Cardiovascular therapeutics Flashcards
What occurs in coronary artery disease?
narrowing of the lumen of blood vessels due to the formation of atheromas plaques in the intima
Symptoms occur when thrombosis and plaque rupture take place
How is CAD treated?
not possible to offer treatment to those suffering consequences therefore preventative measures are vitally important
- leading causes of death in the developed world
- majority deaths due to MI occur outside of hospital
What are the 2 key lifestyle factors used to prevent/reduce CAD?
smoking cessation and dietary changes
What is the main treatment for smoking cessation?
NRT - must have parenteral or topical application due to poor GIT absorption + additional support and counseling
What are the side effects of NRT?
Nausea, cramps, cough and insomnia
Caution must be taken in severe CVD as risk of coronary artery spasm
What is an alternative treatment to NRT for smoking cessation?
bupropion - non-selective dopamine reuptake inhibitor
What are the side effects of bupropion?
mood and eating disorders
seizures and CNS tumors
alcohol and benzodiazepine withdrawal
additional care must also be take in liver and renal disease
What is a very important RF for CAD?
Hypertension
What is the current NICE guidelines advice for when to start treating hypertension?
> 160/100 or >140/90 in certain circumstances, such as organ damage, high CVD risk and diabetes
What is the gold standard for diagnosing hypertension?
24 ABPM - avoids life long treatment of white coat hypertension
however if initial BP is >185/110 then ABPM is not undertaken and treatment is started immediately
What do the treatment options for hypertension depend on?
age and ethnicity (due to ascot trial)
What treatments are first line for those = 55 ?
ACE inhibitors or AT2 R blockers
What treatments are first line for those >55 or of afrocaribbean/african ethnicity ?
initially treated with calcium channel blockers
What happens if hypertension persists after one of the treatments?
2 classes of drugs are combined before adding a thiazide diuretic and then the final date is the addition of a beta blocker
Other than hypertension what else are calcium channel blockers used for?
angina and dysrhythmias (diltiazem)
What are the 3 forms of calcium channel blockers?
1) phenylalkalines (verapamil)
2) dihydropyradines (nifedipine)
3) benzothiazepines (diltiazam)
How do calcium channel blockers work?
relax smooth muscle and cardiac muscle by preventing calcium entry (through L type channels) = AV block to slow heart (phenylalkalines and benzothiazepines)
= vasodilation in terms of dihydropyradines
What are the side effects of calcium channel blockers?
flushing, headache, ankle swelling, constipation, heart block, exacerbation of HF
What are thiazide diuretics used to treat and how do they work?
mild HF and hypertension
- act at the Na/Cl pump of the DCT preventing cotransport and therefore leading to the loss of Na, Cl and K in the urine
- loss of theses salts lowers water retention and leads to vasodilation
What are the adverse effects of thiazide diuretics?
diuresis, hyponatraemia and hypokalemia, erectile dysfunction, gout and an association with diabetes
Other than hypertension what other conditions do drugs that act on the RAS treat?
HF, diabetic neuropathy, renal insufficient, ischemia heart disease and after MI (esp. with ventricular damage)
What are the different types of RAS drugs?
1) renin inhibitors (aliskiren) - rarely used due to safety concerns
2) ACE inhibitors - ramipril, enalapril
3) AT2 receptor blockers (candesartan)
What are the side effects of RAS drugs?
hypotension, angioedema, bilateral renal artery stenosis (therefore kidney function must be checked regularly)
What is the most common side effect of ACE inhibitors and why does it occur?
persistent dry cough - inhibition of the kinase enzyme, causing build up of bradykinin
Which group of people are beta-blockers not used for HF and hypertension?
young women due to risk of teratogenicity
What is the additional benefit of carvedilol?
beta blocker + also had alpha-1 blocking activity
What is the additional benefit of nebivolol?
selective beta blocker with additional activity causing NO release
What group of patients is beta-blockers contraindicated in?
asthmatics - due to risk of bronchoconstriction
What are the other adverse effects of beta-blockers?
bradycardia, hypoglycemia, fatigue, cold extremities
What types of cholesterol are bad?
increased plasma LDL and total cholesterol positively correlate with incidence of cardiovascular disease whereas increased HDL cholesterol has a negative correlation
- less strong positive correlation between CVD and plasma triglyceride levels
What are statins used for and how do they work?
commonly prescribed for primary and secondary prevention of strokes, TIAs, MI and angina
up regulate LDL receptor expression on hepatocytes as well as inhibiting the LDL producing enzyme HMG-CoA reductase
What are the risks of statins?
