Sympathomimetics Flashcards
List the G-protein/effector/2nd messengers for alpha 1 receptors:
- G-protein: Gq (stimulatory)
- effector: Phospholipase C
- 2nd messengers: IP3, DAG, Ca2+
List the G-protein/effector/2nd messengers for alpha 2 receptors:
- G-protein: Gi (inhibitory)
- effector: adenylate cyclase
- 2nd messenger: cAMP
List the G-protein/effector/2nd messengers for beta 1 receptors:
- G-protein: Gs (stimulatory)
- effector: adenylate cyclase
- 2nd messenger: cAMP
List the G-protein/effector/2nd messengers for beta 2 receptors:
- G-protein: Gs (stimulatory)
- effector: adenylate cyclase
- 2nd messenger: cAMP
List the 5 2nd messengers involved in adrenergic G-protein coupled receptors:
- cAMP
- cGMP
- IP3
- Ca2+
- DAG
Stimulation of alpha 1 receptors results in what effect on Ca2+?
increased Phospholipase C –> increased Ca2+
Simulation of alpha 2 receptors results in what?
inhibition of adenylate cyclase –> decreased cAMP
Stimulation of beta 1 receptors results in what?
stimulation of adenylate cyclase –> increased cAMP
Stimulation of beta 2 receptors results in what?
stimulation of adenylate cyclase –> increased cAMP
Beta 2 receptors are primarily found in the (heart/lungs) and have a (higher/lower/equal) affinity for Epi.
- lungs
- higher
Beta 1 receptors are primary found in the (heart/lungs) and have a (higher/lower/equal) affinity for Epi.
- heart
- equal
Stimulation of dopamine 1 receptors has what effect?
- stimulation of adenylate cyclase in neurons and vascular smooth muscle
- increased cAMP
Stimulation of dopamine 2 receptors results in what?
- inhibition of adenylate cyclase
- open K+ channels
- decreased Ca2+ influx
Which dopamine receptors are centrally located?
dopamine 2
Where are the catecholamines synthesized?
Dopamine: CNS neurons
Epinephrine: 2nd order neurons of SNS in the adrenal medulla
Norepi: 2nd order neurons of the SNS, adrenal medulla, CNS neurons
Define “sympathomimetic”
a drug that mimics the effect of Epi and Norepi
How are sympathomimetics grouped?
by mode of action and spectrum of affected receptors
- direct mode: directly interacts with and activates receptor
- indirect mode: 1) displace catecholamines from adrenergic nerve ending OR 2) inhibition of reuptake of catecholamines
List the tissues where apha-1 receptors are located;
bladder sphincter
liver
pupil dilator muscle
uterus
vascular smooth muscle
List the tissues where alpha-2 receptors are located:
platelets
post-ganglionic sympathetic neurons
vascular smooth muscle
List the tissues where beta-1 receptors are located:
heart
pancreas
List the tissues where beta-2 receptors are located:
bladder wall
liver
vascular smooth muscle
uterus
List the tissues where beta-3 receptors are located:
adipose tissue
List the alpha-1 agonists:
- Epi
- Norepi
- Phenylephrine
List the alpha-1 antagonists:
- Phentolamine
- Phenoxybenzamine
- Prazosin
List the alpha-2 agonists:
Clonidine
Dexmedetomidine
List the alpha-2 antagonists:
Yohimbine
List the beta-1 agonists:
- Dobutamine
- Dopamine
- Epi
- Norepi
List the beta-2 antagonists:
Atenolol
Metoprolol
List the beta-2 agonists:
Albuterol
Terbutaline
List the beta-2 antagonists:
Propranolol
Receptor selectivity of phenylephrine:
A1 > A2»_space;»» B
Receptor selectivity of clonidine:
A2 > A1»_space;»> B
Receptor selectivity of norepi:
A1 = A2
B1»_space; B2
Receptor selectivity of epinephrine:
A1 = A2
B1 = B2
Receptor selectivity of dobutamine:
B1 > B2»_space;»» A
Receptor selectivity of isoproterenol:
B1 = B2»_space;»> A
Receptor selectivity of albuterol/terbutaline:
B2»_space; B1»_space;»> A
Receptor selectivity of dopamine:
D1 = D2»_space;» B»_space; A
What is the parent drug from which sympathomimetic drugs are derived?
Phenylethylamine
2 effects sympathomimetics can have on the metabolism:
1) enhance glycogenolysis in the liver
2) metabolic acidosis (high presence)
Sympathomimetic effects on blood vessels:
A: increase arterial resistance
B: increase smooth muscle relaxation
Sympathomimetic effects on blood pressure:
pure A: increase peripheral arterial resistance, decrease venous capacitance (increase BP, decrease HR d/t baroreceptor increase vagal tone)
pure B: increase CO, decrease PVR (increased/decreased SBP with decreased DBP)
mixed: skeletal muscle bed relaxation (decreased DBP) + alpha constriction of arterial beds
Sympathomimetic effects on heart:
B1: increase chronotropy, increase conduction velocity through AV node, increase contractility
Sympathomimetic effects on respiratory tract:
B2: bronchodilation
Sympathomimetic effects on eye:
A: mydriasis
Sympathomimetic effects on GI tract:
A & B: relaxation
Sympathomimetic effects on GU tract:
A & B: uterus
A: urinary continence (bladder base and urethral sphincter)
Describe the order of events of formation of Epinephrine:
Tyrosine
Dihydroxyphenylalanine
Dopamine
Norepi
Epi
Tyrosine –> DOPA is catalyzed by…
tyrosine hydroxylase
DOPA –> Dopamine is catalyzed by…
DOPA decarboxylase
Dopamine –> Norepi is catalyzed by…
dopamine-B-hydroxylase
Norepi –> Epi is catalyzed by…
phenylethanolamine-N-methyltransferase
What is the rate limiting step of catecholamine synthesis?
