Adrenergic Drugs Flashcards
a1 type
G protein
Effect
Gq
Inc. IP3, DAG
a2 type
G protein
Effect
Gi
Dec. cAMP
b type
G protein
Effect
Gs
Inc. cAMP
Which D receptors are Gs?
D1 and D5
Inc. cAMP
Which D receptors are Gi?
D2, D3, D4
Dec. cAMP
a1 actions at:
Vascular SM
Pupillary dilator m.
Prostate
Heart
Vascular SM - contraction
Pupillary dilator m. - contraction (pupillary dilation)
Prostate - contraction
Heart - inc. force of contraction
a1 receptors are at which tissues? (4)
Vascular SM
Pupillary dilator m.
Prostate
Heart
a2 actions at:
Platelets
Adrenergic/cholinergic nerve terminals
Some vascular SM
Adipocytes
Platelets - aggregation
Adrenergic/cholinergic nerve terminals - inhibit transmitter release
Some vascular SM - contraction
Adipocytes - inhibit lipolysis
a2 receptors are at which tissues? (4)
Platelets
Adrenergic/cholinergic nerve terminals
Some vascular SM
Adipocytes
b1 actions at:
Heart
JG cells
Heart - inc. rate AND force of contraction
JG cells - inc. renin release
b1 receptors are at which tissues? (2)
Heart
JG cells
b2 actions at:
Respiratory, uterine and vascular SM
Skeletal m.
Liver
Respiratory, uterine and vascular SM: SM relaxation
Skeletal m.: inc. K+ uptake
Liver: activate glycogenolysis and gluconeogenesis
b2 receptors are at which tissues? (3)
Respiratory, uterine and vascular SM
Skeletal m.
Liver
D1 actions at:
SM
SM - dilates renal BVs
D2 actions at:
Nerve endings
Modulate NT release
How do indirect-acting adrenergic drugs produce an effect?
By increased/decreasing conc. of NE at target receptors.
Indirect-acting drugs and their manner of action (3)
- Cocaine: reuptake blockers of DA and NE.
- Phenelzine, selegiline: MAO inhibitors.
- Amphetamines and Ephedrine: releasing agents and direct receptor agonist.
Receptors for phenylephrine
a1>a2
Receptors for clonidine
a2>a1
Receptors for NE
a1=a2; b1>b2
Receptors for Epi
a1=a2; b1=b2
Receptors for Dobutamine
b1>b2 and a1
Receptors for Isoproterenol
b1=b2
Receptors for Albuterol
b2>b1
Receptors for DA
D1=D2
Effects of Epi on cardiac function w/ b1 (3)
Ionotropic effect
Inc. HR
Inc. conduction velocity at AV node
Effects of Epi on cardiac vascular tone w/ b2 and a1 (3)
Inc. systolic BP
May dec. diastolic BP and TPR
MAP does not change
What receptors at which vascular sites are effected by Epi? (3)
Skin vessels and mucous membranes: a1
Skeletal m.: a1 and b2
Renal and cerebral: D1 and a1
*many different types of vascular beds have different receptors, so effects are varied
Epi’s effects on the respiratory system and its receptors (2)
b2 - relaxes bronchial m.
a1 - decrease bronchial secretion and congestion in mucosa
Epi’s effect on skeletal m. and its receptor (1)
b2 - muscle tremor, inc. K+ uptake
-promotes hypokalemia and dec. K+ secretion by kidneys.
Epi’s effect on blood Glc levels and receptor (1)
b2 - enhance liver glycogenolysis and GNG
What effect does Epi have on free fatty levels in blood?
Increases it
What effect doe Epi have on renin release?
Increases it
NE effects on the heart
Cardiac stimulant, but reduces HR
What role does NE have on vasculature?
Potent vasoconstrictor -> increased PVR and BP
What role does NE have on respiration?
None, because there is no b2 effect of NE.
Phenylephrine actions (3)
Decongestant/mydriatic
Severe vasoconstriction, BP elevation
Severe bradycardia
a1
Clonidine actions (4)
Dec sympathetic outflow
Reduce BP
Bradycardia
If applied locally, vasoconstriction*
a2
Isoproterenol actions (3)
Ionotropy and chronotropy -> inc. CO (b1)
Vasodilator (b2)
Bronchodilator (b2)
Dobutamine action (1)
Ionotropy
What is unique about the a1 activity of Dobutamine?
(-) isomer is an agonist
(+) isomer is an antagonist
Albuterol actions (2)
Bronchodilation
Uterine relaxation
DA actions (4)
Vasodilation at renal tissue
Suppress NE release
At higher doses, b1 in heart is activated.
Even higher doses activates a1 in vasculature.
What are indirect adrenergic agonists?
Example (7)
Usually more lipophilic and can easilty penetrate BBB to have CNS effects (stimulant).
Amphetamine Methamphetamine Methylphenidate Cocaine Ephedrine Phenelzine, selegiline Tyramine
Ephedrine indirect action:
It is a mild…
What is it used for clinically? (3)
Release stored cetacholamines w/ some direct action.
Enters CNS.
Nasal decongestant, increased BP, stress incontinence in women.
What is the use of Phenelzine, selegiline?
Antidepressive
Anti-adrenergic synthesis inhibitor (1) and MOA
Metyrosine inhibits tyrosine hydroxylase.
Indirect acting.
Guanethidine is ________.
MOA?
Anti-adrenergic.
Prevents storage of NE.
Indirect acting.
Non-selective a1 and a2 receptor antagonists (2)
Phentolamine
Phenoxybenzamine
a1 receptor selective antagonists (3)
Prazosin
Tamsulosin
Doxazosin
What kind of inhibitor is phentolamine?
Reversible competitive alpha antagonist
Shorter-acting
What kind of inhibitor is phenoxybenzamine?
Non-competitive irreversible alpha antagonist
Longer-acting
Effects of alpha-antagonists on CVS (3)
Dec. PVR and BP
Posttural hypotension
Reflex tachy
Effects of alpha-antagonists on GU system (2)
Prostate SM relaxation
Dec. resistance to urine flow
Effect of alpha-antagonists on the eye (1)
Miosis (pupillary constriction)
Adverse effects of alpha-antagonists examples
Postural hypoTN Tachy Salt/fluid retention Impaired ejaculation Nasal stiffness
Beta-blockers w/ ISA (intrinsic sympathomimetic activity) are known as:
What is the effect?
How are they useful?
Partial agonists at beta adrenergic receptors.
A blunted SNS response.
Less risk for bradycardia and increase in LDL
Beta-blockers’ effects on the heart (3)
Negative ionotropic effect
Negative chronotropic effect
Slow AV conduction
Beta-blockers’ effect on BVs chronically vs. initially
Initially - rise in PVR
Chronically - decrease PVR due to lower BP
Beta-blockers’ effect on the respiratory system (1)
Inc airway resistance
Beta-blockers’ effect on the eyes (1)
Reduce production of aqueous humor and intraocular pressure
Beta-blockers’ effect on metabolism (3)
Inhibit lipolysis
Inc LDL and dec. HDL (inc. the ratio)
Inhibit sugar breakdown in the liver
