Direct acting adrenergic agonists includes:
Albuterol B2, Conidine a2, Dopamine (D1,D2), Epinephrine a1,a2, b1,b2, Isopreterenol B1=B2, NE a1a2, Phenylephrine a1, Salmeterol B2
Indirecting adrenergic agonists
Mixed action (Release NE and directly activates receptor) includes :
How do the potency of catecholamines compare to non-catecholamines?
Catecholamines are more potent.
How do DOA of catecholamines compare to non-catecholamines?
Catecholamines are shorter acting
How do catecholamines compare to non-catecholamines with CNS penetration?
Non-catecholamines are better at penetrating the CNS
Examples of catecholamines:
Epi, NE, and isoproterenol
Examples of non-catecholamines
Phenylephrine, ephedrine and amphetamine
What is shock?
Complex cardiovascular system syndrome with inadequate tissue perfusion, hypotension, and various systemic effects
3 major mechanisms for shock:
Hypovolemia, cardiac insufficiency, altered vascular resistance
How does shock lead to death?
Decreases blood flow to organs like the kidney and dec and inc metabolic acidosis causing death
Ratio of catecholamines released by the adrenal medulla:
85% Epi, 15% NE
NE is inactivated by what two enzymes?
MAO, catechol-o-methyl transferase
Where are a2 receptors primarily located?
Presynaptic nerve endings
Stimulation of a2 receptors causes what?
Feedback inhibition of the ongoing release of NE
a1 receptors cause in increase in what ion?
Stimulation of a1 receptors results in the hydrolysis of what?
Polyphosphoinositides producing diacylglycerol and inositol triphosphates
a2 receptor stimulation causes inhibition of what?
Order of affinity for a-receptors
Epi > NE > Isoproterenol
Order of affinity for b-receptors
Isoproterenol > Epi > NE
Affinity of Epi for a and b receptors are...
How does NEs stimulation of a receptors compares to b receptors?
It stimulates a receptors much more strongly
How does NEs stimulation of b1 and b2 receptors differ?
It stimulates b1 receptors much more than b2 receptors so it can't produce vasodilation in lungs
Can NE produce vasodilation in lungs?
Where are a1 receptors located?
Vasculature, GI and GU smooth muscles, and cardiac muscle
Where are a2 receptors located?
Platelets, nerve terminals, vascular smooth muscle
Where are b1 receptors located?
Cardiac muscles, juxtaglomerular cells
Where are b2 receptors located?
Vascular, bronchial, GI and GU smooth muscle, skeletal muscle
Major effects mediated by a1 receptors include:
Contraction of smooth muscle of blood vessels -> inc bp, contraction of uterus, contraction/closure of sphincters of GI tract and bladder, mydriasis
Major effects mediated by a2 receptors:
Inhibition of NE and insulin release and lipolysis
Major effects mediated by b1 receptors:
Inc hr, inc myocardial contractility, inc lipolysis, inc renin release
Major effects mediated by b2 receptors:
Vasodilation, dec peripheral resistance, bronchodilation, inc muscle/liver gylcogenolysis, inc release of glucagon and insuli, relax uterine smooth muscle
Major effects mediated by b3 receptors:
Why is terbutaline or salmeterol better than Epi for treating asthma?
They don't activate b1 receptors like Epi does.
What is salbutamol/albuterol used for?
Acute asthma , symptom relief during maintenance therapy of asthma and other conditions with reversible airways obstruction, protection against exercise-induced asthma
What kind of drug is salbutamol/albuterol?
It's a short-acting b2 adrenergic receptor agonist used for relief of bronchospasm in conditions such as asthma and copd
Side effects of salbutamol/albuterol?
Hypokalemia, nervouseness, tremor, headache, muscle cramps, dry mouth and palpitation
Major effects mediated by D1 receptors:
Relax vascular smooth muscle (kidney)
Major effects mediated by D2 receptors:
Inhibit NE release
Which receptors increase adenylyl cyclase activity and increase cyclic AMP?
D1, b1, b2, b3
Which receptors decrease adenyly cyclase activity and cAMP?
D2 and a2
How does cocaine work?
It inhibits reuptake of dopamine
What drugs enhance release of NE from vesicles?
Which amphetamine is in cheese and wine & should be avoided when taking MAOIs?
What drug was recently banned by the FDA that's used for weight loss and boost sports performance and energy?
What does ephedra do to the circulatory system?
