Dr. Asmah Nasser, M.D.. Tyrosine tyrosine hydroxylase DOPA DOPA DOPA decarboxylase dopamine DA DA...

Dr. Asmah Nasser, M.D.

Tyrosine tyrosine hydroxylase DOPADOPA DOPA decarboxylase dopamineDA DA -decarboxylase NENE is taken up and stored in granulesNE not stored in storage granules are called as mobile pool (MAO can metabolize these)NE releases via exocytosis as Ca++ enters.NE attaches to receptors in the post-synaptic neuron

NE can be transported back into the pre-synpatic neuron (reuptake)NE can activate the presynaptic receptors (-2 for negative feedback)NE can be metabolized by COMT enzyme

End product of EPI metabolism VMAEnd product of DOPA metabolism VHA

Know the rate limiting enzymeKnow routes of NE after releaseKnow about metabolism within pre-synapse

MAO inhibitors: increase the prejunctional levels of NEMobile pool: displace NE from mobile poolUptake: inhibit the uptake into nerve cell increases levels of NE)Activation of pre-synapse alpha receptorsPostsynaptic receptors

Sympathetic nervous system exerts its effects by acting on: , , and D receptors receptors are subdivided into 1 and 2 receptors are subdivided into 1 and 2 and 3D = Dopamine receptors

Important regulator of the activities of heart and peripheral vasculature, especially in responses to exercise and stress Drugs that mimic the actions of epinephrine are called sympathomimetic drugs or adrenergic drugsHas a wide range of effects and uses*

Two types of drugs, which involve:Displacement of stored catecholamines from the pre-synaptic nerve (amphetamine and tyramine)Inhibition of reuptake of catecholamines already released (cocaine)Some drugs have both direct and indirect actions. Both types of sympathomimetics, direct and indirect, ultimately cause activation of adrenoceptors, leading to the characteristic effects of catecholamines *

A1 Blood vesselsPupil (Iris)Smooth muscle (GI/GU) VasoconstrictionMydriasissphincter contraction Constipation and Urinary retentionA2 Presynaptic neurons Reduces release of norepinephrine (as a negative feedback mechanism) bradycardia,hypotensionB1 HeartContraction Increased heart rateB2 Smooth musclesRelaxation Bronchodilation, urinary retention, constipation, uterus relaxationDArteriesArteriodilation of Arteries (Renal, Mesenteric, Coronary)

Net activity of a drug depends on its affinity for the receptor.

Blood Vessels Vascular smooth muscle tone is regulated by adrenoceptors1 increase arterial resistance. 1 increases heart rate.2 causes smooth muscle relaxation with slight decrease in arterial resistance decrease BP*

A relatively pure 1 agonist such as phenylephrine increases peripheral arterial resistanceThis leads to a dose-dependent rise in blood pressure

A relatively pure agonist such as isoproterenol decreases peripheral resistance by activating 2 receptors (smooth muscle relaxation )*

Phenylephrine

Epinephrine

Isoproterenol

Vascular resistance (tone)

Cutaneous, mucous membranes ()

INCLUDEPICTURE \d "http://www.accessmedicine.com/images/special/uparrow.gif" \* MERGEFORMATINET


0

Skeletal muscle (2, )

or

INCLUDEPICTURE \d "http://www.accessmedicine.com/images/special/downarrow.gif" \* MERGEFORMATINET

Renal (, )

Splanchnic ()


or 2

Total peripheral resistance



or 2


Venous tone (, )

Cardiac

Contractility (1)

0 or





Heart rate (predominantly 1)

INCLUDEPICTURE \d "http://www.accessmedicine.com/images/special/downarrow.gif" \* MERGEFORMATINET (vagal reflex)

or



Stroke volume

0, ,

Cardiac output


Blood pressure

Mean


Diastolic


or 2


Systolic



0 or

Pulse pressure

0



Catecholamines do not cross the BBB effectivelySome drugs i.e. amphetamine/cocaine does cross the BBB and produces stimulant effectsStarts with reducing fatigue and progresses as anorexia, euphoria and insomniaVery high doses-aggressiveness, marked anxiety and convulsions*

