Adrenergic Flashcards
Synthesis of catecholamines
tyrosine - dopa - dopamine - NE - E
RLS of catecholamine synthesis
tyrosine to dopa
RLS inhibited by
metyrosine
Catecholamine transporter
Vesicular monoamine transporter (VMAT)
VMAT inhibited by
reserpine
Reuptake transporter
Norepinephrine transporter (NET)
NET inhibited by
cocaine; tricyclic antidepressants
Metabolizer of NE
MAO-A
Metabolizer of dopamine
MAO-B
MAO is inhibited by
phenelzine
alpha-1 receptor activation
Eye (dilator) - contraction - mydriasis
Arterioles - contraction - increase TPR, DBP, afterload
Veins - contraction - increase VR, preload
Bladder - contraction - urinary retention
Male sex organs - vas deferens - ejaculation
Liver - increase glycogenolysis
Kidney - decrease renin release
alpha-2 receptor activation
Prejunctional nerve terminal - decrease NT release
Platelets - aggregation
Pancreas - decrease insulin secretion
beta-1 receptor activation
SA node - increase HR
AV node - increase conduction velocity
atria/ventricles - increase contractility, conduction velocity, CO, O2 consumption
His-Purkinje - automaticity and conduction velocity
Kidney - renin release
beta-2 receptor activation
Blood vessels - vasodilation - decrease TPR, DBP, afterload
Uterus - relaxation
Bronchioles - dilation
Glycogenolysis and insulin secretion
D1
Renal, mesenteric, coronary vasculature - vasodilation - increased GFR, RBF, Na excretion
Difference between adrenergic action and muscarinic receptor blocking drugs
Adrenergic - mydriasis is not accompanied by cycloplegia
Increased TPR associated with
reflex bradycardia
Decreased TPR associated with
reflex tachycardia
Direct acting drug responses with reserpine/guanethidine
Not reduced
Indirect acting drug responses with reserpine/guanethidine
Abolished
Mixed acting drug responses with reserpine/guanethidine
Reduced
Phenylephrine receptor type
alpha-1
Clinical use of Phenylephrine
Increase BP, increase TPR antihypotensive (hypotension, shock) paroxysmal atrial tachycardia nasal decongestant mydriatic
alpha-2 specific agonists
Clonidine, methyldopa - hypertension
Apraclonidine, brimonidine - glaucoma
beta-2 agonist mechanisms
Relax bronchial smooth muscle/decrease airway resistance Suppress leukotriene/histamine release enhance mucociliary function decrease microvascular permeability inhibit phospholipase A
Therapeutic uses of Metaproterenol
long term treatment of obstructive airway disease
Acute bronchospasm
Selective receptor of Terbutaline
beta-2
Therapeutic uses of Terbutaline
long term treatment of obstructive airway disease
Acute bronchospasm
Emerngency status asthmaticus
Selective receptor of Albuterol
beta-2
Therapeutic uses of Albuterol
treat bronchospasms
delay pre-term labor
Therapeutic uses of Ritodrine
arrest premature labor
prolong pregnancy
Adverse effects of beta-2 agonists
Tremor, restlessness, anxiety
Tachycardia - pts with CAD or arrhythmias
Increased plasma glucose, lactate and FFA
Decreased K
Fenoldopam receptor type
D1
Effects of Fenoldopam
renal, mesenteric, peripheral and coronary vasodilation
Clinical use of Fenoldopam
Hypertensive crisis
Isoproterenol receptor type
beta-1/beta-2
Effects of isoproterenol
decreased TPR, increased HR, increased contractility
Uses of Isoproterenol
Bradycardia, complete heart block, CHF, MI
Effects of Dobutamine
increase heart rate, increase automaticity, increase contractility (TPR unaffected)
Adverse effects of dobutamine
excessive increases in BP and HR
Increased ventricular response in pts with A-fib
Ventricular ectopic activity
Increased size of MI
Uses for dobutamine
short term treatment of CHF and in stress tests
Low dose IV epinephrine effects
Beta-1 receptors - increase PP, HR, SV, CO
Beta-2 receptors - decrease TPR (vasodilation), decrease MAP (reflex tachycardia)
Moderate dose IV epinephrine effects
Similar beta-1/beta-2
alpha-1 receptors - increased TPR, increased BP
High dose IV epinephrine effects
Predominantly alpha-1 - increased TPR, BP without reflex bradycardia
Subcutaneous epinephrine effects
vasoconstriction
Vascular effects of epinephrine
Main sites - arterioles and precapillary sphincters
Cutaneous blood flow reduced (hands/feet)
Skeletal blood flow increased
Cerebral blood flow unchanged
Renal blood flow decreased; GFR unchanged
Pulmonary arterial/venous pressure increased
Coronary blood flow increased
Cardiac effects of epinephrine
HR increases, systole shortens, diastole remains unchanged
