M&R Session 9 Flashcards
What are the four main processes involved in pharmacology?
1) Pharmaceutical process - drug getting to patient?
2) Pharmacokinetic process - drug getting to site of action?
3) Pharmacodynamic process - drug producing the desired pharmacological effect?
4) Therapeutic process - pharmacological effect translated into a therapeutic effect?
Regarding the formulation of a drug, what are the two types of drug consistency and what factors should be considered for one of the forms?
Solid or liquid
Solid - solubility and acid stability in stomach must be considered
(Patient compliance!!)
Describe the two main and sub types of sites of admin with examples?
Two main: Focal or Systemic
Focal: eye, skin, inhalation etc.
Systemic:
(i) Enteral - sublingual, oral, rectal
(ii) Parenteral - SC, IV, IM, inhl, transdermal
What does the term ‘oral bioavailability’ mean?
Proportion of a dose given orally (or by any other route other than IV) that reaches the systemic circulation in an unchanged form.
What can bioavailability be expressed as?
Amount - depends on GI abs + 1st pass metab, (gut abs altered by food + disease)
Rate - depends on pharmaceutical factors and rate of gut absorption.
How is amount and rate measured for bioavail?
Amount - measured by AUC of blood drug level vs time
Rate - measured by peak height and rate of rise of drug level in blood
OR
BIO = AUC oral / AUC injected x 100
What is the therapeutic ratio defined as?
Maximum tolerated dose / minimum effective dose
Defined as LD50/ED50
What is the relationship between therapeutic ratio and formulation?
Need a slow release preparation so [Drug] does not exceed toxic dose.
The [drug] should be between the effective conc and toxic conc = therapeutic window
What is first pass metabolism?
Blood from the gut reaches the liver by the portal system, where the liver could metabolise the drug before it gets to the systemic circulation (e.g. lidocaine, opiates, propranolol, glyceryl trinitrate)
How is FPM avoided?
Parenteral (iv,im,sc)
Rectal (note drainage to both portal and systemic systems)
Sublingual (e.g. use of glyceryl trinitrate in angina)
What is volume of distribution of a drug? How is it obtained?
Theoretical volume into which drug is distributed if this occured instantaneously
Obtained by extrapolation of plasma levels to zero time (t=0)
What determines the effect of an drug nb what form?
Free drug (most drugs bind to plasma proteins e.g. albumin)
Why are protein binding interactions for an object/Class 1 drug?
Is it highly bound to albumin?
Has a small volume of distribution
Has a low therapeutic ratio
e.g. warfarin and tolbutamide
What is an object drug/class 1 and precipitant/class 2 drug?
Class 1 - used at doses lower than number of albumin binding sites (therefore [free drug] is low)
Class 2 - drug is used at doses greater than number of binding sites, and thus displaces the Class 1 drug (therefore [free drug] is high)
What would occur if a Class I and Class II drug were given simultaneously? Why can this be bad?
Displacement of Class I drug occurs by the class II drug.
Temporarily lead to higher free levels of the object drug, and therefore, higher risk of toxicity.
Give examples of object drugs and precipitant drugs?
Object drug : Precipitant drug
Warfarin : Sulfonamides, Aspirin, Phenytoin
Tolbutamide : Sulfonamides, aspirin
What is 1st and zero order kinetics for a drug?
1st - rate of elimination is proportional to drug level. Constant fraction of drug eliminated in unit time. Half life can be defined.
Zero - rate of elimination is a constant
What occurs at low doses and at high doses of [drug] in relation to rate of drug metabolism?
Low doses - drug metab is first order, that is, proportional to drug dose
High dose - drug metab is zero order, that is, constant and independent of drug dose.
What occurs during repeated drug administration? What should be done if a response is needed immediately?
A new steady state is achieved in 5 half lives. Irrespective of dose or frequency of administration.
If an immediate effect is necessary, a loading dose is therefore needed (especially if the half life is long)
Where does the major amounts of metabolism and excretion take place?
Metabolism - predominantly liver
Excretion - predominantly renal
Describe phase I and phase II reactions in the liver?
Phase I - Oxidation, Reduction and/or hydrolysis by CytP450 enzymes
Phase II - Conjugation (glucuronide, acetyl, methyl, sulphate)
What properties do the Cyt P450 enzymes have?
Low substrate specificity
Affinity for lipid soluble drugs
Inducible
When are drug interactions in metabolism likely to matter clinically?
1) Drugs with low therapeutic ratio
2) Drug is being used at minimum effective concentration e.g. OC pill
3) Drug metabolism follows zero order kinetics
Give examples of drug interactions with enzyme inducers/inhibitors and the affected drugs?
Enzyme inducer : Drug affected
Phenobarbitone : Warfarin, Phenytoin
Rifampicin : OC Pill
Cig smoke - Theophylline
Enzyme inhibitor : Drug affected
Cimetidine : Warfarin, Diazepam
What is filtered by the glomerulus in relation to drugs?
Free unbound drug is filtered
What can the kidney tubules do to drugs?
Actively secrete drugs e.g. penicillin secreted by prox tub)
What types of drugs are reabsorbed into the body in the kidney tubules? What is this dependent on?
Lipid - soluble, unionized drugs
Dependent on pH therefore the pK so only the unionized form is absorbed
For weak acids and bases, what conditions are necessary in the urine for reabs?
Weak acid - acidic env for unionzied form e.g. aspirin
Weak base - alkaline env for unionized form e.g. amphetamine
What 4 factors are changed in renal disease for drug prescribing?
1) Half lives of drugs are longer - lower the maintenance dose
2) Longer half lives also means longer time to reach a steady state (5 half lives)
3) Loading dose can be altered unless volume of dist is changed
4) Protein binding can be altered
