Intro to CV Pharmacology Flashcards
Name the major CV receptor types
Alpha 1 – ( α 1 ) receptor subtypes – α 1 a, α 1 b, α 1 d
Alpha 2 – ( α 2 ) receptor subtypes - α 2 a, α 2 b, α 2 c
Name the different alpha receptor types, families, actions and locations.
Alpha 1 (α 1) – Gq receptor family- triggered as a result of Phospholipase C (PLC)- triggers inositol triphosphate 3 (IP3) increase - Ca 2+ increase -
contraction (in smooth muscles)
Alpha 2 (α 2) – Gi receptor family - cAMP decrease - activation of Myosin Light Chain (MLC) Kinase - contraction (in smooth muscles)
- Alpha 2 (α 2) – Gi family - cAMP decrease - Inhibitor of neurotransmitter (NE) release (CNS)
–negative feedback loop - Both Alpha 1 and 2 are GPCR family members
What are Alpha Antagonists used to treat? Provide some examples
Clinical conditions due to adrenal excess or hyper activation of the alpha receptors.
- Pheochromocytoma (noncancerous (benign) tumor that develops in an adrenal gland)
- Chronic hypertension
- Peripheral vascular diseases / occlusive disease / Raynaud’s disease
- Benign Prostate Hyperplasia (BPH) and Urinary obstruction
- Urolithiasis (kidney stones)
Name 2 selective alpha1 blockers, their MOA, receptor affinity, their function and indication for use.
Prazosin and Terazosin.
MOA – A competitive inhibitor at the α receptor.
* Selective for α1 receptors
* Affinity α1 > α2
* It is1000-fold more potent at α1 than α2 receptors.
* Relaxes smooth muscles of both arteries and veins.
* Indication – Hypertension management
2 Non-selective alpha 1 and 2 blockers
Phenoxybenzamine and Phentolamine
Explain the 2 different MOA of the non-selective alpha blockers, and what tissue types they act on. What is the net effect?
MOA 1 - By blocking both α 1 and 2 in peripheral smooth muscles, the nonselective blockers bring about relaxation
MOA 2- By blocking α 2 in sympathetic nerve
terminals, the nonselective blockers suppress
the negative feed back loop thus enhancing NE
release, resulting in increased cardiac rate
Net outcome is reduction of vascular pressure, because of blockade of both α 1 and 2 in vascular
tissue. Therefore, used in controlling hypertension.
What are the 3 Alpha-2 adrenergic agonists, their MOA and clinical indication?
Clonidine, Guanfacine and Methyldopa
MOA- By activating α 2 receptors in sympathetic nerve terminals, these agents cause activation of negative feed back loop preventing NE release, resulting in decrease of both heart rate and vasoconstriction.
Clinical Indication- Severe vasoconstriction/Hypertensive crisis
Where are beta-1 receptors mostly expressed, and what family are they in?
All beta receptors belong to the family of GPCRs.
Present in heart and kidneys.
Effect of B1 receptors on the heart?
B1 - Gs family - Ca2+ increase - increased contraction
Increases HR, SV, CO and BP
Effect of B1 receptors on Kidneys
Acts on juxtaglomerular cells
Beta 1 (β1) – Gs- > leading to renin release
Activates RAAS to increase BP
Explain steps of Beta adrenergic receptor mediated activation of the RAAS. What receptors does Angiotensin II and aldosterone act on?
Angiotensin II activates Angiotension 1 Receptors in adrenal gland stimulating release of aldosterone.
Aldosterone activates minieralcorticoid receptors in distal tubule of kidney causing reabsorption of NaCl and H20.
Where are B2 receptors located, and describe their effects?
Located in the bronchial smooth muscle of the lungs, smooth muscle of bladder and are located in the liver.
Beta 2 (β2) – Gs-> cAMP increase -> inhibition of MLC Kinase -> relaxation
This causes bronchial dilation for more airflow, relaxation of bladder smooth muscle decreasing urination and stimulates gluconeogenesis and glycogenolysis in the liver.
Identify the following:
One First generation non-selective beta blocker
Two B1-selective (2nd gen.) beta blockers
Two Non-selective for alpha and beta (3rd gen)
Non-selective First Gen: Propranolol
B1-Selective 2nd gen: Atenolol and Metoprolol
Non-selective for alpha and beta 3rd. gen: Carvedilol and Labetalol
What type of beta blockers should you avoid in patients w/ respiratory pathologies such as asthma and COPD? Why?
Should avoid prescribing non-selective beta blockers as they will block B2 receptors in bronchial smooth muscle causing vasoconstriction and respiratory distress.
Identify 9 Clinical Indications for beta-blockers
He said to focus on cardiac ones
Heart failure
Hypertension
Arrhythmia
Ischemic Heart Disease
Thyrotoxicosis (associated cardiovascular complications)
Ocular Hypertension
Anxiety and Tremor
Pheochromocytoma
As a prophylactic in Migraine
Identify some organs that beta blockers help reduce the effects of hypertension induced damage.
