Pharmacokinetics (9) Flashcards
What is the pharmacokinetic process?
- Drug getting to site of action
What is meant by a pharmaceutical process?
- Drug getting into patient
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.
