Tyrosine Metabolism Overview

Study Notes

Tyrosine is considered the most significant amino acid.
End product of tyrosine metabolism is Vanillyl Mandelic Acid (VMA), with normal urinary levels ranging from 4 mg to 8 mg per day.
Increased levels of VMA may indicate a tumor in the adrenal medulla, known as Pheochromocytoma.
Tyrosine conversion to dopamine includes a rate-limiting step; this slowest and most important step is critical for catecholamine synthesis.
Dopamine is formed from L-Dopa, leading to the first catecholamine.

Dopamine is transported and stored by the Vesicular Monoamine Transporter (VMAT).
Reserpine, an alkaloid, inhibits this vesicular storage process.
The conversion of dopamine to norepinephrine occurs in the adrenal medulla.
Norepinephrine release involves exocytosis and requires calcium ions (Ca²⁺).
Bretylium, Guanethidine, and Guanadrel are inhibitors of NE release.

Adrenergic agonists, also known as sympathomimetic drugs, activate adrenoceptors.
Epinephrine is a non-selective adrenergic agonist used in cardiac arrest resuscitation and anaphylactic shock (via EpiPen).
Norepinephrine is the drug of choice (DOC) for septic shock.
Dopamine is preferred for shock associated with renal involvement.

Direct agonists activate adrenoceptors directly; indirect agonists enhance the actions of endogenous catecholamines.
Alpha-1 selective agonists are used as nasal and eye decongestants, e.g., Midodrine (for chronic orthostatic hypotension) and Phenylephrine (mydriatic agent).
Bromocriptine acts as a D2-agonist for Parkinson's disease and prolactinemia.

Amphetamine-like releasers increase norepinephrine and blood pressure and are used as stimulants.
Isoproterenol is a non-selective beta agonist and administered for atrioventricular blocks, providing bronchodilator effects.

Antinicotinic effects include dry mouth, mydriasis, tachycardia, and elevated body temperature.
Succinylcholine is a depolarizing neuromuscular blocker with a short duration, used for rapid intubation.
Non-depolarizing blockers cause paralysis without initial contraction.

Neostigmine is the drug of choice for atropine poisoning and used to treat myasthenia gravis.
Pyridostigmine is preferred for chronic myasthenia gravis due to its selectivity and longer duration.
Trimethaphan is rarely used, primarily in emergencies.

Non-selective drugs are contraindicated in acute angle closure glaucoma and prostatic hyperplasia.
Special caution is advised for patients with acid-peptic disease, as these drugs may slow gastric emptying and exacerbate symptoms.