Introduction to Adrenergic drugs

Adrenergic drugs are also known as sympathetic drugs. The sympathetic system is for emergency situations. It is responsible for fight, flight and freight response and also induces anxiety. In the heart it increases HR, conduction and force of contraction. In the eye it causes mydriasis. In the bowel and the bladder, it decreases evacuation. In Penis, it is responsible for ejaculation.

Neurotransmitter in Sympathetic System

The major neurotransmitter in the sympathetic system is nor-adrenaline which acts on alpha and beta receptors. In renal and mesenteric blood vessels, the neurotransmitter is dopamine, which acts on D1 receptors. The adrenal medulla is modified ganglia with acetylcholine as a neurotransmitter. Thermo-regulatory sweat glands the neurotransmitter is acetylcholine.

Receptors in the Sympathetic System

• α1 
• α2
• β1
• β2
• β3
• D1
• D2

Neurotransmission in Sympathetic System

In the presynaptic terminal, Tyrosine is obtained from phenylalanine. The enzyme hydroxylase converts tyrosine into DOPA, and the enzyme decarboxylase converts DOPA into dopamine. Vesicular monoamino transporter 2 (VMAT 2) transports dopamine into the vesicles. Dopamine inside the vesicle will get converted to NA with help of hydroxylase. Entry of Na+ and Ca2+ will fuse with the vesicle and signal the release of NA.

NA acts on the receptors Alpha and Beta on the postsynaptic terminal and will not stay for a long period. The action of NA is terminated by uptake. The process of uptake is done by a transporter known as nor-adrenaline transport (NAT).

The NA is again stored inside the vesicles with the help of VMAT 2. The NA put inside the presynaptic membrane can be metabolized by the enzyme monoaminoxidase (MAO), and its level can be depleted. Some of the NA can leak and get metabolized by the COMT enzyme. When NA is given through the blood vessels, the enzyme COMT metabolizes it faster than MAO. In synapse, the majority of NA is taken up by uptake and remaining is metabolized by MAO. The rate limiting step here is the conversion of tyrosine into DOPA.

If this is slow, the synthesis of NA is affected. Pheochromocytoma is a tumor of adrenal gland where there is excessive synthesis of NA and nor-adrenaline. This can be prevented by giving a drug Metyrosine that inhibits the enzyme hydroxylase. Carbidopa and Benserazide inhibit the decarboxylase and used in the treatment of Parkinson’s disease. Reserpine is a VMAT 2 inhibitor used in the treatment of hypertension. It leads to the depletion of NA by MAO, which causes depression. This leads to the risk of suicide. MAO inhibitors are used to treat depression by decreasing the depletion of NA. Bretylium and Guanethidine inhibit the release of nor-adrenaline, that is these do not allow the release of NA from pre-synaptic terminal.

Also Read: Rational Drug Prescribing and Essential Medicine

Adrenergic Receptors

Alpha Receptors

Alpha receptors have two types: alpha 1 and alpha 2. Let us discuss them one by one.

Alpha 1 Receptors

Eye

Alpha 1 receptor is present in the eye. Alpha 1 agonists cause active mydriasis by acting on the Dilator pupillae, which is required in a fundoscopic or retinoscopic examination. Alpha 1 agonists cause vasoconstriction of the ciliary blood vessels and decrease aqueous humor production. Hence, it is used in the treatment of glaucoma.

Blood vessels

In the blood vessels, Alpha is responsible for vasoconstriction and beta 2 is for vasodilation.

Alpha 1>>> Alpha 2>>> Beta 2

Alpha 1 is major in control while Beta 2 is minor in the blood vessels. When the action is on alpha 1 and alpha 2 the total peripheral resistance increases, resulting in an increased BP. So, the drugs that stimulate alpha receptors (mainly alpha 1) are used to treat hypotension. The role of beta 2 in blood vessels is not significant clinically. Its actions come into play during emergencies.

Bladder

Alpha receptors also play an important role in the trigone of bladder and male prostate. The trigone of the bladder and the sphincters are controlled by alpha 1. When alpha 1 constricts, it leads to urine retention. The detrusor muscle of the bladder has beta 2 and beta 3 receptors, causing relaxation of the detrusor muscle and resulting in urine retention.

Male reproductive system

Seminal vesicles and the vas deferens are also supplied by alpha 1 and are responsible for ejaculation.

Alpha 2 Receptors

Presynaptically The role of alpha 2 is to decrease the release of NA. Presynaptically beta 1 increases the NA release. Post synaptically Alpha 2 is present in the following:

• Blood vessels causing vasoconstriction
• Pancreases causing decreased insulin release.
• Kidney causing decreased renin release. (Beta 1 modulates the release of Renin).
• Ciliary epithelium in the eye causing decrease in cAMP and reduced aqueous humour production

Beta Receptor

Beta 1 receptors

• The major location is in the Heart.
  • When nodal tissue is stimulated, it causes an increase in HR and conduction.
  • When the cardiac muscle is stimulated, it causes an increase in the force of contraction.
  • It can act on both atria and ventricles.
• In the kidney
  • Located in JG cells
  • When there is a fall in BP and decrease in renal blood follow. Beta receptors in JG cells are activated and cause an increase in Renin release.
• In CNS
  • It causes anxiety, increases attention, increases alertness and anorexia.
• In ciliary epithelium of eye
  • Increases cAMP and increases aqueous humour production
  • Beta blockers are used to treat glaucoma to reduce aqueous humour production.

Beta 2 receptors

• In smooth muscle
  • Beta 2 causes relaxation of smooth muscles by increasing cAMP.
  • Bronchus- Bronchodilation
  • Blood vessels- Vasodilation
  • Intestines- Relaxation leading to constipation
  • Detrusor muscle- Relaxation leading to urine retention
  • Uterus- Relaxation during preterm delivery
• In liver
  • They cause glycogenolysis leading to increased glucose
• In Pancreases
  • Cause mild increase in the insulin. The penultimate action is to cause hyperglycemia.
• In skeletal muscles
  • Increases blood flow and increases exercising capacity
  • Can stimulate tremors
• Sympathetic drugs push the potassium ions into the cells, resulting in hypokalemia. Example, adrenaline.
• In ciliary epithelium of eye
  • Increases cAMP and increases aqueous humour production

Beta 3 receptor

Beta 3 is mainly located in the adipose tissue. It causes lipolysis and increases the FFA (free fatty acids). The lipolysis is more significant in brown fat (adipose tissue). As the person becomes an adult, the brown pad is less, so beta 3 agonists are not successful in treating obesity in adults. In the detrusor, it can relax the bladder.

Frequently Asked Question:

Q: What are the effects of Beta 1 adrenergic receptors on the cardiac muscle?

Answer: Beta 1 receptors cause cardiac muscle contraction by increasing cAMP.

Q: What is the role of Alpha 1 and beta 2 receptors in the blood vessels?

Answer: In the blood vessels, Alpha 1 is responsible for vasoconstriction and beta 2 is for vasodilation.

Q: What are indirect sympathomimetics?

Answer: Drugs increasing NA, which acts on alpha and beta receptors are called indirect sympathomimetics.

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