SNS Antagonist Flashcards
(46 cards)
4 main types of adrenoceptors in the SNS?
Alpha 1
Alpha 2
Beta 1
Beta 2
Are the 4 main adrenoceptors pre- or post-synaptic?
Alpha 2 - PRE-synaptic
Other 3 are POST-synaptic
Alpha-1 function?
o VasoCONSTRICTION
o RELAXATION of GIT
Alpha-2 function?
o INHIBITION of NT release
- -VE feedback on NE release
o CONTRACTION of VSMC, CNS
(pre-synaptic!)
Beta-1 function?
o Cardiac STIMULATION
o RELAXATION of GIT
o RENIN release
Beta-2 function?
o BronchoDILATION
o VasoDILATION
o RELAXATION of VSMCs
o Hepatic Glycogenolysis
Beta-3 function?
Lipolysis
Some adrenoceptor antagonists?
Non-selective (a1 & b1) = Labetalol
a1 + b2 = Phentolamine
a1 = Prazosin
b1 + b2 = Propranolol
b1 = Atenolol
Hypertension physiology?
Clue - equation
CO x TPR = BP
Pathophysiology of hypertension?
Constantly >140/90mmHg
Main contributors towards hypertension?
o Blood volume
o CO
o Vascular tone
What are the main tissue targets for anti-hypertensives?
o SNS nerves
- that release the vasoconstrictor NA
o Heart
- CO
o Kidney
- blood volume/vasocontriction
o Arterioles
- control/determine TPR
o CNS
- determine BP set-point
- regulate some systems involved in BP control & autonomic NS
Quick way to decipher is a drug is a beta-blocker?
Ends in -OLOL
Beta-blockers associated with the different tissue targets of anti-hypertensives?
o The heart
- B1
- reduce ionotropic & chronotropic effects
o SNS nerves
- B1/B2
o The kidney
- B1
- reduce renin production
- common long-term feature is reduction in TPR
o Arterioles
- NONE
- if block the A1 receptors, would get dilation = do NOT want this
o CNS
- B1/B2
- reduce sympathetic tone
How can blockade of B1 receptors also help in anti-hypertensive effects?
On the pre-synaptic membrane
SO
blockade of this reduces the +ve feedback on NE release = contribute to anti-hypertensive effects
4 broad types of beta-blockers?
- NON-SELECTIVE
o equal affinity for B1 & B2 receptors
o e.g. Propranolol - B1-SELECTIVE
o more selective for B1
o e.g. Atenolol - MIXED A & B-BLOCKERS
o A1 blockade gives additional vasodilator properties
o e.g. Carvedilol - OTHER
o e.g. Nebivolol - also potentiates NO
o e.g. Sotalol - also inhibits K+ channels
Unwanted effects that can rise due to the use of beta-blockers?
- Bronchoconstriction
o of little importance unless patient has an airway disease (B2) - Cardiac Failure
o need some SNS drive to the heart
o may be problem is have heart disease - Hypoglycaemia
o B-blockers may mask symptoms (e.g. tremors)
o NON-SELECTIVE B-blockers will also block hepatic glycogenolysis (B2) - Fatigue
o CO falls = muscle perfusion falls (B2) - Cold extremities
o loss of B-receptor mediated vasodilation in cutaneous vessels - Bad dreams
4,5,6 = LESS SERIOUS
Propranolol?
B1 & B2 NON-SELECTIVE
During rest = very little effect
During exercise = can REDUCE HR, CO & ABP
As non-selective, produces ALL typical adverse effects
Atenolol?
B1-SELECTIVE
Antagonises the effects of NE on the heart
o BUT also affects any other organ with B1 receptors (e.g. kidneys)
Selectivity is CONCENTRATION-DEPENDANT
o too much and it becomes non-selective
What is the advantage of atenolol over propranolol?
As selective, LESS EFFECT on airways that non-selective drugs
o (and also the liver!)
BUT still not safe with asthmatic patients!
- as could become non-selective!
Carvedilol?
MIXED A & B-BLOCKERS
A1 blockade gives additional vasodilator properties
What advantage does carvediolol have other atenolol & propranolol?
Get a more powerful HYPOTENSIVE EFFECT (as not just affecting cardioselective B1)
o Heart - B1 effect
o Kidneys - B2 effect
o ALSO blocking vasoconstriction of arteries
Labetalol?
A1 & B1 dual-action antagonist
(higher ratio of B1:A1)
o lowers BP via. reduction in TPR
o induces a reduction in HR or CO (this effect wanes after chronic use)
Receptors linked with A1 & A2 receptors?
A1 - linked to STIMULATORY proteins
o Gq-linked
o POST-synaptic on VSMCs
A2 - linked to INHIBITORY proteins
o Gi-linked
o PRE-synaptic autoreceptors inhibiting NE release
