Pharmacology 1: Safe prescribing and pharmacokinetics intro Flashcards
Requirements for a safe prescription?
Right drug dose route site frequency to right patient AND must consider allergies, contraindications, interactions and adverse effects.
what is a black triangle drug?
1 being intensively monitored generally 1 which has been: newly released changed indications changed formulations combination product
what is a serious reaction?
results in or prolongs hospitilisation
what SEs may occur with metformin use?
diarrhoea, abdominal pain, nausea, vomiting, lactic acidosis- as too much glucose for O2 in tissues so revert to anaerobic metabolism
describe a model which can be used for error causation in prescribing?
Reason’s model of error causation:
4 primary components: latent conditions- organisational processes and management decisions
error producing conditions- environ, team, indiv, task factors
active failures- slips, lapses, mistakes (errors) and violation
defences- protect against hazards, mitigate consequences of failure
examples of defences in prescribing errors?
prescription checking by nurses and pharmacists
electronic reviews- e.g. warnings displayed before certain prescriptions allowed to be processed
senior reviews
what is the difference between slips and lapses, and mistakes?
slips and lapses occur with loss of concentration, and maybe memory, meaning that the action isn’t carried out as intended. Mistakes occur when there is poor knowledge or rules are confused, so the action is carried out as intended, but the outcome is not as expected.
What is verapamil and when is it used?
L-type Ca2+ blocker, used in HF and arrhythmias (class IV anti-arrhythmic)
Acts at SAN and AVN in arrhythmia
Has -ve inotropic and chronotropic effects, + causes dilatation of peripheral arterioles and CAs in HF to reduce workload of heart.
common side effect of statins?
muscle pains
4 components to pharmacokinetics?
ADME: absorption, distribution, metabolism and excretion
factors determining OB?
formulation of drug (long or short acting?)
route of administration
age
lipid-soluble>H20-soluble if given with food
vomiting/malabsorption
GI/hepatic disorders, transporter and enzyme avaialability 1st pass metabolism
major factors affecting drug distribution in the body?
lipophilicity/hydrophobicity
degree to which it binds to plasma protein
degree to which it binds to tissue proteins
mass or volume of tissue and density of binding sites within that tissue
what 3 main factors are used as the basis as to whether a drug should be included in a formulary (list of formulae for compounded medicines)
cost
efficacy
safety
what is efficacy?
ability of a drug to activate a receptor and produce a response
what is potency?
how good a drug is at producing a response
measured by EC50= effective conc of a drug giving 50% of maximal response
things to remember when prescribing drugs?
PRESCRIBER patient details reactions- drugs (allergies?) and interactions sign drug chart contraindiciations route IV fluids check blood clotting emetics- induce vomiting to get rid of unwanted substances before absorbed relief- pain, have they enough?
why must patient be monitored if on MXT?
immune system suppressor, so must do FBC to check for BM suppression
what does 1st pass effect mean for drug dosages when prescribing?
a drug which is heavily metabolised by the liver would have to be give at a relatively high dosage in order to achieve its therapeutic effect
define 1st pass metabolism
any metabolism of a drug that occurs prior to its entry into the systemic circulation
where can 1st pass metabolism occur?
gut lumen e.g. gastric acid, proteolytic enzymes e.g. insulin, benzylpenicillin
gut wall e.g. P-glycoprotien efflux pumps e.g. ciclosporin
liver e.g. propranolol and morphine
what is drug distribution?
ability of a drug to dissolve in the body
when are changes in protein binding of a drug important?
if high protein binding
low Vd
narrow therapeutic ratio
what factors affect protein binding of a drug?
hypoalbuminaemia e.g. liver failure, nephrotic syndrome
renal failure
pregnancy
displacement by other drugs
why is high-dose aspirin avoided in patients on warfarin?
increases risk of bleeding as warfarin= class I drug, and aspirin= class II, so aspirin displaces warfarin from protein binding sites, so its free concentration is increased, as class II drugs are given at a dose greater than the number of available albumin binding sites.
how is the half life of a drug related to its volume of distribution and its clearance?
t1/2 is directly proportional to volume of distribution
inversely proportional to clearance
factors affecting tissue distribution?
specific receptor sites in tissues regional blood flow lipid solubility AT disease states e.g. HF, malnourishment drug interactions
why are non-ionised molecules more readily absorbed?
more lipid-soluble
Other than IV, SC and IM, how can a drug be given to avoid the portal circulation?
sub-lingual
rectal
function of conjugation in drug metabolism?
make drugs water-soluble for elimination
what reactions do enzymes in phase I drug metabolism catalyse?
oxidation reduction hydrolysis dealkylation existing functional groups on drug molecules are modified
what can drugs be conjugated with during phase II of drug metabolism?
