Pharmacology Flashcards
What is the most significant change to metabolism of medication in older patients?
Liver mass and decreased blood flow to the liver. This decreases first pass metabolism (required for pro-drug conversion, and reduction in initial peak concentrations of straight drugs), and slows phase I metabolism (the early enzymatic reactions that alter drugs).
If first past metabolism is impaired, what implication does this have for oral drugs?
As with elderly patients, first pass metabolism is inhibited. For pro-drugs, this means lower concentrations of active drug in the circulation that depend on first pass metabolism. It also means higher peak concentrations for drugs that account for an amount of degradation via first pass metabolism when calculating the dose.
If phase 1 metabolism is impaired, what affect does this have on liver metabolised medications?
Decreased clearance of liver metabolised medications.
Does phase 1 metabolism influence peak plasma concentration of drugs metabolised in the liver?
No, just the rate at which they are cleared.
How is ampicillin excreted?
By the kidneys through filtration, but also through tubular secretion.
How do you dose adjust medications that rely on tubular secretion for clearance?
With great difficulty. It’s easy to do this if the drug is filtered - you can just adjust in line with the filtration rate. However predicting how tubular secretion will change from person to person is very hard.
What risks are associated with overdosing penicillins in patients with renal impairment?
Sodium overload, neurotoxicity (seizures, coma), neutropoenia.
What are the unwanted side effects of anti-cholinergic medications?
Dry mouth, drowsiness, blurred vision, urinary retnetion, constipation, tachycardia.
How is azithromycin unique amongst macrolides?
It doesn’t induce CYP3A4, leading to few drug-drug interactions.
Can azithromycin be used in pregnancy?
Yes
What is a biosimilar? Is it different to a generic?
Yes, a biosimilar is a biologic that is designed to act in the same way as a pre-existing medicine, has a similar efficacy and safety profile, but is different in its chemical makeup. A generic medication on the other hand tends to refer to small molecule medication and is an exact copy of the chemical structure of the original.
How can you calculate the steady state plasma concentration of a drug given as an infusion as a fixed rate?
Divide the infusion rate by the clearance rate.
Calculate the steady state plasma concentration of a drug being administered via IV infusion at a rate of 1mg/min that is cleared entirely renally in a patient with a creatine clearance of 120mL/hour
Plasma concentration is calculated by dividing the infusion rate by the clearance rate.
Infusion rate 1mg/min
Drug clearance rate 120mL/hr
= 2ml/min
Plasma concentration = 1/2mg/mL = 0.5mg/mL
Is clopidogrel a prodrug?
Yes
How does clopidogrel work?
Once converted to its activate metabolite by CYP2C19, it irreversibly binds to the adenosine diphospphate P2Y12 receptor on platelets which decreases their aggregation.
Mutations in what cyt P450 enzyme lead to reduced effectiveness of clopidogrel?
CYP2C19
What one of the reasons that P2Y12 inhibitors ticagrelor and prasugrel have been shown to be more efficacious than clopidogrel in the management of ACS?
Likely related to the relatively common CYP2C19 mutation prevalence in the relevent trial populations. When studies have been done that include genetic testing, clopidodrel is just as effective (with a lower bleeding profile) in patients who have wild type CYP2C19.
Paroxetine and fluoxetine inhibit what potently?
CYP2D6. Fluoxetine also inhibits CYP3A4.
Rifampacin potently induces which liver enzymes?
CYP3A4, CYP2D6 and CYP2C19
What drugs need to be given with caution in patient’s who have Addison’s disease?
Anything that induces CYP3A4 may lead to an Addisonian crisis. This is because hydrocortisone is metabolised by CYP3A4 and will rapidly deminish in plasma concentration when CYP3A4 is induced.
What are the strong CYP3A4 inducers?
Carbamazepine, phenytoin, dexamethasone, grisefulvin, nevirapine, phenytoin, riabutin, rifampin, and St John’s wort.
What is the only eGFR calculation validated for drug dosing?
Cockcroft-Gault
In what patient cohort is NM GFR scan inaccurate?
Severe renal infsufficiency (CrCl < 20ml/min)
How do you calculate anion gap?
Na + K - (bicarb + chloride)
What are the causes of high anion gap?
Ethylene glycol, propylene glycol poisoning. Oxoproline (from excessive paracetamol intake), Lactate. MEthanol. Aspirin. Renal failure (as opposed to renal tubular acidosis, which causes a hyperchloraemic, normal anion gap acidosis) and ketones.
The mneumonic is GOLD MARK
What happen to ethylene glycol after it is ingested?
It is metabolised by alcohol dehydrogenase to oxalic acid (this causes the raised anion gap acidosis). The oxalic acid forms crystals in that are eliminated in the urine and look like a square with a cross in them.
Who are toxic alcohol (methanol, ethylene glycol) poisonoing managed?
Gastric levage, induced emesis or activated charcoal all need to be done within 60mins of ingestion. Administration of IV ethanol will prevent oxalic acid formation down as it competes with methanol and ethylene glycol for alcohol dehydrogenase. Fomepizole can be used instead of ethanol - binds to alcohol dehydrogenase 8000 times more strongly than other substrates (ethanol, methanol, ethylene glycol). Once ethanol infusion or fomepizole on board, can do haemodialysis to remove the unmetabolised alcohol. Giving bicarb can help ameliorate metabolic acidosis.
Where does first pass metabolism happen?
In the liver, but also in the intestines.
