Pharmacology Flashcards
What is First pass metabolism?
drug is absorbed through the enteral route and metabolised in the liver before it reaches systemic circulation
What does a first order of drug metabolism mean?
Constant fraction of drug is metabolised
This rate of reaction does not saturate
What does a zero order of drug metabolism mean?
Constant amount is metabolised
This means that this reaction can be saturated, as [drug input] increases
During which [EtOH] is the metabolism a first order reaction?
<10mg/dL
During which [EtOH] is the metabolism a zero order reaction?
> 10mg/dL
At what rate is EtOH metabolised?
1 unit/hr
What is the half life of a drug?
time taken for 50% of drug to be metabolised
What is the function of phase I drug metabolism in the liver?
makes drug more polar/water soluble
Makes a reactive site in the molecule for conjugation to occur
Which types of reaction occur predominantly in phase 1?
hydrolysis
REDOX
Which enzymes catalyse phase 1 reactions?
Oxidation: cytochrome P450 monoxygenases
hydrolysis: esterases or proteases
What are the 3 potential outcomes of a phase 1 reaction?
produce an active metabolite
produce a toxic metabolite
drug inactivation
What are the outcomes of phase II reactions?
conjugation of metabolites/drugs to generate water soluble compounds that can be renally excreted
What are the 5 main ways that drugs may be conjugated in a phase II reaction?
Glucuronidation Sulfation Glutathione AAs Acetylation
What does NAPQI stand for?
N-acetyl p-benzo quinoneimine
What drugs are considered to be inducers of the P450 monoxygenases?
Carbamezapline Rifampicin Alcohol Phenytoin Greseofluvin Phenobarbitone Smoking
Which common drugs are known CYP450 inhibitors?
erythromycin sodium valproate simvostatin omeprazole fluconazole
What are considered clinically significant drug interactions?
(In the context of CYP450 enzymes)
When the substrate of CYP450 has a narrow therapeutic index or there are significant effects at sub-therapeutic or toxic levels
Methods of drug elimination are
renally (majority) faeces (via bile) lungs (volatile gases) tears sweat breast milk
Which drug size can be filtered through glomerular filtration at the nephron?
< 20kDa
What feature of drug solubility can affect filtration at the nephron?
reduced drug filtration if drug is bound to albumin or other plasma protein
(e.g. warfarin is bound to albumin)
Which types of drugs are excreted through active anion transporters at the PCT?
acidic drugs: penicillin salicyclates cephalosporins furosemide
Which types of drugs are excreted through active cation transporters in the PCT?
basic/alkaline drugs: amiloride morphine pethidine quinine
What kinds of drugs are excreted by passive (diffusion) movement?
lipid soluble drugs
e.g. corticosteroids
How do loop diuretics function?
Work on the K+Cl- co-transporter
reduce reuptake of K+, Cl- and Na+
less fluid is reabsorbed (=more urine)
reduces total body fluid
How can intra-vessel pressure be maintained at the nephron?
Vasoconstriction of the efferent arteriole
How do ACEi affect intra-nephron pressures?
ACEi cause vasodilation of the efferent arteriole
Leads to reduction in GFR
What receptors mediate the fight or flight response?
adrenergic receptors these are a type of GPCRs
adrenergic receptors are targeted by
catecholamines such as adrenaline and noradrenaline
What are the different type of adrenergic receptor in SNS? What kind of action do they have?
alpha-1
smooth muscle contraction
noradrenaline > adrenaline
alpha-2
mixed effects
adrenaline > noradrenaline
beta-1
cardiac muscle contraction
adrenaline and noradrenaline
beta-2
smooth muscle relaxation (e.g. bronchodilation)
adrenaline»_space; noradrenaline
What is meant by ‘acetylator status’
deficiency in hepatic N-acetyltransferase
50% of the UK population have this deficiency
Which drugs are affects by acetylator status?
- isoniazid
- hydralazine
- sulfasalazine
