2. DSA Adrenergic Drugs Flashcards
Adrenergic Drugs modulate adrenergic transmission and primarily control the function of the?
sympathetic nervous system, by mimicing the effects of NE/E/Dopamine at the adrenergic receptors in the symp. NS
Types of Adrenergic Receptors: List the effect A1 (ABD) type uses Gq A2 (ABC) type uses Gi B (123) type uses Gs D1/5 uses Gs D2/3/4 uses Gi
A1 (ABD) type uses Gq- increases IP3 and DAG A2 (ABC) type uses Gi- decreases cAMP B (123) type uses Gs- Increases cAMP D1/5 uses Gs- Inc. cAMP D2/3/4 uses Gi- Dec cAMP
activation of a1 receptor leads to what chain of responses?
Gq activated, makes GDP to GTP, activates PLC, activates PIP2, DAG, IP3, DAG activates PKc and IP3 releases Ca to activate a protein kinase
activation of beta-agonists leads to what chain of responses?
Gs activated, GDP to GTP, activates adenyly cyclase, increases cAMP, which activates R2C2 (PKA)
activation of a2 receptor leads to what chain of responses?
inhibition of AC, decrease cAMP, decrease PKA
Direct-acting adrenergic drugs produce their effects via direct interaction with adrenergic receptors while indirect do what?
produce their effects by increasing or reducing the concentration of NE at target receptors (alter NT concentrations at target site)
Classify the following direct adrenomimetics
Phenylphrine
Clonidine
Alpha agonists
Phenylphrine A1>A2
Clonidine A2>A1
Classify the following direct adrenomimetics
Norepinephrine (levophed)
Epinephrine (adernalin)
Mixed alpha and beta agonists
a1=a2,B1>B2
a1=a2, b1=b2
Classify the following direct adrenomimetics
Dobutamine (Dobutrex)
Isoproterenol (Isuprel)
Albuterol (ventolin)
Beta Agonists
b1>b2
B1=b2
b2>b1
Classify the following direct adrenomimetics
Dopamine (Intropin)
Dopamine agonists
D1=D2
What endogenous catecholamine does the following?
Effects of cardiac function (b1) increases
Effects on vascular tone (B2 and A1) increases
Skin vessels via A1
Skeletal muscle via A1/B2
Renal/Cerebral D1 and A1
Effects on respiratory system, etc
Epinephrine
What endogenous catecholamine does the following?
a1=a2,b1>b2
Reduces heart rate
vasoconstrictor
lacks b2 agonist - no bronchodilation/vasodilation
increase peripheral vascular resistance and BP
Role of baroreflex
Norepinephrine
What alpha adrenergic does the following (a1)?
Mydriatic and decongestant
severe vasoconstriction, BP elevation and severe bradycardia
Phenylphrine - a1>a2
What alpha adrenergic does the following (a2)?
a2 in lower brainstem: decreases sympathetic outflow, reduces BP, bradycardia
Local application results in vasoconstriction
regulation of NE release by presynaptic receptors
Clonidine - selective A2>a1
What beta adrenergic does the following (b1=b2)?
non-selective
positive inotropic and chronotropic action, inc. CO (b1)
Vasodilator, dec. arterial pressure B2
Causes bronchodilation B2
Isoproterenol
What beta adrenergic does the following (b1>b2)?
Selective b1
(-) isomer is agonist at a1, (+) isomer is antagonist at a1
potent inotropic action
less prominent chronotropic
Dobutamine
What beta adrenergic does the following (b2>b1)?
selective b2
Cause bronchodilation and relaxation of uterus
Albuterol
What endogenous catecholamine does the following?
D1 stimulation causes vasodilation (renal, cerebral, mesenteric have high density)
Activation of presynaptic D2- supress NE release
Activated B1 in heart at high doses
At higher doses stimulates vascular a1 AR to cause vasoconstriction
Dopamine
Cocaine is an indirect adenergic agonist (indirect sympathomimetic) whats it’s MOA?
inhibits re-uptake of DA and NE
Phenelzine/Selegiline is an indirect adenergic agonist (indirect sympathomimetic) whats it’s MOA?
inhibits MAO
Amphetamine/Methylphenidate is an indirect adenergic agonist (indirect sympathomimetic) whats it’s MOA?
Inhibit re-uptake of DA/NE, increases their release, may have weak direct effect
Ephedrine is an indirect adenergic agonist (indirect sympathomimetic) whats it’s MOA?
releasing agent and direct adrenergic receptor agonist
Indirect adrenergic agonists are more lipophilic, and easily penetrate the BBB. What drug has the following effects?
Simulant effect on mood/alertness
decreases appetite
Drugs of abuse
Amphetamine
Indirect adrenergic agonists are more lipophilic, and easily penetrate the BBB. What drug has the following effects?
Used in children with ADHD
Abuse potential
Methylphenidate
Indirect adrenergic agonists are more lipophilic, and easily penetrate the BBB. What drug has the following effects?
Inhibits transmitter reuptake at synapses
peripheral and intense central action
local anesthetic properties
Heavily abused drug
Cocaine
Indirect adrenergic agonists are more lipophilic, and easily penetrate the BBB. What drug has the following effects?
Plant constituent
long duration of action
used as nasal decongestant, inc. BP, stress incontinence in women
Ephedrine
Indirect adrenergic agonists are more lipophilic, and easily penetrate the BBB. What drug has the following effects?
