Pharmacological actions of cathecholamines Dr Adedunni Olusanya

Objectives Identify cathecholamines Understand their mechanism of actions

Cathecholamine -Intro Made up of a benzene ring Linked to 2 hydroxyl group and an amine group Includes dopamine, norepinephrine and epinephrine Same synthetic pathway – tyrosine is the precursor

Cathecholamines Dopamine – a precursor of other cathecholamine, synthesised in the cytoplasm and stored in vesicles or converted to NE NE – synthesised and stored in vesicles and adsorbed on chromagrannin as a complex with ATP Adrenalin – formed from NE by glucocorticoid induction of N- methyltransferase in the adrenal medulla. NE diffuses into the cytoplasm where it is converted to Adr by the methylating enzyme

Pharmacokinetics Orally inactive Rapidly metabolized by MAO and COMT in the intestinal wall and the liver – very low bioavailability Hence given parenterally

Dopamine Precursor of other naturally occurring catecholamine Major neurotransmitter in the basal ganglia, limbic system, chemoreceptor trigger zone and other parts of the CNS Peripherally acts on renal and mesenteric endothelium

Dopamine (contd) Agonist at D1, D2, A1 and B1 receptors Main effect is on vascular tissue A1 adrenergic receptors - vasoconstriction at high doses B1 and D1 receptor - positive inotropic effect D 1 receptor- dilation of renal and mesenteric vessels

Blood pressure - increases systolic BP No effect on diastolic BP

Clinical uses Severe heart failure To increase BP and urine outflow

Adrenaline Heart - Increases heart rate, conduction and contraction via beta 1 Blood vessel – Vasoconstriction in cutaneous, mucous membrane and renal bed via alpha 1 Dilation in skeletal muscles, livers and coronary vessels via beta 2 No direct effect on cerebral blood vessel Blood pressure Increase in systolic BP Decrease in diastolic blood pressure Decrease in peripheral resistance A moderate increase in mean BP

Adrenalin Respiration Git and bladder Bronchodilation via beta 2 Decongestant on bronchial muscle via alpha one Git and bladder Relaxation of smooth muscles – alpha 1, beta 2 , constriction of sphincters- Alpha 1 Uterus – Relaxation B2 Contraction – Alpha 1

Adrenalin contd Skeletal muscle – Metabolic effects – Adrenalin augments Ach release via alpha 1 receptors (heteroceptors). On muscle fibres – B2 shortens the active phase of contraction and reduced tension is developed in the slow contracting red fibres as well as increased firing of muscle spindles – tremors. Metabolic effects – glycogenolysis leading to hyperglycaemia in the liver - B2 , muscle glycogenolysis leading to hyperlacticidaemia – B2 Fats lipolysis – B1, B2 , B3 Mild effect on insulin secretion – B2 Renin increase via B1

Adverse effects and contraindications Transient restlessness, tremors, anxiety, tremors and pallor Transient hypertension Contraindicated in hypertensive, hyperthyroid and angina patients Contraindicated with halothane use – arrhythmia Contraindicated in patients on Beta blockers- dangerous hypertensive crises may develop because of unopposed alpha blockade

Clinical uses Cardiac stimulant Local vasoconstrictor

Noradrenaline Similar to adrenalin but because of its very low to absent effect on B2 , some differences Blood pressure – Increases both systolic and diastolic , Increased peripheral resistance and mean arterial BP Reduce heart rate – Causes higher blood pressure hence more likely to cause vagal stimulation. Blood vessels – reduced blood flow due to A1 effect on skeletal, skin and mucous membrane and renal vessels No effect on bronchial smooth muscle, GIT, Bladder – relaxation of muscle, contraction of trigone Metabolic effects – insulin secretion inhibited by A 2

Clinical uses of noradrenaline Rarely used