Adrenergic Drugs Flashcards
Direct-acting Adrenomimetic Classes
- Alpha agonists
- Mixed alpha and beta agonists
- Beta agonists
- Dopamine agonists
Alpha agonists
- Phenylephine
- Clonidine
Mixed alpha and beta agonists
- NE
- Epi
Beta agonists
- Dobutamine
- Isopreterenol
- Albuterol
Dopamine agonists
- Dopamine
Indirect adrenominetics classes
- inhibitors of MAO
- inhibitors of reuptake of DA and NE
- Reverse NE and DA uptake mechanisms and increase their release
- Releasing agent and direct adrenergic receptor agonist
Inhibitor of re-uptake of DA and NE
- Cocaine
Inhibitors of MAO
- Phenelzine
- Selegiline
Reverse NE and DA uptake mechanisms
- Amphetamines
- Methylphrnidate
- Tyramine (byproduct of tyrosine metabolism, not a drug)
Releasing agent and a direct adrenergic receptor agonist
- Ephedrine
Direct acting antiandrenergic drug classes
- alpha adrenergic antagonists
- mixed blockers
- beta adrenergic antagonists
Non-selective receptor antagonists
- Phentolamine (reversible, competitive)
- Phenoxybenzamine (non-competitive, irreversible)
Alpha 1 selective antagonists
- Prazosin
- Tamsulosin
- Doxazosin
Mixed antagonists (blockers)
- Labetalol
- Carvedilol
- both are alpha and beta 1 antogonists
Beta 1 and Beta 2 blockers (nonselective)
- Propranolol
- Pindolol
- Nadolol
B1 selective blockers
- Metoprolol
- Betaxolol
- Acebutolol
- Atenolol
Indirect acting antiandrenergic drug groups
- NE release inhibitor
- inhibitor of tyrosine hydroxylase
NE release inhibitor
- Guanethudine (indirect)
Inhibitor of tyrosine hydroxylase
Metyrosine (indirect)
Alpha 1 G protein and effects
Gq - Increase IP3 and DAG
Alpha 2 G protein and effects
Gi - decrease cAMP
Beta type G protein and effects
Gs - increase cAMP
Dopamine type G proteins
- D1 and D5 - Gs - increase cAMP
- D2 - D4 - Gi - decrease cAMP
Epinephrine
- a1 = a2; B1 = B2
- Effects on cardiac function (B1)
- – increase HR
- – Increase force of contraction
- – increase conduction velocity at AV node
- Effects on vascular tone (B2 and a1)
- – increases systolic BP
- – may decrease diastolic BP and TPVR
- Effects on respiratory system
- – relaxed bronchial muscle (b2)
- – decreased bronchial secretion and congestion within bronchial mucosa (a1)
- Skeletal muscle
- – muscle tremor (B2)
- – increase K uptake by skeletal muscle (B2)
- elevates blood glucose levels
- – enhances liver gluconeogenesis and glycogenolysis (B2)
- increases free fatty levels in blood (B)
- increases renin release (B1)
Norepinephrine
- a1 = a2; B1»_space; B2
- cardiac stimulant but reduces HR
- pontent vasoconstrictor
- Lacks B2 agonist effects
- Increases PVR and BP
- Role of baroreflex
Phenylephrine
- alpha agonist; a1
- effective mydriatic and decongestant
- severe vasoconstriction, BP elevation and severe bradycardia
- role of baroreflex in the response to phenylephrine
Clonidine
- selective a2 agonist
- central effect on a2 receptors in lower brainstem area
- – decreasing sympathetoc outflow
- – reduction in BP
- – bradycardia
- local application produces vasoconstriction
Isoproterenol
- B agonist; B1 = B2
- nonselective
- positive inotropic and chronotropic action, increases CO (B1)
- vasodilator, decreases arterial pressure (B2)
- causes bronchodilation (B2)
Dobutamine
- Beta agonist; B1 > B2, a1
- selective B1 agonist
- (-) isomer is agonist; (+) isomer is antagonist (of a1)
- potent inotropic action
- less prominent chronotropic action compared to isoproterenol
Albuterol
- selective B2 agonist
- cause bronchodilation and relaxation of the uterus
Dopamine
- D1 = D2
- D1 stimulation causes vasodilation
- activation of presynaptic D2 suppresses NE release
- activate B1 in heart at higher doses
- at even higher doses, stimulates vascular a1 AR to cause vasoconstriction
Indirect adrenergic agonist properties
- usually more lipophilic compounds
- easily penetrate BBB
Amphetamine , methamphetamine
- marked stimulant effect on mood and alertness
- decrease appetite
- drugs of abuse
Methylphenidate
- used in children with ADHD
- has abuse potential
Cocaine
- inhibits transmitter reuptake at adrenergic synapses
- peripheral and intense central action
- local anesthetic properties
- heavily abused drug
Ephedrine
- releases stored catecholamines w/ some direct action
- long duration of action
- nonselecive
- mild stimulant
- clinical use
- – nasal decongestant
- – increases BP
- – stress incontinence in women
Phenelzine, Selegiline
- inhibitors of MAO
- increase NE stores in CNS
- antidepressant action
Tyramine
- product of tyrosine metabolism found in cheese, cured meats, smoked and pickled fish
