Resistance left ventricle must overcome to circulate blood - increased in hypertension, vasoconstriction - increase in after load causes and increase in cardiac work load

- Nitroglycerin - Nitroprusside

1. Dihydropyridines-nifedipine, nicardipine, amplodipine 2. Phenylalkylamine-Verapamil 3. Benzothiazapines-dilitazem

Smooth Muscle Physiology Flashcards by Allison Cotter

What is resting membrane potential

-40 to -70mV

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contraction occurs when membrane potential is

more positive (depolarized)

*Ca rushes in

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relaxation occurs when membrane potential is

more negative (hyperpolarized)

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describe smooth muscle contraction

agonist binds to gq receptor which activates PLC which converts PIP2 to DAG and IP3 which causes release of Ca from the sarcoplasmic reticulum.

Also Ca rushed in through voltage gated Ca channels.

Then Ca/Calmodulin is activated which activates MLC Kinase.

MLC kinase phosphorylates MLC which causes contracteion.

Active Myosin phosphatase dephsphorylates MLC making MLC relax.

Myosin phosphatase was activated which RhA-GDP (inactive) was converted to RhoA-GTP and then dephosphorylated myosin phosphatase activating it

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Mechanisms of smooth muscle contractin

pharmacological coupling
receptors/Intracellular signaling
neurotransmitters, hormones, paracrine factors

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Mechanisms of smooth muscle relaxation

paracrine factors

membrane potential

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Therapeutic Application for smooth muscle relaxation
CV
Obstetrics
GI Motility
Pulmonary

CV:vasodilators
OB: uterin relaxation
GI Motility: contraction
Pulmonary: bronchodilators

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Preload

volume of blood in the ventricles at the end of diastole (EDP)

-increase in: hypervolemia, regurgitation of cardiac valves

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Afterload

Resistance left ventricle must overcome to circulate blood

increased in hypertension, vasoconstriction
increase in after load causes and increase in cardiac work load

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Pharmacological Actions of Vasodilator drugs

NO
Increase or decrease cell memebrane channela ctivity
increase smooth muscle cAMP or cGMP levels
activate vasodilator receptors
inhibit vasoconstrictor pathways and receptors

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Nitric Oxide donors mechanism of action is via which second messengers

-cGMP and protein kinase G

Nitric oxide combines with the heme group of soluble guanylyl cyclase (sGC),
activating that enzyme and causing an increase in cGMP. An increased smooth
muscle cGMP level activates K+ channels and enhances myosin light chain (MLC)
dephosphorylation to cause relaxation.

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Nitroprusside

arteriole and venule dilator

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Organic Nitrates

Nitroglycerin

- Nitroprusside

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Nitroglycerin

Action: Venous Circulation (dominant) (decrease preload)

Use: Angina/ Coronary Artery Disease

Administration: Sublingual to avoid first pass effect. Reaches therapeutic levels quickly and has short duration (15-30 minutes)

Contraindication: Elevated intracranial pressure

Toxicity: Hypotension, tachycardia

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Nitropruside

Action: NO releasing
Arterial and Venous circulations (decrease afterload and decrease preload)

Use: Hypertensive emergencies-rapid reduction in arterial pressure

Administration:
Intravenus
Rapid offset after discontinuing
Short duration (15-30 minutes)

Toxicity:
Hypotension, cyanide accumulation

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Direct Vasodilators

Hydralazine
Minoxidil
Diazoxide

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Hydralazine

Action: ***Arterial circulation (decrease afterload)

Use: Heart failure/HTN

Administration: oral for long term , combined with nitrates for heart failure

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Minoxidil

Action: ***Arterial circulation decrease afterload, adn K ATP CHannel opener

Use: Heart failure/ Hypertension

Administration: oral for long-term

Toxicity: Hypertrichosis (hair growth)

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Diazoxide

Action: Arterial circulation (decrease afterload)
K channel opener

Use: Hypertensive emergencies

administration:
oral-long acting
IV-rapid decrease in vascular resistance and arterial blood pressure

Toxicity: Hypotension

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Ca Channel blockers

Dihydropyridines-nifedipine, nicardipine, amplodipine
Phenylalkylamine-Verapamil
Benzothiazapines-dilitazem

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Calcium channel blockers infor

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Action: ***Arterial circulation (dominant), Vascular smooth muscle selectivity-dihydropridines are greater ration vascular versus cardiac effects.
Nimodipine has cerebral vascular selectivity

Use: HTN
Angina
Cerebral and coronary vasospasm

Phosphodiesterase Inhibitors what are the effects of the different phosphodiesterases on the vascular smooth muscle vs. the heart

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VSM:
1.cGMP causes relaxation and is broken down by PDE5. So a PDE5 inhibitor would increase cGMP

cAMP causes relaxation and is broken down by PDE3. so a PDE3 inhibitor would increase cAMP

