adrenergic agemts. learning objectives understand the central and peripheral nervous systems, their...

Adrenergic agemts

Learning Objectives

• Understand the central and peripheral nervous systems, their functions, and their relationship to drugs.

• Become aware of the role of neurotransmitters.

• Learn how adrenergic drugs affect body systems and where they work in the body.

Learning Objectives

• Define the action of neuromuscular blocking agents in reducing muscle activity.

• Distinguish between narcotic and nonnarcotic analgesia.

• Become familiar with the various types of agents for migraine headaches.

Divisions of the Nervous System

• Central Nervous System– Brain– Spinal cord

• Peripheral Nervous System– Nerves– Sense organs

Divisions of the Nervous System

• Central Nervous System

• Peripheral Nervous System

Divisions of the Nervous System

• Central Nervous System

• Peripheral Nervous System– Somatic Nervous System– Autonomic Nervous System

Divisions of the Nervous System

• Central Nervous System

• Peripheral Nervous System– Somatic Nervous System

Voluntary action: skeletal muscle contraction and movement

– Autonomic Nervous SystemInvoluntary activities: respiration, circulation, digestion, sweating

Autonomic Nervous System

Review

The nervous system has two components. What are they?

Review

The nervous system has two components. What are they?

Answer – Central nervous system (CNS)– Peripheral nervous system (PNS)

Major Neurotransmitters

• Acetylcholine

• GABA

• Dopamine

• Epinephrine

• Serotonin

Major Neurotransmitters

• Acetylcholine (ACh)– Smooth muscle, cardiac muscle, and

exocrine glands

– Anticholinergics block ACh receptors• GABA

• Dopamine

• Epinephrine

• Serotonin

Major Neurotransmitters

• Acetylcholine

• GABA (gamma-aminobutyric acid)

Regulates message delivery system of the brain

• Dopamine

• Epinephrine

• Serotonin

Major Neurotransmitters

• Acetylcholine

• GABA

• DopamineActs on the CNS and kidneys

• Epinephrine

• Serotonin

Major Neurotransmitters

• Acetylcholine• GABA• Dopamine

• Epinephrine– Acts on cardiac and bronchodilator

receptors– Known as Adrenaline

• Serotonin

Major Neurotransmitters

• Acetylcholine

• GABA

• Dopamine

• Epinephrine

• Serotonin– Acts on smooth muscle and gastric mucosa

(causes vasoconstriction)

– Emotional responses: depression, anxiety

Communication by Neurotransmitters

Neurotransmitters are released from one axon and received by another neuron’s dendrites.

Discussion

What are three important types of receptors in the study of drugs?

Discussion

What are three important types of adrenergic receptors in the study of drugs?

Answer – Alpha– Beta-1– Beta-2

Types of Receptors

• AlphaVasoconstriction, raise BP

• Beta-1Heart stimulation

• Beta-2Vasodilation and bronchodilation

Drugs Affecting TheAutonomic Nervous

SystemAdrenergic Agents and

Adrenergic-Blocking Agents

The Sympathetic Nervous System

in Relationship to the Entire Nervous System

Adrenergic Agents

• Drugs that stimulate the sympathetic nervous system (SNS)

Adrenergic Agents

Also known as

• adrenergic agonists or sympathomimetics

Adrenergic Agents

Mimic the effects of the SNS neurotransmitters:

• norepinephrine (NE) and epinephrine (EPI)

Adrenergic Receptors

• Located throughout the body

• Are receptors for the sympathetic neurotransmitters

Alpha-adrenergic receptors: respond to NE

Beta-adrenergic receptors: respond to EPI

Alpha-Adrenergic Receptors

• Divided into alpha1 and alpha2 receptors

• Differentiated by their location on nerves

Alpha1-Adrenergic Receptors

• Located on postsynaptic effector cells (the cell, muscle, or organ that the nerve stimulates)

Alpha2-Adrenergic Receptors

• Located on presynaptic nerve terminals (the nerve that stimulates the effector cells)

• Control the release of neurotransmitters

The predominant alpha-adrenergic agonist responses are:• Vasoconstriction and CNS stimulation

Beta-Adrenergic Receptors

All are located on postsynaptic effector cells• Beta1-adrenergic receptors—located primarily

in the heart

• Beta2-adrenergic receptors—located in smooth muscle of the bronchioles, arterioles, and visceral organs

