ANS 2 (Sympathetic) Adrenergic Agonists drugs Flashcards
Sympathetic/ adrenergic response of pupils
Mydriasis
Sympathetic/ adrenergic response of heart
Tachycardia
Sympathetic/ adrenergic response of lungs
Bronchodilation
Sympathetic/ adrenergic response of liver
Inc conversion of glycogen to glucose
Sympathetic/ adrenergic response of adrenal glands in kidney
Secretion of noradrenaline and adrenaline
Enumerate the preview pathway of adrenergic transmission
1) hydroxylation of precursor aa tyrosine to DOPA or dihydroxyphenylalanine by the tyrosine hydroxylasr
2) decarboxylation to dopamine by the dopa decarboxylase
3) hyroxylation to noradrenaline /ne by the dopamine beta-hydroxylase
4) methylation to adrenaline or epi by the phenylethanolamine n-methyltransferase
What ion is needed for the tyrosine to enter the cell?
Sodium
As tyrosine enters the cell it will convert to ____ and this will convert to _____ .
Identify also the enzymes
Dopa or dihydroxyphenylalanine
Dopamine
First step of adrenergic transmission
Indicate its inhibitors
Synthesis of dopamine ( rls)
Inh: metyrosine , carbidopa
Second step of adrenergic transmission
Inhibitors?
Uptake of dopamine into vesicles ( converting it within the vesicle to norepi)
Inh: reserpine
Third step of adrenergic transmission
Inh?
Calcium causes release of ne
Inh: guanethidine, bretylium
What drugs causes NE release in adrenergic transmission process?
Amphetamine, methamphetamine, ephedrine, tyramine
Fourth step of adrenergic transmission
Binding of ne to receptors in the postsynaptic cleft
Fifth step of adrenergic transmission which decreases ne, epi and dopamine levels in blood
Inh?
Removal of ne, epi amd dopamine
Inh: cocaine tricyclic antidepressants (tca)
Urine metabolite of dopamine
Vma ( vanillylmabdelic acid)
Urine metabolite of epinephrine
Metanephrine
Urine metabolite of norepi
Normetanephrine
Receptors in heart and its adrenergic responses
Beta 1
Increased heart rate (chonotropy) and constriction ( inotropy) leading to increasef bp
Receptors in blood vessels and its adrenergic effect
Alpha 1: vasoconstriction
Beta 2: vasodilation
Receptors in beta islet cells of pancreas and its adrenergic effect
Alpha 2: decrease insulin and increases glucose, hyperglycemia
Beta 2 : stimulates insulin release
Receptors in bronchus and its adrenergic effect
B2 : bronchodilation
Receptor/s that promotes gluconeogenesis and glycogenolysis and what location?
B2 : metabolism
Receptor/s in presynaptic terminal / autoreceptor and its adrenergic effect
Alpha 2
Dec catecholamine or norepi release and bp
Dec vasomotor tone
Receptor/s in cns and its adrenergic effects
Dopamine 2
Stimulation of cns
D1-like receptors
D1,5
D2-like receptors
D2,3,4
T/f : all alpha receptors produces sympathetic responses
Not all; different response is based on the location and type of receptors
Divisions of adrenergic agonists
Direct acting
Indirect
Mixed
Divisions of direct acting adrenergic agonists Based on chemical structure
Catecholamines
Non-catecholamines
Drugs under catecholamines
Epi Norepi Dopamine Isoproterenol Dobutamine
Drugs under non catecholamines adrenergic agonsist
Phenylephrine
Metaprotereno
Methoxamine
Absence of one or both OH groups on the phenyl ring without other substitutions on the ring (effect?)
Reduce potency if the drugs
Effect of absence of one or both OH groups on the phenyl ring after oral admin
Increases its BA and prolongs duration of action
Increase the cns effects
Effects of substitutions in alpha carbon
Block oxidation by moa or monoamine oxidases and prolong action particularly noncatecholamines
Substitution of hydroxyl on beta carbon
Decreases actions within the cns,
Enhances agonist activity of alpha and beta adrenergic receptors
Contain 3,4-dihydroxybenzene ring
Highest potency in activating alpha or beta receptors
Metabolized by COMT , MAO
brief period action
Polar and do not readily penetrate into the CNS
Catecholamines
Longer half lives because not metabolized by comt and mao
Increased lipid solubility and greater access to the cns
Lack the 3,4-dihydroxybenzene ring
Non-catecholamines
Moa of direct acting sympathomimetic
Directly bind to adrenergic receptors
Classification of direc acting sypathomimetics/ adrenergic agonists
Alpha agonists
Beta agonists
Alpha and beta agonists
3 divisions under alpha agonists
Alpha 1 agonists
Alpha 2 agonists
Alpha 1 and 2 agonists
Drugs under alpha -1 agonists
Phenyelphrine
Phenylpropanolamine
Pseudoephedrine
Methoxamine
Drugs under alpha-2 agonists
Clonidine
Methyldopa
Guanfacine
Guanabenz
Drugs under alpha 1 and 2 agonists
Oxymetazoline
Xylometazoline
Causes intense vasoconstriction
I: hypotensive management, paroxysmal atrial tachycardia, nasal congestion
Ae: hypertensive headache, cardiac irregularities
