Drugs Flashcards
1
Q
What protein is associated with Nicotinic ACh Receptors?
A
Na+/K+ Depolarizing Ion Channel
2
Q
Where are Nicotinic M ACh Receptors located?
A
Skeletal Muscle Neuromuscular Junction
3
Q
Where are Nicotinic N ACh Receptors located?
A
- Ganglia (post-ganglionic cell body)
- Dendrites
CNS
4
Q
What protein is associated with M1 ACh Receptors?
A
Gq GPCR
5
Q
What protein is associated with M2 ACh Receptors?
A
Gi GPCR
6
Q
What protein is associated with M3 ACh Receptors?
A
Gq GPCR
7
Q
What is the MOA of Gq GPCR?
A
PIP2 –> IP3/DAG –> Increase intracellular Ca2+
8
Q
What is the MOA of Gs GPCR?
A
Increase cAMP
9
Q
What is the MOA of Gi GPCR?
A
Decrease cAMP
10
Q
Where are M1 ACh Receptors located?
A
- CNS
- Enteric NS
11
Q
Where are M2 ACh Receptors located?
A
- Atria
- SA node
- AV node
12
Q
Where are M3 ACh Receptors located?
A
- Glands (including sweat)
- Bladder (detrusor, sphincter)
- Lungs
- Smooth Muscle (including endothelium and eye)
13
Q
What protein is associated with M4 ACh Receptors?
A
Gi GPCR
14
Q
What protein is associated with M5 ACh Receptors?
A
Gq GPCR
15
Q
Where are M4 ACh Receptors located?
A
CNS
16
Q
Where are M5 ACh Receptors located?
A
CNS
17
Q
What is Bethanechol?
A
Direct Cholinomimetic Drug (Muscarinic Agonist)
Interacts with MAChRs
Used to treat Non-obstructive GI Dysmotility (Post-op Ileus, Neurogenic Ileus, Congenital Megacolon)
- Causes GI motility
Used to treat Urinary Retention
- Causes Detrusor muscle (bladder) activation and urinary sphincter relaxation
18
Q
What is Atropine?
A
Muscarinic Antagonist
Non-selective M1 = M2 = M3
Used to treat Cholinergic Poisoning when used with Pralidoxime
- Blocks MAChRs from interacting with ACh or other agonists
Used to block vagal reflexes induced by surgical maniulation
Used to treat GI disorders
- Inhibits GI motility
Used to treat bradycardia
Used to treat heart block
Tertiary Agent - CAN cross the BBB
19
Q
What is Pralidoxime?
A
ACh Esterase Regenerator
Used with Atropine to reverse Cholinergic Poisoning (too much ACh or ACh agonists)
Pralidoxime acts peripherally, not centrally
CANNOT cross the BBB
20
Q
What is Carbachol?
A
Direct Cholinomimetic Drug - Nicotinic and Muscarinic Agonist
Interacts with Muscarinic and Nicotinic ACh Receptors
Used to treat acute angle glaucoma
- Causes Ciliary Muscle contraction - outflow of aqueous humor
- Causes Pupillary muscle constriction (miosis)
21
Q
What is Tacrine?
A
Indirect Cholinomimetic Drug - Acetylcholinesterase Inhibitor
Binds to AChE
Tertiary Agent - CAN cross the BBB
Used to treat Alzheimer’s Type Dementia
22
Q
What is Cevimeline?
A
Direct Cholinomimetic Drug
Used as an oral tablet to treat xerostomia (dry mouth) in patients with Sjogrens Syndrome
Metabolzied by P450 pathways and eliminated in urine
23
Q
What is Rivastigmine?
A
Indirect Cholinomimetic Drug - Acetylcholinesterase Inhibitor
Tertiary Agent - CAN Cross the BBB
Used to treat Alzheimer’s Type Dementia
24
Q
What is Methacholine?
A
Direct Cholinomimetic Drug
Causes bronchial smooth muscle contraction
Used for pulmonary testing - can exacerbate Asthma/COPD
25
What is Pyridostigmine?
Indirect Cholinomimetic Drug - Acetylcholinesterase Inhibitor
Carbamic Acid Ester (carbamate)
Quarternary Agent - CANNOT cross the BBB
Used to treat patients with Myasthenia Gravis
Out-competes Myasthenia Gravis Antibodies
Increases ACh in the Neuromuscular Junction endplate
26
What is Pilocarpine?
Direct Cholinomimetic Drug - Muscarinic Agonist
Used to treat xerostomia (dry mouth) in patients with Sjogrens Syndrome or head and neck cancer related xerostomia
Causes several effects on the eye:
- Causes contraction of Pupillary muscles (miosis contraction of pupil)
- Causes contraction of the Ciliary muscles (accommodation of the lens - more round for near site)
- Causes outflow of aqueous humor, reducing occular pressure
Used to treat glaucoma
27
What is Physostigmine?
