Adrenergic Drugs Flashcards
What is the biosynthesis and release of Catecholamines pathway? (8)
(1) Phenylalanine to Tyrosine (enzyme: phenylalanine hydroxylase)
(2) Tyrosine uptake into nerve cell
(3) Tyrosine to DOPA (enzyme: tyrosine hydroxylase)
(4) Dopa to Dopamine (enzyme: aromatic acid decarboxylase)
(5) Uptake of Dopamine into storage granules by active transport mechanism (also transports NE)
(6) Dopamine to NE (enzyme: dopamine beta-hydroxylase)
(7) NE to Epinephrine in adrenal medulla (enzyme: phenylethanolamine N- methyl transferase)
(8) Release of NE into synaptic cleft during nerve stimulation. Storage vesicles, containing the NE, fuse with neuronal membrane
What is the rate limiting step of the biosynthesis of Catecholamines?
Tyrosine Hydroxylase
What are 3 Catecholamines? Which one is the most prevalent?
(1) Norepinephrine**
(2) Epinephrine
(3) Dopamine
What are the 3 ways in which catecholamines are removed from biophase?
(1) Neuronal reuptake (uptake 1). Active transport of catecholamine into neuron where metabolized or taken back up into storage granule
(2) Diffusion into circulation
(3) Active transport (uptake 2) into post-junctional cells
What is the most important process in the removal of catecholamines?
Uptake 1 (pre-synaptic uptake mechanism)
What are the 2 ways the catecholamines are metabolized?
(1) Monoamine Oxidase (MAO): located in both neurons and post-junctional cells. Deaminates catecholamines
(2) Catechol-O-methyltransferase (COMT): located in post-junctional cells. Catalyzes the O-methylation of catecholamines
What are the two systems that impact the Sympathetic Nervous System? What do they do?
- Sympathomimetics: mimics SNS activation and enhances SNS activity
- Sympatholytics: block sympathetic neurotransmission
What are the 3 types of Sympathomimetics?
(1) Direct activity: act directly on the receptor (Epi, NE, Isoproterenol)
(2) Indirect activity: effect catecholamine levels in synapse (e.g. catecholamine release or uptake- Amphetamine, Tyramine, Cocaine, Imipramine)
(3) Combination: have mixed actions (Dopamine, Ephedrine)
What does indirect activity of sympathomimetics mean?
The actions of an indirect agent are dependent upon the presence of endogenous catecholamines (bind to post-synaptic adrenergic receptors)
What are the 3 Catecholamine Receptors?
(1) Alpha-adrenergic receptors
(2) Beta-adrenergic receptors
(3) Dopamine receptors
What are the subtypes of Alpha receptors? What are they known for doing?
(1) Alpha-1: smooth muscle contraction (vasoconstriction)
2) Alpha-2: pre-synaptic regulation of NT release (negative feedback mechanism
What are the non-selective Alpha agonists and antagonists?
- Agonists: Epi>NE>Isoproterenol (Epi and NE are better than Isoproterenol which is a beta agonist)
- Antagonists: Phentolamine and Phenoxybenzamine
What are the subtypes of Beta receptors? What are they known for doing?
(1) Beta-1: cardiac stimulation (heart rate, contractility)
2) Beta-2: smooth muscle: bronchodilation (lung) and vasodilation (e.g. vessels in skeletal muscle
What are the selective Alpha receptor subtypes?
Alpha-1: selective agonist- Phenylephrine
selective antagonist: Prazosin
Alpha-2: selective agonist: Clonidine
selective antagonist: Yohimbine
What is the non-selective Beta antagonist?
Propranolol
What are the Agonists and Antagonists of Beta receptors?
Beta-1: Agonists potency rank Iso>Epi=NE
- selective antagonist: Metoprolol
Beta-2: Agonist potency rank: Iso>Epi>NE
- selective agonists: metaproterenol,
albuterol, ritodrine
What are dopamine receptors?
