Autonomic Pharmacology Flashcards
(111 cards)
1
Q
What drugs are part of the Direct-Acting Cholinoceptor Agonists: Choline Esters class?
A
Acetylcholine
Methacholine
Carbachol
Bethanechol
Mnemonic: Ace Met Beth in his Car and Ester on a date
2
Q
Characteristics of Choline Esters
A
All have cationic quaternary ammonium –> makes them insoluble in lipids
(Poor GI absorption/Poor CNS distribution)
3
Q
Which two Choline Esters are insusceptible to Cholinesterase?
A
Carbachol
Bethanechol
Mnemonic: Beth avoids AchE in her Car
4
Q
What is the action of Choline Esters similar to?
A
M2 or M3 Activation
5
Q
Acetylcholine
- Class
- Muscarinic Effects
- Nicotinic Effects
A
Class: ***Prototype*** Choline Ester (Direct-Acting Cholinoceptor Agonist)
Muscarinic:
Cardiovascular-
Low Doses: Vasodilation –> reflex tachycardia
High Doses (M2 Effects): Bradycardia ; Decreased A-V conduction; (-) Inotropy
Bronchial constriction, increased bronchial secretion
Salivary excretion, tears, sweat
Urinary bladder contraction
Eye short-lasting miosis
Nicotinic: NOT COMMONLY SEEN, since Ach does not penetrate the fat surrounding skeletal muscle and autonomic ganglia
6
Q
Acetylcholine
- Clinical Uses (2)
A
Use:
Eye Surgery (short-lasting MIOSIS)
PROVOCATION TEST in Coronary Angiography (Dx: Coronary Vasospasm)
7
Q
Methacholine (Provocholine)
- Class/About
- Clinical Uses
A
Class: Choline Ester (Direct-Acting Cholinoceptor Agonist)
Similar to Ach in action, but has longer half life
Use:
- Methacholine Challenge (inhaled) –> Bronchiolar Hypersensitivity (excessive BronchoCONSTRICTION)
- Belladonna alkaloid poisoning (SubQ) –> Dose would NOT elicit normal MUSCARINIC effects in someone with this
8
Q
Carbachol
- Class
- Effects
- Clinical Uses
A
Class: Choline Ester (Direct-Acting Cholinoceptor Agonist)
Effects:
Therapeutic Doses: Activate both NICOTINIC and MUSCARINIC cholinoceptors (Nicotinic effects - Autonomic Ganglia, Adrenal Medulla, Skeletal muscle)
High Doses: Muscarinic effects - May include CARDIAC ARREST
Use:
Glaucoma (contracts Ciliary muscle, enlarges canal of Schlemm, increases drainage of Aq. Hum., Decreases Intraocular Pressure)
9
Q
Bethanechol (Urecholine)
- Class
- Effects
- Clinical Uses
A
Class: Quaternary Choline Ester (Direct-Acting Cholinoceptor Agonist)
Effects: Acts Predominantly on M3 (NO nicotinic effects)
Genitourinary: increased detrusor tone, decreases outlet resistance of internal sphincter
Gastrointestinal: increased motility and secretion
Weak effects on M2 - minimal cardiac effects
Clinical Uses:
Gastric Atony after vagotomy to reduce reflux (INCREASES lower esophageal sphincter tone)
Gastric Emptying Abnormalities
Urinary RETENTION (in the ABSENCE of obstruction)
Mnemonic: Beth think Bladder
10
Q
What drugs are part of the Direct-Acting Cholinoceptor Agonists: Muscarinic Alkaloids class?
A
Muscarine
Pilocarpaine
Mnemonic: Al has a Pile of Muscles
11
Q
Muscarine
- Class
- Properties
A
Class: Muscarinic Alkaloid (Direct-Acting Cholinoceptor Agonist) Quaternary Ammonium Compound
Properties: No Nicotinic Activity; 100x more potent than Ach and has a longer duration of action than Ach, as it is not broken down by AchE because it is not a choline ester)
12
Q
Muscarine Poisoning
- Cause
- Symptoms
A
Cause: Mushrooms (e.g. Amanita Muscaria)
Sx: A very WET PICTURE
- Salivation, sweat, tear flow
- Abdominal pain, nausea, diarrhea, blurred vision, dyspnea
- Severe Cases: cardiac/respiratory failure and Death
***Symptoms normally subside within 2 hours***
13
Q
Pilocarpine (Isopto Carpine, Salagen)
- Class
- Effects
- Clinical Use
A
Class: Muscarinic Alkaloid (Direct-Acting Cholinoceptor Agonist) Tertiary Amine
Effects: Produces Ophthalmic (M3) Effects similar to Ach (applied Topically)
Contracts iris sphincter muscles –> Miosis
Frees entrance to Canal of Schlemm –> Narrow-angle Glaucoma
Enhances tone of trabecular network –> Wide-angle Glaucoma
Contracts the ciliary muscle (Lens becomes more spherical) –> Accomodation__/LOSS of FAR vision
Uses:
GLAUCOMA (***Drug of choice***), Xerostomia (dry mouth - given orally), tests the AUTONOMIC STATE (similar to Methacholine Challenge)
14
Q
What drugs are part of the Direct-Acting Cholinoceptor Agonists: Nicotinic Alkaloids class?
A
Nicotine
Succinylcholine
Mnemonic: Nicotine Succs
15
Q
Nicotine
- Class
- Action on NM
A
Class: ***Prototype***Nicotinic Alkaloid (Direct-Acting Cholinoceptor Agonist)
NM Action:
Skeletal Muscle Contraction
Fasciculations, spasm
Depolarizing Blockade –> Paralysis (Similar to Succinylcholine under neuromuscular blocking drugs)
16
Q
Nicotine
- Action on NN
A
NN Action: Stimulate both sympathetic and parasympathetic post-ganglion neurons
Cardiac: increased heart rate (sympathetic > parasymp)
Vascular: mostly sympathetic innervation –> peripheral vasoconstriction
GI: increased gut motility/secretion
Carotid Bodies: increased respiratory rate
Medullary Emetic Chemoreceptors: nausea and vomiting
17
Q
Nicotine
- Clinical Indications
A
Smoking cessation
-Stimulates the hypothalamus to secrete more cortisol
18
Q
What are some Contraindications (3) and Drug Interactions (3) to consider when administering Direct-Acting Cholinoceptor Agonists?
