EXAM #1: AND PHARMACOLOGY - ADRENERGIC Flashcards
What is the rate limiting step in catecholamine synthesis? What enzymes catalyzes this reaction?
Tyrosine–>DOPA, which is catalyzed by the enzyme “Tyrosine Hydroxylase”
What drug blocks the conversion of Tyrosine to DOPA?
Metyrosine
How are synthesized catecholamines transported into vesicles?
VMAT (vesicular monoamine transporter)
What drug blocks VMAT?
Reserpine
Clinically, how is reserpine used?
To treat resistive HTN
What facilitates binding of vesicles containing catecholamines to the nerve terminal membrane?
VAMPs
What drug blocks VAMPs?
Bretyilum
What are the three methods that terminate catecholamine action?
1) Simple diffusion
2) Neuronal reuptake
2) Extra-neuronal uptake
What enzyme metabolizes catecholamines that diffuse into the circulation?
COMT
“Catechol-O-methyl-transferase”
What transporter facilitates the neuronal reuptake of NE?
NET1
What drugs can inhibit NET1? What is the effect of these drugs?
- Cocaine
- Tricyclic antidepressants
These drugs increase the concentration of NE in the synaptic cleft
What are the analogs to NET for DA and 5-HT?
DAT
SERT
What transporter facilitates extraneuronal reuptake of catecholarmines? What drugs can block these transporters?
- ENT/ NET2
Corticosteroids can block these transporters.
What is the fate of catecholamines that have been reuptaken into a nerve terminal?
1) Restored in vesicles for release
2) Metabolism by monoamine oxidase (MAO)
Note that there are two isoforms of MAO, MAO-A and MAO-B.
- MAO-A= NE, 5-HT, and tyramine
- MAO-B= DA
What drug can inhibit MAO?
Phenelzine
Draw the mechanisms G-protein linked second messenger activation.
p. 244 First Aid
What is the mnemonic to remember the receptor types and their associated g-protein class?
“Qiss and qiq till you’re siq of sqs.”
Outline the mnemonic to remember the receptor types and their associated g-protein class.
p. 244 First Aid
List the Gq-coupled receptors. What is the mnemonic to remember these receptors?
H1 Alpha-1 V1 M1 M3
“HAVe 1 M and M”
List the Gs-coupled receptors.
B1 B2 D1 H2 V2
List the Gi-coupled receptors. What is the mnemonic to remember these receptors?
M2
Alpha-2
D2
“MAD 2s”
Where are alpha-1 receptors located?
Vascular smooth muscle
- Arterioles
- Veins
Radial (dilator) muscle of the eye
Bowel and bladder sphincters
- Bladder trigone and sphincter
- Male sex organ
Liver
Kidney
What is the consequence of alpha-1 activation in the eye?
Contraction–>mydriasis
What is the effect of alpha-1 activation in the arterioles?
Contraction leading to:
- Increased TPR
- Increased diastolic pressure
- Increased afterload
What is the effect of alpha-1 activation in the veins?
Contraction leading to:
- Increased venous return
- Increased preload
What is the effect of alpha-1 activation in the bladder trigone and sphincter?
Contraction leading to urinary retention
What is the effect of alpha-1 activation in the male sex organ?
Ejaculation
What is the effect of alpha-1 activation in the liver?
Increased glycogenolysis
What is the effect of alpha-1 activation in the kidney?
Decreased renin release
List the locations of alpha-2 receptors.
Prejunctional nerve terminals
- Decreased SNS output
Platelets
- Aggregation
Pancreas
- Decreased insulin release
- Decreased lipolysis
What is the effect of alpha-2 activation in the prejunctional nerve terminal?
Decreased NE synthesis and release
What is the effect of alpha-2 activation in the platelets?
Platelet aggregation
What is the effect of alpha-2 activation in the pancreas?
Decreased insulin secretion
List the locations of B1 receptors.
Heart
- Increased rate
- Increased contractility
Kidney
- Increased renin release
Increased lipolysis
What is the effect of Beta-1 activation in the heart?
SA Node= positive chronotrope
AV node= positive dromotrope
Atrial and ventricular muscle=
- positive ionotrope
- increased conduction velocity, CO, and O2 consumption
What is the effect of Beta-1 activation in the kidney?
Increased Renin release
List the locations of Beta-2 receptors.
- Heart= increased rate and contractility
- Liver= increased lipolysis
- Pancreas= Increased insulin release
- Eye
1) Ciliary epithelium= aqueous humor production
2) Ciliary m.= relaxation - Vascular smooth muscle= vasodilation
- Bronchioles= bronchodilation
- Uterus= decreased uterine contraction
What is the effect of Beta-2 activation in the vasculature?
Vasodilation leading to:
- Decreased TPR
- Decreased diastolic BP
- Decreased afterload
What is the effect of Beta-2 activation in the uterus?
Relaxation
What is the effect of Beta-2 activation in the bronchioles?
Bronchodilation
What is the effect of Beta-2 activation in the skeletal muscle?
- Glycogenolysis
- Muscle contraction/ tremors
What is the effect of Beta-2 activation in the liver?
Glycogenolysis
What is the effect of Beta-2 activation in the pancreas?
Insulin secretion
What is the effect of muscarinic stimulation of the eye?
Stimulation of M receptors causes:
1) Miosis (sphincter m.)
2) Spasm of accomodation and opening the Canal of Schlemm
What is the result of muscarinic blockade on the eyes?
1) Mydriasis
2) Paralysis of accommodation, or “cycloplegia”
What is the effect of sympathetic alpha-1 stimulation on the eye?
Myrdiasis
How does the mydriasis caused by adrenergic stimulation differ from that caused by muscarinic stimulation?
Alpha-1= pupillary radial muscle; thus, there is NO cycloplegia
Muscarinic= mydriasis WITH cycloplegia b/c of effects of ciliary m.
Where are D1 receptors located?
Renal, mesenteric, and coronary vasculature
What is the effect of D1 stimulation?
Vasodilation
In the kidney, this leads to:
- Increased GFR, RBF and Na+ excretion
Draw the autonomic feedback loop controlling arterial blood pressure. Draw the hormonal ANS feedback loop controlling blood pressure.
N/A
What is the meeting point between the autonomic and hormonal feedback loops controlling blood pressure?
Mean Arterial Pressure (MAP)
What will changes in the MAP evoke?
Powerful homeostaic responses
Note that if a drug has induced a change in MAP, homeostatic responses to that change may produce the OPPOSITE action of the intended drug,
What is reflex bradycardia?
Reflexive lowering of heart rate in response to an increase in MAP or increase in TPR–>increase in MAP
What is reflex tachycardia?
Reflexive raising of heart rate in response to a decrease in TPR–>decrease in MAP