Indirect Cholinomimetic Drug - Acetylcholinesterase Inhibitor
Binding to AChE is covalent and irreversible
Tertiary Agent - CAN cross the BBB
Used to reverse Atropine overdose (diminished cholinergic signaling - excessive sympathetic state) - peripheral and central effects
Used to treat Alzheimer's Type Dementia
28
What is Varenicline?
Direct Cholinomimetic Drug - Nicotinic Agonist
Interacts with Nicotinic ACh Receptors
Does NOT interact with MAChRs
Used only to help quite smoking
29
What is Neostigmine?
Indirect Cholinomimetic Drug - Acetylcholinesterase Inhibitor
Carbamic Acid Ester (carbamate)
Binding to AChE is non-covalent and reversible
Used to treat Myasthenia Gravis
- Outcompetes Myasthenia Gravis Antibodies
- Increases ACh in the Neuromuscular Junction endplate
Used to reverse pharmacological paralysis induced by Neuromuscular Blocking drugs during surgical anesthesia
Quaternary Agent - CANNOT cross the BBB
30
What is Abenonium?
Indirect Cholinomimetic Drug - Acetylcholinesterase Inhibitor
Quaternary Agent - CANNOT cross the BBB
31
What is Scopolamine?
Muscarinic Antagonist
Used to treat motion sickness
Used in Ophthalmology
- Causes mydriasis (pupil dilation)
- Blocks cholinergic activation of Pupillary muscle constriction
CAN cross the BBB
Can be administered by injection, orally, or transdermal patch
32
What is Donepezil?
Indirect Cholinomimetic Drug - Acetylcholinesterase Inhibitor
Used to treat Alzheimer's Type Dementia
Tertiary Agent - CAN cross the BBB
33
What is Ipratropium?
Muscarinic Antagonist
Specificity for M3 receptors
Used to treat respiratory disorders (COPD/Asthma)
- Block muscarinic activity, promoting sympathetics (Bronchodilation, reduced pulmonary secretions)
Dissociates from M3 faster than Tiotropium
Has shorter bronchodilator action
34
What is Echothiphate?
Indirect cholinomimetic Drug - Acetylcholinesterase Inhibitor
Organophosphate
Binding to AChE is covalent and irreversible
Quaternary Agent - CANNOT cross the BBB
35
What is Oxybutinin?
Muscarinic Agonist
Specificity for M3 receptors
Used to treat urinary disorders (overactive bladder)
- Relieves bladder spasms after urologic surgery
Relax smooth muscle in the ureters and bladder wall
Side effects:
o Dry mouth, dizziness, constipation, blurred vision, dry eyes, urinary tract infections
36
What is Edrophonium?
Indirect Cholinomimetic Drug - Acetylcholinesterase Inhibitor
Alcohol; positively charged
Binding to AChE is non-covalent and reversible
Outcompetes MG Antibodies
Has short half-life, only effective for 5-10 min, thus not very effective MG treatment
Used for Tensilon Test
- Reverses muscle weakness in undertreated MG patients (POSITIVE TENSILON TEST)
- If it fails to reverse muscle weakness, then you have a NEGATIVE TENSILON TEST (this indicates patient is in Cholinergic Crisis; aka too much ACh or agonist)
Quaternary Agent - CANNOT cross the BBB
37
What is Tiotropium?
Muscarinic Antagonist
Specificity for M3 receptor
Used to treat respiratory disorders (Asthma/COPD)
Blocks muscarinic activity, promoting sympathetics (Bronchodilation, reduced pulmonary secretions)
Dissociates from M3 receptor slower than Ipratropium
- Longer bronchodilator action
38
What is Galantamine?
Indirect Cholinomimetic Drug - Acetylcholinesterase inhibitor
Used to treat Alzheimer's Type Dementia
Tertiary Agent - CAN cross the BBB
39
What is Tolterodine?
Muscarinic Antagonist
Used for urinary disorders (overactive bladder)
- Relieves adult urinary incontinence
40
What is Benztropine?
Muscarinic Antagonist
Selectivity for M1
Centrally acting
Used for movement disorders (Parkinson's Disease)
Treat tremor and rigidity in Parkinson's
- Blocks excess cholinergic activity (excessive M1 activation is associated with cogwheel rigidity)
41
What is Mecamylamine?
Ganglion Blocker
Competitively block action of ACh and similar agonists at NAChRs of both the parasympathetic and sympathetic autonomic ganglia
- Block all autonomic flow
CAN cross the BBB
Enhances sympathetic tone:
- CNS: sedation, tremor, choreiform movements, and mental aberrations
- Eye: Cycloplegia (paralysis of ciliary muscles; loss of accommodation; lens can’t be adjusted), Moderate dilation of pupil
- Cardiovascular: Decreased blood pressure, diminished contractility, moderate tachycardia
- GI: Reduced secretion, profound motility inhibition
- GU: Urination hesitancy, erection/ejaculation prevented
Used to treat hypertension
42
What is Trihexyphenidyl?
Muscarinic Antagonist
Specificity for M1
Used for movement disorders (Parkinson’s)
CAN cross the BBB
Centrally acting
Treat tremor and rigidity in Parkinson’s
- Blocks excess cholinergic activity (excessive M1 activation is associated with cogwheel rigidity)
43
What is the general functions of the M1 receptor when activated at its various locations?