A
Contraindications:
Peptic Ulcers (Increased Gastric Acid secretion)
GI Tract Disorders
Asthma (Bronchoconstriction)
Drug Interactions: Drugs having antimuscarinic properties can block the effects of muscarinic agonists
(e.g. Quinidine (antiarrhythmics), Procainamide (antiarrhythmics), Tricyclic Antidepressants
19
Q
What drugs are part of the Indirect-Acting Cholinesterase Inhibitors/Cholinomimetics: Reversible class?
A
Edrophonium
Neostigmine
Physostigmine
Donepezil
Tacrine
Mnemonic: Ed and Don Physically Tackled Neo
20
Q
Edrophonium
- Class
- Characteristics
- Clinical Uses
A
Class: Indirect-Acting Cholinesterase Inhibitors/Cholinomimetic: Reversible
Characteristics: Short-acting
Uses: Diagnosis of MYASTHENIA GRAVIS (MG) ; If Edrophonium IMPROVES the symptoms, then it confirms diagnosis of MG vs. Cholinergic crisis, neurasthenic/infectious/endocrine/congenital/neoplastic/degenerative neuromuscular disorders
21
Q
Neostigmine, Pyridostigmine
- Class
- Characteristics
- Clinical Uses
A
Class: Indirect-Acting Cholinesterase Inhibitors/Cholinomimetic: Reversible
Chracteristics: Quaternary amines (NO CNS ENTRY), Intermediate Acting
Uses: Ileus (Abdominal Distension), Urinary Retention (Non-obstructive), Myasthenia, Reversal of non-depolarizing NM Blockers
Mnemonic: Neostigmine has Neo (No) CNS action
22
Q
Physostigmine
- Class
- Characteristics
- Clinical Uses
A
Class: Indirect-Acting Cholinesterase Inhibitors/Cholinomimetics: Reversible
Characteristics: Tertiary Amine (ENTERS CNS), Intermediate Acting
Uses: Glaucoma (2nd line due to blocked accomodation and causation of myopia); antidote to Atropine Overdose
Mnemonic: Physostigmine physically enters the CNS
23
Q
Donepezil, Tacrine
- Class
- Characteristics
- Clinical Uses
A
Class: Indirect-Acting Cholinesterase Inhibitors/Cholinomimetics: Reversible
Characteristics: Lipid-soluble (ENTERS CNS)
Use: Treats Alzheimer Disease (increases cholinergic neurotransmitters in the CNS)
24
Q
Organophosphates
- Class
- Characteristics
- Clinical Uses
A
Class: Indirect-Acting Cholinesterase Inhibitors/Cholinomimetics: IRr__eversible
Characteristics: Lipid-soluble (CNS ENTRY), Long-acting IRREVERSIBLE inhibitors of AchE
Uses: Glaucoma (echothiophosphate), Insecticides (malathion, parathion), Nerve Gas (sarin)
25
Symptoms of **AchE Inhibitor/Cholinomimetic** **_Toxicity_**
**D** - Diarrhea
**U** - Uncontrolled urination (contraction of detrusor)
**M** - Miosis (constriction of sphincter)
**B** - Bronchiolar constriction
**B** - Bradycardia (decreased contractility)
**E** - Excitement, convulsion, coma
**L** - Lacrimation (tears)
**S** - Sweating
**S** - Salivation
26
How is **AchE Inhibitor/Cholinomimetic _Toxicity_** managed clinically?
Symptomatic
Airway control/oxygen delivery
Cardiovascular support
_Antidote:_ **Atropine** (muscarinic receptor antagonist)
-Relieves tracheobronchial/salivary secretion, broncho**_constriction_**, _bradycardia_, peripheral ganglionic and central _actions of anti-AchE_
_Regeration of AchE_: **Praladoxim (2-PAM)**
- Reverses phosphorylation of AchE (by AchE inhibitors)
- _Does not_ work for *neostigmine*, *physostigmine*, or *rapidly-aged phosphorylated AchEs*
27
What drugs are part of the **Cholinoceptor-Blocking Drugs: _Muscarinic Receptor Antagonist (Antimuscarinic)_** class?
Atropine
Ipratropium
Benztropine
Mnemonic: **Ipra**y for a **Benz** and **Atrop**hy
28
**Atropine**
1. Class
2. Characteristics
**Class:** \*\*\*_Prototype_\*\*\* Muscarinic Receptor Antagonists (Antimuscarinic)
**Characteristics:** Tertiary Amine (**ENTERS CNS**), _Competes with Ach & M at receptors_ ; **_DOES NOT DISTINGUISH_** between **M1, M2, M3** receptors
29
**Atropine**
1. Pharacologic Effects (in order of increasing dose)
Decreased secretions (salivary, bronchiolar, sweat)
Mydriasis and Cycloplegia
Hyperthermia
Tachycardia
Sedation
Urinary retention and constipation
Behavioral excitation and hallucinations
\*\*\*Note: completely **counteracts** **vasodilation** caused by **choline esters**
**_DOES NOT_** _affect **blood pressure**_ when given **_ALONE_**
30
**Atropine**
1. Clinical Uses
**Uses:**
Antispasmodic (_relaxes_)
Antisecretory (_dries_)
Management of AchE inhibitor overdose
Antidiarrheal (_dries_)
Ophthalmology
_Prevents vagal reaction_ (pericardiocentesis) by **increasing heart rate**
**Treatment of acute intoxication:** Symptomatic, _Physostigmine_
31
**Ipratropium (Atrovent)**
1. Class
2. Characteristics
3. Clinical Uses
**Class:** _Non-selective_ Muscarinic Receptor Antagonist (Antimuscarinic)
**Characteristics:** Mainly acts on **_M3 in Bronchial smooth muscle/glands_** when *inhaled* ; Quaternary amine (**NO CNS ENTRY**)
- **Decreases** bronchoconstriction
- **Decreases** bronchial constriction
**Uses:** \*\*\*1ST LINE THERAPY\*\*\* for ***_COPD_*** ; also used for _asthma_ (2nd line therapy)
32
**Benztropine (Cogentin)**
1. Class
2. Characteristics
3. Clinical Uses
**Class:** Muscarinic Receptor Antagonists (Antimuscarinic)
**Characteristics:** Tertiary Amine (**CNS ENTRY**) ; Acts on **Muscarinic** receptors in the _BRAIN_ and _PARASYMPATHETIC EFFECTOR SITES_
- Re-establishes **_*Dopaminergic-Cholinergic Balance***_ in patients with _***Parkinson's Disease*_** (PD: decreased dopaminergic --\> _cholinergic goes unchecked_)
- **Decreases** GI/GU secretions (_Dries_) and _motility_
- **Increases** heart rate
**Uses:** ***_Parkinson's Disease_*** (2nd or 3rd line therapy to **antipsychotic**)
33
What drugs are part of the **Cholinoceptor-Blocking Drugs: _Nicotinic Receptor Antagonists (NN & NM)/GANGLION BLOCKING AGENTS_** class?
