sympatholytics

1. Anti-adrenergic Drugs/Sympatholytics
• These are the drugs that antagonize the action
of adrenaline & related drugs.
• They are competitive antagonist of α or β or
both receptors.
• Classification:
Alpha (α) blocker
•α1 selective
•α2 selective
•Nonselective
Beta (β) blocker
•Nonselective
•Cardioselective (β1)

2. α1 selective Prazosin, Terazosin,
Doxazosin, Tamsulosin
α2 selective Yohimbine, Idazoxan,
Atipamezole
Non- selective α blocker Phenoxybenzamine,
Phentolamine, tolazoline,
ergotamine, ergotoxine,
chlorpromazine
Alpha (α) blockers

3. Actions:
• Vasodilation (venous):- Fall in BP
• Reflex tachycardia
• Nasal congestion
• Miosis
• Increase intestinal motility
• Trigone, sphincter& prostate tone is reduced:-
Improve urine flow
• Inhibit ejaculation:- Impotence

4. Prazosin, Terzosin, Doxazosin & Tamsulosin
• These are selective competitive blockers of the α1
receptor.
• Prazosin, Terzosin & Doxazosin are useful in the
treatment of hypertension as they cause dilation of
artery. It can cause first dose effect so started at low
dose at bedtime. They are orally effective with high
plasma protein bound, metabolised in liver &
excreted from bile.
• Tamsulosin is uroselective (α1A & α1D) indicated for
the treatment of benign prostatic hypertrophy
(BPH).
• Uses: HTN, BPH, CHF, Raynaud’s disease

5. • Yohimbine is a selective competitive α2 blocker.
It is found as a component of the bark of the
yohimbe tree.
• It directly blocks α2 receptors and has been used
to relieve vasoconstriction associated with
Raynaud disease.
• Yohimbine is contraindicated in CNS and
cardiovascular conditions because it is a CNS and
cardiovascular stimulant.

6. • Phenoxybenzamine is nonselective, linking covalently
to both α1 and α2 receptors. The actions of
phenoxybenzamine last about 24 hours after a single
administration.
• Dose: 20-60mg/day oral
• Phentolamine produces a competitive block of α1 and
α2 receptors. This drug’s action lasts for approximately
4 hours after a single administration.
• Dose: 5mg i.v. repeated as required
• Uses:
• Pheochromocytoma
• Hypertension
• Secondary shock
• Benign prostatic hypertrophy
• Peripheral vascular disease

7. Non-selective β-blocker Propanolol, sotalol,
timolol, pindolol,
labetalol, carvedilol
Cardioselective (β1) Atenolol, Metoprolol,
Acebutol, Esmolol
Beta (β)-blockers

8. Propanolol
• Propanolol is the β-adrenergic antagonist and blocks
both β1 and β2 receptors with equal affinity.
Pharmacological Actions:
1. Cardio Vascular System (CVS)
• Heart: HR, FOC, A-V conduction
2. Respiratory Tract
• Increased bronchial resistance (β2 blockade)
3. CNS
• Subtle behaviour changes, forgetfulness, increased dreaming
and nightmares
• Anti-anxiety effect (peripheral action of propranolol)
4. Metabolic
• Blocks adrenergically mediated lipolysis
• Inhibits glygenolysis in heart, skeletal muscles, liver
• May reduce carbohydrate tolerance (decreased insulin release)

9. 5. Skeletal muscle
• Inhibits adrenergically provoked tremor (β2 blockade)
• Attenuate exercise capacity
6. Eye
• Reduced secretion of aqueous humour and intra ocular
tension
7. Uterus
• Relaxant activity of β agonists blocked
• Dose: 10mg BD to 160mg QID oral, 2-5mg i.v. parenteral

10. Timolol
• Timolol blocks β1 and β2 adrenoceptors and is more
potent than propranolol.
• Timolol reduces the production of aqueous humor in
the eye. It is used topically in the treatment of chronic
open-angle glaucoma and occasionally for systemic
treatment of hypertension. (0.25-5% eyedrops)
Labetalol and carvedilol
• Labetalol and carvedilol are β blockers with additional
α1blocking actions that produce peripheral
vasodilation, thereby reducing blood pressure.
• It is useful in treating hypertensive patients with
increased peripheral vascular resistance.

