adrenergics Flashcards
catecholamines and sympathomimetics
peripheral excitatory action on smooth muscle (blood vessel, radial muscle, glands)
peripheral inhibitory action on smooth muscle (gut, bronchial tree, blood vessels in muscle)
cardiac excitatory action that increases heart rate and contraction
metabolic actions (increases glycogenolysis, lipolysis)
endocrine actions: decrease insulin release, increase renin release
CNS: resp stim, increase wakefulness, psychomotor activity, reduction in appetite
endogenous catecholamines
norepinephrine, epinephrine, and dopamine
epinephrine
receptor selectivity, CV effects, Resp effects, metabolic effects, absorption/fate and excretion, therapeutic uses
naturally occuring, synthesized in adrenal medulla
Receptor selectivity: a1 a2 B1 B2
Cv effect: potent vasopressor via (a1) can dialate some beds at low loses (B2), with large bolus- rapid increase in BP (a1) and increase in HR/cont/CO (B1). w/ low dose- increase in HR/cont/CO B1, increase in systolic pressure, but decrease in diastolic pressure (B2 dialation of sk muscle) MAP doesnt change
Resp: powerful bronchodilation (B2)
met: increase in glucose and fatty acids in blood
abftex: not effective with oral, short T12
Therapeutic uses: releif of hypersensitivity reaction to drugs and other allergens, co administered with anesthetics to increase duration, bradyarrhthmias
ophthalmic uses: mydriatic, decrease hemorrhage, conjuctival decongestion
Norepinephrine
receptor selectivity, CV effects, Resp effects, metabolic effects, absorption/fate and excretion, therapeutic uses
receptor selectivity (a1 a2 B1)
CV: a1 mainly, PVR up, increases BP, can cause reflex bradycardia
resp: no B 2 activity
abftex: like epi
therapeutics: used as a vasoconstrictor shock hypotension
dopamine
receptor selectivity, CV effects, therapeutic uses
receptor selectivity (D1, B1 a1
CV: low doese (D1 receptro effects), vasodilation of renal and mesenteric aa, decrease peripheral receptors
med dose (D1 and B1) increase HR/cont/CO increases systolic w/o diastolic
high dose (D1 B1 a1 effects)- cardiostimulation and genrealized vasoconstriction
therapeutic uses: sever decompensated hrt failure shock, only used IV
non selective B-adrenergic receptor agonists
isoproterenol, dobutamine,
Isoproterenol receptor selectivity, CV effects, Resp effects, metabolic effects, absorption/fate and excretion, therapeutic uses
receptors: B1 and B2
CV: decrease PR, increased HR/Cf/CO, decreased MAP
resp: bronchodilation
abftex: metabolized by COMT in liver, duration of action is brief
therapeutic: emergency use (IV) to stimulate HR during bradycardia/heart block
dobutamine receptor selectivity, CV effects, Resp effects, metabolic effects, absorption/fate and excretion, therapeutic uses
receptor selectivity: (-) and (+) isomers
- isomer: a1 agonist and B agonist
+ isomer: a1 antagonist and B agonist
racemic mix for overall B1 agonist effects
CV effects: increased CR/cont/CO
minimal change in peripheral resist and BP
therapeutics: short T.5 admin IV, short term of cardiac decompensation
cardiac stress test
B2- selective adrenergic agonists
Albuterol (short acting) and Salmeterol (long)
albuterol receptor
act on B2 adrenergic receptors, adrenergic receptors, administered by inhalation or orally
short acting relief of bronchoconstriction
side effects: tremor anxiety and tachycardia (B1 activation)
salmeterol
B2 receptor only inhaled, long acting, with inhalation
COPD, moderate or severe persistent asthma, not suitable for monotherapy
a1- selective adrenergic receptor agonist
phenylephrine
potent vasoconstrictors due to stimulation of alpha1 receptors in vascular smooth muscle
clinical utility of the drugs is limited but treat for hypotension
some useful as nasal decongestant
acts only on alpha1 (increases systolic and diastolic BP, decreases HR (reflex), decreases blood flow to most vascular receptors
therapeutics:
ophthalmic: mydriatic
nasal decongestant
hypotension
a2 selective adrenergic receptor agonists
clonidine, methyldopa
used for the treatment of systemic hypertension