The beta-adrenergic agonist response results in:

• Bronchial, GI, and uterine smooth muscle relaxation

• Glycogenolysis

• Cardiac stimulation

Dopaminergic Receptors• An additional adrenergic receptor• Stimulated by dopamine• Causes dilation of the following blood vessels,

resulting in INCREASED blood flow– Renal

– Mesenteric

– Coronary

– Cerebral

Adrenergic Receptor Responsesto Stimulation

LOCATION RECEPTOR RESPONSECardiovascular

Blood vessels alpha1 and beta2 Constriction /dilation

Cardiac muscle beta1 Increasedcontractility

AV Node beta1 Increased heart rate

SA Node beta1 Increased heart rate

Adrenergic Receptor Responsesto Stimulation

LOCATION RECEPTOR RESPONSEGastrointestinal

Muscle beta2 Decreased motility

Sphincters alpha1 Constriction

Adrenergic Receptor Responsesto Stimulation

LOCATION RECEPTOR RESPONSEGenitourinary

Bladder alpha1 Constrictionsphincter

Penis alpha1 Ejaculation

Uterus alpha1 and beta2 Contraction/relaxation

Adrenergic Receptor Responsesto Stimulation

LOCATION RECEPTOR RESPONSERespiratory

Bronchial beta2 Dilation/relaxationmuscles

Catecholamines

Substances that can produce a sympathomimetic response

Endogenous:• epinephrine, norepinephrine,dopamine

Synthetic:• isoproterenol, dobutamine, phenylephrine

Adrenergic Agents Mechanism of Action

Direct-acting sympathomimetic:• Binds directly to the receptor and causes a

physiologic response

Direct-Acting Sympathomimetics

Adrenergic Agents Mechanism of Action

Indirect-acting sympathomimetic:• Causes the release of catecholamine from the

storage sites (vesicles) in the nerve endings• The catecholamine then binds to the receptors and

causes a physiologic response

Indirect-Acting Sympathomimetics

Adrenergic Agents Mechanism of Action

Mixed-acting sympathomimetic:• Directly stimulates the receptor by binding

to it

AND• Indirectly stimulates the receptor by causing

the release of stored neurotransmitters from the vesicles in the nerve endings

Mixed-Acting Sympathomimetics

Drug Effects of Adrenergic Agents

Stimulation of alpha-adrenergic receptors on smooth muscles results in:

• Vasoconstriction of blood vessels• Relaxation of GI smooth muscles• Contraction of the uterus and bladder• Male ejaculation• Decreased insulin release• Contraction of the ciliary muscles of the eye

(dilated pupils)

Drug Effects of Adrenergic Agents

Stimulation of beta2-adrenergic receptors on the airways results in:

• Bronchodilation (relaxation of the bronchi)• Uterine relaxation• Glycogenolysis in the liver

Drug Effects of Adrenergic Agents

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)

• Increased conduction through the AV node (positive dromotropic effect)

Adrenergic Agents: Therapeutic Uses

• Anorexiants: adjuncts to diet in the short-term management of obesityExamples: benzphetamine

phenterminedextroamphetamineDexedrine

Adrenergic Agents: Therapeutic Uses

Bronchodilators: treatment of asthma and bronchitis

• Agents that stimulate beta2-adrenergic receptors of bronchial smooth muscles causing relaxationExamples:albuterol ephedrine epinephrineisoetharine isoproterenol levalbuterolmetaproterenol salmeterol terbutaline

• These agents may also affect uterine and vascular smooth muscles.

Adrenergic Agents: Therapeutic Uses

• Reduction of intraocular pressure and mydriasis (pupil dilation): treatment of open-angle glaucoma

Examples: epinephrine and dipivefrin

Adrenergic Agents: Therapeutic Uses

Nasal decongestant: • Intranasal (topical) application causes constriction

of dilated arterioles and reduction of nasal blood flow, thus decreasing congestion.

