Pharm I-The ANS Flashcards
1
Q
Na+ dependent transport of choline into the presynaptic nerves is the first step in the synthesis of acetylcholine.
This drugs blocks this step and will stop ACh synthesis.
A
Hemicholinium
2
Q
Ca++ dependent release of neurotransmitters from autonomic neurons is inhibited by ________.
A
Botulinum toxin
3
Q
ACh is a neurotransmitter at these sites _______.
A
4
Q
Inhibitory post-synaptic potential (IPSP) is due to increased permeability of what ion(s)?
A
- K+
- Cl-
5
Q
Receptor subtypes for ACh are muscarinic and nicotinic. Which class is G-protein coupled and which is ligand gated ion channel?
A
- Nicotinic are ligand gated ion channels
- Muscarinic are G-protein coupled
6
Q
_______ is the site of NM receptors and these receptors are selectively blocked by _______.
A
Neuromuscular junctions (at the ends of somatic nerves), curare (and analogs).
7
Q
______ is a modified ganglia and has NN receptors; when activated by ACh ______ is released.
A
Adrenal medulla, adrenaline
8
Q
These muscarinic subtypes activate the IP3-DAG pathway and increase intracellaular Ca2+
A
M1, M3, and M5
9
Q
Constriction of ______ muscles of the iris causes pupillary constriction termed ______
A
circular, miosis
10
Q
Activation of _____ receptors causes miosis
A
M3
11
Q
Activation of _____ receptors contricts the _____ muscles of the iris and causes mydriasis
A
⍺-1, radial
12
Q
Activation of ____ receptors on the ciliary muscles of the lens helps with far vision by _____
A
β2 receptors, dilation of the ciliary muscles
13
Q
Activation of _____ receptors on the ciliary muscles of the lens helps with near vision by _____
A
M3 receptors, constriction of the ciliary muscles
14
Q
Parasympathetic nervous system, via the vagus, DOES NOT supply this part of the heart.
A
The ventricles
15
Q
Vascular endothelial cells release nitric oxide (EDRF) when this receptor is activated on their cell-surface.
A
M3
* Remember, this will only occur if a muscarinic agonist is given IV as the PNS nerves DO NOT supply the vasculature.
16
Q
_____ receptor antagonists relax the ______ muscles and are useful t/t options for patients with urinary incontinence.
A
M3, detrusor
* Remember, this effect can cause urinary retention in patients with prostatic hyperplasia/hypertrophy
17
Q
Agonist for this receptor is used to inhibit uterine contractions and delay premature labor.
A
β2
18
Q
Male erection is caused by vasodilation induced by_____, which in turn is released by activation ____ receptor
A
Nitric Oxide, M3
19
Q
Used in the t/t of BPH, blockers of ____ receptors increase urinary flow and cause retrograde ejaculation
A
⍺1
* Remember, ⍺1 receptors mediate contraction of urinary bladder trigone and sphincter, thus inhibit bladder emptying (you don’t wanna pee during flight or fight)
20
Q
What is tonic pupil?
A
A pupil with parasympathetic denervation that constricts poorly to light but reacts better to accommodation (near response), such that the initially larger pupil becomes smaller than its normal fellow and remains tonically constricted, redilating very slowly when exposed to dark.
21
Q
ACh when applied to ____ cells causes vasoconstriction, but causes vasodilation when applied to _____ cells.
A
Vascular smooth muscle, endothelial cells
* Both actions are M3-mediated
* This means that when vasculature is denuded of endothelial cells it constricts in response to ACh, while before it dilates.
22
Q
Name two cholinergic agonists with only muscarinic activity that do not activate nicotinic receptors
A
Pilocarpine
Bethanechol
23
Q
Agonists of _____ receptors will induce depolarization block at the NMJ and include, ______, ________, _______.
A
NM
ACh, succinylcholine, nicotine
24
Q
Name key cholinergic agonists that are NOT substrates for hydrolysis by acetylcholinestrases (AChE)
A
- Carbachol
- Bethanechol
- Muscarine
- Pilocarpine
25
Acetylcholinesterase inhibitors will prolong the duration of action of these compounds.
1. Acetlycholine
2. Methacholine
3. Succinylcholine is a substrate for plasma cholinestrases
26
List reversible inhibitors of acetylcholinestrases (AChE).
1. Physostigmine
2. Neostigmine
3. Pyridostigmine
4. Edrophonium
5. Donepezil
27
List irreversible inhibitors of acetylcholinestrases (AChE).
1. Organophosphates
1. Dyflos
2. Echothiophate
3. The "thions"-parathion, malathion
28
The only AChE inhibitors to be orally absorbed **and** cross the blood-brain barrier and cornea are?
