Adrenergics Flashcards
alpha 1 receptor
DAG IP3 Ca++ NE can act on it post synaptic; constriction f vessels; skin GI kidneys brain (will increase TPR and BP)
alpha 2
decrease production of cAMP, inhibit further release of NE from neuron, acts presynaptically, also reduces insulin (negative feedback), also inhibit acetylcholine
beta 2 smooth muscle
smooth muscle receptor + Epi – increase cAMP, reduce Ca++ intracellularly and sensitivity to myofilament, smooth muscle relaxes blood vessel dilates, reduce TPR BP goes down
beta 1 receptor cardiac myocyte
increase cAMP, increase PKA, phosphorylate L type channel on membrane increase influx of Ca++, increaes intracellular Ca++, cardiac myocyte will contract more and increase cardiac output
Beta 1 general
tachycardia, increase lipolysis, increase myocardial contractility, increase renin
Beta 2 general
vasodilate, decrease TPR, bronchodilation, increase muscle and liver glycogenolysis, increase glucagon, relax uterine smooth muscle
alpha 1 a
Tamsulosin selective alpha1A antagonist used to treat benign prostatic hyperplasia with fewer cardiovascular side effects. Alpha 1A primarily found urinary tracts, prostate gland
Oxymetazoline
alpha 1 and alpha 2 agonist; OTC in decongenstants and opthalmic drops, stimulate receptors on nasal mucosa and conjunctiva; absorbed in circulation, produces nervousness, headaches, troubled sleeping, local irritation and sneezing, rebound congestion and dependence
Phenylephrine
alpha 1 agonist, vasoconstrictor, raises systolic and diastolic BP, no effect on heart, produces reflex bradycardia, tx for hypotension in hospitalized pts wtih rapid HR, decongestant (replaced by pseudoephedrine) used in opthalmic sln for mydriasis; large doses can cause hypertension, headache and cardiac irregularities
Clonidine
alpha 2 agonist; acts on presynaptic neurons, decreases sympathetic outflow to the periphery, antihypertensive, minimizes withdrawal symptoms from opiates, tobacco, smoking, benzoiazepines, produces lethargy, sedation, consitpation, xerostomia, abrupt discontinuation causes rebound hypertension
Dobutamine
B1 agonist; increase heart rate and CO with no net effect on vasculature, used in heart failure to increase CO and as inotropic support after cardiac surgery; use w cuation in A Fib patients because it increases AV conduction
Albuterol & terbutaline
short acting B2 agonists; bronchodilators used in meter dose inhalers. albuterol is choice of tx in acute asthma, terbutaline not used in US and used to suppres premature labor; causes tremor, restlessness, apprehension, anxiety, oral may cause tachycardia or arrhytmia (b1) in pts w cardiac disease, contra w MAO inhibitors
Salmeterol and Formoterol
long acting selective B2 agonists; bronchodilators in meter dose inhaler cause sustain bronchodilation for 12 hrs. Salmeterol has delyaed onset. effective w corticosteroid. some increase in asthma related deaths. tx for nocturnal asthma.
Mirabegron
beta 3 agonist, relaxes detrusor smooth muscle, increase bladder capacity, may increase bp, may increase digoxin, decrease cyp2D6 that may enhance effect of drug metabolized by this pathwway like metoprolol
indirect adrenergic agonist
indirect agonist, can inhibit reuptake, cause release, inhibit degradation, potentiate effects of NE or Epi produced endogenously
Amphetamine
inc nonvesicular release of Da and NE from nerve terminals, CNS stimulant, can increase BP (alpha 1) can stim B1 on heart. indirect adrenergic agonist
Tyramine
can enter nerve terminal and displace stored NE (derivative of tyrosine) can enter nerve from same Na transporter to enter nerve. not clinically used but found in fermented food (aged cheese and wine) byproduct of tyrosine metabolism, normally metabolized by MAO in GI but if taking MAO inhibitor then serious vasopressor effect. indirect adrenergic agonist.