Stresses it and increases bp
At which receptor does epinephrine action predominate at low doses?
At which receptor does epinephrine action predominate at high doses?
Which adrenergic receptor causes inc release of glucagaon and glycogenolysis -> hyperglycemia?
What do a1 receptors do to vascular smooth muscles and bp?
Contract and increase
What do b2 receptors do to vascular smooth muscle and bp?
Relax and decrease
What's epinephrine used for?
Treat bronchospasm, glaucoma, anaphylactic shock, and to localize anesthesia
What are the cardiovascular actions of NE?
It increases systolic and diastolic bp and causes physiological antagonism.
What happens when NE is taken with atropine?
What's NE used to treat?
What induces reflex bradycardia due to + inotropy & chronotropy & subsequent vagal stimulation?
What receptors does isoproterenol act on?
b1 and b2
Actions of isoproterenol
Increases hr, force of contraction, co, dilates arterioles of skeletal muscle, dec peripheral resistance MAP and diastolic bp
Bronchodilator in asthma, to stimulate heart
Dopamine acts on which adrenergic receptors?
alpha and beta receptors
Actions of Dopamine
Increases h.r. & force of contraction, and vasoconstriction at high doses. dilates renal & splanchnic nerves, inc blood flow to kidneys
Which adrenergic receptors does dopamine activate at high conc?
What therapeutic uses for dopamine?
To treat congestive heart failure
Dopamine is better than which drug at treating congestive heart failure?
What is dobutamine?
It's synthetic, direct acting catecholamine
What are the actions of dobutamine?
It increases h.r & force of contraction
What's dobutamine used for clinically?
To treat CHF
Clinical actions of isoproterenol?
Bronchodilation, peripheral dilation & increased cardiac output
Clinical actions of dopamine?
Increased cardiac output and increased blood flow to the kidney unlike NE
What does NE do to all the blood vessels?
It constricts them and restricts blood flow to them
In cases of severe shock, dopamine is used alongside what drug?
What does nitroprusside do?
It produces venous and arteriolar dilation
What are the side effects of dopamine?
Reduced urine flow, tachycardia, and development of arrhythmias
Actions of amphetamines
Central stimulant, inc b.p (a&b) releases stored catecholamines
What's ephedrine used to treat?
Asthma and nasal decongestant
What's the kind of duration of action does ephedrine have and why?
Long duration of action because it's a poor substrate for COMT and MAO
Actions of Epherine
Inc b.p. , bronchodilate, CNS stimulant: inc alertness, dec fatigue, prevents sleep
What are amphetamines used to treat?
Attention deficit disorder and narcolepsy
What is tachyphylaxis?
Rapid decrease in the physiologic response to a drug after a few does aka acute tolerance
Examples of drugs that produce tachyphylaxis?
Ephedrine, and beta-receptor agonists
Examples of indirect acting agonists?
Amphetamine and tyramine
Examples of mixed action adrenergic agonists?
Ephedrine & metaraminol
Adverse effects of adrenergic agonists
Cardiac arrhythmias, headache, hyperactivity, nausea, insomnia, & tremors
Clinical uses of phenylephrine
Nasal decongestion, mydriasis, tx of supraventricular tachycardia, causes reflex bradycardia
What receptors does phenyephrine act on?
What receptors do albuterol/salmuterol act on?
What receptors do amphetamines act on?
alpha, beta CNS
What receptors does ephedrine act on?
alpha, beta, CNS
What receptors does isoproterenol act on?
beta-1 and beta-2
What receptors does NE act on?
alpha-1, alpha-2, and beta-1
What receptors Epi act on?
alpha -1, alpha-2, beta-1, beta-2
What's dopamine's effect on b.p.?
Increase systolic, no effect on diastoic
What's dobutamine's effect on b.p.?
What's Epinephrine's effect on b.p.?
What's NE's effect on b.p.?
What's isoproterenol's effect on b.p.?
Which drug causes necrosis, hypertension, and reduced blood flow to organs as side effect?
Which drug in contraindicated in pts receiving b-blockers?
Which drug causes restlessness, throbbing headache, tremor, palpitations, cerebral hemorrhaging, and cardiac arrhythmias?
Which drug causes angina pain a well as arrhythmias, headache, hypertension, & peripheral vasocostriction?
Which drug may lead to an infarct and cause ventricular ectopic activity while increasing b.p. and h.r.?