Circulation/vascular tone Flashcards
alpha adrenoceptors
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
b2 adrenoceptors
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)
M3 receptors
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
RAS
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
HTN - cause
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
ACE inhibitors
- captopril
- enalapril
- lisinopril
- ramipril
vasodilators used in HTN, HF, RENAL DYSFUNCTION (Especially in diabetic patients to slow progression of diabetic or reduced renal function neuropathy)
ACE inhibitors - MOA
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
ACE INHIBITORS – DON’T
CONTRAINDICATIONS
-pregnancy
-renovascular DISEASE
AORTIC STENOSIS
adverse effect
- cough
- hypotension
- dizzy/headache
- diarrhoea
- muscle cramp
Angiotensin 2 receptor antagonists
losartan
valsartan
Angiotensin 2 receptor antagonists - moa
inhibit angiotensin 2 receptor = vasodilation and reduction in peripheral resistance
Angiotensin 2 receptor antagonists - don’t
contraindication
- pregnancy
- renal artery stenosis and aortic stenosis
adverse effect
- cough (more of an ACE inhibitor thing)
- orthostatic hypotension
- dizziness
- headache
- fatigue
- hyperkalaemia /rash
Calcium antagonists
diltiazem- cardioselective
verapamil-^^
nifedipine = more of an effect on vascular tone
a-1 adrenoceptor antagonists
prazosin
doxazosin
a-1 adrenoceptor antagonists - moa
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
a-1 adrenoceptor antagonists - indication
HTN (ESPECIALLY CHF PATIENTS)
Prostate hyperplasia (reduced bladder and prostate resistance
CAD
a-1 adrenoceptor antagonists - DONT
Prazosin not to CHF due to aortic stenosis
SE postural hypotension dizziness headache and fatigue weakness palpitations nausea
hydralazine
third line
mild to moderate HTN
Inteferes with action of inositol triphosphate in vascular smooth muscle reducing peripheral resistance and blood pressure
minoxidil
last due to SE
Hyperpolarisation of smooth muscle = less calcium entry = inhibited smooth muscle contraction
sodium nitroprusside
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
GUIDELINES ON HTN -
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
GUIDELINES ON HTN - DIAGNOSIS
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
HTN GUIDELINES - management
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]
pathway for drug treatment
https://pathways.nice.org.uk/pathways/hypertension/treatment-steps-for-hypertension#content=view-index&path=view%3A/pathways/hypertension/treatment-steps-for-hypertension.xml
