Sympathomimetics

Treatment of ashthma and acute bronchospasm

Albuterol, metaporterenol, terbutaline

Epinephrine works on what receptors?

All Alpha and Beta receptors.

Beta signaling

All beta receptors stimulate adenylyl cyclase via the coupling protein Gs, which leads to an increase in cAMP.

Conditions in which a decrease in blood flow is desired

Alpha 1 agonists may be useful Epinephrine, norepinephrine, phenylephrine

Alpha 2 agonist effect on vascular system

Alpha 2 agnosits like clonidine cause vasoconstriction when adminestered intravenously or topically, but when given orally they accumulate in the CNS and cause blood pressure drop.

Phenylephrine

Alpha agonist

Treatment for narcolepsy and ADHD

Amphetamine Methylphenidate

Amphetamine and tyramine differences

Amphetamine is resistant to MAO metabolism Tyramine is metabolized quickly by MAO except for patients who are on MAO inhibitors

Phenylephrine

An alpha agonist that causes decongestant effects and mydriasis.

Clonidine

An alpha2 selective agonist that causes causes vasoconstriction when administered intravenously or locally into the conjunctival sac. Given chronically though, they actually reduce sympathetic outflow and reduce vasoconstriction. Used as a treatment of hypertension

Treatment of glaucoma

Apraclonidine and brimonidine

A 7 year old boy with a history of bee sting allergy is brought to the emergency department after being stung several times. Which of the following are probable signs that he is having an anaphylactic reaction? A. Bronchodilation, tachycardia, hypertension, vomiting, diarrhea B. Bronchospasm, tachycardia, hypotension, laryngeal edema C. Diarrhia, bradycardia, edema D. Laryngeal edema, bradycardia, hypotension, diarrhea E. Miosis, tachycardia, vomiting, diarrhea

B. Anaphylaxis is caused by the release of several mediators. Leukotrienes and certain proteins are the most important of these. They cause bronchospasm and laryngeal edema and marked vasodilation with severe hypotension. Tachycardia is a common reflex response to the hypotension. GI disturbance is not as common or as worrisome.

A group of volunteers are involved in a study of a new autonomic drug. When administered by intravenous bolus, the BP increases When given orally for 1 week, the BP decreases. Which of the following existing drugs does the new drug most resemble? A. Atropine B. Clonidine C. Phentolamine D. Phenylephrine E. Propanolol

B. The dual blood pressure effects of the drug suggests that it initially is causing an direct alpha agonist vasoconstrictor effect, but when given for a week, it is accumulating in a blood pressure controlling center in the CNS and reducing sympathetic outflow.

A new drug was given by subcutaneous injection to 25 normal subjects in a phase 1 clinical trial. The CV effects are: Systolic BP: 116 to 156 Diastolic BP: 76 to 96 Cardiac output: 5.0 to 7.7 Heart rate: 71.2 to 94.3 Which of the following drugs does the new experimental agent most resemble? A. Atropine B. Epinephrine C. Isoproterenol D. Phenylephrine E. Physostigmine

B. The intvestigational agent caused a marked increase in both systolic and diastolic pressures as well as a moderate increase in pulse pressure. These changes suggest a strong alpha effect on vessels and an increase in stroke volume, a beta agonist action in the heart. The heart rate increased significantly, reflecting a beta response. Note that the stroke volume also increased. This behaves like a mixed alpha and beta agonist. Epinephrine is the only one of those listed.

A condition in which an increase in blood flow is desired

Beta 1 agonists may be useful Norepinephrine and Dobutamine are used for sepsis and cardiogenic shock

Albuterol

Beta 2 agonist Prompt onset for acute bronchospasm Deivered via aerosol inhaler. Side effects: tachycardia, tremor

Beta agonist effect on vascular system

Beta 2 agonists (albuterol, metraproterenol) and nonselective Beta agonists (isoproterenol) cause signifcant reduction in arterial tone in the skeletal muscle. Reduce resistance and blood pressure.

Isoproterenol

Beta agonist

Isoproterenol

Beta agonist. Primarily used in nebulizer to treat acute asthma

GI effects of sympathomimetics

Both Alpha and Beta receptors cause relaxation of the smooth muscle of the gut.

A 65 year old woman with impaired renal function and a necrotic ulcer in the sole of her right foot is admitted to the ER. She has long standing type 2 diabetes and you wish to examine her retinas for vascular changes. Which of the following drugs is a good choice when pupillary dilation - but not cycloplegia - is desired? A. Isoproterenol B. Norepinephrine C. Phenylephrine D. Pilocarpine E. Tropicamide

C. Antimuscarinics are mydriatic and cycloplegic; alpha-sympathomimetics are only mydriatic. Isoproterneol is a beta agonist. Norepinephrine penetrates the conjuctiva poorly and would cause intense vasoconstriction Pilocarpine causes miosis, not mydriasis Phenylephrine is well absorbed by the conjunctival sac and is an alpha agonist that causes mydriasis.

A 60 year old immigrant from Latin America was told she had hypertension and should be taking antihypertensive medication. She instead takes holistic medicine. One week later she is found unconscious in her apartment. In the ER her blood pressure is 50/0 and her heart rate is 40 bpm. Respirations are 20/min. Pupils are slightly constricted. Bowel sounds are present. Which of the following would be the most effective cardio stimulant? A. Amphetamine B. Clonidine C. Isoproterenol D. Norepeniphrine E. Tyramine

C. Herbal medications of ten contain potent synthetic drugs in addition to their advertised constituents. This patient shows signs of sympathetic autonomic failure: hypotension, inappropriate bradycardia, constricted pupils. These signs are compatible with a large overdose of a drugs that causes marked depletion of catecholamine transmitter such as reserpine, an obsolete but inexpensive antihypertensive Amphetamine and tyramine act through catecholamines in the nerve terminal. These are depleted, so these would not be of use. Clonidine acts primarily on presynaptic nerve endings although it can activate A2 receptors everywhere. Isoprotenerol would stimulate the heart but has no alpha agonist action and might thus exacerbate the hypotension. NE has the necessary combination of direct action and a spectrum that includes A1, A2, and B1 effects.