Hexamethonium
Mecamylamine
Mnemonic: **Mec**ca **Hex**
34
**Hexamethonium and Mecamylamine**
1. Class
2. Characteristics
3. Clinical Uses
**Class:** \*\*\*GANGLION BLOCKING AGENTS\*\*\* Nicotinic Receptor Antagonists (Antinicotinic NN & NM)
**Characteristics:** _Reduce predominant autonimic tone_
-**Prevent _baroreceptor reflex changes in Heart Rate_**
\*\*\*Most are _no longer available_ due to **_TOXICITIES_**\*\*\*
35
What are the effects of **Ganglion Blocking Agents** on Arterioles, Veins, Heart, Iris, Ciliary Muscle, GI Tract, Bladder, Salivary Glands, Sweat Glands?
Arterioles (**SANS**) --\> Vasodilation, hypotension
Veins (**SANS**) --\> Dilation, decreased venous return, decreased CO
Heart (PANS) --\> Tachycardia
Iris (PANS) --\> Mydriasis
Ciliary Muscle (PANS) --\> Cycloplegia (paralysis --\> loss of accomodation)
GI Tract (PANS) --\> Decreased tone/motility - **constipation**
Bladder (PANS) --\> Urinary retention
Salivary Glands (PANS) --\> Xerostomia
Sweat Glands (**SANS**) --\> Anhidrosis
36
What drugs are in the **Cholinoceptor-Blocking: _Neuromuscular Blocking Drugs (Antinicotinic NM)_** class?
D-tubocurarine (**Non-depolarizing**)
Succinylcholine (**Depolarizing**)
37
What are some important properties of **Neuromuscular Blocking Drugs**? Clinical Uses?
- They all structurally **_resemble Ach_**
- Interfere with transmission at the **_neuromuscular endplate_**
- Interefere by **preventing channel _opening**_ (Non-depolarizing) or channel _**closing_** (Depolarizing)
- Highly ionized, Quaternary Amines (**NO CNS ENTRY**)
**Clinical Uses:** Facilitation of **_Tracheal Intubation_** ; optimize surgical conditions while ensuring adequate ventilation
38
**D-Tubocurarine**
1. Class
2. Mechniasm of Action
**Class:** ***_Non-Depolarizing_*** Neuromuscular (NM) Blocking Drug
**MoA:**
_Small Doses:_ Prevent opening of Na+ channel by **binding to receptor** and **competing with Ach**
_Large Doses:_ **enter channel pores**
-**Block pre-junctional Na+ channels** --\> Decreased Ach release
39
**Succinylcholine (Anectine)**
1. Class
2. Mechanism of Action
**Class:** ***_Depolarizing_*** Neuromuscular (NM) Blocking Drug
**MoA:**
_Phase 1 Blockade:_ Binding to NM receptors --\> **persistant _depolarization_** --\> **paralysis**
-Augmented by _AchE inhibitors_
_Phase 2 Blockade:_ End plate is finally **repolarized**, however, is ***_DESENSITIZED_*** and will not depolarize easily again
40
What are some clinical uses of **Neuromuscular Blockers** (i.e. D-tubocurarine and Succinylcholine)?
1. _Decrease neuromuscular transmission during anesthsia_
- Larger muscles are more resistant than smaller muscles
- Diaphragm responds **last** (recovery is in reverse order)
2. _Tracheal Intubation_
3. Control of _Ventilation_
4. Treatment of _Convulsions_
- Decreased manifestations of seizures
- **No effect on central processes** that occur during convulsion
41
What are some _side effects_ of **Neuromuscular Blockers?**
1. _Cardiovascular_: **Hypotension** (Histamine release due to **_Tubocurarine_**) --\> _prevented with ANTIHISTAMINES_
- **High doses** --\> Ganglion blockade --\> severe **HYPOtension**
2. _Hyperkalemia_ (response to **_Succinylcholine_** from patients with **burns, nerve damage,** or **neuromuscular disease**)
3. _Increased Intraocular Pressure_ (due to **_Succinylcholine_** ; only contraindicated if **anterior chamber is OPEN** due to trauma)
4. _Increased Gastric Pressure_ (can cause aspiration/regurgitation in **heavily-muscled patients**)
5. _Muscle Pain_ (**heavily-muscled** and **largely-dosed patients**)
42
What drugs are part of the **Selective Direct Acting Adrenergic Agonist** class?
