Sympathomimetics Flashcards by Carmina Mislang

 Constitute a group of drugs used for
Cardiovascular
Respiratory
Other conditions

adrenomimetics

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Type of adrenomimetics based on mode of action
 Bind to and activate the adrenoceptors
 Result to sympathetic stimulation

DIRECT-ACTING SYMPATHOMIMETICS

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INDIRECT-ACTING SYMPATHOMIMETICS

 Displacement of stored cathecolamines in the synapse

releasers

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example of releasers

tyramine, amphetamine

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INDIRECT-ACTING SYMPATHOMIMETICS

Inhibit the reuptake of cathecolamines by nerve terminals

Reuptake inhibitors

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example of Reuptake inhibitors

Cocaine, tricyclic antidepressants

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	Constitute a third class of adrenoceptors
	Drugs mentioned have little effect on dopamine receptors
	May act as a potent dopamine receptor agonist itself
	Intermediate doses activate beta receptors
	Large doses activate alpha receptors

DOPAMINE

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dopamine

Intermediate doses activate – receptors

beta

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dopamine

Large doses activate –receptors

dopamine

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 Drug preferentially binds to one subgroup of receptors at concentrations too low to interact with another receptor

RECEPTOR SELECTIVITY

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 Parent compound of sympathetic drug

phenylethylamine

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effect of Increasing the size of alkyl substituents

Enhanced activity for beta 2 receptors

Lowers alpha receptor activity

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 Methyl substitution on NE yields —-
Effect:
Enhanced activity for beta 2 receptors

epinephrine

Effect: Enhanced activity for beta 2 receptors

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 Isopropyl substitution on NE yields

isoproterenol

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 -OH groups at the C? and C? positions yield cathecolamines

c3 and c4

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effect of  Absence of one or both –OH group

Increases bioavailability after oral administration
 COMT resistant
 Increase distribution to the CNS
 Amphetamine and ephedrine

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effect of C. Substitution on the alpha carbon

 Add methyl group

MAO resistant

Amphetamine and ephedrine

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effect of D. Substitution on the beta carbon

 Add OH group

Facilitates activation of adrenoceptors
For storage of cathecolamines
Direct-acting sympathomimetics
Dopamine does not contain beta-OH group

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does dopamine contain a beta-OH group

Dopamine does not contain beta-OH group

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comparative competency for alpha receptors

E > NE> isoproterenol

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receptor responsible for
Increase in phosphatidyl inositol (IP3)
Release of calcium

alpha 1

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receptor responsible for decrease cAMP

D1 and alpha 2

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comparative competency BETA RECEPTOR ACTIVATION

Isoproterenol > epinephrine > NE

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receptors responsible for increase cAMP

B1, B2, B3

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Penetrates the CNS producing stimulant effects

Amphetamine

ORGAN SYSTEM EFFECTS B. EYE 

Pupillary dilator responds with mydriasis  Accommodation is not significantly affected  Alpha agonists reduce intraocular pressure by increasing outflow of aqueous humor

---- agonists reduce intraocular pressure by increasing outflow of aqueous humor

Alpha

ALPHA agonists reduce intraocular pressure by

increasing outflow of aqueous humor

EFFECT OF BETA ANTAGONISTS IN AQUEOUS HUMOR

 Beta antagonists decrease production of aqueous humor

ORGAN SYSTEM EFFECTS | BRONCHI

C. BRONCHI  Marked relaxation of the smooth muscles of the bronchi  Most efficacious and reliable for reversing bronchospasm

 Well endowed with both alpha and beta receptors  Located on the smooth muscles and neurons of the enteric nervous system 

GIT

WHAT ORGAN | Activation of either receptors leads to the relaxation of the smooth muscles

GIT

---- agonist causes uterine relaxation in pregnancy

Beta2

Responsible for Vasoconstriction

Alpha1 agonists

agonists that can reduce PVR and BP

beta2

causes vasodilatation in the splanchnic and renal vascular beds

Dopamine

 Well supplied with beta1 and beta2 receptors

G. HEART

 increases renin release | 

Beta1

increases insulin secretion (gluconeogenesis)

Beta2

Stimulate lipolysis

beta3

 Drug of choice for the immediate treatment of anaphylactic shock  Rapid acting  Pressor agent  Used for cardiac arrest

EPINEPHRINE

 Narcolepsy  Attention deficit disorder  With appropriate control, weight reduction

PHENYLISOPROPYLAMINES (AMPHETAMINES)

 Used topically to produce mydriasis  Used to reduce conjunctival itching and congestion caused by irritation and allergy

PHENYLEPHRINE

 Drugs of choice in the treatment of acute asthmatic attacks (3)

TERBUTALINE, ALBUTEROL, METAPROTERENOL

 Long-acting |  Recommended for prophylaxis of asthma

SALMETEROL

? agonists maybe useful in situations like Acute cardiac failure, Some types of shock

Beta1

? agonists are useful in situations in which vasoconstriction is needed

Alpha1

 Used to suppress premature labor |  Cardiac stimulant effect may be hazardous to both mother and fetus

RITODRINE, TERBUTALINE

 Long-acting oral sympathomimetic usedto improve urinary incontinence in children and the elderly with enuresis  Mediated by the alpha receptors in the trigone of the bladder

EPHEDRINE

 Pressor agent  Cardiac arrest  Anaphylactic shock

EPINEPHRINE

 Potent vasodilator

ISOPROTERENOL

 Congestive heart failure |  Inotropic effect

DOBUTAMINE

 Inotropic effect  Lower doses cause renal vasodilation  Higher doses cause vasoconstriction

