Pharmacology - Autonomic Drugs Flashcards
(50 cards)
1
Q
Central and peripheral nervous system
- The adrenal medulla and sweat glands
- Botulinum toxin
A
- The adrenal medulla and sweat glands
- Part of the sympathetic nervous system but are innervated by cholinergic fibers.
- Botulinum toxin
- Prevents release of neurotransmitter at all cholinergic terminals.
2
Q
ACh receptors
- Nicotinic ACh receptors
- Mechanism
- Subtypes
- Muscarinic ACh receptors
- Mechanism
- Subtypes
A
-
Nicotinic ACh receptors
- Mechanism
- Ligand-gated Na+/K+ channels
- 2 subtypes
- NN (found in autonomic ganglia)
- NM (found in neuromuscular junction)
- Mechanism
- Muscarinic ACh receptors
- Mechanism
- G-protein–coupled receptors that usually act through 2nd messengers
- 5 subtypes
- M1, M2, M3, M4, and M5
- Mechanism
3
Q
α1 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Sympathetic G-protein–linked 2nd messenger
- G-protein class
- q
- Major functions
- Increase vascular smooth muscle contraction
- Increase pupillary dilator muscle contraction (mydriasis)
- Increase intestinal and bladder sphincter muscle contraction
4
Q
α2 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Sympathetic G-protein–linked 2nd messenger
- G-protein class
- i
- Major functions
- Decrease sympathetic outflow
- Decrease insulin release
- Decrease lipolysis
- Increase platelet aggregation
5
Q
β1 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Sympathetic G-protein–linked 2nd messenger
- G-protein class
- s
- Major functions
- Increase heart rate
- Increase contractility
- Increase renin release
- Increase lipolysis
6
Q
β2 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Sympathetic G-protein–linked 2nd messenger
- G-protein class
- s
- Major functions
- Vasodilation
- Bronchodilation
- Increase heart rate
- Increase contractility
- Increase lipolysis
- Increase insulin release
- Decrease uterine tone (tocolysis)
- Ciliary muscle relaxation
- Increase aqueous humor production
7
Q
M1 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Parasympathetic G-protein–linked 2nd messenger
- G-protein class
- q
- Major functions
- CNS
- Enteric nervous system
8
Q
M2 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Parasympathetic G-protein–linked 2nd messenger
- G-protein class
- i
- Major functions
- Decrease heart rate and contractility of atria
9
Q
M3 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Parasympathetic G-protein–linked 2nd messenger
- G-protein class
- q
- Major functions
- Decrease exocrine gland secretions (e.g., lacrimal, salivary, gastric acid)
- Increase gut peristalsis
- Increase bladder contraction
- Bronchoconstriction
- Increase pupillary sphincter muscle contraction (miosis)
- Ciliary muscle contraction (accommodation)
10
Q
D1 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Dopamine G-protein–linked 2nd messenger
- G-protein class
- s
- Major functions
- Relaxes renal vascular smooth muscle
11
Q
D2 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Dopamine G-protein–linked 2nd messenger
- G-protein class
- i
- Major functions
- Modulates transmitter release, especially in brain
12
Q
H1 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Histamine G-protein–linked 2nd messenger
- G-protein class
- q
- Major functions
- Increase nasal and bronchial mucus production
- Increase vascular permeability
- Contraction of bronchioles
- Pruritus
- Pain
13
Q
H2 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Histamine G-protein–linked 2nd messenger
- G-protein class
- s
- Major functions
- Increase gastric acid secretion
14
Q
V1 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Vasopressin G-protein–linked 2nd messenger
- G-protein class
- q
- Major functions
- Increase vascular smooth muscle contraction
15
Q
V2 receptor
- Type
- G-protein class
- Major functions
A
- Type
- Vasopressin G-protein–linked 2nd messenger
- G-protein class
- s
- Major functions
- Increase H2O permeability and reabsorption in the collecting tubules of the
kidney - V2** is found in the 2 kidneys**
- Increase H2O permeability and reabsorption in the collecting tubules of the
16
Q
G-protein–linked 2nd messengers (224)
A
- “Qiss (kiss) and qiq (kick) till you’re siq (sick) of sqs (super qinky sex).”
- α1 q
- α2 i
- β1 s
- β2 s
- M1 q
- M2 i
- M3 q
- D1 s
- D2 i
- H1 q
- H2 s
- V1 q
- V2 s
17
Q
Autonomic drugs (245)
A
- Release of norepinephrine from a sympathetic nerve ending is modulated by norepinephrine itself, acting on presynaptic α2-autoreceptors, angiotensin II, and other substances.
18
Q
Bethanechol
- Type of agent
- Clinical applications
- Action
A
- Type of agent
- Direct cholinomimetic agent
- Clinical applications
- Postoperative ileus, neurogenic ileus, and urinary retention
- Action
- Activates bowel and bladder smooth muscle
- Resistant to AChE.
