Pharmacology Flashcards
Acetylcholine
Muscarinic and nicotinic agonist
Use: To obtain miosis after delivery of the lens in cataract surgery and other procedures where rapid miosis (eye constriction) is required
Methacholine
Muscarinic agonist
Use: Diagnosis of bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma
Bethanechol
Muscarinic agonist
Use: Post-operative urinary retention and atony of the urinary bladder
Pilocarpine
Partial muscarinic agonist
-Tertiary amine
-Stable to hydrolysis by acetylcholinesterase
Use: Glaucoma
-Treatment of dry mouth due to radiotherapy for cancer of head and neck
Nicotine
Agonist at nicotinic receptors
-Tertiary amine
-Depending on the dose, nicotine depolarizes autonomic ganglia, resulting first in stimulation and then paralysis
-Low doses: ganglionic stimulation by depolarization
-Response resembles simultaneous discharge of both parasympathetic and sympathetic nervous systems
-High doses: ganglionic blockage and neuromuscular blockade
Use: Smoking cessation therapy
Muscarinic Agonists: Adverse effects
-Sweating
-Salivation
-Flushing
-Low blood pressure
-Nausea
-Abdominal pain
-Diarrhea
-Bronchospasm
Edrophonium
Binds reversibly to the active site of the enzyme
-Inhibition is short-lived
Carbamates
Form a covalent bond with the enzyme
-Physostigmine
-Neostigmine
-Pyridostigmine
Organophosphates
Phosphorylate the enzyme. The covalent bond formed is extremely stable and hydrolyzes very slowly
-Malathion
-Sarin
Indirect-acting Cholinergic Agents (Anticholinesterases)
MOA: cholinesterase inhibitors act by inhibiting acetylcholinesterase: they increase concentration of endogenous acetylcholine
Effects on the Cardiovascular System
Vascular smooth muscle: cholinesterase inhibitors have minimal effects because most vascular beds lack cholinergic innervation
Effects on the Neuromuscular Junction
Cholinesterase inhibitors increase strength of contraction
-Useful to reverse action of nondepolarizing neuromuscular blockers
-Useful in myasthenia gravis
Edrophonium
Quaternary ammonium
-Does not enter CNS
-Diagnosis of myasthenia gravis: this agent leads to rapid increase in muscle strength
-Used to reverse the neuromuscular block produced by non-depolarizing muscular blockers
Physostigmine
Tertiary amine
-Can enter and stimulate CNS
-Use: treatment of overdoses of anticholinergic drugs
Neostigmine
Quaternary ammonium
-Dose not enter CNS
Use: Urinary retention
-Reversal of effects of non-depolarizing neuromuscular blockers after surgery
-Treatment of myasthenia gravis
Pyridostigmine
Quaternary ammonium
-Does not enter CNS
-Treatment for myasthenia gravis
Organophosphates
-Synthetic compounds:
Many are extremely toxic
-Insecticides: Malathion (fogging on campus for example)
-Sarin: synthetic toxic agent used in terrorist attack in Japan
Atropine
-Prototype of muscarinic antagonists
-Reversible competitive antagonist at muscarinic receptors
-Tertiary amine: both central and peripheral muscarinic blocker
Actions of Atropine
M3: blockage:
Eye: Mydriasis & cycloplegia
GI: Reduces gastric motility
Urinary system: Decreases hypermotility of urinary bladder
Secretions: Salivary, sweat and lachrymal glands are blocked
-Inhibition of sweat glands may cause high body temperature
Atrial M2 blockade
CV system: Moderate to high therapeutic doses cause tachycardia
Belladonna Alkaloids
Uses: Antidote for cholinergic agonists
-Blocks respiratory tract secretions prior to surgery
Adverse effects of belladonna alkaloids
Dry mouth
Blurred vision
Sandy eyes
Tachycardia
Constipation
Urinary retention
Belladonna Alkaloids effects on CNS
-Restlessness
-Confusion
-Hallucinations
-Delirium
Scopolamine
Prevention of motion sickness
Quaternary Ammonium Muscarinic Antagonists
Ipratropium
Uses for Ipratropium
Treatment of chronic obstructive pulmonary disease (COPD)
-Asthma
Tertiary Amine Muscarinic Antagonists
Tropicamide
Uses for Tropicamide
Mydriatic for fundoscopy
-Produces mydriasis with cycloplegia
Contraindications of Antimuscarinic Agents
-Contraindicated in patients with angle-closure glaucoma