Used and misused as a CNS stimulant Amphetamine easily enters the CNSIt has marked stimulant effects on mood and alertness and a depressant effect on appetite. Its peripheral actions are mediated primarily through the release of catecholaminesMethamphenidate (N-methylamphetamine) is very similar to amphetamine with a higher ratio of central to peripheral actions .??? Lipolysis from Beta3*

The radial pupillary dilator muscle of the iris contains 1 receptorsActivation causes mydriasis and stimulants also have important effects on intraocular pressure. agonists decreases the outflow of aqueous humor from the eye and antagonists (timolol) decrease the production of aqueous humor. *

Bronchial smooth muscle contains 2 receptors that cause bronchodilation The blood vessels of the upper respiratory tract mucosa contain 1 receptors. Decongestants are 1 agonists, causes vasoconstriction.*

The bladder base, urethral sphincter, and prostate contain 1 receptors that mediate contraction and therefore promote urinary rentention. are found in the Uterus causing smooth muscle relaxation.

A very potent vasoconstrictor and cardiac stimulant. The rise in systolic blood pressure that occurs after epinephrine is due to its positive inotropic and chronotropic actions on the heart (predominantly 1 receptors) and the vasoconstriction induced in many vascular beds (1 receptors). Epinephrine also activates 2 receptors in skeletal muscle blood vessels, leading to their dilation. Consequently, TPR may fall, Contributes to increased blood flow during exercise.Not absorbed if given orally. Must be given IV*

Uses: Anaphylactic Shock Increases local anesthestic action (by vasoconstriction)Cardiac arrestContraindications:HyperthyroidismHTNArrthymias

AnaphylaxisImmediate (type I) IgE-mediated reactionsCharacterized by bronchospasm, mucous membrane congestion, angioedema, and severe hypotension Treatment: Epinephrine and Steroids

Phenylephrine :MOA: Alpha 1 receptor agonistMetabolism: Degraded rapidly by MAOVery low Bioavailability Causes vasoconstriction of vessels. Nasal and ophthalmic preparations.Uses: Nasal DecongestantMydriasis (doesnt cause cycloplegia)Side effects/Contraindications: Closed angle Glaucoma. Rebound congestion.

*

Clonidine Alpha 2 receptor agonist negative feedback Decreased release of NEUsed in Hypertension, diabetic diarrhea, narcotic addicts and to treat benzodiazepam withdrawal effectsCrosse BBBSide effects: Orthostatic hypotension, dry mouth, sedation, rebound hypertension, Sexual Dysfunction*

-methyldopaDoesnt cross placentaUses: HTN, Gestational HTN, Chronic HTN during Pregnancy

Oxymetazoline and XylometazolineHigher affinity for 1 than 2 (partial 2 agonist)Also causes vasoconctriction.Used as a nasal decongestant

At low concentrations: Stimulates D receptors, causes Vasodilation of arteries (renal, coronary, GI)At intermediate doses: Stiumates Beta 1 receptors tachycardiaAt high doses: stimuates alpha 1 receptors VasoconstrictionUses: Cardiogenic shock (beta 1 stimulation), CHF, Hypotension (alpha 1 stimulation)Adverse effects: HTN, Tachycardia, arrythmias

Cocaine: is a local anesthetic with a peripheral sympathomimetic actionThe action results from inhibition of transmitter reuptake at pre-synapse.Readily enters the CNS and produces an amphetamine-like effect that is shorter lasting and more intense. The major action of cocaine in the central nervous system is to inhibit dopamine reuptake into neurons in the "pleasure centers" of the brain. Increased epinephrine leads to systemic symptoms of sympathetic effects.*

Drugs used in Depression Like Cocaine, TCA inhibits the reuptake of NE to the pre-synaptic neuron, as well as serotonin. If TCA Is given in adjunct with another adrenergic agonist Hypertensive Crisis

It is a normal by-product of tyrosine metabolism in the bodyAlso found in high concentrations in fermented foods such as cheese and fish.If administered parenterally, it has an indirect sympathomimetic action caused by the release of stored catecholamines. Just like amphetamines, it increases the number of catecholeamines at the synapse.*

