Cardio

What are the NICE treatment targets for hypertension?

What are goals of treatment for hypertension?

Reduction in CDV damage
Preservation of renal function
Limitation of left ventricular hypertrophy
Prevention of ischaemic heart disease
Reduction in mortality of strokes and MIs

What are the NICE treatment targets for hypertension with diabetes?

What lifestyle changes can be made in hypertension?

Reduce alcohol consumption
Weight reduction
Reduce caffeine
Reduce fat and salt
Increase fruit and olive fish
Increase exercise
Smoking cessation

What is stage 1 hypertension?

140-159/90-99

What is stage 2 hypertension?

\>160/\>100

What is stage 3 hypertension?

systolic \>180 and/or diastolic \>120
Same day referral

How do ACE inhibitors lower blood pressure?

Blocks production of angiotensin converting enzyme, stopping conversion of angiotensin 1 to angiotensin 2. When angiotensin 2 is released it causes vasoconstriction to increase BP, and acts on adrenal gland to increase fluid retention and increase BP. Therefore this doesn't occur

What is a common ACEi?

Ramipril

What is a side effect of ACE inhibitors?

dry cough -due to rise in bradykinin from the vasodilation which causes cough
Increase in K+ -causing arrhythmias
Angioedema
Severe 1st dose hypotension (take at night)

When should ACE inhibitors be avoided?

Renovascular disease
ACEi can lead to renal underperfusion
eGFR should be monitored before and during use
Contraindicated in pregnancy

Why are ACEi effective in diabetes?

Prevent nephropathy

What are ARBs?

Angiotensin 1 Receptor Blockers
Block the action of A2 at the AT1 receptor
Doesn't give rise to a cough

What are examples of ARBs?

- sartans. Losartan. Valsartan. Candesartan

How are calcium channel blockers used in hypertension?

Inhibit voltage operated Ca2+ channels on vascular smooth muscle leading to vasodilation and reduction in BP

What are examples of calcium channel blockers?

Verapamil (rate limiting), diltiazem, amlodipine (dihydropyridine)

What are side effects of calcium channel blockers?

Peripheral oedema
Constipation

What's the difference between rate limiting and dihydropyridine calcium channel blockers?

Rate limiting have greater effects on cardiac tissue
DHPs have a greater effect on vascular smooth muscle

How do thiazide diuretics reduce blood pressure?

Inhibit Na+/Cl- in distal convoluted tubule causing Na+ to leak and water to follow. Reduction in circulating volume and vasodilation

What are side effects of thiazide diuretics?

Hypokalaemia
Postural hypotension
Impaired glucose control
Urination
Impotence

When should thiazides not be used?

if creatinine clearance is less than 30-50 ml/min as it's ineffective in renal impairment
Don't use in gout

What are examples of thiazides?

Bendroflumethiazide

How do alpha blockers reduce blood pressure?

Competitive receptor antagonists of alpha 1 adrenoceptors which are coupled with vasoconstrictors so stops vasoconstriction

Why are alpha blockers last choice antihypertensives?

-Widespread side effects, which makes them poorly tolerated
Postural hypotension

How do beta blockers decrease BP?

Decreases heart rate and myocardial contraction, which both decrease cardiac output
A reduction in sympathetically evoked renin release

What are examples of beta blockers?

propranolol, atenolol, metoprolol

Why are beta blockers not 1st line treatment for hypertension?

Reduced effectiveness at preventing strokes and increased risk of diabetes

What is the first line treatment of hypertension?

ACEi or ARB
unless \>55 or black ethnicity then CCB

What is the second line treatment of hypertension?

Add one of a ACEi/ARB or CCB or diuretic that isn't already in regime

What is the third line treatment of hypertension?

ACEi/ARB + CCB + Diuretic

What is the fourth line treatment of hypertension?

Add alpha or beta blocker
Or spiromolactone

How do HMG-CoA Reductase Inhibitors work?

HMG-CoA reductase is an enzyme involved in the synthesis of cholesterol so when this is inhibited it reduces cholesterol synthesis

What are the HMG-CoA reductase inhibitors?

Statins (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin)

What is the role of statins?

Reduce plasma cholesterol
Reduction in cholesterol synthesis leads to upregulation of hepatic LDL promoting LDL uptake from plasma by the liver for excretion

Where do statins act?

liver they are hepatoselective
As the liver is the main site of cholesterol synthesis and extrahepatic sites synthesise essential cholesterol
However only 5% reaches systemic circulation after first pass metabolism

What types of hyperlipoproteinaemia are statins effective in?

