Sympathetic system

Releases NE from stores at nerve endings & releases E from adrenal medulla

Sympathomemtic amines as E, NE, Dopamine & Isoproternol are called Catecholamines,

 these amines share the following properties: Rapid inactivation by MAO & COMT enzymes Poor penetration to CNS. Orally inactive. Brief duration of action.

 Types of adrenergic receptors

receptors are stimulated by E & NE Alpha 1 receptors The image below shows the synaptic cleft, presynaptic and postsynaptic membranes. Alpha 1 receptors are located on the postsynaptic membrane of effector organs.

 Activation of alpha 1 receptors increases vascular smooth muscle contraction, producing increases in blood presure. Dilatation of the pupil closure of internal sphincter of the bladder.

 Alpha 2 receptors Although alpha 2 receptors are found on presynaptic neurons, they work mainly as autoreceptors to mediate feedback inhibition of sympathetic transmission.

1 & 2 receptors are both stimulated by Isoprenaline & E

NE acts as a 1 stimulator. 1 responses: rate & excitability of the heart with C.O. 2 responses: vasodilation, bronchodilation, in blood glucose level, Relaxed uterine smooth muscle

 Beta 1 receptors Beta 1 receptors are located mainly at the heart and the kidney.

Stimulation of beta1-adrenergic receptors on the myocardium, AV node, and SA node results in CARDIAC STIMULATION:

Increased force of contraction (positive inotropic effect) Increased heart rate (positive chronotropic effect)

 Beta 2 receptors

 Bronchial smooth muscle

Beta 2 receptor activation promotes bronchodilation, this physiological property is enhanced by inhaled Beta 2 agonists used in the treatment of asthma. Some drugs under this category include: salbutamol

 Uterine contraction

Drugs that bind to Beta 2 receptors (Beta 2 agonists) are used in the treatment of premature labour, this clinical application illustrates how Beta 2 receptors mediate tocolysis on the uterine muscle. Ritodrine is an example of a tocolytic drug.

Classification of Sympathomimetics/Adrenomimetics
1. Direct-Acting sympathomimetics directly stimulate the adrenergic receptor (e.g. epinephrine, norepinephrine) 2. Indirect-Acting sympathomimetics which stimulates the release of norepinephrine from the terminal nerve endings (e.g. amphetamine) 3. Mixed-Acting sympathomimetics (both direct and indirect acting)

 Sympathomemtic Drugs Epinephrine (E) Can be prepared synthetically Orally inactive, give by S.C. or I.M.
Actions HR & force of contraction palpitation systolic BP & little change of diastolic BP Bronchodilation glucose level

 Therapeutic uses Anaphylactic shock Stimulates the heart in cardiac arrest Can be used to prolong local anesthetic action

 Norepinephrine (NE)
Actions

both systolic & diastolic blood pressure

Uses: Treatment of shock ( BP) given by I.V. infusion, but because of its effect (vasoconstriction) it blood flow in essential organs tissue damage

 Isoprenaline: Actions Bronchodilation Stimulates the heart & may produce fatal arrhythmia Uses Slow I.V. infusion in sever bradycardia

Dopamine Stimulate 1 & Dopaminergic receptor. Actions: Heart rate & force of contraction it dilates renal arterioles blood flow to the kidneys
Uses: Treatment of shock Treatment of congestive heart failure

 Selective Adrenergic Agonists: Selective 1 agonists: E.g. Phenylephrine, used locally as nasal decongestant. Selective 2 agonists: E.g. Clonidine, used for treatment of hypertension

 Selective 1 agonists: E.g. Dobutamine, used to C.O. in heart failure Selective 2 agonists: E.g. Salbutamol, used in asthma

 Indirect Acting Sympathomimetic Drugs

E.g. Amphetamine, its main effect on the CNS MOA: NE release from presynaptic terminals It may produce euphoria, mental activity, appetite risk of dependence

MOA of amphetamine

 Uses Narcolepsy Hyperactivity in children

Should not be used for appetite control

Adrenergic Blockers

Adrenergic Blockers adrenoceptor antagonists non selective antagonists

E.g. Phentolamine, cause BP S/Es: Postural hypotension

 Selective 1 antagonists
E.g. Prazocin, Terazocin Action: Cause vasodilation, BP Uses Treatment of Hypertension Benign Prostatic Hyperplasia

S/Es
commonly observed with blockers: reflex tachycardia, vertigo, postural hypotension)

adrenoceptor antagonists

nonselective beta blockers 1. Propranolol Blocks 1, 2

Therapeuticuses: Hypertension. Glaucoma. Migraine.

Angina pectoris & cardiac arrhythmias. Anxiety. Hyperthyroidism (Thyrotoxicosis) Essential Tremor.

2.Timolol Blocks 1, 2
Uses: Topically for glaucoma

 Selective beta blockers

Atenolol Blocks 1 Beta blockers selective for these receptors are called cardioselective beta blockers Uses
For hypertensive patients with impaired pulmonary function (but the patient should be carefully monitored)

 Labetolol: Antagonist of both 1 & adrenoceptors

S/Es:

1. 2. 3. 4. 5. 6.

Bronchoconstriction Hypotension blood flow to the extremities Nightmares Masking symptoms of hypoglycemia Sexual dysfunction in males

Dental implications
Xerostomia (dry mouth) Dryness of the mouth, or xerostomia, results from diminished secretions of saliva. More than two 250 medications claim xerostomia as a side effect. Drugs that produce xerostomia as a side effect include anticholinergics,antidepressants, antihistamines/decongestants, antipsychotics, diuretics, hypnotics, systemic bronchodilators, muscle relaxants,beta-blockers,

 Medications that produce xerostomia, also may increase the incidence of root surface caries (cavities). Medications with significant anticholinergic activity, have the potential to cause xerostomia. Clinical presentation of xerostomia includes oral fissuring, ulceration, and epithelial atrophy.