- “Bethany, call (bethanechol) me, maybe, if you want to activate your bowels and bladder.”
19
Q
Carbachol
- Type
- Clinical applications
- Action
A
- Type of agent
- Direct cholinomimetic agent
- Clinical applications
- Glaucoma, pupillary constriction, and relief of intraocular pressure
- Action
- Carbon copy of acetylcholine.
20
Q
Pilocarpine
- Type
- Clinical applications
- Action
A
- Type of agent
- Direct cholinomimetic agent
- Clinical applications
- Potent stimulator of sweat, tears, and saliva
- Open-angle and closed-angle glaucoma
- Action
- Contracts ciliary muscle of eye (open-angle glaucoma), pupillary sphincter (closed-angle glaucoma)
- Resistant to AChE.
- “You cry, drool, and sweat on your ‘pilow.’ ”
21
Q
Methacholine
- Type
- Clinical applications
- Action
A
- Type of agent
- Direct cholinomimetic agent
- Clinical applications
- Challenge test for diagnosis of asthma
- Action
- Stimulates muscarinic receptors in airway when inhaled.
22
Q
Neostigmine
- Type
- Clinical applications
- Action
A
- Type of agent
- Indirect cholinomimetic agent (anticholinesterase)
- Clinical applications
- Postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade (postoperative)
- Action
- Increases endogenous ACh.
- Neo CNS = No CNS penetration.
23
Q
Pyridostigmine
- Type
- Clinical applications
- Action
A
- Type of agent
- Indirect cholinomimetic agent (anticholinesterase)
- Clinical applications
- Myasthenia gravis (long acting)
- Does not penetrate CNS
- Action
- Increases endogenous ACh
- Increases strength.
- Pyridostigmine gets rid of myasthenia gravis.
24
Q
Physostigmine
- Type
- Clinical applications
- Action
A
- Type of agent
- Indirect cholinomimetic agent (anticholinesterase)
- Clinical applications
- Anticholinergic toxicity (crosses blood-brain barrier –> CNS)
- Action
- Increases endogenous ACh.
- Physostigmine “phyxes” atropine overdose.
25
Donepezil, rivastigmine, galantamine
* Type
* Clinical applications
* Action
* Type of agent
* Indirect cholinomimetic agent (anticholinesterase)
* Clinical applications
* Alzheimer disease
* Action
* Increases endogenous ACh.
26
Edrophonium
* Type
* Clinical applications
* Action
* Type of agent
* Indirect cholinomimetic agent (anticholinesterase)
* Clinical applications
* Historically, diagnosis of myasthenia gravis (extremely short acting).
* Myasthenia now diagnosed by anti-AChR Ab (antiacetylcholine receptor antibody) test.
* Action
* Increases endogenous ACh.
27
Cholinomimetic agents caution
* With all cholinomimetic agents, watch for exacerbation of COPD, asthma, and peptic ulcers when giving to susceptible patients.
28
Cholinesterase inhibitor poisoning
* Often due to...
* Causes...
* Organophosphates
* Antidote
* Often due to...
* Organophosphates, such as parathion, that **irreversibly** inhibit AChE.
* Causes...
* **_D_**iarrhea, **_U_**rination, **_M_**iosis, **_B_**ronchospasm, **_B_**radycardia, **_E_**xcitation of skeletal muscle and CNS, **_L_**acrimation, **_S_**weating, and **_S_**alivation.
* **_DUMBBELSS_.**
* Organophosphates
* Components of insecticides
* Poisoning usually seen in farmers.
* Antidote
* Aropine (competitive inhibitor) + pralidoxime (regenerates AChE if given early).
29
Muscarinic antagonists
* For each
* Organ system(s)
* Application(s)
* Atropine, homatropine, tropicamide
* Benztropine
* Scopolamine
* Ipratropium, tiotropium
* Oxybutynin, darifenacin, and solifenacin
* Glycopyrrolate
* Atropine, homatropine, tropicamide
* _Organ system(s)_: Eye
* _Application(s)_: Produce mydriasis and cycloplegia.
* **_Benz_**tropine
* _Organ system(s)_: CNS
* _Application(s)_: **_Park_**inson disease
* **“_Park_ my _Benz_.”**
* Scopolamine
* _Organ system(s)_: CNS
* _Application(s)_: Motion sickness.
* **_Ipra_**tropium, tiotropium
* _Organ system(s)_: Respiratory
* _Application(s)_: COPD, asthma
* **“_I pray_ I can breathe soon!”**
* Oxybutynin, darifenacin, and solifenacin
* _Organ system(s)_: Genitourinary
* _Application(s)_:
* Reduce urgency in mild cystitis and reduce bladder spasms.
* Other agents: tolterodine, fesoterodine, trospium.
