Adrenergic Drugs Flashcards
What is the G protein and effect of alpha-1 type receptor?
G protein: Gq
Effect: Increased IP3, DAG common to all
What is the G protein and effect of alpha-2 type receptor?
G protein: Gi
Effect: Decreased cAMP common to all
What is the G protein and effect of Beta-type receptor?
G protein: Gs
Effect: Increased cAMP common to all
What is the G protein and effect of Dopamine-type receptor D1-D5?
- D1: Gs; Increased cAMP
- D2: Gi; Decreased cAMP
- D3: Gi; Decreased cAMP
- D4: Gi; Decreased cAMP
- D5: Gs; Increased cAMP
What is the location and effects of activation of alpha-1 type receptor?
- Most vascular smooth muscle (innervated): Contraction
- Pupillary dilator muscle: Contraction (dilates muscle)
- Prostate: Contraction
- Heart: Increases force of contraction
What is the location and effects of activation of alpha-2 type receptor?
- Postsynaptic CNS neurons: Probably multiple actions
- Platelets: Aggregation
- Adrenergic and cholinergic nerve terminals: Inhibits transmitter release
- Some vascular smooth muscle: Contraction
- Fat cells: Inhibits lipolysis
What is the location and effects of activation of Beta-1 type receptor?
• Heart, juxtaglomerular cells: Increases force and rate of contraction; increases renin release
What is the location and effects of activation of Beta-2 type receptor?
- Respiratory, uterine and vascular smooth muscle: Promotes smooth muscle relaxation
- Skeletal muscle: Promotes potassium uptake
- Human liver: Activates glycogenolysis and gluconeogenesis
What is the location and effects of activation of Beta-3 type receptor?
- Bladder: Relaxes detrusor muscle
* Fat cells: Activates lipolysis
What is the location and effects of activation of D1 type receptor?
• Smooth muscle: Dilates renal blood vessels
What is the location and effects of activation of D2 type receptor?
• Nerve endings: Modulates transmitter release
Direct Adrenomimetics: Alpha Agonists
• Phenylephrine (Neo-Synephrine)
- a1 > a2»_space;»> B
• Clonidine (Catapres)
- a2> a1»_space;»> B
Direct Adrenomimetics: Mixed alpha and beta agonists
• Norepinephrine (Levophed)
- a1 = a2; B1»_space; B2
• Epinephrine (Adrenalin)
- a1 = a2; B1 = B2
Direct Adrenomimetics: Beta agonists
• Dobutamine (Dobutrex)
- B1 > B2»_space;» a
• Isoproterenol (Isuprel)
- B1 = B2»_space;» a
• Albuterol (Ventolin)
- B2»_space; B1»_space;» a
Direct Adrenomimetics: Dopamine agonists
• Dopamine (Intropin)
- D1 =D2»_space; B»_space; a
Indirect Adrenomimetics:
- Inhibits re-uptake of DA and NE
Cocaine
Indirect Adrenomimetics:
- Inhibitors of MAO
- Selegiline (Eldepryl)
* Phenelzine (Nardil)
Indirect Adrenomimetics:
- Reverse NE and DA uptake mechanisms and increase their release
- Amphetamines
- Methylphenidate (Ritalin)
- Tyramine (a byproduct of tyrosine metabolism, not a drug)
Indirect Adrenomimetics:
- Releasing agent AND a direct adrenergic receptor agonist
Ephedrine
Direct acting antiadrenergic drugs: alpha adrenoceptor antagonists
- Non-selective (a 1 and a 2) receptor antagonists
- alpha-1 receptor selective (all end in -osin)
• Non-selective (a1 and a2) receptor antagonists
- Phentolamine (OraVerse)
- Phenoxybenzamine (Dibenzyline)
• Alpha- 1 receptor selective
- Prazosin (Minipress)
- Tamsulosin (Flomax)
- Doxazosin (Cardura)
Direct acting antiadrenergic drugs: Mixed Blockers
- Labetalol (Trandate) (B- and alpha-1 antagonist)
* Carvedilol (Coreg) (B- and alpha-1 antagonist)
Direct acting antiadrenergic drugs: Beta Adrenoceptor Blockers
- B1 and B2 blockers
- B1 selective
• B1 and B2 blockers
- Propranolol (Inderal)
- Pindolol (Visken)
- Nadolol (Corgard)
• B1 selective
- Metoprolol (Toprol)
- Betaxolol (Kerlone)
- Acebutolol (Sectral)
- Atenolol (Tenormin)
Indirect acting antiadrenergic drugs:
- Norepinephrine release inhibitor
- Inhibitor of tyrosine hydroxylase
• Norepinephrine release inhibitor
- Guanethidine (Ismelin)
• Inhibitor of tyrosine hydroxylase
- Metyrosine (Demser)
Intrinsic activities of beta-blockers at the receptors:
Which ones are antagonists?
– Atenolol
– Nadolol
– Propranolol
– Betaxolol
Intrinsic activities of beta-blockers at the receptors:
Which ones are partial agonists?