well tolerated but risk of myositis
very rare cases the proteins released in the breakdown of muscle can lead to rhabdomyolysis and renal failure
Other than statins, what are another type of lipid lowering drugs?
fibrates = benzafibrate, fenofibrate - less powerful at reducing cholesterol levels but increase HDL and lower triglycerides - actions stem from increasing LDL uptake at the liver
What are the side effects of fibrates?
myositis
contraindicated in those with liver problems
What is ezetimibe?
cholesterol lowering drug - inhibits cholesterol absorption from the gut
rarely used and increases risk of rhabdomyolysis if used in conjunction with a statin
What have anti-coagulants been shown to be beneficial against?
reduce risk of death in MI and stroke patients
most commonly used = aspirin (anti-platelet)
What is aspirin mainly used in?
secondary prevention but also been suggested to have a cancer preventative effect
How does aspirin work?
irreversible COX inhibitor preventing production of thromboxane in platelets
also temporarily reduces production of platelet aggregating inhibitor PG12, but endothelial cells that produce PG12 are able to synthesize more enzyme
What are the side effects of aspirin?
mostly GIT bleeding and dyspepsia
overdose- tinnitus, vertigo and decreased hearing
Why is aspirin contraindicated in children and who else?
due to risk of reye’s syndrome - encephalopathy and liver failure
can’t be used alongside warfarin (bleeding risk) or uricostatic agents (due to risk of gout)
Other than aspirin what are some other anti-platelet drugs?
IIb/IIIa receptor inhibitors as well as ADP blockers (clopidogrel and prasugrel)
How do ADP blockers work?
irreversibly inhibit ADP induced platelet aggregation causing an additive effect with aspirin due to different pathways
What is prasugrel?
not a prodrug therefore can be used in patients with low levels of liver enzyme cyp2c19
What is ticagrelor?
reversible ADP blocker
What are examples of anti-coagulants that function at the coagulation cascade?
warfarin - blocks vit K - needs close monitoring - can be reversed by giving vit K
Dabigatran blocks thrombin
Apixaban - blocks activated factor X
What is prescribed in patients that have a STEMI?
Prasugrel or ticagrelor are prescribed after having had percutaneous coronary intervention (PCI)
What is prescribed for non-STEMIs?
aspirin and clopidogrel
Aspirin also given after TIA
When are IIb/IIIa inhibitors?
only used during cardiac catheter procedures if clots are visibly forming
What drugs are typically used to treat angina?
vasodilators such as calcium channel inhibitors and nitrates
nitrates work through release of NO = ventricular relaxation, venorelaxation to lower preload, coronary vasodilator and arterial vasodilation= lower after load
What is the major issue with nitrates?
tolerance - leading to postural hypotension and headaches
What are examples of short and long acting nitrates?
acute attacks use GTN
longer acting preps oral isosorbide mononitrate
When are intravenous nitrates used?
acute coronary syndrome and acute HF
Other than vasodilators what else is used in angina?
beta blockers to slow heart rate to reduce cardiac work
Ca channel blockers are also used
What are the key first things that need to be done for an MI?
pain relief and re-open occluded vessels
determine whether its an NSTEMI or STEMI on ECG
What constitutes a STEMI?
ST elevation with initial T wave inversion and later Q wave inversion
How is a NSTEMI differentiated from angina?
based on troponin T levels
What are the treatments for MI?
Diamorphine - pain
Metoclopramide - nausea
aspirin, heparin and clopidogrel - thin blood
PCI and thrombolysis must be performed
How does thrombolysis work?
drugs activate plasminogen, degrading fibrin to break up thrombi
Streptokinase was the dominant treatment for past but has now been replaced by alteplase
How is a NSTEMI treated?
angiography before treatment plan is formed whereas all STEMIs have PCI
What is HF?
End stage of CVD - had incredibly poor prognosis but treatment is available to treat symptoms and improve QoL
What are the aims of the treatments for HF?
Reduce fluid load and edema using loop directions (furosemide) = blocks Na/K/2Cl in ascending loop of hence
What are at the adverse effects of loop diuretics (furosemide)?
hypovolemia, hypotension, hypokalemia and hypomagnesemia and hyperuricaemia
Other than loop diuretics what other treatments help to treat HF?
ACE inhibitors (ramipril) spironolactone = aldosterone antagonist = promotes Na loss and increase k retention aiding fluid loss Low dose Beta blockers