Inhibits monoamine oxidase
increase NE stores in CNS
Antidepressant
Phenelzine/Selegiline
Indirect adrenergic agonists are more lipophilic, and easily penetrate the BBB. What drug has the following effects?
product of tyrosine metabolism found at high conc. in cheese, cured meats, smoked/pickled fish
releases stored NE from presynaptic terminal
metabolized by MAO in liver
May increase BP in patients taking MAO inhibitors
Tyramine
What can be used to increase BP in hypotensive emergencies like hemorrhagic shock, overdose of antihypertensives, and CNS depressants? (2)
Norepinephrine
Phenylphrine
What can be used for chronic hypotension to increase BP? 1
Ephdrine
What can be used for cardiogenic shock due to massive acute MI to increase BP? 2
Dopamine
Dobutamine
What can be used for acute and severe heart failure? 2
acute: short term use of dobutamine
severe HF w/ reduced renal perfusion: dopamine
What is commonly used for long term hypertension treatment?
A2 agonists
What can be used for emergency therapy for complete AV block and cardiac arrest? 2
Epinephrine
Isoproterenol
What can be used for narcolepsy- which are sudden breif sleep attacks? 2
Amphetamines
Methylphenidate (ADHD)
What can be used for obesity- central inhibition of appetite and increased energy expenditure? 2
Ephedrine
Amphetamines
Beta 2 selective agonist albuterol is good for bronchial asthma, what can be used for decongestion of mucous membranes? 2
Phenylephrine
Ephedrine
Epinephrine is used for anaphylaxis which controls both the respiratory and cardiovascular components. What can be used for examination of the retina, and glaucoma? 2
Induction of mydriasis for examination of the retina via phenylphrine
Glaucoma via A2 selective agonists
Adverse effects of adrenergic agonists:
Elevation in BP
Inc. cardiac work leading to MI or heart failure
Sinus tachycardia and ventricular arrhythmias
What are the follow a cause of?
Insomnia, No appetite, anxiety, psychoses, convulsions
Central Nervous system toxicity - ONLY indirect acting lipophilic drugs
There are also drugs that inhibit adrenergic transmission instead of activating them. They do thi by directly antagonizing the receptor, preventing storage and depleting NE, and?
inhibiting synthesis of tyrosine hydroxylase
What drugs are alpha adrenoceptor antagonists- nonselective (a1/2)? 2
Phentolamine
Phenoxybenzamine
What drugs are alpha1 receptor selective adrenoceptor antagonists? (3) NOTE: all end in -osin
Prazosin (minipress)
Tamsulosin (flomax)
Doxazosin (cardura)
Whats the main differences between phentolamine and phenoxybenzamine?
Phentolamine is a reversible competitive a antagonist; noncovalent, shorter acting, effect dec d/t high concentrations of agonist
Phenoxybenzamine is an irreversible non-competitive a antagonist; longer acting- effect not antagonized by agonist
Alpha antagonists effect the CV system by dec. peripheral vascular resistance and BP, postural hypotension and reflex tachycardia. What do they do for the genitourinary system (2) and the eye?
Relax SM of the prostate
Dec. resistance to the flow of urine
eye: relax of pupillary dilator muscle-miosis
What alpha antagonists are used to treat pheochromocytomas, which cause catecholamine excess leading to tacycardia, arrhythmias, and hypertension? 2
Phentolamine
Pheoxybenzamine
What alpha antagonists are used to treat chronic hypertension, treatment is usually well tolerated with nonselective a blockers NOT used? 2
Prazosin
Doxazosin
Phentolamine and injected papaverine is used for Erectile dysfunction. What alpha antagonist is used to treat benign prostate hyperplasia- treating the chronic urinary obstruction?
Tamulosin (a1a more than a1b)
If using prazosin/doxazosin might see larger drop in BP
All of the following are what? Postural hypotension Tachycardia Retention of fluid and salt impaired ejaculation nasal stuffiness
Adverse effects of alpha antagonists (seen less with a1 selective antagonists)
What 2 drugs are the mixed blockers (b and a) of antiadrenergic drugs (antagonists)?
Labetalol
Carvedilol
What are 3 nonselective beta adrenoceptor antagonists?
Propranolol
Pindolol
Nadolol
What are 4 b1 selective antiadrenergic drugs?
Metoprolol
Betaxolol
Acebutolol
Atenolol
What is the intrinsic activity of the following beta blockers? Atenolol Nadolol Propranolol Betaxolol
Antagonists
What are the intrinsic activities of the following beta blockers?
Acebutolol
Labetalol
Pindolol
Partial agonists
What are the intrinsic activities of the following beta blockers?
Carvedilol
Metoprolol
Inverse Agonists
Beta blockers with what are partial agonists at beta adrenergic receptors which block sympathetic effects but have submaximal effects of their own= blunted sympathetic response?
ISA - intrinsic sympathomimetic activty
The pharmacodynamics of b-blockers on the heart are negative inotropic and chronotropic effect, and slow AV node conduction. What does it do in blood vessels and the RAAS system?
Blood Vessels: rise in peripheral vascular resistance initially, chronically- decreases PVR
RAAS- inhibits renin release
The pharmacodynamics of b-blockers on the metabolism include inhibiting lipolysis, increase VLDL, dec. HDL reducing HDL/LDL cholesterol ration, and inhibits glycogenolysis and gluconeogenesisi in the liver. What are its effects on the resp. system and the eye?
increase airway resistance
Reduce production of aqueous humor- reducing intraocular pressure
beta blockers are used for hypertension, angina pectoris and cardiac arrhythmias. What are the medications used for MI? (2)
long-term use in post infarction period:
Propranolol
Metoprolol
Betaxolol is used for glaucoma, not propranolol. Hyperthyroidism causes excessive catecholamine action on the heart. What is used to treat?
Propranolol
