ANS Pharmacology
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- What is the order of affinity of EPI, NE, and ISO on alpha receptors?
- EPI > NE >> ISO
- What is the order of affinity of EPI, NE, and ISO on beta-1 receptors?
- ISO > EPI = NE
- What is the order of affinity of EPI, NE, and ISO on beta-2 receptors?
- ISO > EPI >> NE
- What are the cardiovascular effects of Isoproterenol?
-
Heart:
↑ Rate
↑ Contractility
Vascular Smooth Muscle:
↓ Peripheral Resistance
? Blood Pressure - What are the cardiovascular effects of Norepinephrine?
-
Heart:
↑ Rate (but then goes down b/c of vagal reflex)
↑ Contractility (but then goes down b/c of vagal reflex)
Vascular Smooth Muscle:
↑↑ Peripheral Resistance
↑↑ Blood Pressure - What is the reflex cardiovascular effect of NE?
-
↓ Heart Rate
↓ Contractility
Secondary to increase in BP -> strong vagal compensation overcomes direct effects on heart - What are the cardiovascular effects of EPI?
-
Heart:
↑ Contractility
↑ Heart Rate
Vascular Smooth Muscle:
↓ Peripheral Resistance
↑ BP (mean) - Indirect-acting phenylethylamines lack what group?
- β-OH
- Which stereoisomer of phenylethylamines is the active form?
- L (or S)
- What alteration to phenylethylamines greatly increases their oral effectiveness and duration of action?
- Removal of one or both ring hydroxyls
- What alteration to phenylethylamines allows them to cross the blood-brain barrier?
- Removal of both ring hydroxyls
- What alteration to phenylethylamines enhances their resistance to MAO?
- Presence of an α-carbon substituent
- What are the contraindications or reasons for caution in sympathomimetic therapy? (8)
-
1. Cardiac disease
2. HTN
3. Cerebral arteriosclerosis
4. DM
5. Hyperthyroidism
6. During general anesthesia with halothane or cyclopropane
7. Pregnancy
8. Pts receiving therapy w/ beta-receptor antagonists - Where in the cell is Acetyl CoA synthesized?
- Mitochondria
- Where do cholinergic cells store ACh?
-
In vesicles
In the cytoplasm - Where do AChE inhibitors act on the AChE molecule?
- At the esteratic site
- Where in the body are muscarinic receptors located?
-
Autonomic effector cells
Certain autonomic ganglion cells
CNS - Which receptor, muscarinic or nicotinic, has faster response time?
- Nicotinic
- What type of receptors are muscarinic receptors?
- G-protein-linked
- Activation of Mâ‚, M₃, and Mâ‚… muscarinic receptors exerts what effect on cells?
-
↑ IP₃ and DAG to ↑ Caâºâº and Naâº
Causes increase in contraction and secretion - Activation of Mâ‚‚ and Mâ‚„ muscarinic receptors exerts what effect on cells?
-
Inhibition of cAMP formation
Increased K⁺ conductance
Decreased Ca⁺⁺ conductance - Where in the body are nicotinic receptors located?
-
Autonmoic ganglia
Skeletal muscle (NMJ)
CNS - What type of receptor are nicotinic receptors?
- Ligand-gated ion channels
- Cholinomimetics are routinely used in the management of what four things?
-
1. Gastrointestinal atony
2. Nonobstructive urinary bladder atony
3. Opthalmic disorders (glaucoma)
4. Myasthenia gravis - What are the most common side effects associated with usual therapeautic doses of cholinergic agonists?
-
Salivation
Lacrimation
Urination
Defecation
Sweating
(SLUDS) - Which direct acting cholinomimetic is characterized by its short duration of action and what is it commonly used for?
-
Methacholine
Used diagnostically to test for bronchial hyperactivity and asthmatic conditions - Which direct acting cholinomimetic is used to increase tone and contraction of the intestine and urinary bladder?
- Bethanechol
- Which direct acting cholinomimetics are regarded as being selective for muscarinic receptors?
-
Methacholine
Bethanechol - Which non-selective direct acting cholinomimetic agent is used in the treatment of glaucoma?
- Carbachol
- Why is pilocarpine not a substrate for cholinesterases?
- It is not a choline ester
- What are four contraindications to the use of cholinomimetics?
-
1. Asthma
2. Peptic ulcer
3. Coronary insufficiency
4. Hyperthyroidism (causes a-fib) - What are the three groups of cholinesterase inhibitors?
-
1. Quaternary alcohols
2. Carbamate esters
3. Organophosphates - Which group of cholinesterase inhibitors is considered irreversible?
- Organophosphates
- What are three reversible cholinesterase-inhibiting drugs?
-
Edrophonium
Neostigmine
Physostigmine - What group of cholinesterase inhibitors does edrophonium belong to and what is its use?