formation of DOPA from tyrosine by tyrosine hydroxylase
The rate limiting step of catecholamine synthesis is regulated by what mechanism?
Norepinephrine negative feedback loop
In what 3 ways are catecholamines removed from the site of action?
1) reuptake into the presynaptic nerve (80%)
2) reuptake by extraneuronal tissues (contain the MAO and COMT)
3) diffuse away from synaptic cleft (enters circulation and metabolized in kidney and livery by COMT and MAO)
What is COMT short for?
catechol-O-methyltransferase
Describe the effects of Epinephrine:
- positive inotropic and chronotropic actions on heart
- vasoconstriction
- decreased total peripheral resistance (–> DBP) in skeletal muscle beds
Dose/onset/duration of Epi:
- dose: 10-100mcg bolus; 0.01-0.2 mcg/kg/min
- onset: 30-60 sec
- duration: 5-10 min
Describe the effects of Norepi:
- vasoconstriction
- increased SBP, DBP, coronary blood flor
- ? decreased HR
- decreased blood flow to major organs
Dose/onset/duration of Norepi:
- dose: 0.04-0.4 mcg/kg/min
- onset: <1 min
- duration: 2-10 min
Describe the effects of dopamine:
D1: vasodilation, increased renal/mesenteric/coronary/cerebral BF
D2: inhibits Norepi release
B1: increase myocardial contractility/SV/CO, inotropic
A: vasoconstriction
Describe the effects of Isoproterenol:
- pure B1 & B2 agonist
- positive chronotropic and inotropic effects
- increased rate of cardiac pacemaker discharge
- potent vasodilator (decreased SVR & pulm VR)
- increase CO, decrease DBP, slight increase SBP
- potent relaxation of bronchial smooth muscle
Which sympathomimetic is used in inhaler form in the cath lab?
Isoproterenol
Describe the effects of Dobutamine:
- selective B1 agonist
- increased myocardial rate and force of contraction
- facilitates AV conduction
“Sympathectomy” is another name for what?
spinal anesthesia
Why might a patient get nauseated after receiving a spinal?
increased vagal activity after sympathectomy causes increased peristalsis of the GI tract
(treat the BP w/ Ephedrine and the nausea should improve)
What is the MOA of Phenylephrine?
- pure A agonist
- acts directly on the receptors
Describe the effects of Phenylephrine:
- intense peripheral vasoconstriction
- increased SBP, DBP
- reflex bradycardia
- decongestant
What is the MOA of Ephedrine?
- both A and B stimulation
- mixed direct and indirect actions
- prevents breakdown of NE by MAO –> increased release of stored NE
Describe the effects of Ephedrine:
- increased CO, BP, HR
Why should Ephedrine be used cautiously in patients on MAOIs?
MAOIs sensitize the patient to indirectly acting sympathomimetics –> hypertensive emergency
Where does Vasopressin act on the body?
direct action on vascular smooth muscle
What are some precautions to using vasopressin?
- reduction in CO, myocardial contractility, and coronary BF
Describe albuterol’s MOA:
- short-acting B2 agonist
- inhaled
- used for rapid relief of wheezing, bronchospasm, and airflow obstruction
Describe Salmeterol/Formoterol’s MOA:
- long-acting B2 agonist
- always used in combination therapy
What are 2 side effects of inhaled B2 agonists?
- tremors
- tachycardia
What drug is a quick treatment for hyperkalemia?
inhaled Albuterol
Describe the MOA and uses of Terbutaline:
- B2 agonist
- tocolytic
What is the MOA of selective phosphodiesterase inhibitors?
- decrease hydrolysis of cAMP
- augmentation of myocardial performance independent of the SNS
Describe the effects of selective phosphodiesterase inhibitors:
- positive inotropic effects
- vascular and smooth muscle relaxation
What patients would benefit from selective phosphodiesterase inhibitor therapy?
acute cardiac failure needing increased myocardial contractility and vasodilation
What drug class does Milrinone belong to? What is this drug used for?
- selective phosphodiesterase inhibitor
- has minimal effect on HR and myocardial O2 consumption
- beneficial for LV dysfunction after cardiac sx
Ionized calcium is a potent (chronotrope/inotrope).
inotrope
What does the drug Levosimenden do?
- increases contractility by increasing the sensitivity of the myocardium to Ca2+
- increases CO
- decreases SVR and pulm VR
