1. SYMPATHOMIMETIC AGENTS
Department of Pharmacology

2. Sympathomimetic amines – Classification based on use
1. Pressor agents Cardiac stimulants
Dopamine Adrenaline
Phenylephrine Dobutamine
Methoxamine Isoprenaline
Noradrenaline
3. Bronchodilators 4. Nasal decongestants
Adrenaline Ephedrine
Salbutamol (Albuterol) Pseudoephedrine
Terbutaline Oxymetazoline

3. Classification… 5. Anorectics 6. CNS stimulants Fenfluramine Ephedrine
Amphetamine
7. Uterine relaxants & vasodilators
Salbutamol
Isoxsuprine
Nylidrin

4. Must Read
Other methods of Classification of sympathomimmetics with their examples

5. Review Major effects mediated by  &  -adrenoceptors1 2 1 2
Vasoconstriction
Inhibition of NE release
+ve chronotropic
Vasodilation
 PR
Inhibition of insulin release
+ve inotropic
Slight  in PR
 BP
Increased lipolysis
Bronchodilation
Mydriasis
Uterine relaxation
Contraction of prostatic capsule
 Muscle & liver glycogenolysis

6. Epinephrine (Adrenaline)
Source: adrenal medulla & synthetic
Agonist at  & ß-receptors
CVS:
Heart – ß1 stimulation –
+ve chronotropic
+ve inotropic
 COP   BP
 Oxygen consumption
 Automaticity

7. BP: Biphasic response – a rise followed by a slight fall before returning to basal level.
receptors are predominant in number.
ß receptors are more sensitive & action is persistent.
Initial rise in BP – predominant  action Fall - due to persistent ß2 receptor action.
Dale’s vasomotor reversal
Following  blocker (phenoxybenzamine) – only ß2 stimulation  BP – Dale’s reversal

8. Dale’s vasomotor reversalα β
Epinephrine
α blocker
Epinephrine

9. Lungs – ß2 Receptors
Bronchodilatation
 release of inflammatory mediators
used in Bronchial asthma, Anaphylactic shock
Skeletal muscle - ß2 – Blood vessels dilated
Uterus – ß2 receptor stimulation – relaxation
Hence, used in Premature labor
Metabolic – Hyperglycemia - α & ß
Lipolysis – ß3 receptors

10. Eye – Mydriasis – on systemic administration
Secretions:  renin secretion (ß1)
ADME: Oral - Bioavailability is poor due to metabolism by MAO & COMT in the intestine & liver.
Routes: SC, IM, topical
Intracardiac – in emergencies like cardiac arrest due to drowning, anaesthesia, electrocution.
IV - very, very rarely used as IV adrenaline may cause death due to ventricular arrhythmias.

11. Always check concentrations of adrenaline before injecting as low concentrations (1 in 100,000) are used for epistaxis & high concentrations for bronchial asthma (1 in 1000)
ADR: Tachycardia, palpitation, anxiety, tremor
BP- cerebral hemorrhage, ventricular arrhythmia after iv injection
Norepinephrine: , ß1 agonist
sympathetic neurotransmitter

12. Isoproterenol: Nonselective ß agonist
Direct & reflex myocardial stimulation
No more used in bronchial asthma. Why????
Phenylephrine, Oxymetazoline: 1 agonists
Less potent & longer acting than NE
Uses:
Shock (hypotension) - Vasopressors
Nasal decongestion
Mydriatic (dilates pupil) topically

13. Clonidine: 2 agonist -  sym. activity
Uses: Hypertension, addiction, Menopausal flushes
Dobutamine:
1 >>> 2
+ve inotropic,  COP
No change in PR, hence, no reflex tachycardia
No  in O2 consumption
Uses: as inotropic in pump failure due to myocardial infarction, cardiac surgery etc.

14. Dopamine Catecholamine - Receptor action: DA >>  >> 
Neurotransmitter in basal ganglia
Metabolized by MAO & COMT
In low doses – increases urine output by increasing renal blood flow (RBF) to kidney by DA - R stimulation which causes dilatation of renal artery.
RBF  GFR   urine output & Na+ excretion
 splanchnic blood flow also.
Given in higher doses – myocardial stimulation
ß1 agonist -  in HR & FOC   COP  BP  O2 consumption of heart

15. In still higher doses – dopamine produces Vasoconstriction by acting as 1 agonist & this results in  in blood flow to various organs.
Uses Cardiogenic shock & septic shock – DOC
CCF with oliguria, renal failure
ADR: Angina, cardiac arrhythmias

