Adrenergics/Antiadrenergics Flashcards
What is the catecholamine synthesis pathway?
Tyrosine –> dopa –> dopamine –> norepinephrine –> epinephrine
Which type of antiadrenergic causes the worst tachycardia?
Non-selective alpha blockers (worse than selective a1 blockers)
This is because blocking a1 drops BP and blocking a2 prevents feedback inhibition of NE release –> two factors that cause your HR to increase
What enzymes metabolize catecholamines?
Monoamine oxidase (MAO) and catechol-o-methyl-transferase (COMT)
Both are in the liver, kidneys, and GI tract
Discuss what happens with chronic adrenergic agonist/antagonist use.
Chronic adrenergic agonist use can lead to desensitization and downregulation, while chronic antagonist use can have the opposite effect
What three drugs block the NET (norepinephrine transporter) to increase synaptic NE?
CIA - cocaine, imipramine, and atomoxetine
Describe the mechanism of action of tyramine.
The large load of tyramine displaces NE from vesicles forcing NE out where it can be degraded by MAO (this is why you get hypertensive crisis if on MAOI and have tyramine)
*Tyra Banks is mean because she throws out and degrades excited models when their pictures suck, and then they all have hypertension because they’re depressed and have no skills because they’re models and it’s a midlife crisis.
Describe the mechanism of action of guanethidine.
Enters via NET and concentrates in the vesicles blocking NE so MAO metabolizes it.
*Guanethidine is the ugly girl who wishes she was Tyra Banks but she’s fat and just gets physically in the way of excited models.
Describe the mechanism of action of reserpine
It blocks VMAT (the transport protein that brings neurotransmitters into vesicles), depleting vesicular NE over time (gradual effect).
*Reserpine = no more reserve
What are the xanthines and how do they work?
Caffeine and theophylline. They are antagonists at adenosine receptors causing CNS stimulation.
*THEY DON’T BIND ADRENERGIC RECEPTORS
Where are B1 receptors located and what happens when stimulated?
In the heart; increase HR, contractility, conduction, and irritability
What happens when you stimulate B2?
Vasodilation –> decreased BP, bronchodilation, increased glycogen breakdown
What happens when you stimulate a1 receptors?
Decreased secretions, increased BP/automaticity/HR/conduction velocity/CO/oxygen consumption, decreased cardiac efficiency, decreased glycogen synthesis, bladder sphincter contraction
What happens with B3 stimulation?
Increased free fatty acids, relaxation of the detrusor muscle
What is the mechanism of action of epinephrine?
Agonist to it all, a1, a2, B1, B2, B3
What drug interactions are relevant when giving epinephrine?
Any alpha blockers. It will cause a dip in blood pressure from B2 effects, which is called “epi reversal”
What are the primary clinical uses of epinephrine?
Drug of choice for anaphylaxis, also used to support BP and in cardiac arrest to resuscitate the heart
What is the mechanism of action and use of norepinephrine?
It is an a1 and B1 agonist used for shock
What drug is a non-specific beta agonist?
Isoproterenol
*Iso, equal, likes both betas because equality.
What is the clinical use of isoproterenol?
Used in emergencies to stimulate the heart in patients with heart block and when preparing to insert a pacemaker.
*Better start up your heart again before you turn to ice…
Describe the mechanism of action and clinical use of dopamine.
It is an agonist at DA receptors, B1, B2, and at high doses a1. It’s used for cardiogenic shock.
What is a common side effect of dopamine receptor agonists?
The stimulation of the chemoreceptor trigger zone (CTZ) which induces vomiting.
Describe the mechanism of action and clinical use of dobutamine.
It is a B1 agonist, and at high doses a1 agonist. Used to treat heart failure associated w/ MI or open heart because it is mostly selective for B1 giving rise to unique inotropic qualities
Describe the mechanism of action and clinical use of phenylephrine.
An alpha agonist used to treat rhinitis. Is a decongestant of mucous membranes, raises BP, dilates pupils (thus used in eye drops)
Describe the mechanism of action and clinical use of ephedrine.
A weak alpha and beta agonist that also releases NE (CNS stimulant) used as a nasal decongestant and as a pressor agent.
Name the selective B2 agonists and what they treat.
Albuterol and terbutaline, treat asthma.
*Terbutaline sounds like turtle, and they can’t breathe underwater so there ya go - asthma
Describe the mechanism of action and clinical use of amphetamine.
A substrate for NET so it increases synaptic NE via facilitated exchange diffusion (risk of abuse, can cause excessive CNS stim). Used for narcolepsy and weight reduction
*well just think methamphetamine which makes you skinny and you can stay awake looking for drugs
Describe the mechanism of action and clinical use of methylphenidate.
A CNS stimulation, used to treat ADD/ADHD.
Also called RITALIN AHHHH DUH.
Describe the mechanism of action and clinical use of phenoxybenzamine.
An alpha blocker somewhat selective for a1 that is irreversible. Used for pheochromocytoma mgmt (medulla tumor), BPH (relaxes smooth muscle in bladder, prostate capsule, and prostatic urethra to improve flow)
*Pheno for your pheo and your peno…penis……
Describe the mechanism of action and clinical use of phentolamine.
A non-selective alpha blocker used w/ propanolol for pheochromocytoma mgmt.
*remember that non-selective alpha blockers have worse reflex tachycardia
How does a2 help regulate NE release?
There are presynaptic a2 receptors that exert feedback inhibition when stimulated by NE
Describe the mechanism of action and clinical use of propanolol
A non-selective beta blocker that treats angina and SVT arrhythmias
*remember that B1 increases CO (cardiac output) so blocking that has the opposite effect, so drop in CO and all the other B1 things cause drop in BP and HR
Describe the mechanism of action and clinical use of atenolol and esmolol.
Both are selective B1 blockers (so there’s reduced risk of bronchospasm). Esmolol has a short half-life good in emergencies. They decrease HR, myocardial O2 demand, etc.
Describe the mechanism of action and clinical use of timolol.
A non-selective beta blocker (though it’s used for it’s B1 effects) to treat glaucoma by decreasing aqueous humor production
Describe the mechanism of action and clinical use of prazosin.
An alpha blocker for htn and BPH
What two drugs are a2 agonists and what is their effect?
Clonidine and methyldopa.
As a2 agonists they cause inhibition of NE release, useful in treating essential htn
What side effects are associated with clonidine?
It is used to treat opioid withdrawal symptoms but ironically can have abrupt withdrawal itself when stopped causing hypertensive crisis
*Clonidine clobbers you with hypertension if you don’t take it.