Examples:epinephrine ephedrine naphazoline

phenylephrinetetrahydrozoline

Adrenergic Agents: Therapeutic Uses

Ophthalmic • Topical application to the eye surface affects

the vasculature of the eye, stimulating alpha receptors on small arterioles, thus relieving conjunctival congestion.Examples: epinephrine naphazoline

phenylephrine tetrahydrozoline

Adrenergic Agents: Therapeutic Uses

Vasoactive sympathomimetics (pressors, inotropes), also called cardioselective sympathomimetics

• Used to support the heart during cardiac failure or shock.Examples:dobutamine dopamine ephedrine epinephrine fenoldopam isoproterenolmethoxamine norepinephrine phenylephrine

Adrenergic Agents: Side EffectsAlpha-Adrenergic Effects• CNS:

– headache, restlessness, excitement, insomnia, euphoria

• Cardiovascular:– palpitations (dysrhythmias), tachycardia,

vasoconstriction, hypertension

• Other:– anorexia, dry mouth, nausea, vomiting, taste changes

(rare)

Adrenergic Agents: Side EffectsBeta-Adrenergic Effects• CNS:

– mild tremors, headache, nervousness, dizziness

• Cardiovascular:– increased heart rate, palpitations (dysrhythmias),

fluctuations in BP

• Other:– sweating, nausea, vomiting, muscle cramps

Adrenergic Agents: Interactions• Anesthetic agents

• Tricyclic antidepressants

• MAOIs

• Antihistamines

• Thyroid preparations

• Antihypertensives

• Will directly antagonize another adrenergic agent, resulting in reduced effects

Adrenergic Agents: Nursing Implications

• Assess for allergies and history of hypertension, cardiac dysrhythmias, or other cardiovascular disease.

• Assess renal, hepatic, and cardiac function before treatment.

• Perform baseline assessment of vital signs, peripheral pulses, skin color, temperature, and capillary refill. Include postural blood pressure and pulse.

• Follow administration guidelines carefully.

Adrenergic Agents: Nursing Implications

IV administration:• Check IV site often for infiltration• Use clear IV solutions• Use an infusion device/IV pump• Infuse agent slowly to avoid dangerous

cardiovascular effects• Monitor cardiac rhythm

Adrenergic Agents: Nursing Implications

With chronic lung disease:

• Instruct patients to avoid factors that exacerbate their condition.

• Encourage fluid intake (up to 3000 mL per day) if permitted.

• Educate about proper dosing and equipment care.

Salmeterol is indicated for PREVENTION of bronchospasms, not management

of acute symptoms.

Adrenergic Agents: Nursing Implications

• Overuse of nasal decongestants may cause rebound nasal congestion or ulcerations.

• Avoid OTC or other medications because of possible interactions.

• Administering two adrenergic agents together may precipitate severe cardiovascular effects such as tachycardia or hypertension.

• Inform patients taking inhaled isoproterenol that their sputum or saliva may turn pink.

Adrenergic Agents: Nursing Implications

Monitor for therapeutic effects (cardiovascular uses):

• Decreased edema• Increased urinary output• Return to normal vital signs• Improved skin color and temperature• Increased LOC

Adrenergic Agents: Nursing Implications

Monitor for therapeutic effects (asthma):• Return to normal respiratory rate• Improved breath sounds, fewer rales• Increased air exchange• Decreased cough• Less dyspnea• Improved blood gases• Increased activity tolerance

Adrenergic-Blocking Agents

• Bind to adrenergic receptors, but inhibit or block stimulation of the sympathetic nervous system (SNS)

Adrenergic Blocking Agents

• Have the opposite effect of adrenergic agents

• Also known as– adrenergic antagonists or sympatholytics

Adrenergic Blocking Agents

• Sympatholytics inhibit—or LYSE—sympathetic neurotransmitters

(norepinephrine and epinephrine)

Adrenergic Blocking Agents

Classified by the type of adrenergic receptor they block

• Alpha1 and alpha2 receptors

• Beta1 and beta2 receptors

Alpha-Blocker Mechanisms

Adrenergic-Blocking Agents: Drug Effects and Therapeutic

UsesErgot Alkaloids (Alpha-Blockers)• Constrict dilated arteries going to the brain

(carotid arteries)• Used to treat vascular headaches (migraines)• Stimulate uterine contractions by inducing

vasoconstriction• Used to control postpartum bleeding

Adrenergic-Blocking Agents: Drug Effects and Therapeutic

UsesAlpha-Blockers• Cause both arterial and venous dilation, reducing

peripheral vascular resistance and BP• Used to treat hypertension• Effect on receptors on prostate gland and bladder

decreased resistance to urinary outflow, thus reducing urinary obstruction and relieving effects of BPH

Adrenergic-Blocking Agents: Drug Effects and Therapeutic

UsesAlpha-Blockers• Phentolamine

– Quickly reverses the potent vasoconstrictive effects of extravasated vasopressors such as norepinephrine or epinephrine.