Heart
1. Only cAMP is active. and is broken down by PDE3. SO a PDE3 inhibitor would increase cAMP which would increase contractility bc in the heart cAMP increases contractility

Wht is the differenc ebetween what cAMP does in the VSM vs in the heart

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cAMP in the VSM causes relaxation and therefore vasodilation,

cAMP in the heart causes an increase in contractility

PDE3 Inhibitors

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Milrinone, Inamrinone

heart
*phosphorylation of Ca Channels-inotropic

*Phosphorylates microfilaments-Inotropic

Phosphorylates K Channels and repolarizes-Chronotropic

VSM:
Inhibits myosin light chain kinase
phosphorylates K channels-hyperpolarization

Milrinone, Inamrinone

Action: PDE3 inhibition increases cAMP Use: heart failure Administration: *IV-short term life threatening heart failure *oral forms were withdrawn due to sudden cardiac death

PDE5 Inhibitors

Sildenafil, Tadalafi

Action: PDe5 inhibition increases cGMP Use: erectile dysfunction, pulmonary hypertension

Miscellaneous vasodilators

Fenoldopam | Prazosin

Fenoldopam

Action: Dopamine D1 receptor agonist, **Arterial dominant, Natriuretic Use: Hypertensive emergencies, Post-operative hypertension (IV)

Prazosin

Action: Alpha adrenergic blocker (a1), **Arterial and venous circulations use: hypertension

Tocolytic drugs

Atosiban

nonapeptide oxytocin receptor antagonist to decrease frequency of uterine contractions, Use: Inhibit uterine contractions-prevent preterm labor

PGE1 Analogs

Misoprostol and Alprostadil

Misoprostol

oral or sublingual stimulate uterin contractions/prevent treat postpartum hemorrhage (btw we learned this as a side effect in the last lecture and elarned that is main use is to decrease gastric acid secretions)

Alprostadil

smooth muscle relaxing to maintain ductus arteriosus patent in neonates awaiting cardiac surgery, and erectile dysfunction

Labor inducing drugs

Oxytocin | Ergonovine

Oxytcin

uterine contractions

Ergonovine

Ergot alkaloid rye fungi -small doses-evoke rhythmic contractions of uterus high doses-powerful and prolonged uterine contractions

Gastrointestinal Motility

Metoclopramide

Action: Dopamine D2 receptor antagonist allows for increased cholinergic smooth muscle stimulation use: GERD, prevent or treat emesis, impaired gastric emptying

bethanechol

muscarinic receptor agonist - increases gastrointestinal and bladder contractions * does not cross blood brain barrier * not hydrolyzed by cholinesterase-long duration -use: Diabetic neuropathy patients with GI and urinary motility problems

Erythtomycin

- Action: Macrolide antibiotic, stimulates motilin receptors on GI smooth muscl to promote migrating motor complexes (increase gastric emptying) use: intravenous gastroparesis (tolerance), acute upper GI hemorrhage to promote gastric emptying for endoscopy

Bronchodilators | -B2 Adrenergic Agonists

Albuterol, Pirbuterol, Terbutaline, Salmeterol, Formoterol

Action: B2 receptor agonists- smooth muscle decrease calcium and K channel activation, bronchodilation, prevent microvascular leakage and bronchial mucosal edema, increase mucous clearance use: Asthma and COPD terbutaline-inhibit uterine contractions with premature labor Administration-inhaled long acting Toxicity: TACHYCARDIA (bc there are B2 receptors in the heart that function to increase heart rate

Bronchodilators – Anti-Cholinergic

Ipratropium, Tiotropium

Action: Muscarini receptor antagonists-inhibit airway smooth muscle contraction, inhibits mucous secretions use: Asthma and COPD Administration: inhaled long acting

Bronchodilators

Methylxanthine, Theophylline, Aminophylline

Action: PDE inhibition, Adenosine receptor antagonism, anti-inflammatory Use: Asthma and COPD Administration: oral

Pulmonary HTN

- Prostacyclin (PGI2) and the IP receptor - Endothelin-1 and ETA receptor - Nitric xide and sGC

Epoprostenol, Iloprost

Action: PGI2 (IP) receptor agonists- lowers peripheral, pulmoary and coronary vascular resistance use: pulmonary hypertension Administration: IV and Inhalation, short half lives (5-30 min)

Bosentan, Ambrisentan

Action: ETA receptor Antagonists- lowers pulmonary resistance in PAH Use: Pulmonary HTN Administration: Oral IV and inhalation

Nitric Oxide and Pulmonary HTN

Action: Reduces pulmonary artery pressure, improves perfusion to ventilated areas Use: Pulmonary HTN, Acute hypoxemia, Cardiopulmonary resuscitation Administration: Inhalation

Smooth Muscle Physiology Flashcards

(52 cards)