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Flashcards in deck_797765 Deck (62)

Define pharmacokinetics

What the body does to a drug


Define pharmacodynamics

What the drug does to the body


Give four questions which should be asked when administering a drug,

Is the drug getting into the patient?(pharmaceutical process)Is the drug getting to the site of action? (pharmacokinetic process)Is the drug producing the desired pharmacological effects? (pharacodynamic process)Is the pharmacologic effect translated into a therapeutic effect? (therapeutic process)


What are the two methods of drug formulation?What is another factor on the administration of a drug?

Solid, liquidCompliance - simplified regime


If solid, what extra factors must be considered?

Solubility and acidic stability in stomach must be considered


Give two sites of administration?

Local (eye, skin, inhalation)Systemic (enteral or parenteral)


Give three examples of enteral systemic administration

Sublingual Oral Rectal


Give five examples of parenteral systemic administration

Subcutaneous/intramuscular/intravenous injection, inhalation, transdermal


Define the term oral bioavailability

Oral Bioavailability is the proportion of a dose given orally (Or by any other route other than intravenous) that reaches the systemic circulation in an unchanged form.


What can bioavailability be measured by?

1) Amount (depends on GI absorption and first pass metabolism)2) Rate of availability (depends on pharmaceutical factors and rate of gut absorption)


What are two factors which effect gut absorption?

Altered by food or disease


How is amount measured on graph?

Area under curve of blood drug level vs. time


How is rate measured on a graph?

peak height and rate of rise of drug level in blood


What is maximum tolerated dose?

Lethal Dose to 50% of people


What is minimum effective dose?

Effective Dose in 50% of people


What is the equation for measuring therapeutic ratio?

Maximum Tolerated Dose/Minimum Effective Dose(LD50/ED50)


Advantage of local admin?

Less systemic side effects, more direct action


What is the first pass effect?

Substances absorbed from the lumen of the ileum enter the venous blood, which drains into the hepatic portal vein and is transported directly to the liver. Liver is main site of drug metabolism, so any drug which enters it may be extensively metabolised before it reaches systemic circulation - first pass effect


How can the first pass effect be avoided?

The parenteral, sublingual or rectal routes can avoid it.Glyceryl trinitrate is a particular example


How much of an oral dose of paracetamol is metabolised via first pass effect?



Define drug distribution

The theoretical volume into which a drug has distributed assuming that mixing occurs instantaneously


What is drug distribution calculated by?

mount Given / Plasma Concentration at Time 0


What happens to many drugs once they reach circulation?

Protein binding interaction - this is significant as it is the free concentration of drug which has an effect, not the total


What does rate of action depend on?



When is protein binding important? (3)

The drug is highly bound to albumin (>90%)The drug has a small volume of distributionThe drug has a low therapeutic index


Give two examples of drugs where protein binding is important

Warfarin and tolbutamide


What is an object drug? (class 1)

Drug is used at a dose that is much lower than the number of albumin binding sites


What is a precipitant drug? (class 2)

Drug is used at a dose that is greater than the number of available binding sites.


What drug should you take now?

Caffeine, you look a little tired.I mean, not tired drawn out, just fatigued? Go ahead scamp, it's going to be a couple of weeks of intense revision - you can afford to go make a coffee (or a tea, if you prefer!).


Name three object drugs and their precipitants

Warfarin - Sulphonamides, aspirin, phenytoinTolbutamide - Sulphonamides, aspiinPhenytoin - Valproate


What happens if class 1 and class 2 drugs are given simultaneously?

When the drugs are administered simultaneously, Object (class1) drugs are displaced by precipitant drugs (Class II), raising the free levels of the object drug and therefore, higher risk of toxicity.


What law do enzymes which metabolise drugs follow?Why are the effects of drugs transient?

Michaelis Mentin KineticsAs free drug level rises, so to does rate of elimination


What is the standard equation for rate of metabolism?

V max x (concentration)/Km + (C)


In a situatioon where a drug is used at concentration lowerer than km, what is the equation?

