Lecture 13 (EXAM 3) Flashcards
The function of Alpha-1 agonists
-Vasoconstriction: for normal vaso-motor tone - state of contraction of the vascular smooth muscles
-inhibit sinus secretion (watery and mucous) -> DECONGESTANTS
-CONTRACTION of the urinary bladder sphincter (keeps urine in the bladder)
-Alpha1 subtypes: Alpha-1a, Alpha-1b, Alpha-1d (no pharmacological relevance at the moment)
Use of Alpha-1 agonists
-Decongestants and formerly OTC diet
Examples of Alpha-1 agonists
-Pseudophedrine, phenylephrine, phenylpropanolamine
-Oxymetazoline (12 hr nasal spray, resistant to destruction by MAO and COMT
Other Alpha-1 agonists
(NOT IN USE IN THE US)
Methoxamine (Vasoxyl) - Vasoconstrictor in hypotensive states (f.e. standing up and α1 can’t react fast enough so the brain doesn’t get enough blood - dizziness) OR brain damage in elderly due to low BP during surgery -> postoperative cognitive dysfunction
Mephentermine:
used for hypotension (α1-vasoconstriction, ß1 (HR))
cardiac stimulant (NE release and ß1 increase)
abusable -addictive performance enhancer
What is orthostatic hypotension?
Filling dizzy when standing up
due to alpha1 receptors not acting fast enough -> low BP -> insufficient blood flow to the brain
Alpha-1 agonists
Metaraminol (Aramine)
-direct and indirect-acting (NE release)
-vasoconstrictive
-used for paroxysmal (sudden) supraventricular tachycardia
Midodrine (ProAmatine)
-Treats of autonomic insufficiency
-Treats postural hypotension (orthostatic hypotension- dizzy when standing up)
Why would an alpha-1 agonist that vasoconstrictors, be used to treat tachycardia (high HR)
Because of the baroreceptor-mediated bradycardia effect
Use of Norepinephrine (Levophed) as a drug
Treats severe hypotension
Treats Shock: BP is not compatible with living
-> Hypovolemic, hemorrhagic (blood loss, or not drinking enough)
->Neurogenic
-> Septic (infection of the bloodstream caused by endotoxins)
How does UCP (uncoupling proteins) stimulate weight loss?
They are lipophilic and bind drag H+ back -> no H+ gradient, no ATP synthesis BUT the e- transport is still active causing heat
-UCP decouples oxidative phosphorylation
in the refrigerator, UCP are activated to produce heat -> break down of fat as a source of heat
-2,4-dinitrophenol (DNP) -> caused cataracts in the eye
Effect of Alpha-2 Agonists on presynaptic neurons
Inhibition of NE-release
-> acts on brain stem -> NO Vasoconstriction -> Brachycardia
-> Work in the CNS: inhibition in NE in the locus ceruleus area of the brain (spread in higher centers of the brain (cortex) -> locus ceruleus is for the state of readiness
->Analgesia: acts on the substantia gelatinosa on the spinal cord
How do Alpha-2 Agonists act inhibitory?
OPPOSITE of Alpha-1
-Alpha-2 receptor act inhibitory due to inhibitory G-proteins
decrease cAMP, Ca++ or increase K+ conduction (hyperpolarize the membrane)
-AUTORECEPTOR inhibits Ca++ intake which is needed for NE-vesicles to fuse with the membrane and release NE
How do Alpha-2 receptors decrease the sensation of pain?
Through inhibitory interneurons from the brain that activates Alpha-2 receptors -> causing inhibition NE release from the primary neuron (pain-signal transmitting neuron)
Example of Alpha-2 Agonists
Clonidine, guanabenz, guanfacine (used for hypotension before)
-Clonidine use:
Drug-withdrawal
pre-anesthetic (sedation making patients more responsive to anesthetics - center of alertness is firing too much - nervous)
may act partially through imidazoline receptors
More examples of Alpha-2 Agonists
-Tizanidine (Zanaflex): Anti-spasticity effect
-Apraclonidine (Iopidine) and Brimonidine (Alphagan): Anti-glaucoma agents
-Tetrahydrozoline: vasoconstriction in the eye (used as soporific (cause sleepiness)
What are Imidazoline receptors?
Similar to Alpha-2 receptors
-located in the blood pressure regulating area of the brain
-may explain of blood pressure effects of clonidine and Apraclonidine
