Adrenergic antagonist drug

Epinephrine or Adrenaline

It is a natural catecholamine, Norepinephrine (NE) is methylated to yield epinephrine in the adrenal medulla which is stored in chromaffin cells. 

It is metabolized by MAO and COMT. 
Neuronal Uptake: 
Uptake 1 (Neuronal) inhibited by: Cocaine, Amphetamine, Tricyclic Antidepressants (TCAS).
Uptake 2 (Extra-Neuronal) Inhibited by: Cortisone. 
Uptake 3 (Vesicle Uptake): Inhibited by: Reserpine. 

Pharmacological Action. 

 Local Effects: 

Vasoconstriction (VC) in nose. 

Heart (B1):

(+ve) inotropic, chronotropic & dromotropic. 

Blood Vessels (BV): 

Skin BV (alpha-1) VC. 

Skeletal muscles BV (B2) VD. 

The cumulative effect is an increase in systolic blood pressure (B1) and slight decrease in diastolic pressure (B2). 

Lung:

Powerful bronchodilatation (B2). 

GIT:

Relax gastro-intestinal and genito-urinary muscles. 

Eye:

Active Mydriasis. 

Dipivefrin 

is an epinephrine pro-drug used in open-angle glaucoma, easily passes from cornea and penetrate into the anterior chamber than epinephrine. 

Hyperglycaemic effect:

1) increase glycogenolysis (B2)

2) decrease insulin release (alpha-2). 

3) increase glucagon release (B2). 

Uses

1) Bronchospasm (acute asthma).

 2) Anaphylactic shock: drug of choice (is a physiological antagonism of histamine). 

3) Cardiac arrest. 

4) Local infiltration anesthetics.

5) Epistaxis (Nosebleed).

Norepinephrine or Noradrenaline 

It is a naturally catecholamine. 

Act on alpha-receptors more than beta-receptors (Great VC).

It is rapidly metabolized by MAO and COMT.

Uses:

as a vasopressor in treatment vasodilatory shock.

Local side effects:

Blanching along the site of the infused vein (due to potent vasoconstrictor effects).

Isoprolerenol or Isoprenaline

It is a synthetic catecholamine.

Stimulates both B1 and B2 receptors.

It is rarely used therapeutically due to non-selectivity.

Uses:

1) Heart attack

2) irregular heartbeat (heart block). 

3) Acute attack of bronchial asthma.

Dopamine (DA)

It is a naturally catecholamine.

It is activate apha & B-adrenergic and dopaminergic receptors.

Dose Dependent Effect

Small dose 

activate D-dopaminergic receptors.

Moderate dose 

activate B-adrenergic receptors.

High dose 

activate a-adrenergic receptors.

Pharmacological Action:

1) Cardiac stimulatory effects (B1).

2) Dilates renal blood vessels: Increase blood flow (D1).

3) Vasoconstrictor effects (at very high doses): VC (alpha-1).

Uses:

1)Cardiogenic and septic shock

2)Hypotension

3) severe heart failure.

Dobutamine 

It is a selective B1 receptor agonist thus increase HR & CO.

Major advantage of Dobutamine sympathomimetic drugs it increases CO and does not significantly elevate oxygen demands of the myocardium.

Uses:

Acute heart failure (septic cardiogenic shock). 

Adverse effects:

1) hypertension

2) tachycardia

3) phlebitis

4) nausea

5) headache

6) anginal pain

Fenoldopam

For continuous IV infusion only

Rapid-acting vasodilator 

uses:

treat severe hypertension

Side effects:

1) Headache

2) flushing

3) dizziness

4) tachycardia. 

Phenylephrine 

It is a vasoconstrictor thus increase blood pressure.

Induces reflex bradycardia when given parenterally.

Uses:

1) Hypotension (Vasopressor)

2) Haemorrhoids

3) Decongestant

4) Mydriatic.

Midodrine

Used for the treatment and management of hypotension. 

Naphazoline ,Tetrahydrozoline ,Xylometazoline ,Oxymetazoline

They are vasoconstrictor decongestants are founds in eye drops and nasal drops or sprays.

