Monitoring drug therapy Flashcards
What dose of levothyroxine would you prescribe to Mr. Martin and what action would you want to take at any follow up appointment?
-2 approaches, either start him at 125 or more commonly start low and build up.
Clinical effect-see if he feels less tired
Biomarker-TSH (as when you have a high T4 it can suppress TSH, so want this to be normal)
5 years later:
Mr. Martin returns to his GP complaining that he has been having mild palpitations consistently for the past 2 weeks. At times he feels light-headed but he has never fainted. He denies any history of chest pain at rest or with exertion, orthopnea, or paroxysmal nocturnal dyspnea. He admits that he lives a very sedentary lifestyle and does little exercise.
On physical examination he is in no obvious distress. His weight is 86kg. He continues to take 2.5mg bendroflumethiazide and thyroxine and his blood pressure is 126/78 mm Hg. His pulse is 110 beats per minute (BPM) and the rhythm is irregularly irregular. He has no pedal edema, jugular venous distension, or heart murmur on auscultation. At his last follow up appointment to check his thyroid function, he had a normal complete blood count, thyroid and renal function, liver enzymes, and fasting blood glucose.
If score of 0 probs don’t need anticoagulation but if 1 or above anticoagulate.
Treatment is nothing or full anticoagulation, despite what this slide says, there is no half way house, don’t give antiplatelet
Since he has 0 risk of bleed, best to anticoagulate
What two drugs would the cardiologist be most likely to prescribe for Mr. Martin and explain the mechanism of action of the two drug classes.
Apixaban
Digoxin- he is asthmatic so stay away from beta blocker! Also he didn’t like calcium channel blockers, and he’s sedentary digoxin
Anything over 48 hours you don’t worry about Rhythm control, as once over 48hours you worry about clot formation so you don’t want to risk anything that could dislodge the clot.
Digoxin MOA:
- Blocks potassium moving into the cell
- Target sodium potassium atp-ase in cardiac muscle
- Stopping sodium leaving, so increase in intracellular sodium
- Sodium calcium exchange pump-affected as a result. Built up sodium impairs this protein and so positive inotrope effect, more calcium left in muscle so it beats more forcefully
-Digoxin also tends to slow heart rate through avn. But it allows heart to beat with more force so you get increased cardiac force.
Digoxin induces an increase in intracellular sodium that will drive an influx of calcium in the heart and cause an increase in contractility. Cardiac output increases with a subsequent decrease in ventricular filling pressures. [2] AV Node Inhibition: Digoxin has vagomimetic effects on the AV node
Apixaban inhibits free and clot-bound FXa, and prothrombinase activity. Apixaban has no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin. By inhibiting FXa, apixaban decreases thrombin generation and thrombus development.
Bendroflumethiazide-In late distal tubule at urine side there is sodium chloride cotransport molecule. The sodium passes further down the kidnye and the kidney then rapidly tries to reabsorb and it has to do that in exchange for potassium. promotes potassium loss
If potassium starts to drop it will also be low in heart so digoxin has less competition and has a more effect. Might start to see signs of digoxin toxicity
Any kidney issue-digoxin levels will build up and you can get digoxin toxicity
Can also look at blood potassium and if low worry about digoxin toxicity
Apixaban-just ask about bleeding
Digoxin toxicity signs
Therapeutic window-distance between favourable response and toxicity. Want this to be big
Hazard ratio over 1-slips into toxic effect
Hazard ratio below one-only therapeutic effect
With digoxin the window is very narrow, so we have to monitor digoxin very closely
Compared to other drugs eg bisoprolol as patient is safe in broad dose range
Max dose is 4g so big overdose
Way in which you determine whether they need treatment is measure amount of paracetamol in blood and use graph using time she took it.
Never take blood until 4 hour time point as not had time to absorb
21 hour of acetylcysteine infusion-so they have to be admitted
Paracetamol can be metabolised in 2 ways. Either gluconoride or sulphate-non harmful, but small amount is metabolised into napqi which is toxic at high levels.
Anything greater than 4g will have higher levels of ALL metabolites, same percentages, but 5 x amount of NAPQI
When treat NAC, you boost glutathione stores since its a precursor to it, so protects liver
1) glutathione depleted eg malnourished
2) People who induce cyp450 ensyme eg Alcoholics -malnourished and induced cyp450 enzymes so higher percentage metabolised down harmful route
