ANS - 9 Flashcards
What effect would an antagonist alone have on receptor activation?
no effect
Side effects of a1 receptor antagonists:
- orthostatic hypotension
- inhibition of ejaculation
- nasal stuffiness
- tachycardia
Non-selective a-adrenergic receptor antagonists: What is this base structure?
B-Haloalkylamines
non-selective a receptor antagonists examples
- Phenoxybenzamine
- Phentolamine
Selective a1 receptor antagonists examples
- Prazosin
- Terazosin
- Doxazosin
Non-selective a adrenergic receptor antagonists: Phenoxybenzamine (Dibenzyline)
* Also blocks ___, histamine, and ___ receptors
* ___ antagonist resulting from covalent modification of receptor
- ACh, serotonin
- irreversible
What is this?
Phenoxybenzamine (Dibenzyline)
B-Haloalkylamines: Mechanism of receptor inactivation -
* The ___ ion is highly reactive and forms a ___ bond
- Aziridinium
- covalent
Non-selective a-adrenergic receptor antagonists:
Imidazolines
* competitive (___) blocker
* potent vaso___, but induces pronounced reflex ___cardia
* block of presynaptic a2 receptors may promote release of ___
* Also blocks 5-HT receptors, and is a ___ and histamine receptor agonist.
- reversible
- vasodilator, tachycardia
- NE
- muscarinic
Example:
What is this?
Non-selective a receptor antagonist - Imidazoline
* Phentolamine (Regitine)
What does a reversible receptor blockade graph look like?
slide to the right
What does an irreversible receptor blockade graph look like?
decreasing
Phenoxybenzamine action:
* non-competitive (___) antagonist
* non selective (__ and ___ receptors)
* new receptors must be synthesized in order to restore receptor function leading to a long drug effect
- irreversible
- a1 and a2
Phentolamine action:
* ___ (reversible) antagonist
* ___ (a1 and a2 receptors)
*competitive
* non-selective
Phenoxybenzamine and Phentolamine: Clinical Use - ___ (tumor of adrenal medulla that results in excessive epinephrine and norepinephrine synthesis and release)
pheochromocytoma
Problems with Phenoxybenzamine and Phentolamine:
* Not useful in treatment of hypertension due to __ effects
* By blocking __ receptors, we get greater release of NE at the heart and increased HR
a2
a2 is responsible for prejunctional inhibition of NE release
a1 -adrenergic receptor antagonists: Quinazolines
* extensive metabolism, excreted mainly in the ___.
* Vaso___
* ___ of smooth muscle in enlargesd prostate and bladder base
* Vary in half life (Prazosin 3 hrs, Terazosin 12 hrs, and Doxazosin 20 hrs)
* “___-dose” effect
- bile
- vasodilation
- relaxation
- first dose effect
What is this?
a1 receptor antagonist
* Quinazoline
Examples
* Prazosin (Minipres)
* Terazosin (Hytrin)
* Doxazosin (Cardura)
It is an a1 receptor antagonist if it has a ___ ring and ends in ___
Quinazoline, “-osin”
Selective a1 antagonists: Prazosin - Action:
* Selective ___ a1 antagonists
* Decrease total ___ resistance
* vaso___
- competitive
- peripheral
- vasodilation
Prazosin clinical use
- Hypertension
- Reynaud’s disease
- Benign prostatic
- hyperplasia (BPH) a1a
Minor problem with Prazosin
fall in BP
a1a Antagonist: Tamsulosin (Flomax)
* very selective to prostate urethra as this is rich in ___ receptors
* less prone to induce fall in ___ as compared to classical a1 blockers such as ___
* Used for BPH (an a1a antagonist prevent the contraction the ____ muscle which contributes to the resistance to outflow of urine).
- a1a
- BP, Prazosin
- trigone
a2 - receptor antagonists
Example: Yohimbine (Yocon)
* ___ alkaloid
* Blockade of a2 receptors ___ sympathetic discharge
* Folklore suggests use in treatment of ____
- indole
- increases
- male impotence
What is this?
Yohimbine (Yocon)
indole alkaloid = a2 antagonist
Beta Blockers: Therapeutic Indications
- angina
- migraine
- glaucoma
- cardiac arrhythmia
- post-myocardial infarction
- hypertension
- congestive heart failure (I and II)
What are the receptors for epinephrine?