lower BP via CNS represses sympathetic tone
clonidine
orally active a2 agonist reduces sympathetic outflow
decreases peripheral resistance HR and CO
Major therapeutic use: anti hypertensive agent
side effects: occur in 50% of pts (drymouth and sedation)
methyldopa
orally active prodrug
methyldopamine-> methyl NE
treats hypertension in pregnancy
sedation and dry mouth
tyramine
indirect acting sympathomimetic
releases NE from sympathetic nerves cause sympathomimetic actions
not used as a therapeutic, found in high levels in certain foods (wines beer cheese) MAO-A inactivates it
in patients taking MAO inhibitors, ingestion of tyramine can cause hypertensive crisis
amphetamine
powerful CNS stimulation and sympathomimetic actions
effective after oral administration- long t1/2
d more effective than I
releases NE and other biogenic amines dopamine from storage sites in nerve terminals
CNS- stimulant, appetite suppresant, stimulates resp
dependance and tolerance can develop
for narcolepsy and ADHD
pseudophedrine
direct a1 agonist activity with slight B2 agonist activity (orally effective but less CNS stim than amphetamine
major therapeutic use nasal decongestant (a1)
adrenergic neuron blocker
drugs that disrupt adrenergic neuron function by inhibiting the synthesis, storage, release of NE
drugs historically used as antihypertensive agents
Guanethidine and guanadrel, reserpine
guanethidine and guanadrel
inhibit NE release and deplete neuronal stores
orally active compounds used to treat severe hypertenstion
Guanethidine, polar compound, does not enter CNS
long acting, taken into adrenergic nerves by the NE transporter (NET)- effects inhibited by tricyclic anti depressents, side effects lots including orthostatic hypotension sexual function, diarrhea, muscle weakness, edema
reserpine
diffuses into adrenergic nerves, transport doesnt require the NET
treats hypertension, can enter brain and CNS (dpression suicide) sedation
adrenergic receptor antagonists
inhibit the interaction of NE, epi, and sympathomimetics
compounds have been devlpd that have different binding affinities fot the various receptors
alpha blockers
specifically block a receptors
a1: arterial/venous visceral smooth muscle (prostate and bladder)
a2: inhibition of NE from nerve terminals
non selective a blockers
phenoxybenzamine, phentolamine both block both a1 and a2
phenoxybenzamine- irreversible antagonist- orally active long duration, block lasts, need to resynthesize receptors
phentolamine- competitive reversible antagonist, orally active block can be overcome by agonist
use for pheochromocytoma
sid e: hypotension reflex cardiostimulation (tachycardia)
a1- specific blockers
prazosin and tamsulosin
Prazosin
orally active competitve blocker, minimal tachycardia bc of a1 only
decreases vascular tone
produces favorable effects on lipid profile
hyper tension and shrt term treatment of congestive heart failure
1st dose orthostatic hypotension
tamsulosin
favors prostate
effective for treatment of benign prostatic hyperplasia
no hypertension
B blockers
3 classes: non subtype selective (first gen), B1 selective (2nd gen), B antagonist w/ additional CV actions
general B blocker effects of CV effects, Resp effects, metabolic effects, absorption/fate and excretion, therapeutic uses
CV: slows HR/cont, reduces sinus rate, lowers BP
Pulm: B2 blockade can cause bronchoconstriction
metab: lowers glucose and lipid in blood vessels
pertension)
side effects: cv (heart failure), brady cardia; pulm exacerbate COPD and asthma; CNS fatigue, sleep disturbances; met (hypoglycemia);
use to treat CV disease (angina hy), glaucoma, tremors
non specific B blocker
propranolol, Timolol
propranolol
orally bioavailable large 1st passs w/ shot T12 enters CNS
hypertension, angina, cardiac arrythmia, MI, pheochromcytoma, tremmors
timolol
no intrinsic activity
B1 selective blockers
both have decreased pulm side effects
metoprolol, atenolol (less CNS)
third generation B blockers
have other CV actions
Labetalol: antagonist of a1 B1 B2 (emergency hypertension)
Carvedilol: anagonist of a1 B1 B2: MI heart failure