Phenylephrine (a1)
Clonidine (a2)
Terbutaline (B2)
Fenoldopam (D1)
Mnemonic: You can **Find Old Pam** playing the P**ine** **TPC**
43
**Phenylephrine (Neo-Synephrine)**
1. Class
2. Mechanism of Action
3. Clinical Uses
**Class:** alpha 1 - Selective Adrenergic Receptor Agonist
**MoA:**
- Activate **alpha adrenergic receptors** on vascular smooth muscle --\> _increased blood pressure_ and _increased TPR_
- Activate **Beta receptors** _only at HIGH concentrations_
**Use:**
- _Antihypotensive_
- _Paroxysmal Atrial Tachycardia_
- Nasal _Decongestant_
- _Mydriatic_
44
**Clonidine (Catapres)**
1. Class
2. Mechanism of Action
3. Clinical Uses
**Class:** alpha 2 - Selective Adrenergic Receptor Agonist
**MoA:** Activate **Central alpha 2 receptors** --\> Decreased Central sympathetic outflow --\> **_Decreased Blood Pressure_**
**Uses:** Systemic Hypertension
45
**a-methyldopa (Aldomet)**
1. Class
2. Mechanism of Action
3. Clinical Uses
**Class:** alpha 2 - Selective Adrenergic Receptor Agonist
**MoA:** Activate **Central alpha 2 receptors** --\> Decreased Central sympathetic outflow --\> **_Decreased Blood Pressure_**
**Uses:** Systemic Hypertension
46
**Apraclonidine (Lodipine)**
1. Class
2. Mechanism of Action
3. Clinical Uses
**Class:** alpha 2 - Selective Adrengergic Receptor Agonist
**MoA:** _Decreased_ **aqueous humor production** --\> **Decreased _Intraocular pressure_**
**Use:** ***_GLAUCOMA_***
47
**Brimonidine (Alphagan)**
1. Class
2. Mechanism of Action
3. Clinical Uses
**Class:** alpha 2 - Selective Adrengergic Receptor Agonist
**MoA:** _Decreased_ **aqueous humor production** --\> **_Decreased Intraocular pressure_**
**Use: *_GLAUCOMA_***
48
What are some adverse effects of **alpha 2 - Selective Adrenergic Receptor Agonists**?
Dry Mouth
Sedation
Hypotension
49
**Metaproterenol (Metaprel)**
1. Class
2. Mechanism of Action
3. Clinical Uses
**Class:** Beta 2 - Selective Adrenergic Receptor Agonists
**MoA:**
\*\*\*Resistant to methylation by _COMT_\*\*\*
-**Beta 2-Selective** (_LESS_ selective than Albuterol or Terbutaline)
**Uses:** _Long-term_ treatment of **obstructive airway diseases - _ASTHMA**_ ; treats _**Acute Bronchospasm_**
50
**Terbutaline (Bricanyl)**
1. Class
2. Mechanism of Action
3. Clinical Uses
**Class:** Beta 2 - Selective Adrenergic Receptor Agonists
**MoA:** \*\*\*NOT a substrate for _COMT methylation_\*\*\*
-**Beta 2-Selective**
**Uses:**
- _Long-term_ treatment of **obstructive airway diseases**
- **Acute Bronchospasm**
- _Emergency treatment_ of **_Status Asthmaticus_** (IV use)
51
**Albuterol (Ventolin, Salbutamol)**
1. Class
2. Mechanism of Action
3. Clinical Uses
**Class:** Beta 2 - Selective Adrenergic Recptor Agonist
**MoA:**
- **Beta 2 - Selective** (Same as **_Terbutaline_**)
- Treats **Acute Bronchospasm**
**Uses:**
(Same as **_Terbutaline_**)
-**_Delays PRETERM LABOR_**
52
**Ritodrine (Yutopar)**
1. Class
2. Mechanism of Action
3. Clinical Uses
**Class:** Beta 2 - Selective Adrenergic Receptor Agonist
**MoA:**
-**Beta 2 - Selective Agonist**
**Uses:**
- Designed specificall for use as a **_*\*\*\*UTERINE RELAXANT\*\*\**_**
- Arrests **Premature Labor**
- **Prolongs Pregnancy**
53
What are some **adverse effects** of **Beta 2 - Selective Adrenergic Receptor Agonists**?
Caused by a result of **excessive activation of Beta receptors**
1. _Tachycardia_ (especially those with **CAD** or **arrhythmia**)
- Risk for adverse CV events INCREASED with use of **MAO inhibitors**, as they allow **buildup of Beta 2 agonists in plasma** ; wait 2 weeks between MAO use and Beta 2 administration)
2. _Increased_ **glucose, lactate,** and **free fatty acids**
3. _Decreased_ **plasma K+ (potassium)** (especially in patients with **cardiac disease** --\> taking ***Digoxin*** and ***diuretics***)
54
How can Beta 2 - Selective Adrenergic Receptor Agonist **adverse effects** be **_reduced_**?
By using ***_INHALATION THERAPY_*** rather than parenteral or oral
55
**Fenoldopam (Corlopam)**
1. Class
2. Mechanism of Action
3. Clinical Uses
4. Side Effects
**Class:** D1 - Selective Adrenergic Receptor Agonist
**MoA:**
- Mainl a **D1 Receptor Agonist**
- Some _stimulation of alpha 2 (a2) adrenoceptors_ --\> feedback **inhibition** of **Norepinephrine release**
- Leads to _renal, peripheral, and coronary **vasoDILATION**_
**Use:**
**_*\*\*\*HYPERTENSIVE CRISIS\*\*\**_** (Given IV)
**Side Effect:** Hypotension
56
What drugs are in the **Non-Selective Direct Acting Adrenergic Agonist** class?