B1, B2 > a1, a2
What are the receptors for norepinephrine?
a1, a2, B1
What is the base structure for Beta blockers?
Aryloxypropanolamines
note: non-carbon atom in side chain (O)
T or F: The S configuration of the beta blocker hydroxyl is much more active than the R configuration.
True
most B blockers are used clinically as racemic mixtures
T or F: The aromatic moiety is the primary determinant of B blocker activity (and B1 selectivity)
True
Non-selective Beta blockers:
Propranolol
* ___philic (determined by bulky __ ring)
* Extensive ___ metabolism, “first pass”
* Local anesthetic properties
* Blockade is activity dependent
* good for patients with ___ failure
- lipophilic, double
- hepatic (liver)
- kidney
What is this?
Propanolol (Inderal)
Pharmacological effects of Propanolol:
* ___ cardiac output and HR
* ___ renin release
* ___ VLDL and ___ HDL
* ___ lipolysis
* ___ glycogenolysis and glucose release in response to hypoglycemia
* ___ bronchial airway resistance
- decrease
- reduce
- increase, decrease
- inhibit
- inhibit
- increase
Non-selective Beta Blockers: Nadolol (Corgard)
* less ___ than propranolol
* long half life (___), More hydrophilic = longer half life
* mostly excreted unchanged in the ___
* administered ___
* uses: hypertension, angina, ___
* good for patients with ___ issues
- lipophilic
- 20 hours
- urine
- orally
- migraine
- liver
Non-selective Beta Blockers: Timolol (Timoptic, Blocadren)
* ___ nucleus with morpholine ring
* Administered: ___ and ___
* uses: glaucoma (ciliary epithelium), hypertension, angina, migraine
- thiadiazole
- oral, opthalmic
What is this?
Timolol (Timoptic, Blocadren)
T or F: Beta blockers affect pupil size
False; only M3 (miosis) and a1 (mydrasis) control pupil size
Probelms with Beta Blockers: Propranolol and Timolol
- Use cautiously in asthmatics due to blockade of B2 receptors (prevents bronchodilation)
- rebound hypertension if discontinued abruptly (must taper dose!)
Non-selective Beta Blockers: Pindolol (Visken)
* possesses ____ (ISA)
* ___ agonist
* less likely to cause ___cardia and lipid abnormalities. (Good for patients with severe ___cardia or little cardiac reserve)
* Administered ___
* Uses: hypertension, angina, migraine
- intrinsic sympathomimetic activity
- partial
- bradycardia (twice)
- orally
T or F: Pindolol and Carteolol are partial agonists.
True
Non-Selective Beta antagonist: Carteolol
*possesses ____ (ISA)
* ___ agonist
* less likely to cause ___cardia and lipid abnormalities. (Good for patients with severe ___cardia or little cardiac reserve)
* Administered: ___ and ___
* Uses: hypertension and ___
- intrinsic sympathomimetic activity
- partial
- bradycardia (twice)
- orally and ophthalmic
- glaucoma
Selective B1-receptor antagonists: base structure
only one ring
Selective B1-receptor antagonists: (Metoprolol, Bisoprolol)
* ___-substituted ___ derivatives
* “cardio___”
* Less bronch___
* moderate lipophilicity
* half life: 3-4 hours
* Significant ___ metabolism
* Administered: ___ and ___
* Uses: hypertension, angina, antiarrhythmic, congestive heart failure
- para, phenyl
- cardioselective
- less bronchoconstriction
- first pass
- orally and parenteral
used only for heart stuff
B1 selective antagonist - Metoprolol:
Clinical use: ___, angina, cardiac arrhythmias, ischemic heart disease
Problems: minor ___ hypertension if discontinued abruptly (___ dose)
- hypertension
- rebound, taper
Selective B1 antagonists: Atenolol (Tenormin)
* “cardio___”
* Less bronch___
* ___ lipophilicity, “water-soluble metoprolol”
* half life: 6-9 hours
* Administered: ___ and ___
* Uses: ___ and angina
- cardioselective
- bronchoconstriction
- low
- orally and parenteral
- hypertension
What is this?