– Acebutolol
– Labetalol
– Pindolol
Intrinsic activities of beta-blockers at the receptors:
Which ones are inverse agonists?
– Carvedilol
– Metoprolol
Epinephrine effects on Cardiac Function (B1)
– Increases the force of contraction (positive inotropic effect)
– Increases heart rate
– Increases conduction velocity at AV node
Epinephrine effects on Vascular Tone (B2 and a1)
• Increases systolic BP
• May decrease diastolic BP and total peripheral
vascular resistance
• Mean arterial pressure often remains unchanged
•Significant differences in receptor types found in
vascular beds
- Skin vessels and mucous membranes = mostly a1
- skeletal muscle = a1 and B2
- Renal, cerebral = D1 and a1
Epinephrine effects on respiratory system
- Relaxes bronchial muscle (B2)
* Decreases bronchial secretion and congestion within bronchial mucosa (a1)
Epinephrine: Other Effects
- Skeletal muscle?
- Glucose?
- Free fatty levels?
- Renin?
• Effects on skeletal muscle:
- Causes muscle tremor (B2)
- Increases K+ uptake by skeletal muscle (B2)
- Promotes hypokalemia and decreases K+ excretion by kidneys
• Elevates blood glucose levels
- Enhances liver glycogenolysis and gluconeogenesis (B2)
- Increases free fatty levels in blood (B)
- Increases renin release (B1)
Norepinephrine Effects
- Potent cardiac stimulant but reduces heart rate
- Potent vasoconstrictor
- Lacks vasodilation
- Increases peripheral vascular resistance and blood pressure
- Role of baroreflex
Alpha Agonist (a1>a2) : Phenylephrine Effects
– Effective mydriatic and decongestant
– Causes severe vasoconstriction, blood pressure elevation, and severe bradycardia
– Role of baroreflex in the response to
phenylephrine
Alpha Agonist: Clonidine (selective a2)
• Central effect on presynaptic a2 receptors in the lower brainstem area - Decreasing sympathetic outflow - Reduction in blood pressure - Bradycardia
•Local application
produces
vasoconstriction
Beta Agonist (B1=B2): Isoproterenol Effects
– Non-selective beta agonist
– Positive inotropic and chronotropic action, increases cardiac output ( B1)
– Vasodilator, decreases arterial pressure ( B2)
– Causes bronchodilation ( B2)
Beta Agonist (B1>B2): Dobutamine
• Selective B1 agonist
• a1 receptor activity
- (-) isomer is an agonist at the receptors while (+) isomer is an a1 antagonist
- Potent inotropic action
- Less prominent chronotropic action as compared to isoproterenol
Beta Agonist (B2>B1): Albuterol
- Selective B2 agonists
* Cause bronchodilation and relaxation of uterus
Dopamine (D1=D2) Effects
•D1 stimulation causes vasodilation
- High density of D1 receptors in renal, cerebral, mesenteric and coronary vessels
• Activation of presynaptic D2-
suppresses norepinephrine release
- Activation B1 in heart at higher doses
- At still higher doses stimulates vascular a1 AR to cause vasoconstriction
Drug used to increase BP:
For hypotensive emergencies - hemorrhagic shock, overdose of antihypertensives, CNS depressants
- Norepinephrine
* Phenylephrine
Drug used to increase BP:
For chronic hypotension
Ephedrine
Drug used to increase BP:
For cardiogenic shock – due to massive acute myocardial infarction
- Dopamine
* Dobutamine
Drugs used for heart failure:
- Acute HF
- Congestive severe HF
– Short-term use of dobutamine in acute HF
– Dopamine in congestive severe HF with reduced renal perfusion
What drug is used for hypertension?
Alpha-2 agonists for the long-term treatment
What drug is used for emergency therapy for complete AV block and cardiac arrest
– Epinephrine
– Isoproterenol
What drug is used for Narcolepsy – sudden brief sleep attacks
– Amphetamines
– Methylphenidate
What drug is used for ADHD – short attention span, learning problems, and hyperkinetic physical behavior
Methylphenidate
What drug is used for Obesity – central inhibition of appetite and increased energy expenditure
– Ephedrine
– Amphetamines
What drug is used for Bronchial asthma
– Beta-2 selective agonist
• Albuterol
What drug is used for decongestion of mucous membranes
– Phenylephrine – Ephedrine
What drug is used for Anaphylaxis – immediate (type 1) allergic reaction characterized by respiratory and cardiovascular components
– Respiratory component - bronchospasm and upper airway congestion
– Cardiovascular component- severe hypotension, cardiac depression
– Epinephrine - effective at both components
What drug is used for Ophthalmic applications:
– Examination of retina – induction of mydriasis
Phenylephrine
What drug is used for Ophthalmic applications:
– Glaucoma
Alpha-2 selective agonists
What drug is used for Genitourinary applications:
Stress urinary incontinence
Ephedrine