CNS and renal localization (Agonist selectivity: Dopamine»Epi)
What is the selective antagonist of B-1 receptors?
Metoprolol
What are the selective agonists for B-2 receptors?
Metaproterenol, Albuterol, Ritodrine
What type of receptor does Norepinephrine work on?
A-1=A-2=B1»B2
What are the cardiovascular actions of Norepinephrine? What is the change in cardiac output?
- Increase TPR
- Increase BP (increase in S and D)
- Reflex decrease in HR
- No change in CO (increase in SV due to increase in venous return and B-1 effects in ventricle)
What is the formula for BP?
BP= HR x SV x TPR
- HR x SV= CO-
What type of receptor does Phenylephrine work on?
A-1 agonist
What are the cardiovascular actions of Phenylephrine?
Similar to NE (increase TPR, BP, decrease HR)
What type of receptors do Epinephrine work on?
B-1=B2>A-1=A-2
What are the cardiovascular actions of low dose of Epinephrine? High dose?
- Decrease in TPR
- Slight increase to no change in mean BP
- Increase HR
- Decrease renal and cutaneous flow
- At high dose, like NE -
What type of receptors does Isoproterenol work on?
B-1 and B2 agonists
What are the cardiovascular actions of Isoproterenol?
Similar to lose dose Epi with subtle difference
- Slight decrease in mean BP due to greater decreases in TPR and DBP (but not enough to stimulate reflex)
What type of receptors does Ephedrine work on?
Mainly indirect action but some direct (A and B agonists)
What are the cardiovascular actions of Ephedrine?
- Increase contractility
- Increase HR at low/mod doses
- High dose: Increase SBP, DBP, MBP with reflex bradycardia
What other action does Ephedrine do?
Bronchodilation via B-2 in lungs
- Long duration of action
What type of receptors does Albuterol work on?
B2 selective agonist
What does Albuterol do?
- Relaxation of airway smooth muscle
- are stimulated in vasculature with systemic administration
What type of receptors does Dopamine work on?
Dopamine, B1 and alpha agonists
What are the cardiovascular actions of Dopamine?
- increase renal blood flow
- Moderate dose: increase contractility and HR, increase CO, tachycardia less than isoproterenol
- High dose: increase TPR
What type of receptors does Dobutamine work on?
B1 and some A agonist
What are the cardiovascular actions of Dobutamine?
- Increase in contractility, HR, and CO (tachycardia less than iso)
- High dose: Increase in TPR
What type of receptors do Phenoxybenzazmine and Phentolamine work on? Which is irreversible?
non-selective alpha antagonists; Phenoxybenzamine irreversible
What are the cardiovascular actions of Phenoxybenzamine and Phentolamine?
- Decrease in TPR
- Increase in BP in upright individual
- No change or slight decrease in supine
- Reflex increase in HR
What are the adverse effects of Phenoxybenzamine and Phentolamine?
postural hypotension and tachycardia
What type of receptors does Prazosin work on?
alpha 1 selective antagonist
What cardiovascular actions act upon Prazosin?
Similar to non-selective drugs
- Less reflex increase in HR
What type of receptors does Propranolol work on?
non-selective beta antagonists
What are the cardiovascular actions on Propranolol?
B-1:
- Decrease HR, AV nodal conduction, contractility, CO
- Decrease renin release; decrease BP in hypertensive patient
B-2:
- acute increase peripheral vascular resistance
- increase airway resistance
What are the adverse effects of Propranolol? Precautions?
(1) Cardiac depression
(2) Lassitude
(3) depression
- asthma and diabetes precautions
What type of receptors does Metoprolol work on?
Beta 1 selective antagonists
What are the cardiovascular actions of Metoprolol?
B-1:
- Decrease HR, AV nodal conduction, contractility, CO
- Decrease renin release; decrease BP in hypertensive patient
- Little or no effect on airway resistance and peripheral vascular resistance