Atenolol (Tenormin)
B1 selective antagonists
T or F: Bisoprolol is refered to as “water soluble metoprolol”
False; Atenolol is known as the “water-soluble metoprolol”
the terminal amide causes less lipophilicity (more h2o soluble)
Selective B1 receptor antagonists: Esmolol (Brevibloc)
* Very __ acting
* half life: 9 ___
* rapid hydrolysis by ___ found in RBCs
* Administed: ___
* Incompatible with ___
* Uses: supraventricular ___, atrial fibrillation/flutter, perioperative hypertension
- short acting
- minutes
- esterases
- parenteral
- sodium bicarbonate
- tachycardia
What is this?
Esmolol
B1-receptor antagonists
3rd generation B1-adrenergic receptors: Nebivolol (Bystolic)
* ___ lipid solubility
* Vaso___ due to nitric oxide
* Hypertension
* looks hella weird
- low
- vasodilation
What is this?
Nebivolol (Bystolic)
3rd generation B1 antagonist
Side effects of B-blockers
- bradycardia
- AV block
- sedation
- mask symptoms of hypoglycemia
- withdrawal syndrome
T or F: Chronic use of beta blockers causes more beta receptors to grow.
True; this is when abruptly stopping therapy is bad (more receptors=worse effects)
Contraindications for beta blockers
- asthma
- COPD
- congestive heart failure (type IV)
Mixed (a and B) adrenergic receptor antagonists: Labetalol -
* non-selective __ receptor antagonist
* __ selective receptor antagonist
* two ___ carbons
* (1__,1’R)-isomer possesses B-blocking activity
* (1__,1’R)-isomer possesses greatest a1 receptor blocking activity
* B blocking activity prevents ____ normally associated with a1 receptor antagonist
* Administered: ___ and ___
* use: hypertension, hypertensive crisis
- beta
- a1
- asymmetric
- 1R
- 1S
- reflex tachycardia
- orally and parenteral
T or F: mixed adrenergic antagonists end in “lol” not “olol”
True
Mixed (a and B) adrenergic receptor antagonists: Carvedilol (Coreg)
* non-selective __ receptor antagonist
* __ selective receptor antagonist
* both enantiomers antagonize ___ receptors
* only (S)-enantiomer possesses ___ blocking activity
* B blocking activity prevents ____ normally associated with a1 receptor antagonist
* administered ___
* uses: hypertension, congestive heart failure
- Beta
- a1
- a1
- Beta
- reflex tachycardia
- orally
What is this? Which side is beta? Which side is alpha?
Carvedilol (Coreg)
mixed adrenergic agonist
* beta = three ring side (left)
* alpha = one ring side (right)
T or F: Carvedilol has a 1:10 ratio for alpha:beta antagonism
True
The clinical difference between Carvedilol and Labetalol
- Carvedilol: heart failure; hypertension
- Labetalol: Hypertension particularly hypertensive emergencies
- Problems: Minor but rebound hypertension if discontinued abruptly– taper dose
Indirect-acting Sympatholytics - Metyrosine (action):
* inhibits ___ hydroxylase
* Depletes ___ everywhere
- tyrosine hydroxylase
- catecholamines
Indirect-acting Sympatholytics - Metyrosine (clinical use):
* ___ management of ___ (tumor of adrenal medulla that results in excessive Epi and NE synthesis/release)
perioperative, pheochromocytoma
Indirect-acting Sympatholytics - Metyrosine (Problem)
depletes catecholamines everywhere
Drugs that reduce storage or release of NE - Bretylium tosylate (Bretylol):
* aromatic ___ ammonium
* mechanism not really known
* displaces NE and prevents further release (depletion)
* local anesthetic
* adminstered: ___
* uses: ___ (ventricular fibrillation)
* Guanethidine also does this (random note at bottom of slide)
- quaternary
- parenteral
- antiarrhythmic
Catecholamine depleters: Reserpine (Serpasil)
* ___ alkaloid obtained from Rauwolfia serpentina root
* irreversibly blocks ___
* deplete vesicular pool of __
* ___ onset of action
* sustained effect (___)
* used for ___ (rarely due to adverse effects)
* may cause ___
- indole
- vesicular monoamine transporters (VMAT)
- NE
- slow
- weeks
- hypertension
- depression
Problems with Reserpine
- orthostatic hypotension
- increased GI activity
- sedation (CNS)
- severe depression/suicidal ideation (CNS)