– Restores blood flow and prevents tissue necrosis.

Adrenergic-Blocking Agents: Side Effects

Alpha BlockersBody System Side/Adverse EffectsCardiovascular Palpitations, orthostatic

hypotension, tachycardia, edema, dysrhythmias,

chest pain

CNS Dizziness, headache, drowsiness,anxiety, depression, vertigo,weakness, numbness, fatigue

Adrenergic-Blocking Agents: Side Effects

Alpha Blockers

Body System Side/Adverse EffectsGastrointestinal Nausea, vomiting, diarrhea,

constipation, abdominal pain

Other Incontinence, nose bleeding,tinnitus, dry mouth, pharyngitis,rhinitis

Beta Blockers

• Block stimulation of beta receptors in the SNS

• Compete with norepinephrine and epinephrine

• Selective and nonselective beta blockers

Beta Receptors

Beta1 Receptors• Located primarily on the heart• Beta blockers selective for these receptors

are called cardioselective beta blockers

Beta Receptors

Beta2 Receptors

• Located primarily on smooth muscles of bronchioles and blood vessels

Nonspecific Beta Blockers

• Beta blockers that block both beta1 and beta2 receptors

Salbutamol (ventolin)

selective b2-adrenomimetic of direct action

Administration • inhalations during attacks of bronchial asthma and bronchial spasms of other etiology, • передчасних child delivery, бурхливій child delivery

Beta Blockers: Mechanism of Action

Cardioselective (Beta1)• Decreases heart rate• Prolongs SA node recovery• Slows conduction rate through the AV node• Decreases myocardial contractility, thus

decreasing myocardial oxygen demand

Beta Blockers: Mechanism of Action

Nonspecific (Beta1 and Beta2)• Effects on heart: Same as cardioselective• Bronchioles: Constriction, resulting in

narrowing of airways and shortness of breath

• Blood vessels: Vasoconstriction

Beta Blockers: Therapeutic Uses

• Anti-angina: decreases demand formyocardial oxygen

• Cardioprotective: inhibits stimulation bycirculating

catecholamines

• Class II antidysrhythmic

Terbutalin (brikanil) and phenoterol (berotek, partusisten)

are stimulants of mostly 2-adrenal receptors. They posses broncholytic and tokolytic activity

Beta Blockers: Therapeutic Uses

• Antihypertensive

• Treatment of migraine headaches

• Glaucoma (topical use)

Beta Blockers: Side Effects

Body System Side/Adverse EffectsBlood Agranulocytosis,

thrombocytopenia

Cardiovascular AV block, bradycardia, congestiveheart failure, peripheral vascularinsufficiency

CNS Dizziness, mental depression,lethargy, hallucinations

Adrenergic-Blocking Agents: Side Effects

Beta Blockers

Body System Side/Adverse EffectsGastrointestinal Nausea, dry mouth, vomiting,

diarrhea, cramps, ischemic colitis

Other Impotence, rash, alopecia,bronchospasms

Adrenergic Blocking Agents: Nursing Implications

• Assess for allergies and history of COPD, hypotension, cardiac dysrhythmias, bradycardia, CHF, or other cardiovascular problems

Any preexisting condition that might be exacerbated by the use of these agents might

be a CONTRAINDICATION to their use.

Adrenergic Blocking Agents: Nursing Implications

• Remember that alpha blockers may precipitate hypotension.

• Remember that beta blockers may precipitate bradycardia, hypotension, heart block, CHF, and bronchoconstriction.

Adrenergic Blocking Agents: Nursing Implications

• Avoid OTC medications because of possible interactions.

• Possible drug interactions may occur with:– Antacids (aluminum hydroxide type)– Antimuscarinics/anticholinergics– Diuretics and cardiovascular drugs– Neuromuscular blocking agents– Oral hypoglycemic agents

Adrenergic Blocking Agents: Nursing Implications

• Encourage patients to take medications as prescribed.