11. Acebutolol, Atenolol, Metoprolol & Esmolol
• Cardioselective β blockers, such as acebutolol,
atenolol, and metoprolol antagonize β1 receptors. This
cardio selectivity is pronounced at low doses.
• These drugs lower blood pressure in hypertension and
increase exercise tolerance in angina.
• Esmolol has a very short lifetime due to metabolism
of an ester linkage. It is only given intravenously if
required during surgery or diagnostic procedures.
• The cardiospecific blockers have relatively little effect
on pulmonary function, peripheral resistance, and
carbohydrate metabolism.
• Dose: Acebutolol 200-400mg OD, Atenolol 12.5-50mg OD

12. Uses:
• Hypertension
• Stable Angina
• Cardiac arrhythmias
• Myocardial infarction
• Congestive heart failure
• Hypertrophic obstructive cardiomyopathy
• Dissecting aortic aneurysm
• Pheochromocytoma
• Thyrotoxicosis
• Migraine
• Anxiety
• Essential tremor
• Glaucoma

13. Adverse Effects:
• Can accentuate myocardial insufficiency and precipitate
CHF/edema
• Bradycardia
• Exacerbates variant angina
• Impaired Carbohydrate tolerance
• Altered plasma lipid profile
• Tiredness and reduced exercise capacity
• Cold hands and feet
• Others: G.I. upset, lack of drive, nightmares, forgetfulness,
hallucinations, sexual distress in male
Contraindications:
• Sudden withdrawal : rebound hypertension, worsening of
angina, sudden death
• Worsens COPD; can produce acute Bronchial asthma
• Partial or complete heart block

15. Glaucoma
•Glaucoma is an eye disease that is associated with
increased intraocular pressure, in which damage to the eye
(optic) nerve can lead to loss of vision and even blindness.
•It can be open angle glaucoma & angle closure glaucoma.
Drugs for Glaucoma:
1. Beta blockers: Timolol, Betaxolol, Levobunolol
2. Alpha agonists: Dipivefrine, Apraclonidine, Brimonidine
3. Prostaglandin analogues: Latanoprost, Travoprost
4. Carbonic anhydrase inhibitors: Acetazolamide, Dorzolamide
5. Anticholinesterase/Miotics: Pilocarpine

16. Timolol, Acetazolamide
Latanoprost

17. 1. Beta (β) blockers: Timolol, Betaxolol, Levobunolol
Topical β blockers have been the first line drugs in treatment of
glaucoma. They lower i.o.t. by reducing aqueous formation. Ocular β
blockers are lipophilic with high ocular penetration.
2. Alpha (α) agonists: Dipivefrine, Apraclonidine
Dipivefrine is a prodrug of Adrenaline that penetrates cornea. The
released Adr (from dipivefrine) lowers i.o.t. by augmenting
uveoscleral outflow, β2 receptor mediated increase in hydraulic
conductivity of trabecular filtering cells, as well as by reducing
aqueous formation (α1 + α2 receptor mediated).
Apraclonidine is a polar clonidine congener which does not cross
blood-brain barrier, but applied topically (0.5–1%) that lowers i.o.t. by
~25%.

18. 3. Prostaglandin analogues: Latanoprost, Travoprost
Prostaglandins at low concentration lowers i.o.t without inducing
ocular inflammation. It acts by increasing uveoscleral outflow,
increasing permeability of tissues in ciliary muscle or by an
action on episcleral vessels. Ciliary body COX-2 has been found to
be down regulated in wide angle glaucoma indicating a
physiological role of PGs in aqueous humor dynamics.
4. Carbonic anhydrase inhibitors: Acetazolamide, Dorzolamide
Oral treatment with acetazolamide (0.25 g 6–12 hourly) reduces
aqueous formation by limiting generation of bicarbonate ion in
the ciliary epithelium. It is used to supplement ocular
hypotensive drugs for short term indications like angle closure,
before and after ocular surgery/laser therapy.

19. 5. Anticholinesterase/Miotics: Pilocarpine
Pilocarpine is used to treat glaucoma and is the drug of choice in
the emergency lowering of intraocular pressure of both narrow-
angle (or closed-angle) and wide-angle (also called open-angle)
glaucoma. It is extremely effective in opening the trabecular
meshwork around Schlemm’s canal, causing an immediate drop
in intraocular pressure as a result of the increased drainage of
aqueous humour. (action within few minutes, lasts 4-8 hours)
Mechanism of action: Pilocarpine produces rapid miosis,
contraction of the ciliary muscle & fall in intraocular pressure. It
acts through direct stimulation of muscarinic receptors and
smooth muscle such as the iris and secretory glands.
• It is used as 0.5-4% eye drop.
Adverse effects: Pilocarpine can enter the brain and cause CNS
disturbances, sweating & salivation.
Nursing Management: Parenteral atropine 2mg (until
atropinization) is administered to counteract the toxicity of
pilocarpine