Circulation/vascular tone

Question 1

alpha adrenoceptors

Answer 1

contraction of vascular smooth muscle

activates phospholipase C

increases inositol triphosphate = release of calcium from ER

Calcium binds to calmodulin = myosin light chain kinase activation = contraction

Question 2

b2 adrenoceptors

Answer 2

relaxation of vascular smooth muscle through activation of adenylyl cyclase.

causes increased cAMP levels = activate protein kinase A which phosphorylates and inactivates myosin light chain kinase (MLCK)

Question 3

M3 receptors

Answer 3

m3 activation relaxes vascular smooth muscle by releasing endothelium derived relaxing factor (EDRF) (NO) = guanyl cyclase is activated increasing cGMP levels and activating protein kinase G.

protein kinase G inhibits contraction by phosphorylating contractile proteins

Question 4

RAS

Answer 4

decreased plasma volume activates RAS.

BECAUSE;

• less gfr/flow to the macula densa (less Na+ in macula densa)
• lower arterial BP
• Increased renal sympathetic activity

Juxtaglomeural cells in KIDNEY release RENIN

LIVER releases ANGIOTENSINOGEN

RENIN converts ANGIOTENSINOGEN TO angiotensin 1

angiotensin 1 to 2 (ACE INHIB)

ANGIOTENSIN 2 =

• potent vasoconstriction
• release of noradrenaline (vasoconstriction)
• aldosterone release

Aldosterone =

• Na+ reabsorbed in collecting ducts
• water reabsorbed more
• increased BP
• THIS IS INHIBITED BY SPIRINALACTONE

ACE = inactivates bradykinin which is an endogenous vasodilator

RENAL DISEASE / RENAL ARTERY OCCLUSION CAN CAUSE ACTIVATION OF RAS AND DEVELOPMENT OF HTN

Question 5

HTN - cause

Answer 5

Primary

• 90-95%
• no cause but associated with age(40+) , obesity, inactivity, smoking and alcohol, genetic predisposition

Secondary

• 5-10%
• renal disease (RAS) activation
• endocrine disease E.G.
• -> pheochromocytoma (adrenaline releasing tumour of medulla in adrenal gland )
• ->steroid secreting tumour of the adrenal cortex

Question 6

ACE inhibitors

• captopril
• enalapril
• lisinopril
• ramipril

Answer 6

vasodilators used in HTN, HF, RENAL DYSFUNCTION (Especially in diabetic patients to slow progression of diabetic or reduced renal function neuropathy)

Question 7

ACE inhibitors - MOA

Answer 7

inhibit ACE = reduced angiotensin 2 and aldosterone levels.
also increase bradykinin levels

this leads to vasodilation = reduces peripheral resistance = change in HR CO and less sodium retention

Question 8

ACE INHIBITORS – DON’T

Answer 8

CONTRAINDICATIONS
-pregnancy
-renovascular DISEASE
AORTIC STENOSIS

adverse effect

• cough
• hypotension
• dizzy/headache
• diarrhoea
• muscle cramp

Question 9

Angiotensin 2 receptor antagonists

Answer 9

losartan

valsartan

Question 10

Angiotensin 2 receptor antagonists - moa

Answer 10

inhibit angiotensin 2 receptor = vasodilation and reduction in peripheral resistance

Question 11

Angiotensin 2 receptor antagonists - don’t

Answer 11

contraindication

• pregnancy
• renal artery stenosis and aortic stenosis

adverse effect

• cough (more of an ACE inhibitor thing)
• orthostatic hypotension
• dizziness
• headache
• fatigue
• hyperkalaemia /rash

Question 12

Calcium antagonists

Answer 12

diltiazem- cardioselective
verapamil-^^
nifedipine = more of an effect on vascular tone

Question 13

a-1 adrenoceptor antagonists

Answer 13

prazosin

doxazosin

Question 14

a-1 adrenoceptor antagonists - moa

Answer 14

inhibit a1 adrenoceptor mediated vasoconstriction = reduced vasoconstriction = reduced peripheral resistance/venous pressure = lower LDL cholesterol /VLDL and triglyceride levels and increase HDL levels = reduced risk of CAD

Question 15

a-1 adrenoceptor antagonists - indication

Answer 15

HTN (ESPECIALLY CHF PATIENTS)
Prostate hyperplasia (reduced bladder and prostate resistance
CAD

Question 16

a-1 adrenoceptor antagonists - DONT

Answer 16

Prazosin not to CHF due to aortic stenosis

SE
postural hypotension
dizziness
headache and fatigue
weakness
palpitations
nausea

Question 17

hydralazine

Answer 17

third line

mild to moderate HTN

Inteferes with action of inositol triphosphate in vascular smooth muscle reducing peripheral resistance and blood pressure

Question 18

minoxidil

Answer 18

last due to SE

Hyperpolarisation of smooth muscle = less calcium entry = inhibited smooth muscle contraction

Question 19

sodium nitroprusside

Answer 19

pro drug that spontaneously decomposes into NO inside smooth muscles cells. Activates guanylyl cyclase thus increasing cGMP levels and causing vasodilation

given in emergency and controlled hypotension in surgery and HF

Question 20

GUIDELINES ON HTN -

Answer 20

When considering a diagnosis of hypertension, measure blood pressure in both arms.