It works by constricting swollen vessels in the eye or nose reduces eye redness (relieve irritation) & nose congestion.

Oxymetazoline is a drug of choice for epistaxis.

Clonidine 

it is an alpha-2 agonist (centrally and peripherally).

Mechanism of action:

1) Stimulate presynaptic alpha-2 receptors:

decrease NE release.

2) Stimulate central alpha-2 receptors:

decrease Sympathetic outflow.

3) Stimulate Imidazoline receptor:

Sympatho-inhibitory action

Uses:

1) Hypertension.

2) ADHD.

3) Withdrawal symptoms.

4) Migraine Prophylaxis.

5) Psychiatric disorders.

6) Hot flashes (menopause).

7) Diagnosis of pheochromocytoma

Side Effects:

1) Dry mouth

2) drowsiness

3) dizziness

4) sedation.

Clonidine withdrawal:

Clonidine therapy should be gradually tapered off. Sudden dis continuation can cause hypertension due to a rebound in sympathetic outflow, treated by alpha-1 & B blockers.

alpha-Methyldopa

Mechanism of action:

1) Methyldopa is converted into the false transmitter (metabolite) called; alpha-methylnorepinephrine, in the CNS by dopamine beta-hydroxylase (DBH) enzyme thus the false transmitter is central alpha-2 agonist thus decrease sympathetic out flow thus decrease NE release thus decrease renin release thus decrease blood pressure.

2) It is a competitive inhibitor of dopa-decarboxylase enzyme that which converts L-dopa into dopamine thus Dopamine is a precursor for norepinephrine and subsequently epinephrine.

Uses:

1) Gestational hypertension

2) pre-eclampsia (pregnancy-induced hypertension).

Side Effects:

1) Postural hypotension

2) Sedation

3) drowsiness

4) increase prolactin hormone.

Apraclonidine ,Brimonidine

Used in glaucoma therapy.

Lofexidine

Used to relieve symptoms of heroin withdrawal symptoms.

Metaproterenol or Orciprenaline Salbutamol or Albutero Terbutaline Ritodrine 

it is short-acting B2-adrenoceptor Agonists (SABA) used to stop premature labor

Formoterol & Salmeterol 

long-acting B2-adrenoceptor Agonists (LABA)

Indacaterol 

these drugs uses: Bronchospasm and COPD.

Side Effects: Palpitations (parenterally) & Muscle tremors

Amphetamine & Dextroamphetamine 

It is a potent CNS stimulant.

It is has a mood-elevating (euphoria) efflect.

Mechanism of action

Increase release of NE.

Uses:

1) ADHD

2) Narcolepsy

3) (Of-label) Performance-enhancing

4) depression and obesity treatment. 

Methamphetamine

It is like amphetamine but; much stronger, act quicker, and can be considered more addicting.

Uses:

1) ADHD

2) exogenous obesity.

Methylphenidate

Amphetamine derivatives with less side effects.

Addiction and psychological dependence are rare. 

It is the most prescribed medications in ADHD.

it is also effective in the treatment of narcolepsy.

Modafinil

It is a wakefulness-promoting agent.

Uses: sleep disorders; such as narcolepsy.

Tyramine

Not clinically used, It is found in fermented foods, such as aged cheese (ripe cheese).

Like amphetamines, tyramine increase release of NE. "Chees Reaction"

It is metabolized by MAO in the GIT and liver, but, if the patient is taking MAO inhibitors, tyramine is not metabolized, as well as NE is not metabolized thus powerful increase in NE release from nerve ending thus serious vasopressor effects thus Hypertensive crisis (treated by ai and ß blockers).

Ephedrine

Orally sympathomimetic drug.

Mechanism of Action:

Direct and indirect actions (mixed-action).

Uses:

1) Hypotension associated with anaesthesia

2) Nasal congestion (due to nasal decongestant effect).

Side Effects:

1) Palpitation

2) headache

3) insomnia

Pseudoephedrine

It has fewer CNS and CVS side effects than ephedrine.

It used widely as a combination to relieve common cold symptoms.

Uses:

1) Nasal congestion

2) sinus congestion

3) eustachian tube congestion.