Cardiac and vascular pharmacology Flashcards
What are the symptoms of Congestive Heart Failure (CHF) ?
Patient become breathless on very minor exercise left ankle oedema Cardiac output (CO) below the normal range. Reminder : BP = CO * TPR (Total Peripheral Resistance)
What are the 2 methods of treating CHF ?
Indirect - reduce work by decreasing vascular resistance (either after load - arterial pressure, or pre load - venous pressure) : - ACE inhibitors - vasodilators - diuretics or Direct inotropes : - cardiac glycosides (digitoxin) - beta-1 AR agonists (dobutamine)
What is the effect of digitoxin (foxglove) given to a patient w/ CHF on his:
- CO
- HR
- cardiac area
- body weight
- urine output
- increase in CO
- decrease in cardiac area
- decrease in HR
- decrease in body weight
- increase in urine output
What is the effect of digitoxin on isolated cadiac tissue ?
- increase in intracellular [CA2+]
- increase in force of contraction
By what mechanism does digitoxin increase intracellular [Ca2+] ?
- digitoxin inhibits the Na+/K+ - ATPase
- this leads to a rise in inrtracellular [Na+]
- this diminishes the driving force for the Na+/Ca2+ NCX, which leads to accumulation of Ca2+ inside the cell
- higher intracellular [Ca2+] leads to a stronger contraction
- in addition, digitoxin stimulates vagal activity
- this leads to inhibition of the AV node (beneficial for control of atrial fibrillation and treatment of heart block)
Why is digitoxin not an optimal drug ?
It has a low therapeutic index.
Which drugs represented a major advance in the treatment of CHF ?
How do these work ?
Beta 1-AR antagonists e.g. carvedilol (also an alpha1-AR antagonists)
Mechanism : reduce the sympathetic stimulation of the heart
First line along w/ ACE inhibitors (indirect)
What is hypertension ?
Hypertension is a disease characterized by a general increase in peripheral resistance.
How can hypertension be treated ?
“Switch off” NA release from the sympathetic nervous system and/or relax vascular smooth muscle.
What drugs can be given to treat hypertension ?
- hemamethonium = ganglion nAChR blocker
- prazosin = alpha-1 antagonist (on blood vessels)
- clonidine = alpha-2 receptor agonist (autoreceptor, -ve feedback) + inhibits vasmotor center in the medulla
- α-methyl dihydroxyphenylalanine, α-methylDOPA or α-methylnoradrenaline = false transmitters
- minoxidil, nifedipine = direct vasodilators
What is minoxidil ?
How does it work ?
Minoxidil = direct vasodilator
Mechanism of action = blocks the action of ATP on ATP sensitive K+ channels (K(ATP)) :
- Normally ATP binding to these channels inhibits K+ conductance causing them to close
- If ATP binding is blocked, K(ATP) remain open, causing hyperpolarisation
- Hyperpolarisation leads to closing of L-type Ca2+ channels = vasodilation
What is nifedipine ?
How does it work ?
Nifedipine = direct vasodilator
Mechanism of action = blocks L-type Ca2+ channels, which inhibits the rise in intracellular Ca2+
=> hyperpolarization –> relaxation
What are the symptoms of hypertension ?
Hypertension is ASYMPTOMATIC until the occurrence of a stroke of angina.
What are the symptoms of angina ?
What is the cause of this disease ?
Symptoms : pain running down the left arm and chest on exercise
Cause : partial occlusion of the coronary artery
What are the 2 main ways of treating angina ?
Reduce oxygen demand : - β-adrenoceptor antagonists e.g. propranolol, atenolol (=cardioselective) - Reduce sympathetic increases in HR Inprove coronary flow : - Nitrates - Calcium channel antagonists e.g. nifedipine --> blocks coronary arterial spasm Also : - surgery --> bypass - stents
