EXAM 2 - ESSAY QUESTIONS Flashcards
How do antidepressants work at the synapse?
In the synapse, antidepressants are reuptake inhibitors such as tricyclic antidepressants. They work by preventing the reuptake of norepinephrine back into the neuron, thus increasing the amount of norepinephrine in the synapse to increase binding.
Acetylcholine process in the neuron
Choline is reuptaken into the cell by CHT, it combines with acetyl-CoA to form acetylcholine by CHAT, and then its moved into the vesicles by VAT. It then binds to the cell wall via SNAPs and VAMPs, SNAPs keep VP2 in place and VAMPs are the part of exocytosis.
Norepinephrine process in the neuron
Tyrosine enters the neuron and breaks down into dopa tyrosine via tyrosine hydroxylase, to form dopamine, and dopamine is moved into the vesicles via VMAT. The Vesicles move down the cell wall via SNAP and VAMP is the exocytosis process to dump it into the synapse.
Target for drugs at the synapse
Synthesis of neurotransmitters, storage of neurotransmitters, vesicle secretion (Botox preventing SNAPs from working), Vesicle cycling and endocytosis, Reuptake of neurotransmitters, biotransformation of neurotransmitters (MAOIs) and neurotransmitter receptors (succinylcholine)
Why is atropine contraindicated in glaucoma?
Specifically narrow-angled glaucoma. Atropine will relax the ciliary muscle which would completely obstruct the aqueous humor duct and lead to increase ocular pressure. This would be a medical emergency, and can cause blindness. Probably give a Cholinomimetic (Carbechol?)
Explain the steps the Gq GPCR takes to trigger a cellular response
Gq is Alpha 1 receptors and M1,3,5.
Gq activates phospholipase C, which will increase DAG and IP3, resulting vasoconstriction in A1 receptors. This releases calcium from the sarcoplasmic reticulum, resulting in excitatory smooth muscle and contraction/constriction of vessels.
Explain the steps Gs GPCRs take to trigger a cellular response
Gs is found in Beta 1 and Beta 2 receptors
Gs excitation increase adenylyl Cyclase, which increases cAMP which will increase contractility and heart rate in Beta 1 receptors. In beta 2 receptors, increased cAMP will dilate the bronchioles.
Hormonal vs autonomic regulation of blood pressure
Hormonal response to blood pressure is via the RAAS system, which can only raise blood pressure via activation of RAAS. The autonomic response is based on baroreceptors detecting hypo or hypertension in the blood vessels, and therefore activating sympathetic or parasympathetic nervous system. For hypotension, sympathetic is activated, and for hypertension, parasympathetic is activated.
Organophosphate toxicity
SLUDGE-M
Saliva
Lacrimal productive
Urination
Defecation
GI
Emesis
Miosis (pupil constriction)
Treated with Atropine for bradycardia, and pralidoxime which helps with organophosphate aging by attacking covalent bond of the binding on acetylcholinesterase.
Organophosphate poisoning is a Paraympathetic/acetlycholine overdose essentially.
Differentiate the bodies response to pure alpha agonist, mixed agonist, and Beta agonist
Alpha (Phenylephrine): Increase vasoconstriction and blood pressure, Decrease HR, decreased cardiac output
Beta (isoproterenol): Increased contractility and heart rate, decreased blood pressure/Vascular resistance
Mixed: Epinephrine alpha 1, beta 1/2. Increased vasoconstriction, contractility, heart rate, relaxation of bronchioles. Dilation of skeletal muscle.
Clonidine MOA and effects
Clonidine is a alpha 2 agonist, its transiently increases blood pressure by binding to alpha 1 receptors before it crosses blood brain barrier, where it then lowers blood pressure by binding to Alpha 2 receptors in central nervous system. It decreases sympathetic nervous system response and increases sympathetic response. Causes hypotension and mild sedation.
Pathogenesis and treatment of pulmonary hypertension
Endothelin-1 (ET-1) binds to ETA and ETB receptors in the lungs, causing vasoconstriction and vascular remodeling in pulmonary hypertension. This overexpression of ET-1 leads to increased pressure in the pulmonary arteries. Causes include chronic hypertension, genetic mutations, and chronic clots. Endothelin receptor antagonists (ERAs) are used to block these effects and reduce symptoms.
Endothelin receptor antagonist is Bosentan
Epoprostenol is a prostacyclin that is a vasodilator in the lungs.
Nitric oxide pathway
Arginine turns into nitric oxide via eNOS -> NO turns into Guanylyl Cyclase - > GC turns GTP into cGMP which then cGMP will dilate peripheral vessels/relax heart
Muscle contraction pathway
Calcium enters the cell -> activates myosin light chain kinase -> activates actin for contraction
