Test 2 part III Flashcards
Which variable is the primary stimulus that controls the loop of integration of CV function?
MAP
Changes in _____ will result in secondary compensatory responses that are aiming to achieve ______.
MAP; homeostasis
The SNS has a direct influence over 4 variables in the cardiovascular system:
- Peripheral Vascular Resistance (PVR)
- Heart Rate (HR)
- Contractile Force
- Venous Tone
The PNS has a direct influence over 1 variable in the cardiovascular system:
- Heart Rate
What are the other names for parasympathomimetics?
- Cholinoreceptor stimulators
- Cholinomimetc
Direct Acting Parasympathomimetic drugs have what action?
They act directly on nicotinic and/or muscarinic receptors.
What are the two categories of Direct Acting Parasympathomimetics?
- Choline Esters
- Alkaloids
What are the example drugs given for Choline Esters?
- Acetylcholine
- Bethanechol
- Carbocol
- Methacholine
Which direct acting parasympathomimetics are structurally similar to acetylcholine?
Choline Esters
What are the example drugs given for the Alkaloids?
- Nicotine
- Muscarine
- Pilocarpine
- Lobeline
Which category of Direct Acting parasympathomimetics are quaternary amines?
Choline Esters
Drugs that are hydrophilic, permanently ionized, and cannot cross the blood-brain barrier (have a small Vd)
Quaternary Amines
Which type of Direct Acting Parasympathomimetics are tertiary amines?
Alkaloids (nicotine, muscarine, etc.)
Drugs that are hydrophobic, lipid soluble, and can cross the blood-brain barrier (have a large Vd)
Tertiary
What is the mechanism of action for Indirect Acting Parasympathomimetics?
Drugs that form an irreversible or reversible bond with Acetylcholinesterase (Ach-E), increasing the availability of Ach in the system.
What are the three subtypes of Indirect Acting Parasympathomimetics?
- Simple Alcohols (Quaternary Amines)
- Carbamic Acid Esters (Quaternary or Tertiary)
- Organic Derivatives of Phosphoric Acid
Which indirect acting parasympathomimetic forms a bond for the shortest duration (non-covalent) with Ach-E?
Edrophonium (this is why it is used for the Tensilon Test)
Which Indirect Acting Parasympathomimetic is tertiary?
Physostigmine (used in central anticholinergic toxicity)
Which type of Indirect Acting Parasympathomimetics form an irreversible bond with Ach-E?
Organic derivatives of Phosphoric Acid (nerve gasses)
Which Organo-Phosphate (an indirect acting parasympathomimetic) is non-toxic in ophthalmic form? It is highly polar, so not well absorbed.
Ecothiopate
Is Neostigmine tertiary or quaternary?
Quaternary
Signal transduction via Nicotinic receptors is done through ______, found at the Neuromuscular End Plate (somatic system), Autonomic Ganglion Cells (both PNS and SNS), and in the CNS.
Ion Channels
Signal transduction via Muscarinic receptors is via _____, found at effector organs (nerves, heart & smooth muscle, glands, and endothelium)
GPCRs
All Adrenergic receptors (Stimulating SNS response) utilize __________ type receptors for signal transduction.
G-Coupled Protein
The vasculature of the skin and splanchnic vessels have predominantly ____ receptors, and _____ results when stimulated by what NTs?
Alpha; Constriction; NE and Epi
What is the effect of skeletal muscle vessels depending on alpha or beta activation?
Constrict; Dilate
Alpha agonism has what effect on nasal mucosa?
Vasoconstriction of nasal mucosa and decongestion
Which receptors, when stimulated, activate adenylyl cyclase, leading to increased cAMP?
- Beta 1
- Beta 2
- Beta 3
- Dopa 1
Which receptors, when stimulated, inhibit adenylyl cyclase, leading to decreased cAMP?
- M2
- Alpha 2
- Dopa 2
(2 MAD that you can’t go to CAMP)
Which receptors, when stimulated, cause the formation of IP3 and DAG?
- M1
- M3
- Alpha 1
What does the formation of IP3 lead to?
Increased calcium release
What does the formation of DAG do?
Activates protein kinase C
What are the effects associated with an increase in cAMP?
- Mobilization of stored energy
- Inc HR and inc Contractility
- Regulate Ca+ (increases sequestration of Ca)
- Regulate sex hormones
- Relax smooth muscle
- Conserve water
Chronic exposure to an agonist = decreased effect in the tissue to further stimulation by that agent.
Desensitization
What time range can desensitization occur over?
Can happen slowly over hours or days or within minutes
What are the two types of desensitization?
- Homologous
- Heterologous
Which type of desensitization occurs when loss of responsiveness occurs exclusively of the receptors that have been exposed to repeated or sustained activation by an agonist?
Homologous Desensitization
An example of which type of desensitization is when Phosphorylation of receptors occurs by members of the G-protein coupled receptor kinase (GRK) family
Homologous Desensitization
Which type of desensitization occurs when loss of responsiveness from one receptor to an agonist also results in the loss of responsiveness of another receptor that has not been directly stimulated by that agonist?
Heterologous Desensitization
Which of the following occurs with 2nd messenger mediated desensitization due to the activities of protein kinase A and protein kinase C?
Heterologous Desensitization
What is the prototype drug for sympathomimetics, the parent compound from which all sympathomimetic drugs are derived?
Phenylethylamine
What is the mechanism of action of Direct Acting Sympathomimetics?
Drugs cause the activation of adrenoreceptors leading to some or all of the characteristic effects of endogenous catecholamines
The pharmacologic effects of direct acting sympathomimetics depends on:
- Route of administration
- Affinity for adrenoreceptor
- Adrenoreceptor subtypes in the target tissue (TT)
What are the mechanism of actions for Indirect Acting Sympathomimetics?
- Drugs displace stored catecholamines from the adrenergic nerve ending (ex: Ephedrine)
- Decrease the clearance of NE by inhibiting reuptake of circulating catecholamines (cocaine) or preventing the enzymatic metabolism of NE (MAOI and COMT inhibitors)
What is the mechanism of action for Cocaine?
Decrease the clearance of NE by inhibiting reuptake of circulating catecholamines (blocking NET)
What is the mechanism of action for MAOIs and COMT inhibitors?
Prevents the enzymatic metabolism of NE
Which drug is the prototype drug for beta antagonists?
Propanolol
What are the categories of sympatholytic drugs?
- Alpha Antagonists
- Beta Antagonists
What are the two categories of alpha antagonists?
- Reversible
- Irreversible
What is the mechanism of action of beta antagonist drugs?
Competitively reduce receptor occupancy by catecholamines; reversible antagonists