- releases stored NE from presynaptic terminals (if given parenterally)
- is metabolized by MAO in live
- may lead to increase in BP in patients taking MAO inhibitors
Which adrenergic agonist used to increase BP
- hypotensive emergencies
- – NE
- – Phenylephrine
- Chronic hypertension
- – ephedrine
- cardiogenic shock
- – dopamine
- – dobutamine
Heart Failure
- short term use of dobutamine in acute HF
- dopamine in congestive severe HF w/ reduced renal perfusion
Hypertension drug
Alpha 2 agonists for long term treatment
Emergency therapy for complete AV block and cardiac arrest
- Epi
- Isoproterenol
Narcolepsy Drugs
- amphetamines
- methyphenidate
ADHD drug
- methylphenidate
Obesity drug
- ephedrine
- amphetamines
Decongestion of mucous membranes
- phenyephrine
- ephedrine
Examination of retina (mydriasis)
- phenylephrine
Glaucoma
- alpha-2 selective agonists
GU applications
- ephedrine for urinary incontinence
CV adverse effects of adrenergic agonists
- elevation of BP
- Increased cardiac work may precipitate myocardial ischemia and heart failure
- sinus tachycardia and serious ventricular arrhythmias, may induce sudden cardiac death
Central nervous system toxicity
- insomnia
- lack of appetite
- anxiety, restlessness
- psychoses
- convulsions and hemorrhagic stroke (cocaine)
Effects of Alpha antagonists on CV system
- decreased PVR and BP
- postural hypotension
- reflex tachycardia
Effects of Alpha antagonists on GU system
- relaxation of sm muscle in prostate
- decreased resistance to the flow of urine
Effects of Alpha antagonists on the eye
- relaxation of pupillary dilator muscle - miosis
Pheochromocytoma treatment
- antag
- phentolamine
- phenoxybenzamine
Chronic (essential) hypertension treatment
- antag
- Prozosin, Doxasin (a1 selective)
- – work well in moderate hypertension
- – generally well tolerated
Erectile dysfunction treatment
- combination of phentolamine and papaverine
BPH treatment
- Tamsulosin
- – greater affinity for a1A
- Prozosin and doxazosim are also effective but will cause more pronounced drop in BP
Adverse Effects of alpha antagonists
- seen less with a1 selective
- postural hypotension
- tachycardia
- retention of fluid and salt
- impaired ejaculation
- nasal stiffness
B blocker antagonists
- Atenolol
- Nadolol
- Propranolol
- Betaxolol
B blocker partial agonists
- acebutolol
- Lebetalol
- Pindolol
B blocker inverse agonists
- Carvedilol
- Metoprolol
Full agonists
- fully activate receptors
- produce maximal pharmacological effect when all receptors occupied
- maximal intrinsic activity
Partial agonists
- partially activate upon binding
- produce sub-maximal effect
- intrinsic efficacy varies depending on drug
Inverse agonists
- decrease receptor signaling
- decrease response at receptors with significant level of constitutive receptor activity
- intrinsic activity present and related to inhibition of receptor function
Antagonists
- do not activate the receptor upon binding
- no effect is agonist is not present
- no intrinsic activity
Effects of B-blocker on CV
Heart - negative inotropic and chronotropic effect - slow AV node conduction Blood vessels - initially - rise in PVR - chronic - decrease in PVR RAS - inhibit renin release
Effects of B-blocker on respiratory system
- increase airway resistance
Effects of B-blocker on Eye
- reduce production of aqueous humor - reduce intracular pressure
Metabolic Effects of B-blocker
- inhibit lipolysis
- increase VLDL and decrease HDL
- inhibit glycogenolysis and glugoneogenesis in the liver
Clinical uses of Beta blockers
- hypertension (both b and mixed blockers)
- angina pectoris
- MI
- cardiac arrhythmias
- heart failure
- glaucoma
- hyperthyroidism (propranolol)
CNS B-blocker adverse effects
- sedation
- sleep disturbances
- depression
- switch to more hydrophilic drug
Respiratory B-blocker adverse effects
- increased airway resistance
- trigger bronchospasm and asthma attack in susceptible people
- switch to B1 selective
CV B-blocker adverse effects
- depression of HR, cardiac contractibility and excitability
- exacerbation of peripheral vascular disease
Lipid profile B-blocker adverse effects
- chronic use - increase VLDL, decrease HDL
- seen with both selective and non-selective
- switch to partial agonist
Hypoglycemic episodes B-blocker adverse effects
- switch to B1 selective
- more on slide 49
Abrupt discontinuation of B blocker therapy
- increased numbers and responsiveness of receptors to endogenous agonists
- enhanced cardiac stimulation and arrhythmias
