1. SYMPATHOMIMETIC DRUGS

2. ALPHA ADRENERGIC AGONISTS
1-Selective Agonists
Major effects due to stimulation of 1 receptors
in vascular smooth muscle
Increase in peripheral vascular resistance & BP
Clinical utility limited – some use in hypotension and shock states

3. 1 – Selective Agonists Phenylephrine
Direct simulation of 1 receptors
Methoxamine
Methoxamine: Relatively selective 1-agonist; No action at  receptors.
CV effects :  BP, Reflex bradycardia
May be used IV in hypotensive states
Phenylephrine: 1 selective,  actions at much higher doses
Effects similar to methoxamine
Uses: nasal decongestant,
mydriatic – local instillation

4. 1 – Selective Agonists Xylometazoline Oxymetazoline Naphazoline:
Direct 1 – agonists,
Used as nasal decongestants
Rebound hyperaemia occurs

5. Used primarily for treatment of systemic hypertension.
Selective actions on 2-adrenoceptors
Decrease release of NE from presynaptic terminals
Act at brainstem level to  central sympathetic tone
2 – Selective Agonists

6. 2 – Selective Agonists Clonidine:–
Selective action on 2 (partial agonist with high affinity)
Developed as a nasal decongestant
Produces hypotension, sedation, bradycardia and mild
analgesia
Major effects on BP
IV :  in BP (peripheral  receptors on blood vessels)
– short lasting
Followed by prolonged hypotensive effect
Mainly central (lower brainstem) +  NE release from
terminals.
Oral: The early hypertensive phase is not seen
Additional effects: Bradycardia ( Vagal tone)
Sedation
Mild analgesia

7. Clonidine….
Well absorbed orally – 100 % bioavailability
Peak effect 1-3 hours
50 % excreted unchanged
ADVERSE EFFECTS :
Dry mouth, sedation, sexual dysfunction
Marked bradycardia in some
Rebound hypertension following sudden stoppage
USES: Hypertension
Tt. of symptoms of narcotic withdrawal
Menopausal hot flashes (lower doses)
Guanfacine and Guanabenz : similar to clonidine

8. 2 – Selective Agonists
α-Methyldopa :
Converted to α-MNA which acts like clonidine
Prodrug
Tizanidine: Has same effects like clonidine
Used mainly for relieving muscle spasticity of
cerebral or spinal origin
Apraclonidine: Used locally to  IO pressure
? aqueous formation

9. BETA ADRENERGIC AGONISTS
Isoproterenol ( Isoprenaline)
Synthetic catecholamine
Extremely potent  receptor agonist – NON SELECTIVE
Little effect on  receptors
+ve inotropic and chronotropic actions – palpitations, HR, arrhythmias
Potent vasodilator – marked  in CO,  in diastolic and mean BP
Relaxes all smooth muscles (esp. bronchial and GIT)
USES: Bradycardia and heart block – has been replaced by other drugs

10. (also has  receptor actions)
DOBUTAMINE :
1- selective agonist
(also has  receptor actions)
Resembles Dopamine But no action on DA receptors
Major actions are  receptor mediated
EFFECTS:
+ve inotropic and chronotropic effects > isoprenaline
 in SA node automaticity
< than Isoprenaline
Total peripheral resistance not affected much

11. DOBUTAMINE : ADVERSE EFFECTS:
Excessive  in HR and BP (specially in hypertensives)
Ventricular ectopics may occur
 in infarct size in MI – ( in oxygen demand)
Tolerance to effects may develop in some cases
USES:
Short term Tt. of cardiac decompensation
eg. Cardiac surgery, MI
Plasma t ½ of 2 minutes hence given by infusion

12. 2- selective agonists Selectivity is relative – lost at higher doses
Developed mainly for use as Bronchodilators with low CV effects
Also used for Uterine Relaxant effect

13. 2- selective agonists
Terbutaline, Albuterol (salbutamol), Metaproterenol , Salmeterol
Not metabolized by COMT -- Better oral bioavailability
Pharmacological effects:
Bronchodilatation - 2 receptors on bronchial smooth muscle
May also :- Suppress release of leukotrienes and
histamine
Enhance mucociliary function
 microvascular permeability
 phospholipase A2 activity
Uterine relaxant action -- 2 receptors on uterine muscle