* Glycopyrrolate
* _Organ system(s)_: Gastrointestinal, respiratory
* _Application(s)_:
* Parenteral: preoperative use to reduce airway secretions.
* Oral: drooling, peptic ulcer.
30
Atropine
* Definition
* Action(s) in each organ system
* Eye
* Airway
* Stomach
* Gut
* Bladder
* Toxicity
* Definition
* Muscarinic antagonist.
* Used to treat bradycardia and for ophthalmic applications.
* Blocks **_DUMBB_**e**_LSS_**.
* **_D_**iarrhea, **_U_**rination, **_M_**iosis, **_B_**ronchospasm, **_B_**radycardia, **_L_**acrimation, **_S_**weating, and **_S_**alivation
* Skeletal muscle and CNS excitation mediated by nicotinic receptors.
* Action(s) in each organ system
* Eye --\> increase pupil dilation, cycloplegia
* Airway --\> decrease secretions
* Stomach --\> decrease acid secretion
* Gut --\> decrease motility
* Bladder --\> decrease urgency in cystitis
* Toxicity
* Increase body **_temperature_** (due to decreased sweating); rapid pulse; dry mouth; **_dry, flushed skin_**; **_cycloplegia_**; constipation; **_disorientation_**
* **_Hot_**** as a hare**
* **_Dry_ as a bone**
* **_Red_ as a beet**
* **_Blind_ as a bat**
* **_Mad_ as a hatter**
* Can cause acute angle-closure glaucoma in elderly (due to mydriasis), urinary retention in men with prostatic hyperplasia, and hyperthermia in infants
* Jimson weed (Datura) --\> gardeners pupil (mydriasis due to plant alkaloids)
31
Epinephrine
* Type of drug
* Effect
* Applications
* Type of drug
* Direct sympathomimetic
* Effect
* β \> α
* Applications
* Anaphylaxis
* Open angle glaucoma
* Asthma
* Hypotension
* α effects predominate at high doses
32
Norepinephrine
* Type of drug
* Effect
* Applications
* Type of drug
* Direct sympathomimetic
* Effect
* α1 \> α2 \> β1
* Applications
* Hypotension (but decrease renal perfusion)
33
Isoproterenol
* Type of drug
* Effect
* Applications
* Type of drug
* Direct sympathomimetic
* Effect
* β1 = β2
* Applications
* Electrophysiologic evaluation of tachyarrhythmias.
* Can worsen ischemia.
34
Dopamine
* Type of drug
* Effect
* Applications
* Type of drug
* Direct sympathomimetic
* Effect
* D1 = D2 \> β \> α
* Applications
* Unstable bradycardia, heart failure, shock
* Inotropic and chronotropic α effects predominate at high doses
35
Dobutamine
* Type of drug
* Effect
* Applications
* Type of drug
* Direct sympathomimetic
* Effect
* β1 \> β2, α
* Applications
* Heart failure (inotropic \> chronotropic)
* Cardiac stress testing
36
Phenylephrine
* Type of drug
* Effect
* Applications
* Type of drug
* Direct sympathomimetic
* Effect
* α1 \> α2
* Applications
* Hypotension (vasoconstrictor)
* Ocular procedures (mydriatic)
* Rhinitis (decongestant)
37
Albuterol, salmeterol, terbutaline
* Type of drug
* Effect
* Applications
* Type of drug
* Direct sympathomimetic
* Effect
* β2 \> β1
* Applications
* Albuterol for acute asthma
* Salmeterol for long-term asthma or COPD control
* Terbutaline to reduce premature uterine contractions
38
Amphetamine
* Type of drug
* Effect
* Applications
* Type of drug
* Indirect sympathomimetic
* Effect
* Indirect general agonist
* Reuptake inhibitor
* Releases stored catecholamines
* Applications
* Narcolepsy
* Obesity
* Attention deficit disorder
39
Ephedrine
* Type of drug
* Effect
* Applications
* Type of drug
* Indirect sympathomimetic
* Effect
* Indirect general agonist
* Releases stored catecholamines
* Applications
* Nasal decongestion
* Urinary incontinence
* Hypotension
40
Cocaine
* Type of drug
* Effect
* Applications
* Type of drug
* Indirect sympathomimetic
* Effect
* Indirect general agonist
* Reuptake inhibitor
* Applications
* Causes vasoconstriction and local anesthesia
* Never give β-blockers if cocaine intoxication is suspected
* Can lead to unopposed α1 activation and extreme hypertension
41
Norepinephrine vs. isoproterenol
* Norepinephrine causes increases in systolic and diastolic pressures as a result of α1-mediated vasoconstriction --\> increased mean arterial pressure --\> bradycardia.
* However, isoproterenol (no longer commonly used) has little α effect but causes β2-mediated vasodilation, resulting in decreased mean arterial pressure and increased heart rate through β1 and reflex activity.