Rate of metabolism = Vmax (C)/Km


What are first order kinetics?

metabolism is proportional to drug concentration Constant fraction of drug broken down in unit time. Half life can be defined.


What do first order kinetics look like on a gaph?

straight line when a log scale is on the Y-axis versus time


Define first order kinetics

When the rate of decline of plasma drug level is proportional to drug level. Half life can be defined.


When are 0 order kinetics obeyed?

When drug is used at a concentration much greater than Km


What is the equation for 0 order kinetics?

Rate of metabolism = Vmax (c)/(C)Rate of metabolism effectively = vmax and the enzyme is saturated


Define 0 order kinetics

When the rate of decline of plasma drug level is constant, regardless of concentration. Give a straight line when normal (not log) plasma conc plotted against time


How long until steady state of drug is reached after repeated doses? Irrespective of dose or frequencyof administration

Five half lives


What happens if an immediate effect of drug is needed?

A loading dose is given, which is determined by the volume of distribution


What is the advantage of 1st order kinetics?

Gives predictable therapeutic response from dose increases (most drugs behave this way)


What is the major effect of 0 order kinetics?

Gives a therapeutic response which can suddenly escalate as elimination mechanisms saturate (alcohol, yay!)


What are the two stages of drug elimination?

Metabolism (by liver)Excretion (by kidney)


What is phase 1 of drug metabolism?

Most drug molecules are stable and relatively unreactive (a pro-drug) so in Phase I a reactive group is exposed on the parent molecule or added to the molecule.


Why are reactive groups added or exposed on parent molecule in phase 1 of drug metabolism?

Generates a reactive intermediate that can be conjugated (in Phase II) with a water-soluble molecule to form a water-soluble complex.


What are the three methods via which reactive groups added or exposed on parent molecule in phase 1 of drug metabolism?



What enzymes are needed for phase one of drug metabolism?

Cytochrome P450 and high energy cofactor (NADPH). Enzymes are inducible and inhibitable.Low substrate specificityAffinity for lipid soluble molecules


When do drug interactions matter?

Low therapeutic ratio Drug at minimum effective concentration


Name three enzyme inducers and the drugs the effect

Phenobarbitone - Warfarin, PhenytoinRifampicin - Oral contraceptiveCigarette smoke - Theophylline


Name an enzyme inhibitor found in phase 1 and the drugs it effects

Cimetidine (stomach ulcer treatment) - Warfarin, Diazepam


Name a drug which can bypass phase 1 of drug metabolism



What occurs in phase 2 of drug metabolism?

The reactive intermediate from Phase I is conjugated with a polar molecule to form a water-soluble complex. The process is also known as conjugation.


Name three conjugates involved in phase 2

Glucoronic acidsulphate ions and glutathione


What high energy cofactor is required in phase 2 drug metabolism?

uridine diphosphate glucuronic acid (UDPGA)


Name three potentiators of warfarin, and how they have effect

Alcohol - inhibits metabolismAspririn, suplhonamides, phenytoin - displacement from plasma proteinsBroad spectrum antibiotics - reduced Vit K synthesis


Give two inhibitors of warfarin and their one effect

Barbiturates, rifampicin - Induces liver metabolizing enzymes


What state must a drug be to be excreted by the kidney? Give one method of excretion from tubule

Only the free unbound drug is filtered through glomerular tuft.Drugs can be actively secreted by the tubule


What determines how much of a drug is excreted?

Urine pHPk of drug is pH at which half of it is ionised


What occurs for weak acids in terms of urine excretion?

For weak acids, e.g. aspirin, making the urine alkaline will make the drug ionised, so there will be less tubular absorption because the charged drugs stay in the tubule lumen.Forced alkaline diuresis used in aspirin overdose


What occurs for weak bases in terms of urine excretion?

For weak bases, e.g. amphetamine, the opposite is true and acidic urine will increase excretion. Acid urine will ionise a weak base, making the charged drug stay in the tubule lumen. Forced acidic diuresis to increase excretion.