45-year-old (male) with swollen lips

00:03 A 45 year old male was found to have a blood pressure of 142/90 at a health fair.

00:10 He was later found to also have increased blood pressure on 2 separate occasions after modifying his lifestyle.

00:16 He was then prescribed an antihypertensive drugs.

00:20 After 3 weeks, the following change shown in the picture was observed.

00:25 What is the most likely cause of this finding in the image? Answer choice (A) - Verapamil Answer choice (B) - Amlodipine Answer choice (C ) - Lisinopril Answer choice (D) - Hydrochlorothiazide And answer choice (E ) - Furosemide Now take a moment to come to the answer by yourself before we go through it together.

00:49 Okay let's jump right in to this one So in this case, the subject for this question is pharmacology.

00:54 In which you can see through the answer choices they're showing the various antihypertensive agents, and in the image they're showing us swollen lips as a side effect of a medication and they're asking us to determine through a 2-step process.

01:09 One, what was the clinical observation in the image, hence the swollen lips and two, which of the medications can cause this abnormality.

01:19 And the stem is absolutely required because through the stem you determine that the patient is on antihypertensive agent and you can look at the image to determine the clinical pathology in question.

01:29 So the first thing we have to do when going through this question is determine the diagnosis.

01:34 Now looking at the image, we see that the patient has swollen, edematous, erythematous lips which are typical of what's called "angioneurotic edema".

01:45 Now angioneurotic edema is characterized by erythematous edema, usually near eyes and the lips but can also occur on the hands, feet and even inside the throat.

01:57 So we have our diagnosis of angioneurotic edema.

02:01 Now step 2, we determine the cause of the edema for this patient.

02:05 Now, such edema can be hereditary or acquired.

02:10 Now acquired usually is from a medication used.

02:14 Now in the clinical stem, there is no history that is suggestive that the patient has a hereditary angioneurotic edema which is usually due to an inherited C1 esterase inhibitor deficiency, very high-yield to know.

02:29 Now we do know then that in this case, the patient is receiving an antihypertensive agent.

02:34 Now commonly prescribed antihypertensive agents include thiazide diuretics, ACE inhibitors, ARBs and calcium channel blockers and direct renin inhibitors.

02:46 Now ACE inhibitors, in this case - lisinopril is one of our answer choice (C) is a well recognized cause of angioneurogenic edema which actually can cause increased levels of a potent vasodilator called bradykinin, which is why patients can experience such edema after taking ACE inhibitors.

03:07 Now thus in this case, the correct answer is answer choice (C) - lisinopril.

03:12 Now of the other antihypertensives listed, it is also important to know that calcium channel blockers can actually cause edema but this is peripheral edema - usually in the legs, and is thought to be due to arteriolar dilation and fluid extravasation.

03:29 Now let's refer to the image in question to help us better understand the mechanism of angioedema induced by ACE inhibitors.

03:37 So starting at the top, we see prekallikrein which is then converted into kallikrein and then into HMW kininogen, and that then leads to bradykinin - very very important.

03:50 ACE (Angiotensin converting enzyme) will actually lead to the degradation of bradykinin.

03:57 Now for patient takes a ACE inhibitor such as lisinopril, it prevents this degradation and then you have an increase in the level of bradykinin and that then leads to increased activity at the bradykinin beta-2 receptor which then will cause vasodilation and increased permeability and then clinical edema.

04:19 And thus the ACE inhibitor leading to increased bradykinin will cause the edema.

04:25 Now this is very important to know.

04:26 A future question for USMLE can be the mechanism of action of this edema, not simply the medication used.

04:33 So each question can test different facts - extremely high-yield to know.

04:37 Now let's review some high-yield facts regarding angioneurotic edema and ACE inhibitors.

04:43 Now we know that ACE inhibitors are the leading cause of drug-induced angioedema.

04:48 Now patients will commonly present with swelling of the lips, tongue, face and they usually do not have itching.

04:56 Now symptoms usually occur within the first 3 months of starting treatment but can occur even shortly after the fist dose to up to 2 years after being on ACE inhibitors.

05:06 Thus, if a patient shows up 2 years after being on a treatment, it still can be due to the medication.

05:12 Now signs and symptoms of ACE inhibitor related angioedema can range from mild and clinically insignificant to unfortunately severe and life-threatening edema.

05:21 Now we now know that the mechanism of ACE inhibitor angioneurotic edema .

05:26 is not to be due to accumulation of the highly vasoactive compound called bradykinin which is normally degraded by angiotensin-converting enzyme