Cocaine
adrenergic agonist, indirect. blocks presynaptic Na/Cl dependent transporter (NET DAT) mediating Ne and DA reuptake.enhances sympathetic activity and potentiates the actionso f Ne in cocaine users, increse BP (alpha 1 effect on vasculature)
Mixed acting agents
cause release of NE from nerve endings, and direct action on alpha and beta adrenergic receptors.non catechol so long acting (not broken down by comt or mao)
Ephedrine and Pseudoephedrine
oral absoroption, penetrate CNS (pseudo has less CNS effects), ephedrine elimimated urine, pseudoephedrine metabolized incompletely in liver eliminated in urine; ephedrine increase increase systolic and diastolic, can treat hypotesnsion, ephedrine produces bronchodilation, cns stimulant; pseudo decongenstant otc (but now regulated bc of methamphetamine)
Phenoxybenzamine
irreversible alpha 1 and alpha 2 blocker; long lasting, oral dosing only; major actions on Cardiovascular system and will reverse epinephrine effects. prevents peripheral vasoconstriction, provokes tachycardia, can increase CO by blocking presynaptic alpha 2. see slide for full effects. Used for pheochromocytoma; also Raynaud disease and Frostbite; can cause tachycardia (reflex) and postural/othrostatic hypotension; inhibit ejaculation; fall risk, risk for CV pts
Phentolamine
short acting (4hr) alpha 1 & 2 antagonist, given IV; tx withdrawal from clonidine also hypertensive crisis from tyramine
Prazosin, terazosin, doxazosin, tamsulosion, and alfuzosin
selective alpha 1 blocker on target organ (not alpha 2 presynaptically) decrease TPR and decrease BP. not much effect on CP, renal blood flow or GFR. talmulosin slective alpha 1A for benign prostate, bladder not on any vascular smooth muscle (dilating smooth muscle on neck of bladder); orthotatic hypotesnions, headache, lack of energy, see slide for more (increase antihypertensive w nitrates and also iris billows in eye surgery). these are oral.
Yohimbe
alpha-2 blocker; increase sympathetic outflow, contra in CV disease, pscyh coniditions and renal dysfunction, no longer a Rx drug, OTC herbal is available
Labetalol
alpha and beta blocker
Propanolol
Nadolol (more potent and long duration of action)
Timolol (eye drops, reduces aqueous humor, used in open angle glaucoma) - see slide for 5HT1A blockers
example for Beta (non selective) blockers
oral; 75% first pass effect
large distribution, highly lipophilic passes BBB, extensively metabolized and excreted in urine
used for hypertension, angina pectoris, MI, migraine, hyperthyroidism
antiviral drugs can inhibit propanolol mentabolism, barbituates phenytoin and rifampin can increase metabolism and decrease effect
metoprolol atenolol betaxolol bisoprolol esmolol nebivolol
selective Beta 1 blocker
decrease BP in hypertensive
increase excercise tolerance in angina
no bronchoconstriction effect, cardio-selective blockers, low does highly selective, high dose less selective
esmolol rapibly metabolized used IV to control BP or heart rhythm during surgery and dx procedures
Nebivolol releases NO from endothelial cells
because less effect of B2, raynaud phenomena is less observed
Acebutolol
Pindolol
B blockers but weakly stimulate both B1 and B2 receptors, have intrinsic sympathomimetic activity.
inhibit stimulation of receptors by epi and ne
diminish effects on HR and CO compared to other B blockers, decrease side effects of lipid and carb metabolism, used to decrease hypertension pts with moderate bradycardia, not used for tx of stable angina or arrhythmia due to partial agonist effect
Labetalol
Carvedilol
non selective beta blockers with alpha 1 blocking action
produces peripheral vasodilation in contrast with other beta blockers
useful for tx of hypertensive pts for whom increased peripheral resistance is undesirable
labetalol used as alternative to treat preeclampsia
carvedilol good to tx stable CHP block sympathetic stim of the heart not for acute heart failure can worsen and cause death
see slide for rest