Physostigmine and organophosphates
29
When physostigmine is preadminstered in a pateint, what is the expected change in HR with vagal stimulation?
Marked fall in HR. Greater than vagal stimulation alone.
30
List major clinical uses of AChE inhibitors.
1. Myasthenia gravis-orally, large doses of neostigmine and pyridostigmine
2. Open angle glaucoma-eye drops physostigmine-work by contracting circular ciliary muscles
3. To reverse competitive NMJ block after a surgery-i.v neostigmine
4. Donepezil for alzheimer's d/s
31
List cardinal symptoms of organophosphate poisoning
1. Muscarinic effects
1. Excessive salivation and respiratory secretions-the patient is **"drowning" in his/her secretions**
2. **Pinpoint pupils**
3. Bronchoconstriction
4. Involuntary defecation and urination
5. **Convulsions and coma**
2. Effects of NN receptors on ganglia
1. Activation of SNS ganglia causes tachycardia, hypertension and arrhythmias
3. Effects of NM receptors on NMJ
1. Muscular fasciculations
2. **Depolarizing block causing paralysis of respiratory muscles (cause of death)**
32
List two drugs used in the t/t of organophosphate poisoning
1. Atropine
2. Pralidoxime-AChE reactivator
33
List major effects of cholinergic antagonists.
1. Glandular secretions dry up first
2. Tachycardia is next
3. Mydriasis, photophobia and paralysis of accommodation
4. ↓ GI motility and secretions
5. Bladder contractions ↓
6. Bronchodilation
7. Hallucinations and delirium
34
Quaternary anticholinergic compound with incomplete oral absorption used in the t/t of COPD
Ipratropium bromide
Tiotropium bromide
35
Orally acting, potent antimuscarinic used for pre- anesthesia to reduce glandular secretions
Glycopyrrolate
36
Direct acting smooth muscle relaxant with antimuscarinic properties used in the t/t of irritable bowel syndrome
Dicyclomine
37
Selective M1/M3 antagonist used in the t/t of urinary incontinence and overactive bladder
Oxybutynin
38
Short acting, topically active anticholinergic for mydriasis during test for refraction
Tropicamide
39
Describe the symptoms of anticholinergic overdose (e.g. belladonna poisoning, tricyclic antidepressants overdose, scopolamine overdose)
1. "**Red as a beet**" – Cutaneous vasodilation occurs as a means to dissipate heat by shunting blood to the skin, in order to compensate for the loss of sweat production.
2. "**Dry as a bone**" (anhidrosis) – Sweat glands are innervated by muscarinic receptors, so anticholinergic medications produce dry skin.
3. "**Hot as a hare**" (anhydrotic hyperthermia) – Interference with normal heat dissipation mechanisms (ie, sweating) frequently leads to hyperthermia.
4. "**Blind as a bat**" (nonreactive mydriasis) – Muscarinic input contributes to both pupillary constriction and effective accommodation
5. "**Mad as a hatter**" (delirium; hallucinations) – Blockade of muscarinic receptors in the central nervous system (CNS) accounts for these findings.
6. "**Full as a flask**" – The detrusor muscle of the bladder and the urethral sphincter are both under muscarinic control; anticholinergic substances reduce detrusor contraction (thereby reducing or eliminating the desire to urinate) and prevent normal opening of the urethral sphincter (contributing to urinary retention).
40
The rate limiting step in catecholamine synthesis is the enzyme \_\_\_\_\_\_, and it is inhibited by \_\_\_\_\_\_\_.
Tyrosine hydroxylase, ⍺-methyltyrosine (also called metyrosine)
41
The antimuscarinic with CNS effects used in the t/t of Parkinson’s d/s
Benztropine
42
Reserpine blocks this step in catecholamine synthesis.
Blocks the transport of dopamine **into** the secretory vesicles by blocking VMAT (vesicular monoamine transporter)
43
What are the effects of drugs like **bretylium** and **guanethedine** on catecholamine neurotransmission?
They block the fusion of secretory vesicles with presynaptic membrane and thus, block the release of norepinephrine and other catecholamines
44
How do drugs like **cocaine, angiotensin II, and tricyclic antidepressants** increase adrenergic neurotransmission?
They block NET (norepinephrine transporter), whose key substrates are NE and dopamine, and increase local concentrations of these compounds
45
Activation of presynaptic _____ receptors by NE reduces NE and DA release from adrenergic neurons
⍺2
46
This stress hormone **increases** the synthesis of epinephrine in the adrenal medulla
Glucocorticoids (cortisol)
47
The major mechanism by which the effects of NE are terminated is \_\_\_\_\_\_.