CNS effects of sympathomimetics

Catecholamines don't enter the CNS readily and have limited effects Cocaine and amphetamines can enter and cause alertness and reduction of fatigue, progressing to euphoria and insomnia. Clonidine can cause vasoconstriction through CNS effects.

Amphetamine

Causes the release of stored catecholamines

Gu effects of sympathomimetics

Contains alpha receptors in the bladder and sphincter area. Wall relaxation and sphincter contraction. Sympathomimetics are sometimes used to increase sphincter tone

Several new drugs with autonomic actions were studied in preclinical trials in animals. Autonomic drugs X and Y were given in moderate doses as intravenous boluses. The systolic and diastolic blood pressures changes as shown ( Drug X - systolic stayed steady at 130 but diastolic dropped from 80 to 40; Drug Y - 130/80 to 160/110) Which of the following drugs resembles drug X? A. Atropine B. Bethanechol C. Epinephrine D. Isoproterenol E. Phenylephrine

D. The drug X dose caused a decrease in diastolic BP and no change in systolic. Thus, ther was a large increase in pulse pressure. The decrease in diastolic pressure suggests that the drug decreased vascular resistance, that is, it must have an effect as a muscarinic or beta agonist. The fact is that it also markely increased pulse pressure suggests that it strongly increased stroke volume, a beta agonist effect. The drug with these beta effects is isoproterenol.

Your 30 year old patient has moderately new onset asthma, and you prescribe a highly selective B2 agonist inhaler to be used when needed. In considering the possible drug effects in this patient, you would note that B2 stimulants frequently cause: A. Direct stimulation of renin release B. Hypoglycemia C. Itching due to increase cGMP in mast cells D. Skeletal muscle tremor E. Vasodilation in the skin

D. Tremor is a common B2 effect. Due to increased blood flow to those areas. Blood vessels in the skin have almost exclusively alpha receptors. Stimulation of renin release is a B1 effect. Beta 2 agonists cause hyperglycemia and have little effect on cGMP.

Several new drugs with autonomic actions were studied in preclinical trials in animals. Autonomic drugs X and Y were given in moderate doses as intravenous boluses. The systolic and diastolic blood pressures changes as shown ( Drug X - systolic stayed steady at 130 but diastolic dropped from 80 to 40; Drug Y - 130/80 to 160/110) Which of the following drugs resembles drug Y? A. Atropine B. Bethanechol C. Epinephrine D. Isoproterenol E. Phenylephrine

E. Drug Y caused a marked increase in diastolic pressure, suggestin alpha vasoconstrictor effects. It caused little or no increase in pulse pressure, suggesting negligible Beta agonist action.

Mr. Green had a cardiac transplant 6 months ago. His current BP is 120/70 and HR is 100 bpm. Which of the following drugs would have the least effect on Mr. Green's heart rate? A. Albuterol B. Epinephrine C. Isoproterenol D. Norepinephrine E. Phenylephrine

E. Heart transplantation involves cutting of the autonomic nerves to the heart. As a result, autonomic nerve endings degenerate, and cardiac transmitter stores are absent for at least 2 years following surgery. Therefore, indirect acting sympathomimetics are ineffective in changing heart rate. All the drugs listed are direct acting and all but phenylephrine have effects on Beta receptors. Phenylephrine usually causes reflex bradycardia, which requires intact vagal innervation.

A 7 year old boy with a history of bee sting allergy is brought to the emergency department after being stung several times. What should be given to prevent anaphylaxis?

Epinephrine

Anaphylactic shock treatment

Epinephrine

A2 signaling

Gi cAMP decrease

Alpha 1 toxicity

Hypertension

Alpha 2 actions

Inhibits NE release Lipolysis Inhibits insulin release

Cocaine

Inhibits reuptake of catecholamines

Eye effects of sympathomimetics

Mydriasis and contraction Accomodation is not significantly affected. Outflow of aqueous humor may be facilitated with reduction of pressure.

Initiation of mydriasis

Phenylephrine

Beta 2 actions

Relax airways Relax uternine pathways Relax vascular smooth muscle Stimulate glycogenolysis Stimulate heart rate and force

Beta 1 toxicity

Sinus tachycardia and serious arrhythmias

Beta 2 toxicity

Skeletal muscle tremor

Beta 1 actions

Stimulates increased heart rate and force Stimulates renin release

Heart effects of sypahthomimetics

The heart is well supplied with B1 and B2 receptors. The B1 receptors predominante in some areas though. Both mediate increased cardiac pacemaker activity, increased AV node conduction, and increased cardiac force.

Bronchi effects of sympathomimetics

The smooth muscle of the bronchi relax markedly in response to B2 agonists, like isoproterenol and albuterol.

Sympathomimetics

The sympathomimetics constitute a very important group of drugs used for cardiovascular, respiratory, and other conditions. They are divided into their spectrum of action (Alpha, Beta, etc.) and their mode of action (direct or indirect)

A1 signalling

Through Gq IP3 and DAG cause increased calcium

Alpha 1 agonist effect on vascular system

Vasoconstriction An alpha 1 agonist like phenylephrine contracts vascular smooth muscle in the skin and splenchnic blood vessels. Will often produce a compensatory reflex bradycardia.

Alpha 1 actions

Vasoconstriction Mydriasis Bladder contraction Glycogenolysis