Isoproterenol (B1 B2)
Dobutamine (B1 a1 B2)
Epinephrine (B1 B2 a1)
Norepinephrine (a1 B1)
Dopamine (D1 D2 a)
57
**Isoproterenol (Isuprel)**
1. Class
2. Effects
3. Clinical Uses
**Class:** B1 B2 Agonists
\*\*\***No effect** on alpha (a) receptors\*\*\*
**Effects:**
_-Cardiovascular:_ Decreased **TPR,** Increased **Heart Rate** (arrhythmias), Increased **Myocardial Contractility**
_-Bronchodilation_ (**STRONG**)
**Uses:**
- _Bradycardia_ (Treated via **Reflex Tachycardia** from **B1 receptors**)
- _A-V block_
_-_***_TORSADES de POINTES_*** *(Ventricular Fib)*
***_-Pacemaker Placement_***
58
**Dobutamine (Dobutrex)**
1. Class
2. Effects
**Class:** **B1**, a1, B2 Receptor Agonist
\*\*\*Mainly acts on **Beta 1 (B1)** at **Therapeutic Doses** (considered _Selective_)
-Directly interacts with **a** and **B** receptors; **_DOES NOT_** release **NE** from sympathetic nerve endings
**Effects:**
_Cardiovascular:_ Positive **inotropic effect on heart** ( \>Isoproterenol)
- Positive **Chronotropic** effect (Increased _SA node automaticity_ and _A-V conduction_)
- **TPR** is _NOT AFFECTED_ (Due to **a1-B2 Balance**)
59
**Dobutamine (Dobutrex)**
1. Adverse Effects
2. Clinical Uses
**AE:**
- Excessive **increases in _blood pressure_** _and **heart rate**_
- **Increased _ventricular response_** rate in patients with _A-Fib_
- Ventricular ectopic activity
- May **increase** the **size of Myocardial Infarct**
- _Tolerance_
**Uses:**
- _Short-term_ treatment of **Cardiac Failure (post cardiac surgery, CHF, MI)** --\> \*\*\****_Increases Contraction WITHOUT increasing the Heart Rate_***
- Longer-term efficacy is uncertain
- **Stress Tests** (pts with CAD)
60
**Epinephrine (Adrenaline)**
1. Class
2. Effects
3. Clinical Uses
**Class:** a and B receptor Agonist
\*\*\***Beta (B)** has **_higher affinity**_ for _**Epinephrine_** so **B** goes **First** dosewise
**Effects (IV):**
-_Small Doses:_ **B1** --\> **Increased _Pulse Pressure, Heart Rate, Stroke Volume, and Cardiac Output_**
**B2** --\> **Decreased _Total Peripheral Resistance_**
-_Moderate Doses:_ **B1** --\> (Same as above)
**B2** --\> (Same as above) + **Decreased _Diastolic Blood Pressure_**
**a1** --\> **Increased _TPR and Blood Pressure_** \*\*\****_Counteracts B2_***\*\*\*
-_High Doses_: **a1, B1, and B2** are all **_same as above_**, except that **alpha 1 (a1) _predominates**_ which --\> _**REFLEX BRADYCARDIA_** (Potentially)
**Uses:** Subcutaneously causes **slow absorption, vasoCONSTRICTION** for **_SUTURING_**
61
What is the **Epinephrine Reversal Phenomenon** and **How does it work?**
If you block **a** or **B** receptors ***_prior_*** to administration of Epinephrine, the response will be much more pronounced
**a receptor antagonism** (e.g. _Phentolamine_) --\> **Increased** **_vasoDILATION_** --\> **Decreased _TPR_** --\> **Decreased _Mean Arterial Pressure_**
\*\*\*Opposite with **B receptor antagonism**
62
What are the **Vascular Effects** of **_Epinephrine**_ and where are the _**main sites of action_**?
**Main Sites of Action:** _Smaller ARTERIOLES_ and _Precapillary SPHINCTERS_
Leads to a **General redistribution of blood flow**
- _Cutaneous Flow_ **Decreases**
- _Skeletal Muscle Flow_ **Increases**
- _Cerebral Circulation_ shows **little or no vasoconstriction** (@ thereapeutic doses)
- _Renal Blood Flow_ **Decreases**, _GFR_ \<-\>, _Filtration Fraction_ **Increases**, _Renin Secretion_ **Increases (Beta 1 (B1))**
- _Pulmonary Blood Flow:_ both **PAP** and **PVP** **_Increase_**
- _Coronary Blood Flow_ **Increases** (Increased relative diastole, aortic pressure, and metabolic stimulation)
63
What are the **Cardiac Effects** of **_Epinephrine_**?
Powerful **Cardiac Stimulant: B1**
- **Increased** _Heart Rate_, Shortened _Systole_, _Diastole_ \<-\>
- **Increased** _Inotropy_ (Contraction), _Lusitropy_ (Relaxation; **active process**),and _chronotropy_ (Heart Rate) --\> **Increased _Myocardial Oxygen Consumption_**
- **Increased** _Automaticity_ --\> **Arrhythmias** (potentially)
- ECG Changes
64
What are the **Smooth Muscle** effects of **_Epinephrine_**?
\*\*\***Vascular** smooth muscle is **most affected**
-Most important during **Cardiac Arrest**
_GI Smooth Muscle:_ **Relaxation**
65
What are the **Toxic/Adverse Effects** of **_Epinephrine_**? **Contraindications**?
**AE:**
- Throbbing **headache, tremor, palpitations**
- **_Cerebral Hemorrhage_** (LARGE doses, rapid IV)
- **_Arrhythmias_**
- **_Angina_** (in pts with **CAD**)
\*\*\***Contraindications:** Patients using ***_NON-SELECTIVE BETA BLOCKERS_***\*\*\*
66
What are the **Therapeutic Uses** of **_Epinephrine_**?
- _Hypersensitivity Reactions_ (including **Anaphylaxis**)
- _Cardiac Arrest_
- _Local Anesthetics_
- Post-extubation _croup_, viral _croup_ (Dilates Bronchiole Smooth Muscle)
67
**Norepinephrine**
1. Class
2. Properties
**Class:** a1 \>\> B1 \>\>\>\>\>\> B2 Receptor Agonist
\*\*\*Potent **alpha (a) agonist** ( LITTLE ACTION on B2 receptors
68
**Norepinephrine**
1. Cardiovascular Effects
- **Increase** _Systolic and Diastolic Blood Pressure,_ as well as _Pulse Pressure_
- **Increase** _Coronary Flow_ (Coronary dilation/elevated BP)
- \<-\> / Decrease Cardiac Output
- \*\*\***Increase _Total Peripheral Resistnace (TPR)_**\*\*\*
- **Decrease** _Renal Blood Flow_
- **Decrease** _Splanchnic and Hepatic Blood Flow_
69
**Norepinephrine**
1. Toxicity/Adverse Effects
2. Therapeutic Uses
**AE:** Similar to those of **Epinephrine** (e.g. Restlessness, Throbbing Headache, Tremor, Palpitations, Cerebral Hemorrhage (large doses/Rapid IV), Cardiac Arrhythmias, Angina (pts with CAD))
\*\*\*Greater elevation of **Blood Pressure** (Treats **_HYPOtension_**)\*\*\*
Leads to **Reflex _BRADYcardia_**
**Uses:**
-Treatment of **Hypotension** (dose titration needed)
70
**Dopamine**
1. Class
2. Properties
**Class:** D1, D2, B1, a1 Receptor Agonist
**Properties:**
- Immediate _metabolic precursor_ of **Norepinephrine** and **Epinephrine**
- In _CNS_: Neurotransmitter important in regulation of **movement**
- In _Periphery_: **Synthesized** in the **epithelial cells** of the **proximal tubule** --\> \*\*\****_Local Diuretic/Natriuretic Effects_***\*\*\*
- **Substrate** for both _MAO_ and _COMT_ (**ineffective** if given **orally**)
71
How do **low doses** (**\< 2** ug/kg/min) of **Dopamine** lead to _Increased Urine Output_ via **Presynaptic D2 Receptors**?