16. Selective ß2 agonists
Orciprenaline, salbutamol, terbutaline, ritodrine
Bronchodilatation &  release of mediators of inflammation
Vasodilatation
Uterine relaxation
Cardiac stimulation – negligible at therapeutic doses.
At high doses may produce cardiac stimulation.
Resistant to metabolism by MAO & COMT – hence, duration of action is longer

17. Premature labour-iv infusion – Ritodrine Side effects
Uses of ß2 agonists
Bronchial asthma - aerosol, nebulizer, rotahaler – 10% of the inhaled drug only enters lung.
Oral Tablets
Premature labour-iv infusion – Ritodrine
Side effects
Fine finger tremors
Palpitations

18. Its use by athletes is banned.
Clenbuterol: ß2 agonist. used to ↑ the rate & force of contraction of skeletal muscle by athletes.
Its use by athletes is banned.
Tyramine
Source - Cheese, beer (fermented food).
Metabolised by MAO
Indirect acting - releases NE at synapses.
Tachyphylaxis seen.
Clenbuterol: ß2 agonist. used to ↑ the rate & force of contraction of skeletal muscle by athletes. It acts by causing long term changes in the expression of the sarcoplasmic reticular proteins that control contraction kinetics and thereby increase the rate and force of contraction of skeletal muscle.

19. Sympathomimetic agents – indirect acting
Tyramine, Amphetamine, Ephedrine

20. Ephedrine
Alkaloid from Ephedra vulgaris
Has direct & indirect actions - Tachyphylaxis
Resistant to MAO - Longer acting (4-6 hrs) & Orally effective
Stimulates CNS & CVS
Uses- Nasal decongestant
Pseudoephedrine
Ephedrine isomer
Less CNS & cardiac effects
Use - Nasal decongestant

21. Amphetamine
Synthetic, direct & indirect action
d- amphetamine – more CNS effects & less CVS actions
methamphetamine – more CVS actions
Orally active & long acting
CNS actions - alertness, sed conc., euphoria, talkativeness,  sed work capacity, sed fatigue
High doses - mental confusion, delirium, hallucinations & acute psychosis

22. Appetite suppressant – inhibits feeding centre
Improve physical performance in athletes temporarily - followed by deterioration
Drug of abuse & misused by athletes in sports
Chronic use leads to psychosis & long lasting behavioral abnormalities
ADR: CVS – arrhythmias, ↑ in BP
Uses: Narcolepsy
Obesity - temporary
Attention deficit hyperactivity disorder in children.

23. Clinical uses of sympathomimetic agents
Adrenaline:
Cardiac arrest – IV, intracardiac
Anaphylactic shock – IV
Bronchial asthma – safer drugs are available
To prolong duration of action of local anaesthetics – 1 in lakh concentration
Topically - Glaucoma
Epistaxis
Salbutamol, Terbutaline:
Asthma
Inhibition of premature labor
Adrenaline is used as a topical hemostatic agent on bleeding surfaces such as in the mouth

24. Clinical uses of sympathomimetic agents
Oxymetazoline, Ephedrine, Pseudephedrine :
Nasal decongestants
Phenylephrine: decongestant
Clonidine:
Hypertension
Glaucoma
Postmenopausal flushes
Prophylaxis of migraine

25. Clinical uses of sympathomimetic agents
Dopamine:
Cardiogenic shock & septicaemic shock – DOC
CCF with oliguria, renal failure
Dobutamine:
Cardiogenic shock
Amphetamine:
Narcolepsy
Obesity
Attention deficit hyperkinetic disease
Cardiogenic shock, usually due to massive myocardial infarction, has a poor prognosis. Mechanically assisted perfusion and emergency cardiac surgery have been utilized in some settings. Optimal fluid replacement requires monitoring of pulmonary capillary wedge pressure and other parameters of cardiac function. Positive inotropic agents such as dopamine or dobutamine may have a role in this situation. In low to moderate doses, these drugs may increase cardiac output and, compared with norepinephrine, cause relatively little peripheral vasoconstriction.

26. Objectives for self study – Sympathomimetics 2
Pharmacology of:
Epinephrine - Dale’s vasomotor reversal
Norepineprhine
Isoprenaline
Phenylephrine, Oxymetazoline
Clonidine
Dobutamine
Dopamine
Salbutamol, Terbutaline, Salmeterol
Ephedrine, Pseudoephedrine, Amphetamine, phenylephrine
Uses of sympathomimetic amines