Non catecholamines

NON CATECHOLAMIN

ES-

Dr.D.RAJESH;M.D.

DEPARTMENT Of PHARMACOLOG

YRIMS ONGOLE

Definition

Classification

Drugs

• Compounds lacking catechol hydroxyl groups are called non catecholamines

• CharacteristicsLonger half lives – long duration of actionIncreased lipid solubility – access to CNSEffective orally

CLASSIFICATION

I. Acc. To MOA:1. Direct acting – Phenylephrine, Methoxamine,

Oxymetazoline, Clonidine, Metaproterenol, Salbutamol, Terbutaline, Salmeterol

2. Indirect acting – Amphetamines, Tyramine

3. Mixed action – Ephedrine, Pseudoephedrine, metaraminol

II. Acc. To therapeutic uses:

1. Vasopressor agents: phenylephrine, methoxamine, ephedrine, mephenteramine

2. Bronchodilators – salbutamol, terbutaline, salmeterol, formeterol, bambuterol

3. Nasal decongestants – phenyephrine, naphazoline, oxymetazoline, xylometazoline, pseudoephedrine, phenylpropanolamine

4. CNS stimulants – amphetamine, methamphetamine, dexamphetamine

5. Anorectics – fenfluramine, dexfenflramine, sibutramine

6. Uterine relaxants – ritodrine, isoxsuprine, salbutamol, terbutaline

III.Receptor action:1. α1 agonists – phenylephrine,

methoxamine, metaraminol, mephenteramine

2. α2 agonists – clonidine, apraclonidine

3. β2 agonists – salbutamol, terbutaline, isoetharine, ritodrine

4. β3 agonists – BRL 37344, AD 9677

PHENYLEPHRINE• Selective α1 agonist

• Vasoconstrictor - SBP, DBP

• Reflex bradycardia

• Uses:– Hypotension, shock– Nasal decongestant– Mydriatic

METHOXAMINE• Selective α1 agonist

• Inc. total peripheral resistance

• Not arrythmogenic

• Uses:– Hypotension– PSVT– Nasal decongestant

METARAMINOL• Selective α1 agonist• More direct action, also release NA• Inc. force of contraction, CO, raise BP• Gradual onset, longer duration• Uses:– Ac. hypotensive states – SA/ Shock–Nasal decongestant– PAT

MEPHENTERAMINE

• Acts both directly and indirectly

• BP, cardiac rate and contraction

MIDODRINE

• Prodrug converted to desglymidodrine

• Vasoconstriction

• Use: postural hypotension

OXYMETAZOLINE• Stimulates both α receptors

• Acts on BV of nasal mucosa & conjunctiva

• Use – Eye drops– Nasal decongestant

• SE – nervousness, HA, burning of nasal mucosa, sneezing

Naphazoline, Xylometazoline

• Local vasoconstriction

• Longer duration of action

• SE: atrophic rhinitis, anosmia–Systemic – CNS depression, rise

BP

AMPHETAMINES• It is phenyl isopropylamine• Indirectly acting sympathomimetic• CNS actions: CNS stimulant– Inc. mental & physical activity, euphoria– Clinical dose – wakefulness, dec. fatigue– Larger doses – tremor, restlessness,

confusion

• CVS: Inc. SBP, DBP

• Smooth muscle: contracts bladder sphincter, relax bronchial muscle

• Appetite: suppress appetite – wt. loss

• Weak analgesic, anticonvulsant, anti emetic

• ADR :palpitations, restlessness, HA, anxiety, psychosis

• Ac. Toxicity:– CNS – restlessness, tremors, irritability– Behavior – delirium, confusion, psychosis,

suicidal/ homicidal tendencies– ANS instability – angina, arrythmias, HTN– GI – anorexia, vomiting, abd. Cramps–Mx – symptomatic,• Diazepam• α blocker phentolamine• Peritoneal dialysis

• Dependence: psychological – euphoria, mental confusion, wt loss

• Withdrawal symptoms– Chr. Fatigue, depression– GI disturbances– Drowsiness– Intense craving

• Uses:– ADHD–Narcolepsy

• Only CNS effects

• Piperidine derivative• Used in ADHD

METHAMPHETAMINE

METHYLPHENIDATE

TYRAMINE• Indirect action

• Normal byproduct of tyrosine metabolism

• Metabolized by MAO

• CHEESE REACTION – inc. BP

• Not used clinically

EPHEDRINE• Alkaloid obtained from Ephedra vulgaris• Acts on both α, β receptors

• CVS: BP, CO. – Repeated adm.- tacyphylaxis

• Smooth muscle: relax

• CNS – stimulation – tremors, insomnia, anxiety

• Eye: mydriasis• Metabolic: inc metabolic rate, O2 consump.• SE: GI upset, insomnia, rarely psychosis• Uses:– Br.asthma–Nasal decongestion–Hypotension– Stokes Adams syndrome–Mydriatic–Narcolepsy–Misc. – myasthenia gravis, allergic

bronchospasm

PSEUDOEPHEDRINE• Stereo isomer of ephedrine• Vasoconstriction sp. Mucosa & skin• Use:–Nasal & sinus congestion– Allergic rhinitis– Blocked eustachian tubes–URTI

β2 STIMULANTS• Longer duration of action• Bronchodil, Vasodil, Uterine relax• Uses:– Br. Asthma–Uterine relaxants

• SE: muscle tremor, tachycardia– Less likely arrythmias

ISOXSUPRINE• Smooth muscle relaxant• Use: – Threatened abortion– Dysmenorrhea– Premature labor– Peripheral disease

• SE: nausea, tachycardia, hypotension

ANORECTIC AGENTS• Cause central release of NA/DA

• Inhibit reuptake of NA & DA

β3 agonists

• Polymorphism in β3 receptor gene is related to risk of obesity

• Targets for anti obesity drugs

• BRL 37344 – No FDA clearance• AD 9677 – Phase III CT