0728- Pharmacology of a, b adrenergic drugs- CG

Question 1

Define sympatholytics and name at least 5 examples

Answer 1

antagonistic to or inhibiting the transmission of nerve impulses in the sympathetic nervous system. (as opposed to sympathomimetics- which mimics effects of SNS)

Adrenergic antagonists

a1 (prazosin), B1 (metoprolol), mixed a + B antagonists (labetalol), centrally acting antagonists (methyldopa, clonidine),

Ca channel blockers (verapamil, nifedipine)

ACE inhibitors (ramipril)

Angiotensin 2 blockers (candesartan)

vasodilators (hydralazine)

Question 2

What are the characteristics of a1 and a2 receptors- specifically, name their subtype, location, signalling cascade, effect and function

Answer 2

Question 3

What are the characteristics of b1 and b2 receptors- specifically, name their subtype, location, signalling cascade, effect and function

Answer 3

Question 4

Name a receptor agonists and antagonists, and outline their clinical use

Answer 4

Question 5

Name b receptor agonists and antagonists, and outline their clinical use

Answer 5

Question 6

What are the effects of isoprenaline, adrenaline, noradrenaline on the CVS?

Answer 6

All 3 drugs (agonists) activate adrenergic receptors, evoking sympathetic response. HOWEVER, each drug have different affinities and potencies at different receptors (hence evoke different tissue responses, depending on what receptors are present at target tissue). ARTERIOLAR BEDS IN DIFFERENT ORGANS HAVE DIFFERENT RECEPTORSAND HENCE RESPONSE. IN CONTRAST, VEINS TEND TO HAVE THE SAME RESPONSES

Isoproterenol/isoprenaline more potent at B1 (increase myocyte contraction), compared to a1 (vasoconstriction) and B2 (bronchodilation)

Adrenaline more potent tha noradrenaline at B2

Adrenaline and noradrenaline roughly equal at a1 and b2 (adrenaline slightly higher)

Question 7

(revision) outline the different levels of modulation of vascular tone

Answer 7

Neural control (sympathetic, parasympathetic)

− Very few vessels are parasympathetically innervated (e.g. erectile, salivary glands, some gastrointestinal glands, THE BRAIN- however separated from rest of body by BBB)

− Take home: no direct parasympathetic innervation of vessels (arteries, veins, lymphatics)

Humoral control (via blood)

− Systemic (angiotensin, aldosterone, adrenaline, noradrenaline, vasopressin (ADH), endothelin)

Local control (e.g. metabolites)

(also autoregulation)

Question 8

Name at least 3 pharmacological targets to regulate vascular tone

Answer 8

Neural outflow:

– Brain, brainstem, spinal cord, ganglia (ganglion-blocker).

Synaptic transmission:

– Ca2+-channels, vesicular recycling, transmitter synthesis and break-down (ACh), etc.

Receptors:

– agonists, antagonists; subsynaptic, extrasynaptic: Pharmacology.

Signalling cascades
– G-protein coupled receptors

Smooth muscle contractility

– Ca2+-induced Ca2+-release; electromechanical coupling

Question 9

Describe the concept of haemodynamic steal

Answer 9

– Atherosclerotic plaques hinder vasomotion

– Vasodilation reduces R in each vascular arm and so increases flow in these areas

– Because R around sclerotic plaques does not change much, blood finds easier flow paths (reduced resistance due to dilation), thereby reducing flow over plaque: “haemodynamic steal”.

–> may result in worsened perfusion