• These medications should never be stopped abruptly.

• Report constipation or the development of any urinary hesitancy or bladder distention.

Adrenergic Blocking Agents: Nursing Implications

• Teach patients to change positions slowly to prevent or minimize postural hypotension.

• Avoid caffeine (excessive irritability).• Avoid alcohol ingestion and hazardous

activities until blood levels become stable.• Patients should notify their physician if

palpitations, dyspnea, nausea, or vomiting occur.

Beta Blocking Agents: Nursing Implications

• Rebound hypertension or chest pain may occur if this medication is discontinued abruptly.

• Patients should notify their physician if they become ill and unable to take medication.

• Inform patients that they may notice a decrease in their tolerance for exercise; dizziness and fainting may occur with increased activity. Notify the physician if these problems occur.

Beta Blocking Agents: Nursing Implications

Patients should report the following to their physician:

• Weight gain of more than 2 pounds (1 kg) within a week

• Edema of the feet or ankles• Shortness of breath• Excessive fatigue or weakness• Syncope or dizziness

Adrenergic Blocking Agents: Nursing Implications

Monitor for side effects, including:Hypotension Fatigue

Tachycardia (alpha blockers) Lethargy

Bradycardia Depression

Heart block Insomnia

CHF Vivid nightmares

Increased airway resistance

Adrenergic Blocking Agents: Nursing Implications

Monitor for therapeutic effects• Decreased chest pain in patients with angina• Return to normal BP and P• Other specific effects, depending on the use

Adrenomimetics а) adrenomimetics of direct action

б) adrenomimetics of indirect action or sympathomimetics

Adrenoblockers or adrenolytics

Sympatholytics

І. Adrenomimetics 1.- і -adrenomimetics (adrenalin hydrochloride,

noradrenalin hydrotartrate)2. dopamine-, -, -adrenomimetics (dopamine)3. -adrenomimetics (mesatone, naftizin, galazoline)4. -adrenomimetics (isadrine, salbutamol, phenoterol,

terbutalin, dobutamine)ІІ. Sympathomimetics (ephedrine hydrochloride)ІІІ. Adrenoblockers 1. -adrenoblockers (phentolamine, tropaphen, prasosine,

pyroxan)2. -adrenoblockers (anaprilin, athenolol, talinolol,

acebutolol)3. - і -adrenoblockers (labetalol)ІІІ. Sympatholytics (reserpine, octadine)

Adrenomimetcs

Adrenalin (epinephrine) is a hormone of medullar layer of adrenal glands which is used in a form of a

remedy

adrenaline hydrochloride

It is an adrenomimetic which stimulates 1,- 2- and 1,- 2-adrenoreceptors

Administration sudden stoppage of heart, for example, during surgical

narcosis electric trauma

shock and collapse conditions bronchial spasm

hypoglycemic coma treatment of open-angle glaucoma

Noradrenalin hydrotartrate (norepinephrine)

Is an adrenomimetic of direct action which stimulates 1-, 2- and 1-adrenal receptors

Administration in cases of acute decreasing of blood pressure -

shock and collapse conditions, surgeries, traumasThe drug is absolutely contraindicated for

subcutaneous and intramuscular introductions

Dopamine

Drug of choice for treatment of

shock and collapse of different etiology, including cardiogenic

and hemorrhagic

Mesaton (phenilefrin)Is a synthetic a1-adrenomimetic drug of direct action

Administration • acute hypotensive conditions,• prophylaxis of decreasing of blood pressure in case of infectious diseases, poisonings,• decreasing of blood pressure during narcosis with fluorothan and cyclopropan• nose drops in case of rhinits

Naphtisin

Xylometazolinare a2-adrenomimetics of direct action

Usage for rhinitis in a form of nose drops – 1-2

drops 2-3 times a day

It is not recommended to use the drug in case of chronic cold

Isadrin (isoprenalin, novodrin, euspiran)

– is a synthetic catecholamine, which is a strong stimulant of b1- і b2-adrenal receptors

Administration • bradycardia, atrio-ventricular blockade • bronchial spasm • complex therapy of some kinds of shock (if the patient doesn’t

have hypovolemia)Side effects

• nausea, hands tremor, dryness in mouth,• in patients with ischemic heart disease – attack of stenocardia,• heavy cardiac tachyarrhythmias, even fibrillation of ventricles