14. 2- selective agonists Adverse effects:
Mainly due to excessive dosage loss of selectivity
 CVS effects
Adverse effects are limited when used by inhalational route in Asthma
Terbutaline and Albuterol :
Effective orally, sc, inhalation
Rapid onset, duration 3 – 6 hrs
Use: Long term Tt of COPD ; Ac bronchospasm; Tocolytic
Metaproterenol : less 2 selective

15. 2- selective agonists
Salmeterol : 2 selective and long acting (12 hours)
Onset of action slow
Not suitable alone for Acute attack
Ritodrine: Developed specially as a uterine relaxant
Properties similar to other agents
Rapidly absorbed after oral intake
Administered IV to arrest premature labour

16. Receptor Affinity
Alpha agonists
Phenylephrine, methoxamine
Clonidine, MNA
α1> α2 >>>>> β
α2> α1 >>>>> β
Mixed α and β agonists
Noradrenaline
Adrenaline
α1= α2 ; β1>> β2
α2= α1 ; β1= β2
Beta agonists
Dobutamine
Isoproterenol
Terbutaline, Albuterol, Ritrodine
β1> β2 >>>> α
β1= β2 >>>> α
β2 > β1 >>>> α
Dopamine agonists
Dopamine
D1 = D2 >> β >> α

17. INDIRECTLY ACTING SYMPATHOMIMETICS
By releasing catecholamines from neurones
Amphetamine: Powerful CNS stimulant actions
Orally effective
Abused for psychic effects
wakefulness, mood elevation, alertness,
 self-confidence, concentration,  fatigue
Performance enhanced but chances of errors ↑
Tolerance occurs
Long term use followed by fatigue and exhaustion
Toxicity: Acute – extension of sympathomimetic effects
Chronic – Wt. Loss, psychotic reactions, dependence
Uses: Narcolepsy
Attention-deficit hyperactivity disorder
Obesity - apetite suppression ?

18. INDIRECTLY ACTING SYMPATHOMIMETICS
Tyramine :
Not used clinically
Importance – Present in several foods
(cheese, beer, red wine)
Interaction with MAO inhibitors : severe toxic effects
– severe hypertensive crisis “Cheese Reaction”
Methylphenidate :
Structurally related to amphetamine
Mild CNS stimulant –
actions on mental > motor functions
Used for Attention-deficit hyperactivity disorder
Modafinil : Newer agent,
Similar to amphetamine , lower side effects

19. INDIRECTLY ACTING SYMPATHOMIMETICS
Ephedrine : (& pseudoephedrine)
Mixed actions ( release + direct effects )
Stimulates  and  receptors
Effective orally:  BP, HR, Bronchodilatation, CNS ↑
Duration : several hours – t1/2 3-6 hrs ;
Tachyphylaxis occurs
USES: Bronchodilator, decongestant
ADVERSE EFFECTS :  BP, Insomnia,
Urinary retention in elderly

20. INDIRECTLY ACTING SYMPATHOMIMETICS
Mephentermine Direct
&
Metaraminol Indirect (release of NE)
Effects due to 1 stimulation + Indirect ( + )
HR, force of contraction, CO, systolic and diastolic BP.
Uses : To prevent excessive hypotension during spinal anaesthesia,
Other hypotensive states
To relieve attacks of PAT
Adverse effects: CNS stimulation,
Excessive  BP,
Arrhythmias

21. THERAPEUTIC USES OF SYMPATHOMIMETIC AGENTS
Shock
Hypotensive states
Hypertension (2 –agonists)
Local vascular effects
Nasal decongestant (α1 agonists)
Ophthalmic uses {Mydriasis (α1); Glaucoma (α2)
Asthma and COPD (β2 agonists)
Allergic reactions
Narcolepsy
Weight reduction
Attention-deficit hyperactivity disorder in children
Tocolytic (2 – agonists)

22. INDIRECTLY ACTING SYMPATHOMIMETICS
B. By blocking reuptake of released transmitter
Cocaine :
Peripheral sympathomimetic actions,
Amphetamine like CNS actions - drug of abuse.

23. Alpha methyl DOPA
Alpha methyl DA
Alpha methyl NA ( selective action on α2 )