Drugs and the heart Flashcards
Describe the changes of Action potential in HR and what receptor does what
driven by SA node
If-funny channel-lets Na enter slowly (hyperpolarised activated-use cAMP)-start the process of depolarisation
As current rise Ica(transient) then Ica(long)-cause main depolarisation (reach peak)
At peak depolarisation, Ik let K enter and repolarise-back to a minimum where If activates again-start again
What regulated the action potential in HR?
Sympathetic will increase cAMP activity-If and Ica UP
Parasympathetic-decrease cAMP-Ik UP
What regulates myocardial contractility?
Ca2+ entry after AP-cause RyR to open and let tons of Ca out of SR (75%)-then Ca spark+signal (75%-25%)-bind the troponin-etc
After done, Ca taken back in to SR with ATP
Aalso Ca exchanged with the outside vs a Na
What are the mechanisms leading to angina?
Balance between the myocardial needs (main-Coronary blood flow, O2 content ) and their work (heart rate, preload (starling law-increase work tons), afterload, contractility increases it)
When mismatched-angina
What drugs influence heart rate (best ones)?
B-blockers-decrease If and Ica (by inhbiting SNS by B1)
Calcium antagonists-Decrease Ica (block channel-decrease the drive)
Ivabradine-decrease If (locks the funny receptor/current-but less pronounced as Ca main driver)
What are the most used drugs to reduce heart contractility?
B-blockers-pretty much same as rate-SNS has role in blocking Ca entry
Calcium angatgonists-directly block the Ca channels
How many classes of calcium antagonists is there?
Rate slowing-act on cardiac and smooth muscle-Phenylkylamined (Verapamil), benzothiazepines(deilitazem)
non rate slowing-more potent by mostly act on smooth muscle action-amilodipine (dihydropriidine)
->no effect on heart but vasodilation can cause reflex tachycardia
What 2 other drugs can we use to influence mycardial oxygen supply/demand? What are their effects on pre/after load
Use NO-
promotes relaxation-Also promote K efflux (hyperpolarise cell-more difficult to activate)-increase coronary blood flow
And potassium channel openeners-also promote K efflux-increase coronary blood flow
These also vasodilate rest of body-drop afterload and preload-which decreases mycardial work
What are the main drugs to treat stable angina?
Stable-means that slightly innadequate-so when exercise the coronary vessels just cannot keep up-
Treat-B-blockers and calcium blocker are first line
Can be combines then
Nitrates, then, Ivabradine then Nicorandil (nitrate+K+ agonist)are the next treatment lines
What are the worse side effects of B-blockers? So what do?
Need to be sure not worsening Heart failure (because of CO reduction in people with low CO isnt good)
Increased vascular resistance also not great
Bradycardia-if people have heart block (decrease conduction through AV node)-decrease again
Classically-asthma (b2 in lungs bronchodilate)
Diabetes-SNS would warn about hypoglycemia - (b-blockers) -masks it
not tested: Cold extremities-B2 mediated peripheral vasodilation
diarrhea/impotence/depression/
bad dreams
Can give pindolol-with its intrinsic sympathetic activity can help HF/HB during day to day
or mixed a/b blockers-carvediol-a1 block gives additional help
What are the side effects of calcium blockers?
Depends-but often less dangerous than B-blockers
Verapamil-bradycardia-rare, constipation-common (gut CA channels)
Dihydropyridines-Ankle oedema (dilation of cappilary vessels+ gravity), headaches/flushing (vasodilation), palpitations (Vasodilation->SNS stress response->reflex adrenergic activation)
What are the main issues caused by arrhythmias? How can we classifies arrythmias?
stroke, sudden death, clotting, etc
Want to avoid that with drugs (duh)
700000 in UK have it
management is usually v complex (pacemakers, etc)
Supraventricular, ventricular, Complex
What is the Vaughan Williams (pronouces Vauhn) classification?
Classifies anti-arrythmic drugs via mechanism of action
Class1-sodium channel blockades
Class 2- beta adrenergic blockade
III-prolongation of repolarisation (potassium block)
IV-calcium channel blockers
Kinda outdates because lot of drugs have mixed effects and are in both classes
What are the key drugs used to treat supraventricular arrythmia?
Adenosine-short (30s), quick and effective response (popular)
in SA node Acts on Adenosine receptors -Binds adrenosine receptor: A1 which has Gi effect-downregulate cAMP-decrease funny current
=> reduces the jerky activation by slowing down -gives more time to have normal activation
Also acts on adrenosine receptor A2 on SMC-Gs- activated cAMP then and vasodilates
verapamil-also, but has a longer half life-less popular
Reduction of ventricular responsivness via calcium blocker-depresses SA and subsquent AV
What is Amiodarone?
Blockage of re-entry tachyarrythmias Acts by (probably) blocking mutliple ions channel -espeially K channels (causes longer repolarisation -so reduce chance that re-entry signals activates anything)
But not a safe drug really-control it
Very lipid soluble-accumulate, long half life,