Dopamine (low dose) --\> Presynaptic **D2** receptors (on peripheral circulation nerves) --\> **Decreased** _NE release_ and **Decreased** stimulation of _VSMCs_ --\> **Vasodilation** --\> **Increased** _GFR_ and **Increased** _RBF_ --\> **Increased** _Na+ Filtered_ --\> \*\*\*Na+ Diuresis\*\*\*
72
How do **low doses** (**\< 2** ug/kg/min) of **Dopamine** Increase Urine Output via **Vascular D1 Receptors**?
Dopamine (low dose) --\> **Vascular D1 receptors** (renal, mesenteric, coronary) --\> **Vasodilation** --\> **Increased** _GFR, RBF_ (Renal Blood Flow) --\> **Increased** _Na+ Filtered_ --\> \*\*\*Na+ Diuresis\*\*\*
73
How does **low dose** (**\< 2** ug/kg/min) **Dopamine** cause **Increaed Urine Output** via **Renal Tubular Cell D1 receptors**?
Dopamine (low dose) --\> **Renal Tubular Cell D1 receptors** --\> **Increased** _Proximal, Henle Loop [cAMP]_ --\> **Decreased** _Na+-K+-ATPase_ --\> **Decreased** _Na+ Reabsorption_ --\> \*\*\*Na+ Diuresis\*\*\*
74
**Dopamine**
1. Cardiovascular Effects of **Moderate Doses** (**2-5** ug/kg/min)
- **Increased** _Inotropic Effect (**B1**)_ (Increased cardiac _contractility_, _Tachycardia_, **Increases** _Systolic Blood Pressure/Pulse Pressure_ ; **NO EFFECT** on _Diastolic Blood Pressure_)
- **Release of Norepinephrine** from nerve terminals
- **Little Effect** on _Total Peripheral Resistance_
75
**Dopamine**
1. Precautions, Adverse Reactions, Contraindications
- **Hypovolemia** should be **corrected _before_** use of **Dopamine**
- Tachycardia, Angina, Arrhythmias, Headache, Hypertension
- _Extravasation_ --\> **Ischemic Necrosis** and **Sloughing**
- **MAO Inhibitor** or **Tricyclic Antidepressant** --\> ***_AVOID Dopamine_*** (or use with EXTREME CAUTION)
\*\*\*Inhibit Degradation\*\*\*
76
**Dopamine**
1. Therapeutic Uses
**Uses:**
- Severe **CHF**, particularly in patients with **oliguria** (abnormally small amount of urine) and _low/normal_ **peripheral vascular resistance**
- **Cardiogenic/Septic Shock**
- May _acutely improve_ **Cardiac** and **Renal Function** in severely ill patients with chronic **Heart Disease** or **Renal Failure**
77
**Ephedrine (Ephedrine, Ephedra)**
1. Class
2. Characteristics
**Class:** \*\*\*The ONLY **Mix-Acting** Adrenergic Agonist\*\*\*
Acts on **a1, a2, B1, B2,** and **releasing agent**
**Characteristics:**
- _First orally active_ sympathomimetic drug
- Found in _ma-huang_
- _High bioavailability_ and a relatively _long duration of action_
- A _Mild_ **CNS stimulant**
- **_Pseudoephedrine**_ (ephedrine enantiomer) is a _**Decongestant_**
78
What drugs are part **Indirect-Acting Releasing Agents**?
Amphetamine
Tyramine
79
**Amphetamine**
1. Class
2. Characteristics
**Class:** Indirectly Acting Sympathomimetic Amine _Releasing Agent_
**Characteristics:**
- _Structurally_ related to **Norepinephrine** --\> _Transported_ into the terminal by **NET1**
- _Displaces_ **Norepinephrine** --\> **Norepinephrine** is then released _Independent of Exocytosis_ and does NOT require the presence of Ca++
- Partially active by _inhibiting NET 1_ (**decreasing reuptake** of NE) and partially by _inhibiting MAO_ (**decreasing metabolization** of NE)
80
**Amphetamine**
1. Effects on the **CNS**
- **\*\*\*Releases _Biogenic Amines_** from storage sites in **nerve terminals**
- Stimulates the _medullary respiratory center_
- Stimulates _cortex and reticular activating system_ --\> this **prevents Fatigue** and **delays the need for sleep**
- Treats **obesity** (Decreased food intake)
81
**Amphetamine**
1. **Cardiovascular** Responses
- **Activates** _peripheral alpha (a) and beta (B)_ (like **Norepinephrine**)
- **Increases** _Systolic/Diastolic Blood Pressure_
- **Increases** _Heart Rate_
- **Cardiac arrhythmias** (may occur)
82
**Amphetamine**
1. Effect on the **Bladder Sphincter**
**Increased** Bladder Sphincter _Contraction_
**Treats:** Enuresis and **_Incontinence_**
83
**Tyramine**
1. Class
2. Characteristics
3. Adverse Effects
**Class:** Indirectly Acting Sympathomimetic Amine _Releasing Agent_
**Characteristics:**
- Used to **synthesize Norepinephrine** and **Epinephrine** via the _alternate pathway_
- **Destroyed** by _MAO_ in the **gut wall and liver**
**AE:**
-Action is **Increased** by _MAO inhibition_ --\> Ingestion of **Tyramine-rich** foods \*\*\****_FERMENTED CHEESE_***\*\*\* --\> Sudden and **Dangerous rise** in **_Blood Pressure_**
84
What is the main drug in the **alpha (a) Adrenoceptor Antagonist: a1 \>\>\> a2** class?