Neuronal reuptake of NE via the NET (norepinehrine transporter)
48
The major mechanism by which the effects of epinephrine are terminated is \_\_\_\_\_\_.
Extraneuronal reuptake of epi, mainly in the liver and kidneys
49
Neuron degrade NE via \_\_\_\_\_, a mitochondrial enzyme widely distributed in the body
MAO-A
\* there is NO COMT in sympathetic neurons or synpases
50
This cytoplasmic enzymes degrades, both NE and Epi, in the periphery
COMT
51
The common final product of both NE and Epinephrine metabolism, elevated levels of this compound in urine indicate excess production of catecholamines, like in pheochromocytoma.
VMA (vanillylmandelic acid)
52
This directly acting sympathomimetic non-selectively activates β-receptors, without activating ⍺-receptors
Isoproterenol
53
IV epinephrine will have these effects on the human heart.
1. SA nodal depolarizations increase—elevated HR
2. Increased strength of cardiac contraction—elevated stroke volume
3. Enhanced AV nodal conduction—possible arrhythmias
4. Shorter ERP—arrhythmias
5. Coronary vasodilation—β2 effect
6. Increased cardiac work and oxygen demand
54
Epinephrine, they principle fight or flight hormone, has this effect on the systemic metabolic profile.
Adrenaline decreases insulin/glucagon ratio and thus activates glycogenolysis and causes hyperglycemia. It also elevates plasma lactate and free fatty acid concentrations.
55
The beneficial effect of epinephrine during anaphylaxis is mainly attributable to \_\_\_\_\_\_\_.
its mast cell stabilizing properties and its ability to reduce mucosal congestion.
56
Tyramine is a component of many foods and is inactivated by _______ before it reaches the sympathetic neurons.
MAO-A
57
Tyramine, and indirectly acting sympathomimetic, is transported into the post-ganglionic SNS neurons via the \_\_\_\_\_. Its main effect is to displace _____ from these neurons.
NET (the one inhibited by cocaine)
Norepinephrine
58
Dopamine activates ____ receptors at low doses, _____ receptors at medium doses, and _____ erectors at high doses.
D1, β1, ⍺1
59
By improving cardiac output and increasing renal blood flow, _______ is very effective in the management of severe CHF with anuria.
Dopamine
60
This drug is a **nonselective β-agonist and increases cardiac output _without significant affect on HR_**. Thus, very useful in post cardiac surgery patients and in decompensated MI or cardiogenic shock.
Dobutamine
## Footnote
\* minimal effect on HR means that cardiac work is **not** significantly increased
61
Which receptors are activated by isoproterenol?
β1 and β2
62
What effect will isoproterenol will have on cardiac output, HR, systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure?
* Cardiac output ↑
* HR ↑
* SBP ↑
* DBP ↓
* PP ↑
* MAP ↓
63
Name two short-acting, β2 selective agonists.
Terbutaline
Albuterol
64
β2 selective agonist specifically developed for termination of premature labor.
Ritodrine
65
Selective ⍺-1 agonist, which increases MAP and causes **reflex bradycardia**
Phenylephrine
66
List two major uses of phenylephrine
1. Nasal decongestant
2. Mydriatic in ophthalmology
67
Classified as a “mixed” sympathomimetic, this drug activates ⍺ and β receptors directly; but, major effect is the release of endogenous norepinephrine.
Ephedrine
\*response is reduced by prior t/t with reserpine (↓ NE stores) or guanethidine (↓ NE release)
68
Response to tyramine or amphetamine will be abolished by prior t/t with \_\_\_\_\_\_, \_\_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_\_\_, and \_\_\_\_\_\_\_\_\_.
Reserpine, guanethidine, cocaine, tricyclic antidepressants (imipramine)
69
Majority of the effects of amphetamines are due to \_\_\_\_\_\_\_\_.
Release of endogenous NE or dopamine
70
⍺-2 agonist used in the management of hypertension
Clonidine
## Footnote
\*Clonidine is useful in confirming the diagnosis of pheochromocytoma. Failure to suppress plasma concentrations of norepinephrine in a patient with hypertension suggests pheochromocytoma.
71
Activation of _________ receptors in the _____ reduces sympathetic outflow from the spinal cord and can cause orthostatic hypotension
⍺-2, NTS
72
Used in the management of narcolepsy and childhood ADHD, this drug is similar to amphetamines with greater CNS effects and lesser motor effects.
Methylphenidate (Ritalin)
73
One of the first antihypertensives ever developed, this drug depletes stores of NE, Epi and dopamine by inhibiting VMAT.