IIa (elevated LDL)
IIb (elevated LDL/VLDL)

Do statins help with atherosclerosis?

May lead to regression
Stabilises lesions so they are less likely to rupture
Reduce progression of carotid disease and reduce risk of stroke

What drugs are used post MI?

Statin aspirin B-blocker ACEi

who are statins prescribed for?

Patients with a more than 10% risk of cardiovascular disease at a low intensity of 20mg
Patients who have CVD as secondary prevention at high intensity of 80mg
Normally taken at night when cholesterolsynthesis occurs, except atorvastatin

What are adverse effects of statins?

myopathy rarely leading to rhabdomyolysis (which is breakdown of skeletal muscle blocking the renal tubule)
Increased diabetes risk
Monitor in liver disease

What does simvastatin interact with?

amlodipine, verapamil, diltiazem
Don't use with macrolides

What score is used to assess CDV risk?

QRISK3

What is a cholesterol absorption inhibitor?

Ezetimibe
Acts in GI to inhibit cholesterol uptake
To be used as well as a statin

What is alirocumab?

PCSK9 inhibitor monoclonal antibody
A PCSK9 binds to LDL receptor and leads to degradation, alirocumab increases number of LDL receptors and lowers LDL
Used with statins every 2 weeks

What are fibrates?

Gemfibrozil
Activates PPAR-a to alter lipoprotein metabolism and reduces triglycerides
Used with statins when TGs is raised

How is Hypercholesterolemia treated?

Statin
+/- cholesterol absorption inhibitor

How is hypertriglyceridemia treated?

Lifestyle modifications
- Decr ETOH, dietary fat, and simple carbs
- Incr aerobic exercise, weight loss

Pharm
- Statins
- Fibrate

What is the role of nitrates in ischaemic heart disease?

Release NO, causing venodilation, increasing the amount of blood in the venous system so less blood returning to the heart, leading to decrease in preload and less cardiac work

What is an example of a nitrate used in IHD?

Glyceryl trinitrate (GTN spray)

How should nitrates be taken?

2 doses with a nitrate free period in the middle, as prolonged exposure can reduce effectiveness causing nitrate tolerance

What role do beta blockers have in IHD?

first choice for prevention
negative inotropic and chronotropic effect, so slow hearts and increase diastolic time for coronary blood flow, reducing cardiac work and preventing symptoms

Are beta blockers anti-arrythmic?

yes, they prevent abnormal rhythms and reduce MI risk

What is the role of calcium channel blockers in IHD?

cause vasodilation and improve coronary blood flow preventing symptoms

What specific effects does verapamil have on IHD?

CCB
myocardial depressant
bradycardic actions
class IV anti-arrhythmic activity

What is reflex tachycardia?

Drop in BP, body compensates by increasing HR
This happens with DHPs (class of CCB) so rate limiting CCB are preferred in angina

What is nicorandil?

Potassium channel activator

How does nicorandil treat angina?

Potassium channel activator
It's an NO donor and activator of ATP sensitive K-channels of smooth muscle in blood vessels, causing dilation reducing blood flow to the heart
Add on to prevent attacks

What is Ivabradine?

Inhibits pacemaker (funny) current in SA node to reduce HR.
Does this by inhibiting If channels

What role do antiplatelets play in IHD?

75mg low dose aspiring used
or Clopidogrel
get BP to a target of

What is the 1st line treatment of stable angina?

GTN spray for relief
lifestyle advice
After assessing CVD risk can give anti-platelet, statin

What is 2nd line treatment for angina?

B-blocker or CCB
+/- oral nitrate for prevention of angina attacks

What interaction between CCB and beta blockers needs to be watched out for?

rate limiting CCB (verapamil) and beta blocker can slow heart to fatal amount

When is aspirin used regarding MI?

used as secondary prevention for patients who have already had an MI

How does aspirin work?

irreversible inhibits the enzyme (cyclo-oxygenase) that catalyzes prostaglandin synthesis

Why does aspiring favour PGI2 production over TXA2?