**Prazosin**
Also, Terazosin and Doxazosin
85
What is the main drug in the **alpha (a) Adrenoceptor Antagonist a1 \> a2** class?
**Phenoxybenzamine**
86
Which drug(s) are part of the **alpha (a) Adrenoceptor Antagonist a1 = a2** class?
Phentolamine
87
Which drug(s) are part of the **alpha (a) Adrenoceptor Antagonist a2 \> a1** class?
Yohimbine
Rauwoscine
Torazoline
88
What determines the **effecs** of _Reversible alpha receptor antagonists_? _Irreversible_?
**Reversible:** effects are determined by the **_half-life_** of the inhibitor/antagonist
**Irreversible:** effects are determined by the **_rate of production of new receptors_**
89
What are the **effects** of _alpha receptor antagonists_?
- **Decrease** _blood pressure_ --\> orthostatic hypotension
- _Tachycardia_ (Transient, Reflex Tachycardia)
- **Reverse** the pressor _effects of a and B agonists_
- _Miosis_ (**M3** is unopposed, conracts sphincter)
- _Nasal Stuffiness_
- **Decreased** _resistance to urine flow_
90
What are the **therapeutic uses** of _alpha receptor antagonists_?
- _Pheochromocytoma_ (Rare --\> Releases **Norepinephrine**)
- _Hypertensive emergency_
- _Chronic hypertension_
- _Peripheral vascular disease_ (Small doses)
- _Urinary obstruction_
- _Erectile dysfunction_ (promotes **ejaculation**)
91
**Phenoxybenzamine** **(Dibenzyline)**
1. Class
2. Mechanism
3. Effects
**Class:** alpha (a) receptor antagonist
**MoA:** _Irreversibly_ blocks a1 and a2 (LONG duration of action)
- Also blocks H1, Acetylcholine, and Serotonin (5-HT) receptors
- **Indirect Baroreflex** _activation_
**Effects:**
-**Decreases** _Blood Pressure_ but _Heart Rate_ **Rises** due to **Baroreflex Activation**
92
**Phenoxybenzamine (Dibenzyline)**
1. Clinical Uses
2. Toxicity
**Uses:**
- Treats **_Pheochromocytoma_**
- Treats **High Catecholamine states**
**Toxicity:**
Half life is **\>1 day**
-Orthostatic hypotension, Tachycardia, Myocardial Ischemia (increased heart rate can exacerbate this), Problems with **ejaculation** (due to **alpha 1a blockade**)
93
**Prazosin** **(Minipress)**
1. Class
2. Mechanism
3. Effects
4. Clinical Uses
5. Toxicity
6. Similar drugs
**Class:** alpha (a) adrenoceptor antagonist
**MoA:** _Blocks alpha 1 (a1)_ but **NOT** alpha 2 (a2)
-**Relaxes** _arterial_, _venous_, and _prostate_ smooth muscle
**Effects:**
-**Decreases** _blood pressure_
**Uses:**
-Treats _Hypertension_ and **_Benign Prostatic Hyperplasia_**
**Toxicity:**
-**Larger depressor effect** with **_first dose_** may cause _Orthostatic Hypotension_ (watch for **Tachycardia**)
**Similar Drugs:** Doxa**_zosin_** and Tera**_zosin_**
94
**Tamsulosin (Flomax)**
1. Class
2. Mechanism
3. Effects
4. Clinical Uses
5. Toxicity
**Class:** alpha (a) adrenoceptor antagonist
**MoA:** slightly selective for **_alpha 1A_** (PROSTATE)
**Effects:**
-**alpha 1a (a1A)** **blockade** may relax _prostatic_ smooth muscle **more than** _vascular_ smooth muscle
**Uses:**
-Treats **_*\*\*\*BENIGN PROSTATIC HYPERPLASIA\*\*\**_**
**Toxicity:** _Orthostatic Hypostension_ is **less common** with this subtype
95
**Yohimbine**
1. Class
2. Mechanism
3. Effects
4. Use
5. Toxicity
**Class:** alpha (a) adrenoceptor antagonist
**MoA:** **_Blocks alpha 2 (a2)_** (has **CNS activity**) and **increases** _norepinephrine_ release
**Effects**: **INCREASES** _Blood Pressure_ and _Heart Rate_
**Uses:** Treats \*\*\***Erectile Dysfunction**\*\*\*
-Hypotension, as well, but not as much
**Toxicity:**
- _Anxiety_
- _Excess pressor effect_ if **NET1** is **blocked**
96
**Labetalol**
1. Class
2. Mechanism
3. Effects
4. Use
5. Toxicity
**Class:** **Beta (B)** and **alpha 1 (a1)** adrenoceptor antagonist
**Moa:** \*\*\*Blocks **BOTH** (B \> a1)\*\*\*
**Effects:**
**Decreases** _Blood Pressure_ w/ **limited** **heart rate** increase
**Uses:**
\*\*\*Used in **_High Sympathetic States_**\*\*\* (e.g. **Hypertensive Crisis, Hypertension,** **Pheochromocytoma**)
-Good because it will _not/very limited_ reflex Tachycardia
**Toxicity:**
\*\*\*LESS Tachycardia\*\*\*
97
What are the drugs in the **B1 = B2** **Non-Selective 1st Generation Beta (B) Adrenoceptor Antagonists** class?
**Propranolol**
Nadolol
Timolol
Pindolol\* (ISA)
Mnemonic: These drugs are **N**ot **S**harp like a **Pi****NTi****P**
98
What are the drugs in the **B1 \>\>\> B2 Selective 2nd Generation Beta (B) Adrenoceptor Antagonist** class?
Atenolol
**Metoprolol**
Esmolol
Betaxolol
Acebutolol\* (ISA)
Mnemonic: **S**limey **AMEBA**
\*\*\*Selectivity is **lost** at **HIGH DOSES**\*\*\*
99
What are the drugs in the **B1 = B2 \>or= a1 \> a2 _Vasodilatory_ 3rd Generation _Mixed a-B_ Antagonist** class?