Salbutamol (ventolin)

selective b2-adrenomimetic of direct action

Administration • inhalations during attacks of bronchial asthma and bronchial spasms of other etiology, • передчасних child delivery, бурхливій child delivery

Terbutalin (brikanil) and phenoterol (berotek, partusisten)

are stimulants of mostly 2-adrenal receptors. They posses broncholytic and tokolytic activity

Dobutamin Is a synthetic 1-adrenomimetic

Cardiotonic effects of dobutamin is 5 times stronger than action of dopamine

Administrationsome forms of acute and chronic cardiac

insufficiency intravenous dropping infusion with the speed

of 2,5-10 mcg / (kg.min)

Sympathomimetics

Ephedrine hydrochloride (Ephedrini hydrochloridum)

It is an alkaloid of plants of Ephedra family, which has indirect a-, b-adrenomimetic (sympathomimetic) action

Administration • collapse conditions, for prophylaxis of decreasing of blood pressure before spinal anesthesia, infectious diseases

• treatment of rhinitis (2 %, 3 % solution to drop into nose).

• prophylaxis and elimination of bronchial spasm (inhalations 0,5 %-1 % solutions of drug)

SIDE EFFECTS• неспокій, excitement, tremor, inconsiderable euphoria, insomnia, seizures

• drug addiction

• tachyphylaxy

Adrenoblockers

Alfa-adrenoblockers

Phentolamine, tropaphenare synthetic a1, 2-аdrenoblockers

administration• diagnostics and symptomatic treatment of feochromocytoma• disturbances of peripheral blood circulation in case of endarteritis, Reino’s disease, trophic ulcers, decubitus• complex treatment of hypertensive crises, acute cardiac insufficiency• complex therapy of hypovolemic and cardiogenic shock

Prasosin

Selective a1- adrenoblocker

Administration • treatment of essential hypertension• stabile cardiac insufficiency

Side effects“phenomenon of first dose”: sudden decreasing of blood pressure and even development of orthostatic collapse after first administrations of the drugProphylaxis: administration of half-dose before sleep

Beta-adrenoblockers

Anaprilin Is a selective b1- і b2-adrenoblocker

Administration • ischemic heart disease

• essential hypertension

• cardiac tachyarrhythmias

• acute myocardium infarction

Talinolol or cordanum

is a cardioselective

b-adrenoblocker

Administration• disorders of cardiac rhythm (extrasystolies, paroxysmal tachycardia, fibrillation and scintillation of atria)

• stenocardia

• arterial hypetension

.

Atenolol (tenormin)cardioselelctive -adrenoblocker of long action

Indications for administration• ischemic heart disease • essential hypertension

• cardiac arrhythmias• acute myocardium infarction

Acebutolol (sectral)1-adrenoblocker with internal

sympathomimetic activity

Indications• disorders of cardiac rhythm (tachyarrhythmias)

• hypertension

• ischemic heart disease

Labetolol

-, -adrenoblocker. The drug blocks 1, 2, 1 and 2-adrenoreceptors

Administration • treatment of patients with essential hypertension

• hypertensive crisis

Contraindications Atrio-ventricular blockade,

cardiac insufficiency

Sympatholytics

Reserpin is a sum of раувольфії (plant) alkaloids. Maximal hypotensive action develops after 5-7 days of regular administration of the drug. After the treatment coarse effect can still stay for two weeks.

Administration treatment of different forms of essential hypertension (combined drugs trirezid, cristepin, adelfan, brinerdin)

Side effects• manifestations of parkinsonism• в’ялість, somnolence, depression,• bradycardia• increasing of motor and secretory activity of gastro-intestinal tract, • acute attacks of ulcer disease, diarrhea• swelling of nose mucous membrane with complication of nose breathing

Octadin Is a sympatholytic with strong hypotensive effect. During administration of the drug decreasing of blood pressure develops gradually, after 2-3 days. After quitting of drug administration the effect still stays for 2 weeks.

Administration heavy forms of arterial hypertension

Side effects general weakness, nausea, vomiting, swelling of nose mucous membrane, diarrhea, storing of liquid in the organism, orthostatic collapse.

Thanks for attention!