In patients treated with MAO inhibitors (drug used in Depression and Parkinsons disease) causes an increase in NE levels.Effect of tyramine is greatly intensified, leading to marked increases in BP and HR hypertensive crsis, AKA Cheese syndrome Arrythemia or StrokePatients taking MAO inhibitors must be very careful to avoid tyramine-containing foods. *

Legitimate indications of amphetamine include:Causes released of stored NE from the pre-synapse into the synapse.Narcolepsy & ADHDObesity???Side effects: Insomnia, Decreased apetite, decreases respiratory center

Very potent -receptor agonist and has little effect on receptors. Leads to an increase and Heart rate (1) with a decrease in blood pressure (2)This lead to a marked increase in cardiac output associated with a fall in diastolic and mean arterial pressure

*

Dobutamine: Increases heart rate. Used in cardiogenic shock, acute heart failure.

Terbutaline used in pre-term labor. Causes smooth muscle relaxation in the uterus.Ritodrine Also used in preterm labor

Short acting (rescue drugs): Albuterol, TerbutalineLong acting (maintenance drugs): SalmetrolInhaled Beta agonists is used in Asthma. Causes smooth muscle relaxation at the bronchus (bronchodilaton)Adverse drug effects: Tachycardia, tremors, palpitations

Know about production and metabolism of NEKnow the different receptors of the SNS, the organs they are in, and their net effectsKnow about SNS effect of Eyes, BP, HR, Respiratory system, and GU tractKnow about Cocaine, Amphetamine, and Tyramine, TCAKnow about alpha 1 agonists, alpha 2 agonists, and Beta agonists. Mechanism, Indictions, Side effects

Of the many types of adrenergic receptors found throughout the body, which is most likely responsible for the cardiac stimulation that is observed following an intravenous injection of epinephrine?a. 1-adrenergic receptorsb. 2-adrenergic receptorsc. 1-adrenergic receptorsd. 2-adrenergic receptorse. 3-adrenergic receptors

Ritodrine hydrochloride is used in the treatment ofa. Parkinsons diseaseb. Bronchial asthmac. Depressiond. Hypertensione. Premature labor

Epinephrine may be mixed with certain anesthetics, such as procaine, in order toa. Stimulate local wound repairb. Promote hemostasisc. Enhance their interaction with neural membranes and their ability to depress nerve conductiond. Retard their systemic absorptione. Facilitate their distribution along nerves and fascial planes

The drug of choice for the treatment of anaphylactic shock isa. Epinephrineb. NEc. Isoproterenold. Diphenhydraminee. Atropine

A 60-year-old male with congestive heart failure (CHF) is treated with dobutamine. Select the mechanism of action of dobutamine.a. -adrenergic agonistb. -adrenergic antagonistc. -adrenergic agonistd. -adrenergic antagoniste. Mixed and agonistf. Mixed and antagonist

Of the following structures, which does not respond to -adrenergic receptor stimulation?a. Ciliary muscle of the irisb. Radial muscle of the irisc. Bronchial muscled. Atrioventricular (AV) nodee. Sinoatrial (SA) node

A 16-year-old male treated for bronchial asthma develops skeletal muscle tremors. Which of the following agents may be responsible for this finding?a. Ipratropiumb. Zileutonc. Beclomethasoned. Cromolyne. Salmeterol

Which of the following agents should a patient take for a stuffy, runny nose?a. Oxymetazolineb. Albuterolc. Clonidined. Terbutalinee. Metoprolol

A 10-year-old male displays hyperactivity and is unable to focus on his schoolwork because of an inability to focus on the activity. Which of the following might prove effective in this patient?a. Methylphenidateb. Terbutalinec. Dobutamined. Pancuroniume. Prazosinf. Scopalamine

**

Dr. Asmah Nasser, M.D.. Tyrosine tyrosine hydroxylase DOPA DOPA DOPA decarboxylase dopamine DA DA...

Documents

Transcript of Dr. Asmah Nasser, M.D.. Tyrosine tyrosine hydroxylase DOPA DOPA DOPA decarboxylase dopamine DA DA...