Reserpine
74
Cocaine inhibits _____ and increase NE in the synaptic cleft; whereas, amphetamine use this transporter to get into the neuron and then displace NE.
Norepinephrine transporter (NET)
75
Phenelzine, a non-selective MAO inhibitor, has adverse reactions with certain foods containing \_\_\_\_\_\_. This leads to a hypertensive crisis as excess NE is released from SNS neurons.
Tyramine
\*tyramine is contained in cheese, beer, wine and pickled meats
76
What is Horner’s syndrome?
The pathophysiological basis of Horner’s syndrome (ptosis, miosis and anhydrosis), is loss of sympathetic innervation to the affected region.
77
List common causes of **post-ganglionic** Horner’s syndrome.
1. Internal carotid artery dissection or thrombosis
2. Neck massess
3. Aneurysm of the cavernous sinus
78
List common causes of **pre-ganglionic** Horner’s syndrome.
Trauma, surgery or malignant lesion at the thoracic outlet or the apex of the lung
79
Name two, non-selective ⍺-blockers
1. Phenoxybenzamine (non-competitive)
2. Phentolamine (competitive)
80
\_\_\_\_\_ is a competitive ⍺-1 blocker
1. Prazosin
2. Terazosin
3. Doxazosin
81
Selective ⍺1a blocker, ______ is used for the treatment of benign prostatic hyperplasia.
Tamsulosin
82
What is the expected effect of phenoxybenzamine on—
Blood pressure
Cardiac output
HR
Blood pressure falls due to progressive vasodilation (⍺-1 effect). Cardiac output increases due to baroreflex increase in SNS activity **and** increased central sympathetic outflow (⍺-2 blockade). Thus, diastolic pressure falls more than systolic pressure and pulse pressure increases. Similar mechanisms also underlie tachycardia.
83
Main therapeutic use of phenoxybenzamine is in the management of \_\_\_\_\_.
Pheochromocytoma
84
Blockade of _____ receptors explain the phenomenon of “epinephrine reversal”
⍺-1
## Footnote
\*Epinephrine increases blood pressure in an untreated patient. Prior treatment with ⍺-1 blocker causes epinephrine to reduce blood pressure due to unopposed β2 activation.
85
Clinically, most significant side effect of ⍺-blockers is \_\_\_\_\_\_.
Postural hypotension
86
Name the non-selective β-blocker with intrinsic sympathomimetic activity
Pindolol
87
Name the prototype non-selective β-blocker
Propranolol
88
Name three selective β-1 blockers
1. Atenolol
2. Metoprolol
3. Esmolol
89
Name two, third generation β-1, β-2 blockers with ⍺-1 blocking properties.
1. Labetalol
2. Carvedilol
90
List some relative contraindications for the use of β-blockers
1. Advanced heart failure
2. Cardiomegaly
3. Peripheral vascular disease
4. Asthma or COPD
5. Careful use in insulin-dependent diabetics
91
\_\_\_\_\_\_ is an absolute contraindication for the use of β-blockers
Complete heart block
92
\_\_\_\_\_\_ hormone up regulates β-receptors and β-blockers are useful in the management of diseases caused by excess activity of this hormone.
Thyroid
93
Timolol, β-1 selective blocker is useful in the management of open angle glaucoma. How?
These agents reduce the production of aqueous humor (as opposed to ⍺-1 agonist or M3 antagonist)
94
\_\_\_\_\_\_\_\_\_ is the only ganglionic blocker in use today. It blocks NN receptors in autonomic ganglia and block both, SNS and PNS transmission.
Trimethaphan
95
The most significant cardiovascular effect of ganglionic blockers is, \_\_\_\_\_\_\_\_\_\_.
Orthostatic hypotension
96
Reserpine depletes the neurons of the following major biogenic amines \_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_, \_\_\_\_\_\_\_\_, and \_\_\_\_\_\_\_\_\_.
1. Norepinephrine
2. Epinephrine
3. Dopamine
4. Serotonin
\*Recall, reserpine blocks VMAT an inhibits transport of dopamine of not the neurosecretory vesicles
97
List major side effects of reserpine.
Orthostatic hypotension
Sexual dysfunction
**Depression**
98
What is methyldopa? What is its main indication?
Methyldopa is covered to methyl-norepinephrine and blocks central SNS outflow by **activating central ⍺-2 receptors (like clonidine)**. It does NOT cross the placental barrier and is very useful for hypertension in **pregnancy**.
99
Identify the drugs.
Drug A- prazosin, phentolamine
Drug B- phenoxybenzamine (non-competitive)
100
Name three drugs that can block renin release from the kidneys.
1. Propranolol
2. Atenolol
3. Metoprolol
\* All β-1 blockers