42
Clonidine
* Type of drug
* Applications
* Toxicity
* Type of drug
* Sympatholytic (α2-agonist)
* Applications
* Hypertensive urgency (limited situations)
* Does not decrease renal blood flow
* ADHD, severe pain, and a variety of offlabel indications
* e.g., ethanol and opioid withdrawal
* Toxicity
* CNS depression
* Bradycardia
* Hypotension
* Respiratory depression
* Small pupil size
43
α-methyldopa
* Type of drug
* Applications
* Toxicity
* Type of drug
* Sympatholytic (α2-agonist)
* Applications
* Hypertension in pregnancy
* Safe in pregnancy
* Toxicity
* Direct Coombs (+) hemolytic anemia
* SLE-like syndrome
44
Phenoxybenzamine
* Type of drug
* Applications
* Toxicity
* Type of drug
* Irreversible nonselective α-blocker
* Applications
* Pheochromocytoma (used preoperatively) to prevent catecholamine (hypertensive) crisis
* Toxicity
* Orthostatic hypotension
* Reflex tachycardia
45
Phentolamine
* Type of drug
* Applications
* Type of drug
* Reversible nonselective α-blocker
* Applications
* Give to patients on MAO inhibitors who eat tyramine-containing foods
46
Prazosin, terazosin, doxazosin, tamsulosin
* Type of drug
* Applications
* Toxicity
* Type of drug
* α1 selective (-osin ending) α-blocker
* Applications
* Urinary symptoms of BPH
* PTSD (prazosin)
* Hypertension (except tamsulosin)
* Toxicity
* 1st-dose orthostatic hypotension
* Dizziness
* Headache
47
Mirtazapine
* Type of drug
* Applications
* Toxicity
* Type of drug
* α2 selective α-blocker
* Applications
* Depression
* Toxicity
* Sedation
* Increased serum cholesterol
* Increased appetite
48
a-blockade of epinephrine vs. phenylephrine
* Image: the effects of an α-blocker (e.g., phentolamine) on blood pressure responses to epinephrine and phenylephrine.
* The epinephrine response exhibits reversal of the mean blood pressure change, from a net increase (the α response) to a net decrease (the β2 response).
* The response to phenylephrine is suppressed but not reversed because phenylephrine is a “pure” α-agonist without β action.
49
β-blockers
* Examples
* Selectivity
* β1-selective antagonists (β1 \> β2)
* Nonselective antagonists (β1 = β2)
* Nonselective α- and β-antagonists
* Nebivolol
* Examples
* Metoprolol, acebutolol, betaxolol, carvedilol, esmolol, atenolol, nadolol, timolol, pindolol, labetalol.
* Selectivity
* β1-selective antagonists (β1 \> β2)
* **_A_**cebutolol (partial agonist), **_a_**tenolol, **_b_**etaxolol, **_e_**smolol, **_m_**etoprolol
* **Selective antagonists mostly go from _A_ to _M_ (β_1_ with _1st_ half of alphabet)**
* Nonselective antagonists (β1 = β2)
* **_N_**adolol, **_p_**indolol (partial agonist), **_p_**ropranolol, **_t_**imolol
* **Nonselective antagonists mostly go from _N_ to _Z_ (β_2_ with **_2_**nd half of alphabet)**
* Nonselective α- and β-antagonists
* Carvedilol, labetalol
* **Nonselectives α- and β-antagonists have modified suffixes (instead of “-olol”)**
* Nebivolol
* Combines cardiac-selective β1‑adrenergic blockade with stimulation of β3‑receptors, which activate nitric oxide synthase in the vasculature
50
β-blockers
* Toxicity
* Effects
* Angina pectoris
* MI
* SVT (metoprolol, esmolol)
* Hypertension
* CHF
* Glaucoma (timolol)
* Toxicity
* Impotence, cardiovascular adverse effects (bradycardia, AV block, CHF), CNS adverse effects (seizures, sedation, sleep alterations), dyslipidemia (metoprolol), and asthmatics/ COPDers (may cause exacerbation)
* Avoid in cocaine users due to risk of unopposed α-adrenergic receptor agonist activity
* Despite theoretical concern of masking hypoglycemia in diabetics, benefits likely outweigh risks; not contraindicated
* Effects
* Angina pectoris
* Decrease heart rate and contractility, resulting in decreased O2 consumption
* MI
* β-blockers (metoprolol, carvedilol, and bisoprolol) decrease mortality
* SVT (metoprolol, esmolol)
* Decrease AV conduction velocity (class II antiarrhythmic)
* Hypertension
* Decreases cardiac output
* Decreases renin secretion (due to β1-receptor blockade on JGA cells)
* CHF
* Slows progression of chronic failure
* Glaucoma (timolol)
* Decreases secretion of aqueous humor