-
Quaternary alcohol
Diagnosis of myasthenia gravis
(reversal of muscles weakness is indicative of condition) - What are the two significant characteristics of neostigmine?
-
Longer acting
Stays out of the CNS (quaternary amine) - What are the major therapeutic uses for neostigmine?
-
Nonobtrusive intestinal atony
Nonobtrusive urinary bladder atony
Management of myasthenia gravis - Which reversible cholinesterase inhibitor is sometimes used in the treatment of glaucoma?
- Physostigmine
- How long does "aging" of AChE bound to organophosphates take?
- About 1 hour
- What is the only clinical use of organophosphates and which drugs are used?
-
Glaucoma (as a last resort)
DFP and echothiophate - Does atropine penetrate the CNS?
- Only in large doses
- Which subtypes of muscarinic receptors does atropine block?
- All of them
- What is the classic non-muscarinic effect of atropine?
- Dilation of blood vessels in facial blush area
- Cholinergic blockers are commonly used in the routine management of patients with what? (5)
-
1. Gastric hypermobility and sapsticity
2. Escessive salivation
3. Need for mydriatic and cyclopegic
4. Cystitis, ureteral or biliary colic
5. Parkinson's Disease - What are the three groups of cholinergic blockers?
-
Muscarinc blocking drugs
Ganglionic blockers
Nuromuscular blockers - Name three muscarinic blockers.
-
Atropine
Scopolamine
Ipratropium - What effect does atropine have on NMJs?
- None - it is selective for muscarinic receptors
- Which pts should not receive topical application of atropine to the eye?
- Pts with narrow-angle glaucoma
- What is the key difference between scopolamine and atropine?
- Scopolamine exerts more CNS action (drowsiness and amnesia)
- What is ipratropium used for?
- Administered by inhalation in reversible airway disease
- What are the therapeutic uses of muscarinic blockers? (6)
-
1. Before anesthesia
2. To combat motion sickness
3. To manage Parkinson's disease
4. To treat intestinal spasms
5. To prepare the eye for examiniation; to treat iritis
6. To treat poisoning and certain bronchial conditions - What are nondepolarizing ganglionic blockers used for?
- Short-term control of blood pressure in HTN crises
- What are depolarizing ganglionic blockers used for?
- NOTHING!!!!
- What is the nondepolarizing ganglionic blocker we need to know?
- Trimethaphan camsylate
- How is trimethaphan administered and why?
- Continuous IV b/c of rapid metabolization by plasma ChE
- What is an important side effect of trimethaphan?
- Histamine release
- Curare, atracurium, cecuronium and mivacurium are in what class of drugs?
- Nondepolarizing NMJ Blockers
- Compared to curare, atracurium ...
-
Has shorter duration of action
Has some histamine release - Compared to curare, vecuronium ...
-
Has shorter duration of action
Does not cause histamine release
Does not cause ganglionic blockade - Compared to curare, mivacurium ...
-
Has less histamine release
Is very short acting - What is the order in which curare paralyzes skeletal muscles?
-
Eye muscles
Jaw muscles
Muscles controlling swallowing
Peripheral muscles
Abdominal and intracostal muscles
Diaphragm - Potential complications of curare are what?
-
Hypotension
Bronchoconstriction - What drugs antagonize curare?
-
Neostigmine
Edrophonium - What type of drug is succinylcholine?
- Depolarizing NMJ Blocker
- How long does skeletal muscle paralysis persist following IV injection of succinylcholine?
- 5 minutes
- How is succinylcholine metabolized?
- By plasma pseudo-ChE
- What are therapeutic uses of β1 adrenergic receptor antagonists? (11)
-
1. Ventricular and supraventricular arrhythmias
2. Angina pectoris
3. HTN
4. Cardiac myopathies
5. Long-term prophylaxis after MI
6. Prophylaxis of migraine
7. Hyperthyroidism
8. Glaucoma
9. Management of pheochromocytoma
10. Acute freight/stress syndromes
11. Skeletal muscle tremors - What are therapeutic uses of α-adrenergic receptor antagonists? (8)
-
1. Essential HTN
2. HTN crises
3. Vasopastic conditions
4. Frostbite
5. Therapeutic management of pheochromocytoma
6. Circulatory shock
7. Congestive heart failure
8. Urinary obstruction (BPH) - What effect does propanolol have on blood pressure?
- Initially it raises it, but given chronically it will lower it, especially in pts w/ HTN
- Which has a longer half life, metoprolol or atenolol?
- Atenolol
- Which β1 selective blocker has a very short duration of action?
- Esmolol
- What is the clnical use of labetalol?
- It is a potent antihypertensive
- What undesireable effect of non-selective α receptor antagonists severly limits their clinical use?
-
Tachycardia
(also cause postural hypotension)