Phenylephrine
Otc nasal congestant ( <25 mg)
Ae: hypertension
Phenylpropanolamine
Nasal decongestant taken orally other than phenypropanolamine
Ae: htn
Pseudoephedrine
Same with phenylephrine
Causes intense vasoconstriction
I: paroxysmal atrial tachycardia
Ae: hypertensive headache and vomiting
Methoxamine
Term for a2 agonists because it acts as antagonists but binds at a2 receptors
Sympathoplegic or sympatholytics
Tx of htn
Dec preganglionic sympathetic outflow from brain , dec norepi resulting in dec bp
Ae: orthostatic htn, withrawal induced rebound htn
Clonidine
Doc for gestational htn
Converted to _____ , a potent a2 receptor agonist
Dec preganglionic sympathetic outflow from brain resulting in dec bp
Methyldopa
Alpha-methylnorepinephrine
Ae: mild orthoatatic htn, rebound htn, Coombs positive rbc which causes reversible hemolysis
Methyldopa
Other drug which
I: clinical htn
Potent a2 agonist
Ae: orthostatic htn
Guanabenz, guanfacine
Effects depends on its affinity to each alpha receptor
Alpha 1 and 2 agonists
Higher affinity in alpha 1: nasa decongestant
Oxymetazoline
Xylometazoline
Drugs under b2 agonist
PASing oF FB in MRT Pirbuterol Albuterol/ salbutamol Salmeterol Formoterol Fenoterol Bitolterol Metaproterenol Ritodrine Terbutaline
Drugs under b1and 2 agonists
Isoproterenol
Bronchodilation to manage asthma
Relax uterus in near-term pregnant woman
B2 agonists
Causes intense vasodilation and doesn’t bind to alpha1
Reduces mean arterial preasure
I: heart failure because it stimulates heart more than epi
Ae: same w/ epi
Isoproterenol ( b1&2 agonist)
Rapid onset but brief duration
Aka adrenaline
I: bronchodpasm(b2) , anaphylactic rxn(a1) , cardiac arrest (b1), open angle glaucoma (a1)
Combined with local anesthetics which delays distribution of anesthetic away from the injection site due to vasoconstriction (a1)
Epinephrine
Receptor which has higher affinity with epi
Alpha 1
More intense vasoconstriction than epi because drug fails to bind to b2 receptors or beta
I: hypotension
Norepinephrine
Receptors affected by low dose of dopamine
Dopamine receptors
Receptors affected by moderate doses of dopamine
Dopamine and beta receptors
Receptors affected by high doses of dopamine
Dopamine, beta and alpha receptors ( constricts all vessels)
B1 > b2 > alpha and doesnt bind to dopamine
I: chf
And increases cardiac output (b1)
Dobutamine
Moa of indirect acting adrenergic agonists
Drugs Causing norepi release from presynaptic terminals but do not bind to receptors
Drug causing htn in depressed patients takine maoi
Tyramine
I: narcolepsy, adhd, appetite suppression m, Parkinson’s disease
Improve brain development, and nerve growth due to increase nt activity
Amphetamine, metamphetamine
Moa of Mixed adrenergic agonist
Indirect plus direct
Mixed adrenergic agonist
I: Asthma, nasal congestion, narcolepsy, myasthenia gravis
Longer duration (poor substrate for comt and mao) but leas potent than epi
Ae: less cns toxic than amphetamines
Ephedrine
I: shock, acute hypotension and when norepi or dopamine is not possible
Little cns toxicity
Metaraminol
2 divisions of adrenergic antagonists
Direct and indirect
Divisions under direct adrenergic antagonists
Alpha blockers
Beta blockers
Divisions under alpha blockers
Alpha 1 blockers
Alpha 2 blockers
Alpha 1 and 2 blockers
Drugs under a1 blockers
Trimazosin Prazosin Doxazosin Alfuzosin Terazosin
Drug/s for hypertension, benign prostatic hyperplasia (BPH) hard to urinate
Ae: first-dose syncope (fainting)
Trimazosin Prazosin Doxazosin Alfuzosin Terazosin
Drug/s under a2 blockers
Yohimbine
Indole alkaloid
Found in the bark of the tree Pausinystalia yohimbe and in Rauwolfia root
Treat erectile dysfunction
Yohimbine
2 drugs if a1 and a2 blockers
Phenoxybenzamine
Phentolamine
I: hypertension due to pheochromocytoma or too much adrenaline released from adrenal gland causing a tumor
Or may be due ti intake of MAO
Raynaud’s syndrom
Phenoxybenzamine
Phentolamine
A1 &2 blocker
Irreversible antagonist
Long lasting but short onset
Phenoxybenzamine
A1&2 blocker reversible antagonist
Short half life, rapid onset
Phentolamine
3 phases of raynaud’s syndrome
1) ischemia
2) cyanosis
3) rubor
Prototype ninselective vasoconstrictor
I: hypertension, glaucoma, chronic migraine, severe hyperthroidism, chronic managemnt of stable angina, myocardial infarction, arrythmias
Propranolol
Ae: fasting hypoglycemia due to decrease glycogenolysis
Propranolol
More potent than propranolol
I: htn, angina pectoris
Nadolol
Chronic open angle glaucoma by reducing intraocular pressure
Timolol
Has action potential prolonging class/phase 3 (repolarization) relaxed heart
-life thratening ventricular arrythmias
Sotalol
B1 and b2 blockers that are non selective both a and b
Labetalol
Carvedilol