L7: Sympatholytics Flashcards
What is the classification of Sympatholytics?
I- Adrenergic receptor blockers
▪ α- Adrenergic blockers ▪ β- Adrenergic blockers
II- Centrally acting drugs
▪ α-methyl dopa ▪ Clonidine
What is the action of adrenergic blockers?
These drugs interact with either α- or β-adrenoceptors to prevent or reverse the actions of endogenously released catecholamines or exogenously administered sympathomimetics
What is the classification of alpha-adrenergic blockers?
- Non-selective α-receptor blockers: phenoxybenzamine, phentolamine
- Selective α1-receptor blockers: prazosin , terazosin, doxazosin
- Selective α2-receptor blockers: yohimbine
What are the pharmacological effects of alpha-blockers?
Alpha receptor antagonist drugs lower peripheral vascular resistance (PVR) and blood pressure.
Hence, postural hypotension and reflex tachycardia are common during the use of these drugs.
Other minor effects include miosis, nasal stuffiness, etc
What is the mechanism of action of PHENOXYBENZAMINE?
Irreversible non-selective α1 & α2 antagonist
What are the uses of PHENOXYBENZAMINE?
Pheochromocytoma(with β-blocker)
What are the side effects of PHENOXYBENZAMINE?
Hypotension
Reflex tachycardia
Miosis
What are selective alpha 1 blockers?
Prazosin, terazosin, doxazosin and tamsulsin
What are the characters of prazosin?
Prazosin is the Prototype drug.
All of these agents decrease peripheral resistance and lower arterial BP (like most adrenergic blockers) by:
a) α1- receptor blockade.
b) Direct VD of both arterial and venous smooth muscles.
They cause minimal changes in COP, RBF, and the GFR. (Unlike dopamine)
They don’t trigger reflex tachycardia by the same degree (as the non-selective blockers.)
They improve plasma lipid profile and decrease LDL and TGs
What are the therapeutic uses of prazosin?
1) Mild to moderate hypertension
2) Benign prostatic hyperplesia (BPH):
▪ reduces the tone of the internal sphincter of the urinary bladder.
3) Raynaud’s syndrome
What are the characters of tamsulosin (more selective)?
is the most commonly used for the treatment of BPH because:
- It has a high affinity for α1A & α1D, the 2 receptor subtypes responsible for mediating smooth muscle contraction in prostatic tissue.
- It has little effect on standing BP compared with other α1-blockers. (Like prazosin)
What are the adverse effects of prazosin?
▪ First dose hypotension (syncope)
▪ Fluid retention (salt and water retention)
▪ False-positive test for the antinuclear factor of rheumatoid arthritis
▪ α- blockers can worsen incontinence in women with pelvic floor pathology
What are the characters of yohimbine?
▪ Selective presynaptic α2-blocker that leads to increased norepinephrine release. (As it prevents negative feedback)
What is yohimbine used for?
▪ It is sometimes used as an aphrodisiac (enhance sexual desire) without clinical evidence.
Is pheochromocytoma rare?
It is an uncommon cause of hypertension, estimated to occur in approximately 0.1 to 1 % of hypertensive patients.
How is pheochromocytoma treated?
▪ Clinical awareness of this tumor should be stressed because:
i. Surgical removal is curative in more than 90 % of patients
ii. Tumor excision has a significant effect on hypertension, the most important cause of pheochromocytoma related mortality and morbidity.
What is the selectivity of beta-blockers related to?
The β-receptor–blocking drugs differ in their relative affinities for β1 and β2 receptors; however, the selectivity is dose-related and tends to diminish at higher doses.
What are non-selective beta-blockers?
“Propran - pindo - timo - sota - Nado”
propranolol, pindolol, timolol, sotalol, nadolol
What are cardio-selective beta 1 blockers?
“Nebi - biso - meto - ate” “VPPN”
nebiVolol, bisoProlol, metoProlol, ateNolol,
What are beta-blockers with additional VD action?
“Dileva - Carvedi”
dilevalol, carvedilol
How do some beta-blockers cause VD?
the VD action comes from either: blocking the vascular α1 receptors; increasing PGE2 and PGI2 synthesis; or by the release of endothelial NO.
Pharmacodynamics and chemistry of beta-blockers?
Propranolol is the prototype β-adrenoreceptor antagonist.
β-blockers are absorbed well after oral administration, many have low bioavailability because of extensive first-pass metabolism.
Lipophilic β-blockers (e.g. propranolol) can pass readily to the CNS and are cleared by hepatic metabolism. Hydrophilic β-blockers (e.g. atenolol) have limited penetration to the CNS and are excreted primarily by the kidney with little hepatic metabolism.
β-blockers that undergo hepatic metabolism usually require multiple daily dosing.
Drugs eliminated via the kidney are suitable for once-daily administration
What are the organs affected by beta-blockers?
- CNS
- Eye
- CVS
- Respiratory
- Sk. Ms.
- Metabolic effects
- Specefic properties
What are the effects of beta-blockers on CVS?
They block cardiac β1 receptors and decrease all cardiac properties (↓ contractility and COP, ↓ A-V conduction “bradycardia”, ↓ excitability, and automaticity).
They block the β2-mediated VD in peripheral vessels leading to ↓ blood flow to most tissues.
They decrease blood pressure through:
a. ↓↓ COP by their –ve inotropic and chronotropic effects.
b. ↓↓ renin release from the kidney (β1).
c. ↓↓ norepinephrine release and central sympathetic outflow
(by blocking presynaptic β2).
