Pharmacokinetics (9) Flashcards Preview

ESA 2 Membranes and Receptors > Pharmacokinetics (9) > Flashcards

Flashcards in Pharmacokinetics (9) Deck (38)
Loading flashcards...

What is meant by a pharmaceutical process?

- Drug getting into patient


What is the pharmacokinetic process?

- Drug getting to site of action


What is meant by the pharmacodynamic process?

- Is the drug producing the desired effect.


What is meant by the therapeutic process?

- Drug is translated into a therapeutic process


In the pharmaceutical process what is meant by formulation and compliance?

- Formulation: tablets/liquid - rate of action depends on dissolution
- Compliance: E.g take once a day


What are the advantages of using specific sites of administration?

- Concentrates drug at site of action
- Less systemic absorption and less side effects


What is meant by the oral bioavailability of a drug?

- Proportion of the drug given orally that reaches circulation unchanged


How is bioavailability measured?

- Amount: depends on 1st pass and gut absorption
- Rate: depends on pharmaceutical factors and gut absorption


What does the graph of injected and oral administration of a drug look like. Plasma conc against time

- Injected has immediately high initial amount and decreases linearly over time
- Oral has a slow increase to a much lower peak then plateaus and decreases slowly


What is the therapeutic window?

- The drug concentration between the minimum effective dose and maximum tolerated dose before it becomes toxic.


How can you change the drug to affect the therapeutic window?

- Can't change the therapeutic window but can change the release rate, a slower overall release will allow the drug conc to remain in the therapeutic window for longer.


What is meant by first pass metabolism?

- Drugs that are administered orally are first exposed to the liver
- Here they may be extensively metabolised before reaching rest of body


How can first pass metabolism be avoided?

- Injections: IM, IV and SC
- Rectal (drains to portal and systemic systems)
- Sublingual (under the tongue)


What is volume of distribution?

- The theoretical volume into which the drug is distributed if this occurred instantaneously
- Obtained by extrapolation of plasma levels to 0 time


What are the two possible fates for free drugs?

- Reaches target receptor
- Elimination (kidney/liver)


When are protein binding interactions important?

- When highly bound to albumin (>90%)
- Has small volume of distribution
- Has low therapeutic ratio


What is a class 1 drug?

- Object drug
- Used at a dose lower than number of albumin binding sites


What is meant by a class 2 drug?

- Precipitant
- Used at doses greater than the number of binding sites and thus displacing class 1 drugs


What is meant when binding interactions are said to be transient?

- If free drug levels rise so will the elimination rate
- Steady state is restored quickly in a few days
- Transient = short lived


Give an example of an object drug and its precipitant.

- Warfarin: sulfonamides, aspirin, phenytoin
- Tolbutamide: sulfonamides, aspirin


If you graphed 1st order kinetics what would it look like and why?

- Linear on a log y axis against time
- Rate of elimination is proportional to drug level
- Constant half life


What is the characteristic of zero order kinetics?

- The rate of elimination is constant


How long does it take for a drug level to reach a steady state?

- 5 half lives
- Irrespective of dose/frequency of administration


What can be implemented if the half life of a drug is long but a rapid response is needed?

- Implement a loading dose
- Often determined by volume of distribution.


What is the most common way for drugs to act in?

- 1st order
- Predictable therapeutic response from dose increase


Which drugs undergo zero order reactions?

- Alcohol & pheryroin
- Therapeutic response can suddenly escalate as elimination mechanism saturates


What are the 2 main methods of drug elimination?

- Metabolism: predominantly liver
- Excretion: predominantly renal


How are drugs eliminated in metabolism?

- Drug enters phase 1 or phase 2
- Phase 1: drug is oxidised/reduced/hydrolysed which either activated/inactivates or doesn't change the drug
- Phase 2: conjugation of products normally inactivates the drug


What are the different types of drug interactions and give some examples.

- Enzyme inducer: Phenobarbitone, Rifampicin, cigarette smoke
- Enzyme inhibitor: Cimetidine, Warfarin
- Drug affected: Warfarin, phenytoin, OC pill, Theophylline


How does renal elimination occur?

- Via the glomerulus filtration
- Only free drugs can be filtered


What happens at the proximal tubule?

- Active secretion into the tubule


What happens in the distal tubule?

- Passive reabsorption of lipid-soluble un-ionised drug


What happens in the collecting duct?

- Ionised, lipid-insoluble drug excretion in to urine


Passive reabsorption of a drug is dependent on what in the kidneys?

- pH


What effect does pH have on absorption in the kidney?

- Only non-ionised moiety is lipid soluble and crosses membrane easily


What are the best conditions for a weak acid/base to be absorbed in the kidneys?

- Weak acids: acidic urine increases absorption
- Weak base: alkaline urine increases absorption


What affect does being secreted by the kidneys have on a drug?

- Half lives are longer


As the half lives are longer what is needed clinically when treating?

- Lower maintenance dose of drug (otherwise accumulates and becomes toxic levels)
- Loading does and protein binding can be altered to compensate for a longer half life.