I came across this article recently about some interesting facts about antihypertensive medications and their pharmacology, which I though will be useful for practising clinicians like us!
The article describes about all 4 major types of antihypertensives. But the one which stands out is the angiotension converting enzyme inhibitors----WHY? due to their difference in pharcological actions compared to others.Let me start with a question..
If Mr.X tolerates(no hypotension) 5mg of Lisinopril, can we increase the dose to 40mg straightaway?
Most of us would say "NO". But the author says yes....and the explanation is pretty simple, interesting and true!
Unlike the other antihypertensives(beta blockers,CCB,diuretics), ace-i do not have a linear dose-response relationship....meaning that their BP lowering effect is not proportional to the dose. In other words....the efficacy of ace-i is the same irrespective of their dosage. Again...to make it more simple...a dose of 5mg of Lisinopril will lower the BP to the same extent as 40mg of Lisinopril. So why give 40mg in place of 2.5 mg? Well...the dose correlates with the duration of action.the higher the dose...the longer the duration of action!(Brit J Pharm 1984!)
It looks like...we have the low doses of ace-i in the market mainly to be used in patients with heart failure (who might have a low BP due to their other meds) to see if they can tolerate any hypotension induced by addition of ace-i. Also, the common side effect of ace-i...COUGH ..is not dose related.So here again..the dose doesnt matter.
So the article concludes that..ace-i don't have a linear dose-response curve, and so their dose can be increased to the maximal dose without any major concerns for hypotension. But ...one aspect of ace-i that the article doesn't discuss...is hyperkalemia. Well..the risk of hyperkalemia with ace-i is dose related, and whether it would be a good idea to go for a maximal dose straightaway or to increase it gradually, in this aspect.So..bottom line-----beacuse of the risk of hyperkalemia..we may not be able to go to a maximal dose directly, and not because of risk of hypotension.
A quick word abt hyperkalemia with ace-i : the risk is quite low on its own. The risk is high in CKD(4 fold risk), hepatic disease(almost 5 fold risk), taking>15 tablets(5 to 9 fold risk), advanced age(twice likely)...
(Pharm W Sci 2009)
Finally..the above article was published in American J of Cardio vasc Drugs 2011. The graph(above) is a modified graph from the same study.
The article describes about all 4 major types of antihypertensives. But the one which stands out is the angiotension converting enzyme inhibitors----WHY? due to their difference in pharcological actions compared to others.Let me start with a question..
If Mr.X tolerates(no hypotension) 5mg of Lisinopril, can we increase the dose to 40mg straightaway?
Unlike the other antihypertensives(beta blockers,CCB,diuretics), ace-i do not have a linear dose-response relationship....meaning that their BP lowering effect is not proportional to the dose. In other words....the efficacy of ace-i is the same irrespective of their dosage. Again...to make it more simple...a dose of 5mg of Lisinopril will lower the BP to the same extent as 40mg of Lisinopril. So why give 40mg in place of 2.5 mg? Well...the dose correlates with the duration of action.the higher the dose...the longer the duration of action!(Brit J Pharm 1984!)
It looks like...we have the low doses of ace-i in the market mainly to be used in patients with heart failure (who might have a low BP due to their other meds) to see if they can tolerate any hypotension induced by addition of ace-i. Also, the common side effect of ace-i...COUGH ..is not dose related.So here again..the dose doesnt matter.
So the article concludes that..ace-i don't have a linear dose-response curve, and so their dose can be increased to the maximal dose without any major concerns for hypotension. But ...one aspect of ace-i that the article doesn't discuss...is hyperkalemia. Well..the risk of hyperkalemia with ace-i is dose related, and whether it would be a good idea to go for a maximal dose straightaway or to increase it gradually, in this aspect.So..bottom line-----beacuse of the risk of hyperkalemia..we may not be able to go to a maximal dose directly, and not because of risk of hypotension.
A quick word abt hyperkalemia with ace-i : the risk is quite low on its own. The risk is high in CKD(4 fold risk), hepatic disease(almost 5 fold risk), taking>15 tablets(5 to 9 fold risk), advanced age(twice likely)...
(Pharm W Sci 2009)
Finally..the above article was published in American J of Cardio vasc Drugs 2011. The graph(above) is a modified graph from the same study.
No comments:
Post a Comment