Cardiac & Vascular Flashcards
Congestive Heart Failure characteristics
Disease of cardiac muscle:
- CO below normal range
- breathless on minor exercise
- left ankle oedema
Hypertension
High bp -> VSM issues
- no symptoms with stroke/angine
- increase arterial vascular resistance
BP =
BP = CO x TPR (total peripheral resistance)
Angina
VSM
- pain running down left arm + chest on exercise
- coronary arterial - partial occlusion
Indirect treatment of CHF
Reduce work load
- > decrease vascular resistance
- ACE inhibitors
- vasodilators
- diuretics
What do after load and preload relate to?
arterial and venous pressure respectively
Direct treatment of CHF
Inotropes
- cardiac glycosides
- beta 1 adrenoreceptor agonists e.g. dobutamine
An example of a cardiac glycoside and its mech. of action
Digitoxin increases force of contraction by
- inhibiting Na+/K+ ATPase
- causing [Na+] i accumulation
- Slowing of Ca2+ - Na+ pump
- Ca2+ accumulation by S.R.
Risks of using digitoxin
- non-pacemaker cells can develop pacemaker activity
2. Ectopic beats + dystrhythmia from competition between glycoside and K+ which is enhanced by hypokalaemia
What does it mean to have a low therapeutic index?
Therapeutic dose is near toxic dose
Vagal tone differences with digitoxin
Increase vagal tone by slow A-V conduction -> longer P-R increases refractory period -> prevents fibrillation/ flutter
Overall effects of digitoxin:
- Increase CO then decrease
- Cardiac area decrease
- HR decrease
- body weight decrease
- urine output increase
Examples of beta 1 adrenoreceptor antagonists
Carvedilol (also a1 antagonist) and bisoprolol
Beta 1 adrenoreceptor antagonist uses and mech of action
First line therapy with ACE inhibitors decreasing mortality by 65%
- decrease sympathetic stimulation of heart (indirect)
Hypertension is defined as
> 160/95 mmHg - increase peripheral resistance
General solution for hypertension
Switch of NA release from SNS/ relax VSM
Types of drugs that target hypertension:
- Ganglion blockers e.g. hexamethonium
- Alpha adrenoreceptor antagonists e.g. prazosin whibh blocks sympathetic stimulation -> decrease peripheral resistance
- A2 agonist e.g. clonidine/ alpha-methyl DOPA (pro-drug - false transmitter) -> act centrally
Example of a direct vasodilator
Minoxidil
Minoxidil mech. of action
Block ATP action on KATP (which normally closes channel ) -> hyperpolarisation -> close L-type Ca2+ channels -> vasodilation
L-type Ca2+ channels can also be blocked by
antagonists e.g. nifedipine
-> blocks coronary arterial spasm
Possible angina treatments:
- Beta adrenoreceptor antagonists -> decrease O2 demand by decrease symp. response and increase in HR
- nitrates -> improve coronary flow
- ca2+ antagonists
Organic nitrate mech of action
- nitrite (NO2) anion, liberated within cells when organic nitrates react with tissue sulfhydryl (-SH) groups.
- Within the cell nitrite anions are converted to nitric oxide (NO) which
- activates cytosolic form of the enzyme guanylate cyclase causing an increase in cGMP formation.
- cGMP activates protein kinase G and leads to a cascade of effects in the smooth muscle culminating in
- 5/6 dephosphorylation of myosin light chains and
- sequestration of intracellular Ca2+,with consequent
relaxation.
Main mechanism of anti-anginal drugs:
- Reduce cardiac work due to peripheral arteriole and vein dilation
- dilation of collateral vessels
Glyceral trinitrate
Absorbed rapidly from oral mucosa
- 10 -20 min action -> metabolised rapidly by liver
-> hepatic first pass -> little escapes into systemic circulation
side effects: headache, hypotension risk of fainting
Atenolol
Beta adrenoreceptor antagonist
- blocks sympathetic resp. -> adrenaline circulates on myocardium -> decrease cardiac work during exercise/ stress -> Increase O2 demand -> longer diastole so longer perfusion of coronary arteries
Aspirin
Anti-platelet agent -> changes balance TBA2 between platelet aggregation + PGI2 which inhibits it
-> COX inhibition -> decrease TBA2 without drastically reducing PGI2
Low doses: prophylaxis against thrombosis
Statins e.g. simvastatin
Administered orally
Used for underlying atheromatous disease
inhibits HMG-CoA reductase which is the rate limiting
step in cholesterol synthesis.
Heparins
Inhibits coagulation by activating antithrombin III which inhibits thrombin formation and therefore thrombus formation.
Administered IV or subcutaneously (Low molecular weight heparin).
Side effects: haemorrhage and thrombocyopaenia.
Glycoprotein IIb/IIIa inhibitors e.g. abciximab, tirofiban
IV anti-platelet agents:
- antagonise glycoprotein IIb/IIIa receptor
Why wouldn’t I use diprymidine for a atheromous plaque?
Steal: blood flow to normal increase and to ischemic decrease since collateral between not dilated -> use a nitrate to dilate collateral instead
Why would I use a diuretic or AT1 receptor antagonist instead of an ACE inhibitor for CHF and hypertension?
Diuretics just decrease H20 and Na+. Both diuretics and AT1 e.g. losarten doesn’t affect bradykinin (-> vasoD -> cough) unlike ACE inhibitors
