Thursday 11 August 2011

Sympatholytics

it is also called adrenoceptor blocking drugs or adrenergic receptor blocker


                                                  Adrenergic Receptor Blocker
 


                           α blocker            α + β blocker                     β blocker
α1 (selective)
Prazosin
Doxazosin
α2 (selective)
Idazoxan
Yohimibine
α1 + α2 (non-selective)
Phentolamine
Phenoxybenzamine

Labetalol
β1 (cardio-selective)
Atenolol
Acebutolol
Metoprolol
β2 (selective)
Butoxamine
β1 + β2 (non-selective)
Propranolol
Timolol
Sotalol

How α1-blocker reduces BP ?—they occupy the α1 receptors and prevents the action of adrenaline and nor-adrenaline, thus the smooth muscles of the vessels cannot contract and ↓ PR and ↓ BP.

Adverse effect of α blockers—
1.  Orthostatic / postural hypotension (during sudden change in posture).
2.  Relaxation of the sphincter of the urinary bladder which may cause un-intended dribbling of urine.
3.  α2 blocking can produce inhibition of platelet aggregation.
4.  Tachycardia due to fall of BP.

Miscellaneous α blockers—Labetalol blocks α1, β1, β2. It has also a little blocking effect on α2 and can be used in hypertension. Specially hypertension emergencies.

Indications—
1. Moderate degree HTN
2. Raynaud’s phenomenon—in cold vasospasm and pain
3. In prinz metal angina—prazosin might have beneficial effect
4. Benign prostatic hypertrophy
5. Pheo-chromocytoma

β-blockers—now a days extensively used.

Indications—
1.    Hypertension
 2.  Anxiety
3.    Angina pectoris
 4.  Pheo-chromocytoma
5.    Cardiac arrhythmia
 6.  Thyrotoxicosis
7.    Ischaemic heart disease
 8.  Post myocardial infarct phases.
9.    Glaucoma
10. Muscle tremor, migraine

Adverse effects of β-blockers—
1.  Bronchoconstriction (no response to Salbutamol)
2.  Cardiac failure
3.  Bradycardia (worsening of heart failure)
4.  Hypotension
5.  Hypoglycaemia
6.  Reduce peripheral blood flow
7.  Fatigue, depression, insomnia, dreaming, gut upset, rash

Contraindications—
1.  Bronchial asthma
2.  Left ventricular failure
3.  Diabetic patients treated with hypoglycemic agents (insulin dependent diabetes)
4.  Peripheral vascular disease (Buerger’s disease)
5.  Hypotension (systolic <90mm of Hg)
6.  Bradycardia (HR <55 /min)

Selective and non-selective β-blockers—β1 blocker are the cardio selective. Non-selective are (β12) blocker. Selectivity is also dose dependant. At high doses they may lose their selectivity.

Water and lipid soluble β-blockers—lipid soluble β-blockers can easily cross the BBB and produce CNS effect. They are easily absorbed from the GIT and enter into the hepatocyte and rapidly metabolized, so half life is less. On the other hand the less lipid soluble β-blockers cannot cross the BBB abundantly and less CNS effect. They are not metabolized significantly in the liver and should largely be excreted unchanged through the kidney.

Intrinsic sympathomimetic activity / partial agonist activity of β-blocker—(drug—Acebutolol)—in normal condition during absolute mental and physical rest, β-blockers with ISA will produce like tachycardia and slight ↑ in cardiac contractility. But the same drug in presence of powerful agonist like adrenaline will blunt the effect of adrenaline because the receptors are occupied by the Acebutolol, which is a partial agonist. Thus Acebutolol will blunt / reduce the intensity of tachycardia, rise of cardiac contractility, palpation, during panic, exercise, anger etc.

*** Name of some ISA—Acebutolol, Pindolol, Labetalol.
*** the relation between the exercise and blocking—if the patient takes β-blocker then cannot exercise for long.
*** Nadolol is excreted through the kidney without being metabolized in the liver.
*** β-blocker used as eye-drop are Timolol, Betaxolol.

Pharmacological effects of β-blocker—
On CVS—negative ionotropic and chronotropic effect on heart. It opposes the β2 receptor mediated vasodilatation and also antagonizes the release of Renin.

On Respiratory system—they block the β2 receptors of the bronchial smooth muscle and increases airway resistance by causing bronchoconstriction, specially in asthma. So contraindicated in asthma.

On Eye— the intra-ocular pressure by decreasing the aqueous humor production.

On CNS—Insomnia, Restlessness, Tremor.

Metabolic and endocrine effects of β-blockers—
§    They inhibit sympathetic mediated stimulation of lipolysis.
§    Impair recovery from hypoglycemia specially in diabetic patients on insulin therapy.

Membrane stabilizing effect—
Some β blockers have prominent local anaesthetic action due to blockage of Na-channels.

Propranolol (non-selective β-blockers)—
Indications—
1.   Treatment of HTN (with diuretics)
2.   Cardiac dysrrhythmia
3.   Anginal pain
4.   MI
5.   Glaucoma
6.   Fallot’s tetrallogy
7.   Thyrotoxicosis
8.   Parkinsonism


Antihypertensive



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