**Labetalol**
Carvedilol
100
What are the **Cardiovascular Effects** of **Beta Receptor Antagonists**? **Clincal uses**?
**Effects:**
- **Decreased** _inotropic/chronotropic_ effect --\> Decreased **Blood Pressure** in hypertensive (\*\*\*no effect on normotensive individual; thefore used for **GLAUCOMA**)
- **Decreased** _myocardial oxygen consumption_
- **Decreased** _renin release_
**Uses:**
- Treats **Hypertension**
- **_Glaucoma_ (blocks B1 and B2** in _Ciliary Epithelium_
- _Arrhythmias_
- _Ischemic Heart Disease_
101
What are the **Respiratory Effects** of **Beta Receptor Antagonists**?
-**Beta 2 (B2)** **Blockade** --\> **Increased** _airway resistance_ --\> undesiable in ***_asthma and COPD_***
\*\*\*No Beta Blocker is completely free of **B2-blocking effect**\*\*\*
102
What are the effects of **Beta Receptor Antagonists** in the **Eye**?
**Decreased** _aqueous humor production_ --\> **Decreased** _intraocular pressure_
103
What are the **Metabolic Effects** of **Beta Recptor Antagonists**?
**Inhibits** _lipolysis_
May **decrease** _glucagon release_
**Increases** _VLDL_
**Decreases** _HDL_
**_*\*\*\*BAD EFFECTS ON CHOLESTEROL\*\*\**_**
104
What are the **Therapeutic Uses** of **Beta Receptor Antagonists**?
**Treat:**
- _Hypertension_
- _Ischemic Heart Disease_
- _Arrhythmias_
- _Heart Failure_ - especially **3rd Degree and onward** (caused by reduction in myocardial contraction --\> **reflex INCREASE** in circulating _catecholamines_ (e.g. **Norepinephrine/Epinephrine**) and **INCREASED** _plasma renin activity_ --\> **OVERACTIVATION** of **B1 receptors** in _Heart_ and subsequent **downregulation** of **adrenergic receptors**)
\*\*\*Treated with **really low doses** of **B1-selective antagonists**
- _Glaucoma_
- _Hyperthyroidism_ (Symptomatic; treats **increased heart rate**)
- _Neurologic Diseases_ (e.g. migraines, anxiety, etc.)
105
What are the **3 important Clinical Considerations** for choosing **Beta Blockers**? (List them in order of clinical consideration)
**1. Cardioselectivity** (e.g. AMEBA group) - **DO NOT** use _Non-Selective_ in pts with **Asthma/COPD** (due to **B2 blocking effect** --\> **Bronchiole _CONSTRICTION_**); **Use _Selective**_ and keep the _**Dose Low_**
**2. Intrinsic Sympathomimetic Activity (ISA)**
-e.g. ***_Pindolol_*** and ***_Acebutolol_*** (allows use of **Beta blocker** **_without_ dropping the Heart Rate**)
**3. Lipid Solubility**
106
What are the **four factors** to consider related to **lipid solubility** when using **Beta blockers**?
**1. Plasma Levels and Duration of Action** (fat tissue)
- _Lipophilic Beta-Blockers:_ (e.g. propranolol/metoprolol) produce **lower plasma concentration** and have **less predictable plasma concentration** because they are _metabolized by the liver_
- _Hydrophilic Beta Blockers:_ **longer biological action** (allow _once-a-day dosing_)
**2. CNS**
-_Hydrophilic_ Beta-Blockers enter the brain **much less** than _Lipophilic_
**3. Kidney**
-_Hydrophilic_ are effected by kidney functions; _Lipophilic_ are not
**4. Age**
-**Older** = lower liver function --\> **higher plasma concentrations** of _lipophilic_ Beta Blockers --\> higher incidence of side effects
107
What are the **Adverse Effects** of **Beta Receptor Antagonists**?
- _Fatigue_
- _Worsening **PVD**_ (Due to **B2 blockade** --\> Vasoconstriction in microvasculature)
- _Worsening **Bronchospasm**_
- _Decreased **Sexual Functions**_ (Common)
- _Increased **Diabetes** incidence_
- **_*\*\*\*Masked Symptoms of HYPOGLYCEMIA\*\*\**_**
Pay attention to this, especiall in patients with **advanced diabetes**, due to **downregulation** of neuro contorls of glycemia
Signs = **drop in blood sugar** with **faster heart rate**, **agitation**, **palpitations, \*\*\*SWEATING\*\*\***
\*\*\*If you block beta receptors, these go away, _except **Sweating**_\*\*\*
108
What are the **effects** of **Choline Esters (Direct-Acting Cholinoceptor Agonists****)**?
_Cardiovascular_ --\> **Hypotension**, **Bradycardia**, **SLOWED** **conduction/PROLONGED refractory period**
_GI_--\> **INCREASED** _motility, acid secretion, NVD_
_GU_ --\> **INCONTINENCE**
_Eye_ --\> **Miosis (pupillary CONSTRICTION** via **sphincter muscle**)
_Respiratory_ --\> **Broncho****_CONSTRICTION_**
_Glands_ --\> **INCREASED SECRETION**
109
What drugs are **not effected** by prior treatment with **_Reserpine**_ or _**Guanethidine_** and actually **potentiated** by these drugs, as well as **_Cocaine_**?
**DIRECT-ACTING ADRENERGIC AGONISTS**
Both _Selective_ (e.g. Phenylephrine, Clonidine, Terbutaline, Fenoldopam)
and _Non-Selective_ (e.g. Isoproterenol, Dobutamine, Epinephrine, Norepinephrine, Dopamine)
110
What drugs are **reduced** by prior treatment with **_Reserpine**_ or _**Guanethidine_**?
Ephedrine (a **mix-acting Adrenergic Agonist**)
111
What drugs are **abolished** by prior treatment with **_Reserpine**_ or _**Guanethidine_**?
**INDIRECT-ACTING**
Including _Releasing Agents_ (e.g. Amphetamine and Tyramine)
_Uptake Inhibitors_ (e.g. Cocaine)
and _MAO/COMT Inhibitors_ (e.g. Pargyline and Entacapone)