Positive inotropic, lusitropic, chronotropic effect
Myocardial oxygen consumption and automaticity increased
Epinephrine reversal phenomenon
In presence of alpha antagonist, epinephrine effect on B2 is enhanced causing vasodilation, decreased TPR and MAP
In presence of beta antagonist, alpha-1 effect is enhanced leading to substantial increase in MAP
Therapeutic uses of epinephrine
Relieve hypersensitivity reactions
Prolong anesthetics
Restore cardiac rhythm in pts with cardiac arrest
Relieve respiratory distress due to bronchospasm
Manage post-intubation and infectious croup
Stop bleeding
Contradindications of epinephrine
pts receiving non-selective beta receptor blocking drugs - epinephrine reversal
Adverse effects of epinpehrine
restlessness, headache, tremor
cerebral hemorrhage
cardiac arrhythmias
angina in pts with CAD
Norepinephrine is a potent stimulator of
alpha receptors
Cardiovascular effects of norepinephrine
Increased SBP, DBP, PP, coronary flow, TPR
Decreased CO, RBF, splanchnic/hepatic blood flow
Therapeutic uses of norepinephrine
limited use - treatment of low BP
Lose dose effects of dopamine
Renal blood vessels - vasodilation - increase GFR, RBF and filtered Na (more Na in urine)
Presynaptic D2 receptors - decrease NE release, decrease alpha-adrenergic stimulation of VSMC
Moderate dose effects of dopamine
Beta-1 receptor effects predominate - increase contractility, HR, SBP, PP
No effect on DBP
Increases NE release from nerve terminals
High dose effects of dopamine
alpha-1 effects predominate - generalized vasoconstriction
Contraindications of dopamine
patients with hypovolemia, tachycardia, hypertension, arrhythmias, MAO inhibitors/tricyclic antidepressants
Therapeutic uses of dopamine
severe CHF, cardiogenic/septic shock
Which drug indirectly releases NE and directly activates adrenoreceptors?
ephedrine (decongestant with mild CNS stimulation)
Indirect acting adrenoreceptor agonists are independent of
Calcium
Effects of amphetamine
CNS: releases amines, stimulates medullary respiratory center, stimulates cortex (prevents fatigue/sleep), treats obesity (decrease food intake)
CV: activates peripheral alpha/beta; increases SBP, DBP, HR - arrhythmias may occur
Bladder: increases contraction
Effects of tyramine
used to synthesize NE/E via alternative pathway
susceptible to MAO; actions increased by MAO inhibition
Chiefly peripheral
Effects of alpha-receptor antagonists
decreased BP, tachycardia, epinephrine reversal, miosis, nasal stuffiness, decreased resistance to urine flow
Determining factor for reversible alpha-antagonists
half-life
Determining factor for irreversible alpha-antagonists
rate of receptor generation
Therapeutic uses for alpha-antagonists
Pheochromocytoma Hypertensive emergencies Chronic hypertension Peripheral vascular disease Urinary obstruction Erectile dysfunction
Effects of phenoxybenzamine
irreversible alpha-1 blockade (long duration)
Also blocks H1, ACh, 5-HT receptors
Used in pheochromocytoma
Effects of Prazosin
alpha-1 selective blocker
Relaxes arterial, venous, prostate smooth muscle
Used for HTN, BPH
Can cause orthostatic hypotension
Effects of Tamsulosin
alpha-1a selective
used for prostate hyperplasia
Effects of labetalol
alpha/beta blocker
lowers BP without increasing HR
Treatment of HTN
Effects of beta-blockers
CV: lower BP in pts with HTN but not NTN, suppress RAS, decrease HR, low AV conduction, decrease O2 consumption
Respiratory - increase airway resistance
Eye - decrease intraocular pressure
Metabolic - inhibit lipolysis, decrease glucagon, increase VLDL, decrease HDL
Therapeutic uses of beta-blockers
HTN IHD Arrhythmias HF Glaucoma Hyperthyroidism Neurologic diseases
If a patient has chronic obstructive lung disease or asthma, what type of beta-blocker would be preferred
beta-1 selective blocker
Adverse effects of beta-blockers
fatigue worsening peripheral vascular disease worsening bronchospasms decreased sexual functions Increased diabetes masking hypoglycemia
1st generation beta-blocker
propranolol - non-selective beta blocker; B1=B2
2nd generation beta-blocker
Metoprolol - selective beta blocker; B1»>B2
3rd generation beta blocker
Labetalol - vasodilatory beta blocker; B1=B2>a1>a2
Effects of propranolol
lower HR, BP, renin
used in HTN, angina pectoris, arrhythmias, migraine, hyperthyroidism
Effects of metaprolol
lower HR, BP, renin
used in HTN, angina pectoris, arrythmias