route of elimination, 1/2 life is prolonged, lowering the maintenance dose taking a new 5 x 1/2 life each time the dose changes the loading dose is unchanged unless volume of distribution changes so protein binding of drugs is altered

What happens in 1st order kinetics? how does the graph appear?

linear kinetics | the plot of Log(e) drug level against time is a STRAIGHT line

What happens in 0 order kinetics to the graph?

non-linear kinetics plot of drug level VS time is a STRAIGHT line NOT log

Is elimination of drugs with 0 order kinetics saturable? If so, what do they show with an increasing drug dose in the elimination mechanism?

yes drugs with 0 order kinetics show an initial slow increase in achieved plasma drug level with dose, that accelerates with increasing drug dose as the elimination mechanism becomes saturated (full, at Vmax, can't eliminate drug any quicker as it is at a constant rate, so plasma drug level increases with dose)

What are the 4 factors that can affect the distribution of drugs within the body?

administration of more than 1 drug pH of tissue protein binding obesity

Which process does NOT contribute to drug elimination?

phosphorylation (transfer of Phosphate group onto a drug)