- Allows signal transduction from one nerve to the next
| - Promotes GI tract motility via the enteric NS
44
What is the general functions of the M2 receptor when activated at its various locations?
- Decreases contractility of the Atria
| - Decreases heart rate via the SA node (decrease conduction rate through the AV node)
45
What is the general functions of the M3 receptor when activated at its various locations?
- Secretion of sweat glands
- Secretion of pulmonary glands
- Secretion of GI glands
- Secretion of Lacrimal glands
- Contraction of Ciliary and Pupillary muscles (accommodation and pupil constriction)
- Causes NO release in vascular smooth muscle (increases cGMP, leading to vasodilation)
46
What protein is associated with the alpha-1 adrenergic receptors?
Gq GPCR
47
What protein is associated with the alpha-2 adrenergic receptor?
Gi GPCR
48
What protein is associated with the Beta-1 adrenergic receptor?
Gs GPCR
49
What protein is associated with the Beta-2 adrenergic receptor
Gs GPCR
50
What protein is associated with the Beta-3 adrenergic receptor
Gs GPCR
51
What locations can you find the alpha-1 receptor?
- Most Vascular Smooth muscle
- Pupillary dilator smooth muscle
- Prostate/urinary sphincter smooth muscle
- Heart
52
What locations can you find the alpha-2 receptor?
- Some vascular smooth muscle
- Pancreatic islet cells
- Post-synaptic CNS neurons
- Platelets
- Ciliary body of the eye
- Adrenergic and cholinergic nerve terminals
- Fat cells
53
What locations can you find the beta-1 receptor?
- Heart (including SA and AV nodes)
| - juxtaglomerular cells
54
What locations can you find the beta-2 receptor?
- Respiratory smooth muscle
- Vascular smooth muscle
- Uterine smooth muscle
- Skeletal muscle
- Liver
- Fat cells
- Pancreatic Islet cells
- Ciliary body of the eye
55
What is the general functions of the alpha-1 receptor when activated at its various locations?
- Contraction of vascular smooth muscle --> Increased peripheral arterial and venous resistance (MAP)
- Contraction of dilator muscle --> Pupil dilation
- Contraction of prostatic smooth muscle and urinary sphincter smooth muscle (thus urinary retention)
- Increases force of contraction of the heart
56
What is the general functions of the alpha-2 receptor when activated at its various locations?
- Platelet aggregation
- Decreases insulin release from pancreatic islet cells
- Inhibits neurotransmitter release at adrenergic and cholinergic nerve terminals
- Contraction of vascular smooth muscle
- Inhibit aqueous humor production from the ciliary body in the eye (decreasing eye pressure --> treats glaucoma)
- Inhibits lipolysis in fat cells
57
What is the general functions of the beta-1 receptor when activated at its various locations?
- Increases force and rate of contraction of the heart
| - Increases renin release
58
What is the general functions of the beta-2 receptor when activated at its various locations?
- Respiratory smooth muscle relaxation (dilates bronchioles)
- Uterine muscles relaxation
- Vascular smooth muscle relaxation
- Promotes K+ uptake into the skeletal muscle (as well as systemic HYPOkalemia)
- Activates gluconeogenesis and glycogenolysis in the liver
- Activates lipolysis and free fatty acid release from Fat cells
- Causes the release of Insulin from Pancreatic Islet cells
- Activates aqueous humor production in the ciliary body (causing increased eye pressure)
59
What is the general functions of the beta-3 receptor when activated at its various locations?
- Relaxes the detrusor muscle of the bladder (urinary retention)
- Activates lipolysis
60
What is Phenylephrine?
Direct acting Adrenomimetic Drug
Alpha agonist
- Primarily acts on alpha-1 receptors
Vasoconstrictor (both arteries and veins)
- Causes increase in MAP, Systolic BP, and Diastolic BP (increased venous return)
Causes Mydriasis (pupil dilation)
Induces reflexive bradycardia
- Increased MAP activates baroreceptors which cause the heart to become reflexively bradycardic
Used clinically to dilate pupils for retinal examination
Used clinically to treat Hypotensive emergencies:
- hemorrhagic shock
- Overdose of antihypertensives
- CNS depressants
Used clinically to treat nasal decongenstion
- Vasoconstriction of nasal vessels reduces edema in nasal mucosa
61
What is norepinpehprine?
Direct acting Adrenomimetic Drug
Specificity for alpha receptors over beta receptors (but does interact with both)
Increases cardiac contractility
- Beta-1 activity
Potent Vasoconstrictor
- Increases TPR and BP (MAP, Systolic, and diastolic BP)
Lacks Beta-2 agonist effects (no bronchodilation, no vasodilation)
Induces reflexive bradycardia
- Increased MAP activates baroreceptors which cause the heart to become reflexively bradycardic
Clinically used to treat Hypotensive emergencies:
- Hemorrhagic shock
- Overdose of antihypertensives
- CNS Depressants