DOPAMINE

catecholamines

dopamine, dobutamine, isoproterenol, epinephrine, norepinephrine

 Pressor agent  Mydriatic  Decongestant

PHENYLEPHRINE

 Pressor agent, limited clinical application |  IV form only

METHOXAMINE

 Pressor agent |  Orthostatic hypotension

MIDODRINE

 DRIXINE (brand name) |  Topical decongestants

OXYMETAZOLINE, XYLOMETAZOLINE

 Bronchial asthma

TERBUTALINE

 Inhibits premature labor

RITODRINE

 Local vasoconstrictive |  Anesthetic effect

COCAINE

 Byproduct of tyrosine  Increase BP  Found in fermented food Cheese and wine

TYRAMINE

Not advised for patients taking MAO inhibitors

TYRAMINE

Toxicity of sympathomimetic drugs speciifically endogenous catecholamines

 Limited penetration to the brain  Little CNS toxicity when given systemically  In the periphery

Toxicity in the peripheral vasculature

Excessive vasoconstriction Cardiac arrhythmias Myocardial infarction Pulmonary edema or hemorrhage

? agonists cause hypertension

Alpha

? agonists cause sinus tachycardia | and serious arrhythmia

Beta1

? agonists cause skeletal muscle tremor

Beta 2

? agonists cause skeletal muscle tremor

Beta 2

α1 Most vascular smooth muscle

Contracts (↑ vascular resistance)

Pupillary dilator muscle | α1

Contracts (mydriasis)

Pilomotor smooth muscle | α1

Contracts (erects hair)

Liver (in some species, eg, rat) | α1

Stimulates glycogenolysis

Adrenergic and cholinergic nerve terminals

Inhibits transmitter release

Platelets α2

Stimulates aggregation

Some vascular smooth muscle α2

Contracts

Fat cells α2

Inhibits lipolysis

α2 | Pancreatic β (B) cells

Inhibits insulin release

β1 Heart

Stimulates rate and force

β1Juxtaglomerular cells of kidney

Stimulates renin release

Beta 2 Airways, uterine, and vascular smooth muscle

Relaxes

Liver (human) Beta 2

Stimulates glycogenolysis

Pancreatic β (B) cells Beta 2

Stimulates insulin release

Somatic motor neuron terminals (voluntary muscle) Beta 2

Causes tremor

Heart Beta 2

Stimulates rate and force

β3 Fat cells

Stimulates lipolysis

Dopamine1 (D1) Renal and other splanchnic blood vessels

Dilates (↓ resistance)

Dopamine2 (D2) Nerve terminals

Inhibits adenylyl cyclase

mechanism of action of E

α1, α2, β1, β2, β3 agonist

mechanism of action of NE

α1, α2, β1, agonist

mechanism of action of Dopamine

D1, α1, α2, β1, β2, β3 agonist

mechanism of action of Isoproterenol:

β1, β2, β3 agonist;

mechanism of action of Dobutamine:

β1 agonist

mechanism of action of PHENYLEPHRINE

α1, α2 agonist

mechanism of action of Albuterol, metaproterenol, terbutaline

β2 agonist

Displaces stored catecholamines from nerve endings

Amphetamine, | methamphetamine

Very high addiction liability. Hypertension, arrhythmias, seizures

COCAINE

Displaces stored catecholamines | No clinical use but found in fermented foods

TYRAMINE

An α-agonist drug that reduces conjunctival, nasal, or oropharyngeal mucosal vasodilation by constricting blood vessels in the submucosal tissue

decongestant

``` A derivative (eg, norepinephrine, epinephrine), a relatively polar molecule that is readily metabolized by catechol-O-methyltransferase ```

Catecholamine

catecholamine is derived from

dihydroxyphenylethylamine

A derivative of phenylisopropylamine (eg, amphetamine, ephedrine). Unlike catecholamines, they usually have oral activity, a long half-life, CNS activity, and cause release of stored catecholamines

Phenylisopropylamine

A drug that mimics stimulation of the sympathetic autonomic nervous system

Sympathomimetic

An indirect-acting drug that increases the activity of transmitters in the synapse by inhibiting their reuptake into the presynaptic nerve ending. May act selectively on noradrenergic, serotonergic, or both types of nerve endings

Reuptake inhibitor

 Present in the mitochondria in the adrenergic nerve endings  Inactivates portion of dopamine and norepinephrine in the cytoplasm

MONOAMINE OXIDASE (MAO)

 May increase the stores of these transmitters and other amines in the nerve endings

MONOAMINE OXIDASE INHIBITORS

 Single prototype with effects at all receptors  Alpha1 and alpha2  Beta1,beta2 and beta3

EPINEPHRINE

```  Not a cathecolamine  Resistant to MAO  Resistant to COMT  Orally active  Enter the CNS  Longer effects ```

AMPHETAMINES

Signaling mechanism of adrenoceptors

 G-protein coupled  Need a 2nd messenger to induce sympathetic effect

ALPHA SELECTIVE | alpha1 > alpha2

 PHENYLEPHRINE

ALPHA SELECTIVE | alpha2 > alpha1

CLONIDINE

MIXED (activates both alpha and beta) alpha1 = alpha2 beta1> beta2

 NE

MIXED (activates both alpha and beta) alpha1 = alpha2 beta1 = beta2

EPINEPHRINE

beta1 > beta2

DOBUTAMINE

beta2 > beta1

TERBUTALINE

beta1 = beta2

ISOPROTERENOL