Pharmacology 2 Flashcards
How is vascular tone maintained normally?
Balance between the opposing actions of neurotransmitters, hormones and mediators that have vasoconstriction or vasodilator properties
Give examples of vasoconstrictors
Noradrenaline and adrenaline (alpha adrenoreceptors, ATP, Angiotensin II, ADH, Endothelin, TxA2, 5-Hyrdoxytryptamine (5-HT), ADP
Give examples of vasodilators
Noradrenaline and adrenaline (Beta2 adrenoreceptors, Prostacyclin (PGI2), Nitric Oxide (NO), Atrial Natiuretic Peptide (ANP), Adenosine
How do vasoconstrictors work?
Use various methods to increase intracellular calcium
How do vasodilators work?
Use various methods to decrease intracelluler calcium
Give some examples of the targets for drugs that act on the vasculature
- Membrane receptors (agonists or antagonists)
- Smooth muscle cell enzymes (inhibitors or activators) e.g. guanylate cyclase
- Smooth muscle cell membrane ion channels (inhibitors or activators)
- Enzymes generating or inactivating vasocontrictors or dilators e.g. ACE
How are vasodilators categorised?
According to their mechanism of action or to the blood vessels they affect
e.g.
Arterial Dilators: Reduce afterload by lowering TPR so increase stroke volume nd hence cardiac output - decrease myocardial oxygen consumption and eventually preload
Venodilators: Reduce venouis return via trapping blood in the venous circulation to lower cardiac filling pressure (preload); this reduces cardiac workload
However, most are mixed vasodilators
What types of vasodilator drugs are there?
- Drugs that interfere with naturl vasoconstrictors
- Drugs that mimic or boost natural vasodilator systems
- Drugs that block pathays contributing to the response of vasoconstrictors
What drug types interfere with the natural vasoconstrictors?
- Alpha1-adrenoreceptor antagonists
- Endothelin-1
- Drugs affecting RAAS
How do Alpha1-adrenoreceptor antagonists work?
- Act on both venous and arterial sides of the circulation (mixed dilators)
- Response occurs within the whole animal (greatest effect whenthere is high sympathetic tone to the blood vessels) e.g. congestive heart failure or shock
- Fall in vascular tone usualy is short-lived
How do we manipulate RAAS with drugs to alter angiotensin II production or action?
Drugs can influence RAAS at three points:
1. Renin release: Beta antagonists block renin secretion
2. Angiotensin Converting Enzyme: ACE inhibitors block conversion of Angiotensin I to Angiotensin II
3. AT1 Receptors: Interaction of angiotensin II with vascualr and/or adrenocortical AT1 receptors - AT1 Antagonists block these receptors from binding Angiotensin II
How do drugs that block Endothelin-1 work?
Endothelin-1 is a constrictor peptide produced by endothelial cells, released as a larger precursor cleaved by endothelin converting enzyme (ECE). E1 acts local to the site of production on smooth muscle cell receptors to cause vasoconstriction by binding to ETa receptors.
Drugs include Endothelin receptor antagonists
or
ECE antagonists
What drug types mimic the actions of natural vasodilators?
- Drugs that stimulate production of cGMP (cGMP elevation in smooth muscle cells promotes relxation)
- Drugs that stimulate production of cAMP (cAMP elevation in smooth muscle cells promotes relaxation)
What is the mechanism of action of drugs stimulating cGMP?
- Organic nitrates are metabolised by blood vessels walls to produce Nitric Oxide (NO) - Most active on the venous side therefore reduce preload
- Sodium nitroprusside decomposes to produce a nitric oxide precursor (mixed vasodilator)
What is the mechanism of action of drugs stimulating cAMP?
- Raise cAMP by activation of rceptors on smooth muscle cells: Agonists at Beta2-adrenoreceptors or PGI2 receptors
- Raise cAMP by enzyme inhibition: Phosphodiesterase inhibitors
