Exam 1: Lecture 6: Antihypertensive drugs II

Question 1

Benefits of lower sodium diet on hypertension?

Answer 1

moderate reduction in dietary sodium can reduce BP by 4.8/2.5 in hypertensive individuals, 1.9/1.1 in normotensive people

Question 2

Benefits of weight loss on hypertension?

Answer 2

can lead to reduction in BP by 0.5-2/kg Diastolic

Question 3

DASH

Answer 3

The Dietary Approaches to Stop Hypertension

Question 4

DASH Diet

Answer 4

High in veggies, fruit, low-fat dairy, whole grains, poultry, fish and nuts

low in sweets, sugar, red meats….saturated fat, total fat and cholesterol

Question 5

Benefits of exercise on hypertension?

Answer 5

can decrease systolic by ~4/6, and diastolic by ~3.

have to be consistent, 3-4 sessions per week with moderate intensity

Question 6

What detects BP?

Answer 6

Baroreceptors

arterial baroreceptors become less sensitive in primary hypertension

Question 7

Where does CO and PVR regulation occur?

Answer 7

1. Resistance Arterioles
2. Capacitance Venules
3. Pump output heart

Question 8

Baroreflex and baroreceptor steps

Answer 8

1. Mechanical forces (shear stress.compression,) in arteries
2. Change in tension detected by Piezo channels (working on drugs that act at PIEZO1 channel)
3. Cation influx
4. Transmission of action potential and activation of down stream signaling

negative feedback loop

Question 9

Polypharmacy

Answer 9

using multiple medications

Example: Hydralazine has to have a B-blocker and diuretic added

Question 10

Renin is secreted in response to…

Answer 10

decreased renal artery blood volume

Sympathetic activation

Question 11

Angiotensin II causes….

Answer 11

constriction of vessels = increasing PVR

Secretion of aldosterone, promoting increase Na reabsorption and blood pressure

Secretion of AVP, increasing blood volume

Question 12

Angiotensin II….

Answer 12

Acts at multiple AT receptors but causes vasoconstriction at AT1Rs

Gaq coupled (Gaq -> increase PLC -> PIP2 convert to IP3 and DAG -> increase Ca release -> activation of MLCK -> phosphorylation of MLC -> contraction of SM

Question 13

Captopril (capoten)

Answer 13

Sulfhydryl-containing ACEi

** only one to cross BBB **
some evidence for mood elevation

Indicated: hypertension and heart failure
Rapid onset

Adverse effects: Postural Hypotension, edema, cough, itching, headache, chest pain, metallic taste (-SH group)

Question 14

Enalapril (Vasotec)

Answer 14

First in class dicarboxylate ACEi

Preg class D, cannot be used

Pro drug, active metabolite is enalaprilate

Indicated: hypertension, heart failure, left ventricle dysfunction

developed to remove -SH (metallic taste)

Adverse effects: Dizziness, hypotension, syncope, cough, edema

Question 15

Lisinopril

Answer 15

2nd gen dicarboxylate ACEi

peptide derivative of captoril, not a pro drug

Indicated: hypertension, heart failure, used after acute MI and for diabetic nephropathy

Adverse effect: Dizziness,hypotension,syncope,cough,edema (often given with diuretic)

Question 16

Losartan

Answer 16

ARBs, used in patients that don’t tolerate ACEi well

** Most common formulation is a tetrazole-potassium salt

Indicated: hypertension, heart failure, diabetic nephropathy

Adverse effects: dizziness, headache, studies of increased risk of MI and cancer

Question 17

Aliskiren

Answer 17

Renin inhibitor

Developed for primary hypertension

clinical trials halted a bunch

cant be used with ACEi, ARBs, patients with renal impairment

contraindicated in pregnancy and not a 1st choice med

Question 18

Sodium nitroprusside

Answer 18

Nitrix oxide donor

indicated: infusion for hypertensive crisis or acute heart failure

interacts with oxyhemoglobin in arterioles and venues to release NO, causing dilation of arterioles/venules and therefore decrease afterload and venous preload

bunch of adverse effects: cyanide toxicity, methemoglobinemia, Brady- or tachy- arrhythmia, hypotension, headache, dizziness, palpitations,

Question 19

Hydralazine

Answer 19

Direct-smooth muscle relaxants

Indications: Hypertensive crisis, acute emergent secondary hypertension, rarely as maintenance

used in surgery,ICU, pregnancy

inhibits the release of Ca from Sr in response to increase IP3, decreasing PVR and Afterload

removes 2nd wave but not 1st of contractility

Question 20

Guanethidine

Answer 20

reduces release of catecholamines

Does not cross BBB, no longer used in USA

toxicities include: progressive loss of sympathetic nerve terminals.

side effects: hypotension, sexual dysfunction and diarrhea

numerous adverse drug interactions including with OTC pseudoephedrine