glutathione
glucuronide
sulphate
N-acetyl
name given to drugs which are metabolised to their active forms in the body?
pro-drugs
example of a drug which is active when given, but is also metabolised to produce active metabolites?
codeine to morphine
enzymes involved in phase I drug metabolism?
cytochrome (CYP) p450
influences on phase I drug metabolism?
enzyme-inducing and inhibiting drugs age liver disease hepatic b.flow alcohol and cigarette consumption genetic polymorphisms
where are CYP450 isoenzymes found?
mainly liver
gut
lungs
CYP450 3A is involved in the metabolism of what?
benzodiazepines e.g. diazepam. Used in anxiety states and epilepsy.
Ca2+ channel blockers
most statins
cyclosporin
HIV protease inhibitors e.g. ritonavir, saquinavir
most non-sedating anti-histamines
inhibitors of CYP 3A?
grapefruit juice
cimetidine
macrolides
anti-fungals e.g. fluconazole
CYP 3A inducers?
carbamazepine
St John’s Wort- herbal remedy for depression
rifampicin- inhibits RNA polymerase, targets protein synthesis, e.g. for TB- OCP may not work!
ritonavir- drug used for HIV, alongside HAART
importance of drug reaction between cimetidine (H2 antagonsit) and warfarin?
cimetidine= CYP 3A inhibitor, so warfarin not metabolised- plasma conc increases- increase PTT, increased bleeding risk.
what 3 processes determine the renal excretion of drugs?
glomerular filtration
passive tubular reabsorption
active tubular secretion
example of drugs actively secreted at PCT?
penicillin
what is passive tubular reabsorption in the kidney affected by? Bearing this in mind, why would you want to give alkaline diuresis to a patient who has overdosed on aspirin?
urine flow rate and pH
aspirin= weak acid, alkaline diuresis will make urine alkaline, putting aspirin into its ionised form which cannot be reabsorbed and so will be excreted.
why might we want to monitor a drug?
narrow therapeutic index
0 order kinetics- t1/2 cannot be defined ( remember that most drugs when given at a very high dose will exhibit 0 order kinetics)
drug-drug interactions
long t1/2
known toxic effect
monitoring therapeutic effect e.g. BP and glucose
when is a steady state achieved in drug administration?
when dosage rate (rate entering systemic circulation)= rate of elimination
during repeated drug administration, a new steady state is reached in 3-5 half lives
what might dosing regimen be dependent on?
t1/2
drug interactions
age of patient
renal function
what can be used as a measure of affinity?
Kd= dissociation constant= conc of ligand required to occupy 50% of available receptors.
term given to describe how well a drug produces the maximum response?
intrinsic activity
what do full agonists have in common, and what might differ between them?
same intrinsic activity as elicit maximum response
but may have different efficacies, as receptor activation may occur for different proportions of binding events between the 2 drugs.
what 2 key factors determine OB?
absorption
1st pass metabolism
how does Vd affect initial drug concentrations?
high if small Vd
loading dose required to fill up Vd when small initial concentration
define clearance
the volume of plasma that is completely cleared of the drug per unit time
examples of prodrugs?
tamoxifen
losartan- AngII blocker
codeine
why is genetic variability, an important part of pharmacogenomics, an important factor affecting drug metabolism?
certain populations exhibit polymorphisms or mutations in 1 or more enzymes of drug metabolism, so the rate of some of these reactions is changed, and some eliminated altogether. e.g. metabolism of isoniazid slowed in some populations as reduced synthesis of an enzyme= slow acetylators (N-acetyltransferase enzyme).
also as free isoniazid= inhibitor of CYP 450, makes slow acetylators more prone to adverse drug reactions.
why is safe prescribing even harder with increasing numbers of elderly patients?
co-morbidities
polypharmacy
increased risk of SEs
what is the yellow card scheme?
used in reporting: all suspected reactions from black triangle drugs and unlicensed herbal preparations, established products and vaccines, and all paediatric reactions.
why does plasma drug concentration decrease more slowly in the elimination phase?
reservoir of drug in the tissues that can diffuse back into the blood to replace the drug which is being eliminated
organs other than the liver which can contribute to systemic drug metabolism?
GI tract, kidneys, skin, lungs
how does rate of drug absorption affect peak plasma concentration and duration of drug action?
faster rate= higher peak plasma concentration (Cmax) as all drug absorbed before significant elimination can take place
slower rate= longer duration of action as drug still being absorbed during the elimination phase
how can the BB barrier be bypassed in order for a drug to access the CNS if it can’t pass through the barrier?
intrathecal infusion- drug delivered directly into CSF