TXA2 is made in platelets which have no nuclei so they can't make any more COX enzyme
PGI2 is synthesised in the endothelium which have new nuclei and the ability to produce more COX

How does clopidogrel work?

inhibit ADP-induced expression of GpIIb/IIIa (these bind fibrinogen leading to cross linking of platelets)

When can clopidogrel be used?

in combination with aspirin or for patients who can't take aspirin

What is an anti-platelet?

decreases platelet aggregation inhibiting thrombus formation

What is an anticoagulent?

inhibit coagulation of the blood and stop blood clots from forming

How do heparins work?

activate antithrombin III
antithrombin inactivates clotting factors (9, 10, 11) and thrombin by inhibiting serine proteases

What are examples of low molecular weight heparins?

enoxaparin
tinzaparin

How long does heparin take to act?

immediate action

How is unfractionated heparin monitored?

activated partial thrombin time APTT
this examines intrinsic pathways

Does LMWH require monitoring?

does not require coagulation monitoring

How does warfarin work?

Vit K antagonist
Vit K is essential for production of prothombin and factors 7, 9, 10
warfarin blocks vit K reductase needed for vit K to act as a cofactor
inhibits coagulation cascade

How long does warfarin take to act?

3 days

What are problems with warfarin?

narrow therapeutic window
many drug interactions
however is easily reversible with vit K

How is warfarin monitored?

International Normalized Ratio (INR)/ Prothrombin time (PT)
this is the time for coagulation following the addition of thromboplastin
increased INR means there is increased bleeding risk
more than 8 requires vitamin K for reversal

What can increase INR?

warfarin and liver disease
increased action leads to bleeding: gastric, cerebral, haemoptysis, haemturia, bruising

How is warfarin taken?

never miss a dose
6pm
don't take two together
advised not to become pregnant on this drug (teratogenic)
lots of interactions with OTC medications so be careful

What foods are not recommended in waffarin?

excessive consumption of green veg, rich in Vit K so can oppose action
beetroot
liver

Why should warfarin be avoided in pregnancy?

trimester 1: chondroplasia punctata, optic atrophy, mental retardation
Trimester 3: risk of bleeding/ post-partum haemorrhage

What is the role of a direct oral anticoagulant?

prevents thromboembolism and has rapid onset
less bleeding than warfarin
fewer drug interactions

What is an example of a DOAC?

dabigatran (thrombin inhibitor), apixiban, rivaroxaban (inhibitors of factor 10)

What is the management of heart failure?

ACEi
Beta-blocker
diuretic
SGLT2 inhibitor
(valsartan)

What drugs can worsen heart failure?

rate limiting CCB
NSAIDs (fluid retaining properties and risk of liver damage when paired with ACEi)
Pioglitazone

Why are ACEi used in heart failure?

reduce arterial and venous vasoconstriction reducing after and pre load
reduce salt/water retention by limiting production of aldosterone reducing circulating volume
Inhibits RAAS preventing cardiac modelling

What are examples of ACEi?

Ramipril
Lisinopril

What should be monitored when using ACEi?

eGFR and K+ and BP

What role do ARBs have in heart failure?

acts at AT1 blocking the action of angiotensin 2 giving a similar effect to ACEi

What are examples of ARBs?

- sartans. Losartan. Valsartan. Candesartan

What is the role of beta-blockers in heart failure?

beta 1 selective blockers used
antiarrythmic
oppose the neurohormonal activation which leads to myocyte dysfunction
reduce disease progression

Which beta blockers are used in heart failure?

bisoprolol (beta 1 selective), carvedilol, metoprolol

What is the role of diuretics in heart failure?

reduce circulating volume
reduce preload to the heart
relieve pulmonary and peripheral oedema

What is a side effect of loop diuretics?

hypokalaemia
K+ should be monitored
risk of postural hypotension

What is an example of a loop diuretic?

Furosemide
take in morning so sleep isn't disturbed by needing to pass urine
powerful

What is an example of a mineralocorticosteroid used in heart failure?

eplerenone- aldosterone receptor antagonist

What is the role of a Aldosterone (mineralocorticoid) receptor antagonists in heart failure?

aldosterone drives fibrosis of the heart, so this opposes cardiac fibrosis
risk of hyperkalaemia which is increased when using ACEi/ARB

How does digoxin work in heart failure?

Inhibits the Na/K ATPase pump, which results in a positive inotropic effect (↑ force of contraction) and a negative chronotropic effect (↓ HR)
slowing of the heart also results in improved cardiac filling providing symptomatic relief

when is digoxin used?

not a mainstay use in heart failure anymore but is used in heart failure with atrial fibrillation
it impairs AV conduction and slows heart so is beneficial in AF