If the difference in readings between arms is more than 20 mmHg, repeat the measurements.

If the difference in readings between arms remains more than 20 mmHg on the second measurement, measure subsequent blood pressures in the arm with the higher reading.

If blood pressure measured in the clinic is 140/90 mmHg or higher:

Take a second measurement during the consultation.

If the second measurement is substantially different from the first, take a third measurement.

Record the lower of the last two measurements as the clinic blood pressure.

If the clinic blood pressure is 140/90 mmHg or higher, offer ambulatory blood pressure monitoring (ABPM) to confirm the diagnosis of hypertension.

home BP moniter if can’t tolerate ambulatory

If the person has severe hypertension, consider starting antihypertensive drug treatment immediately, without waiting for the results of ABPM or HBPM. [

While waiting for confirmation of a diagnosis of hypertension, carry out investigations for target organ damage (such as left ventricular hypertrophy, chronic kidney disease and hypertensive retinopathy) (see recommendation 1.3.3) and a formal assessment of cardiovascular risk using a cardiovascular risk assessment tool

ABPM – to confirm a diagnosis of hypertension, ensure that at least two measurements per hour are taken during the person’s usual waking hours (for example, between 08:00 and 22:00). Use the average value of at least 14 measurements taken during the person’s usual waking hours to confirm a diagnosis of hypertension.

When using HBPM to confirm a diagnosis of hypertension, ensure that:

for each blood pressure recording, two consecutive measurements are taken, at least 1 minute apart and with the person seated and

blood pressure is recorded twice daily, ideally in the morning and evening and

blood pressure recording continues for at least 4 days, ideally for 7 days.

Discard the measurements taken on the first day and use the average value of all the remaining measurements to confirm a diagnosis of hypertension

Question 21

GUIDELINES ON HTN - DIAGNOSIS

Answer 21

When considering a diagnosis of hypertension, measure blood pressure in both arms.

If the difference in readings between arms is more than 20 mmHg, repeat the measurements.

If the difference in readings between arms remains more than 20 mmHg on the second measurement, measure subsequent blood pressures in the arm with the higher reading.

If blood pressure measured in the clinic is 140/90 mmHg or higher:

Take a second measurement during the consultation.

If the second measurement is substantially different from the first, take a third measurement.

Record the lower of the last two measurements as the clinic blood pressure.

If the clinic blood pressure is 140/90 mmHg or higher, offer ambulatory blood pressure monitoring (ABPM) to confirm the diagnosis of hypertension.

home BP moniter if can’t tolerate ambulatory

If the person has severe hypertension, consider starting antihypertensive drug treatment immediately, without waiting for the results of ABPM or HBPM. [

While waiting for confirmation of a diagnosis of hypertension, carry out investigations for target organ damage (such as left ventricular hypertrophy, chronic kidney disease and hypertensive retinopathy) (see recommendation 1.3.3) and a formal assessment of cardiovascular risk using a cardiovascular risk assessment tool

ABPM – to confirm a diagnosis of hypertension, ensure that at least two measurements per hour are taken during the person’s usual waking hours (for example, between 08:00 and 22:00). Use the average value of at least 14 measurements taken during the person’s usual waking hours to confirm a diagnosis of hypertension.

When using HBPM to confirm a diagnosis of hypertension, ensure that:

for each blood pressure recording, two consecutive measurements are taken, at least 1 minute apart and with the person seated and

blood pressure is recorded twice daily, ideally in the morning and evening and

blood pressure recording continues for at least 4 days, ideally for 7 days.

Discard the measurements taken on the first day and use the average value of all the remaining measurements to confirm a diagnosis of hypertension

Question 22

HTN GUIDELINES - management

Answer 22

Offer antihypertensive drug treatment to people aged under 80 years with stage 1 hypertension who have one or more of the following:

target organ damage

established cardiovascular disease

renal disease

diabetes

a 10-year cardiovascular risk equivalent to 20% or greater. [2011]

1.5.2 Offer antihypertensive drug treatment to people of any age with stage 2 hypertension.

Aim for a target clinic blood pressure below 140/90 mmHg in people aged under 80 years with treated hypertension. [2011]

1.5.6 Aim for a target clinic blood pressure below 150/90 mmHg in people aged 80 years and over, with treated hypertension. [2

ABPM/HBPM -
below 135/85 mmHg for people aged under 80 years

below 145/85 mmHg for people aged 80 years and over. [2011]

Question 23

pathway for drug treatment

Answer 23

https://pathways.nice.org.uk/pathways/hypertension/treatment-steps-for-hypertension#content=view-index&path=view%3A/pathways/hypertension/treatment-steps-for-hypertension.xml