-Should be used with caution in patients with prostatic hypertrophy and in the elderly
Ganglion Blockers
Hexamethonium was used for hypertension in the past
-Due to their adverse effects, ganglion blockers have been replaced by superior antihypertensive agents
Pharmacological properties
-Effects of ganglion blockers can be predicted by a knowledge of which division of the ANS exercises dominant control of various organs
-The effect of the ganglion blocker is to remove the dominant control
Ganglion blockade may occur by the following mechanisms:
1) Prolonged depolarization (Ex. Nicotine)
2) Antagonism of nicotinic receptors (Ex. Hexamethonium)
Two types of neuromuscular blockers
1) Tubocurarine (Competitive Antagonists: Non-depolarizing blockers)
2) Succinylcholine (Agonists: Depolarizing Blockers)
Tubocurarine
Uses: As adjuvant drugs in anesthesia during surgery to relax skeletal muscle
MOA: Competitive antagonists
Succinylcholine
Uses: Rapid endotracheal intubation
-Electroconvulsive therapy (ECT)
MOA: Succinylcholine binds to the nicotinic receptor and depolarizes the junction
-Persists in the synaptic cleft, stimulating the receptor: receptor desensitizes
-This leads to flaccid paralysis
Drugs that act presynaptically: Inhibitors of acetylcholine release
-Botulinum Toxin
Uses of Botulinum Toxin
Injected locally into muscles for treatment of severe diseases involving muscle spasms
-Approved for cosmetic treatment of facial wrinkles
Adrenergic drugs can treat which kinds of disorders?
-Hypertension
-Angina
-Heart Failure
-Arrhythmias
-Asthma
-Migraine
-Anaphylactic reactions
Norepinephrine has [ 1 ] effect on [ 2 ] receptors, therefore it cannot cause bronchodilation, because receptors in bronchial [ 3 ] muscle are [ 4 ].
1) Little effect
2) Beta-2
3) Smooth muscle
4) Beta-2
Norepinephrine has little effect on beta-2 receptors, therefore it cannot cause bronchodilation, because receptors in bronchial smooth muscle are beta-2.
Epinephrine
Potent bronchodilator.
Skin blood vessels express almost exclusively what type of receptors?
alpha-1 receptors
Low concentrations of epinephrine cause: [ ]
Vasodilation
Locations of Beta-1 receptors
1) Heart
2) Juxtaglomerular cells (Kidney)
3) Adipocytes
Response of Beta-1 receptors signaling
1) increases cAMP, couples with Gs (G-protein coupled receptors)
Effects of Beta-1 receptors signaling on the heart
1) Increases heart rate
2) Heart force
3) AV conduction velocity
Effects of beta-1 receptors signaling on juxtaglomerular cells
Increased renin release
Effects of beta-1 receptors signaling on adipocytes
Increased lipolysis
Effects of beta-2 receptor signaling
increases cAMP, Couples via Gs
Locations of beta-2 receptors
1) Smooth Muscle: Relaxation
2) Skeletal muscle: increased glucogenolysis, increased K+ uptake
3) Pancreatic beta-cells: increased insulin secretion
4) Pancreatic alpha-cells: increased glucagon secretion
5) Liver: increased glucogenolysis, increased gluconeogenesis
6) Adipocytes: increased lipolysis
Locations of beta-3 receptors
Adipocytes
Signaling of beta-3 receptors
increased cAMP, couples via Gs
Locations of alpha-1 receptors
1) Vascular smooth muscle
2) Genitourinary smooth muscle
3) Liver
Signaling of alpha-1 receptors
Increased IP3 and DAG
Increased Ca2+, couples via Gq
Effects of alpha-1 receptors on vascular smooth muscle
Contraction
Effects of alpha-1 receptors on the liver
increased glucogenolysis and gluconeogenesis
Locations of alpha-2 receptors
1) Presynaptic nerve terminals
2) Platelets
3) Adipocytes
4) Pancreatic beta-cells
5) Vascular smooth muscle
Signaling action of alpha-2 receptors
Decreased cAMP
Couples via Gs
Effects of alpha-2 receptors on presynaptic nerve terminals
Inhibition of NE release
Effects of alpha-2 receptors on platelets
Aggregation
Effects of alpha-2 receptors on adipocytes
Inhibition of lipolysis
Effects of alpha-2 receptors on pancreatic beta-cells
decreased insulin secretion
Effects of alpha-2 receptors on vascular smooth muscle
Contraction
D1, D5 receptor locations
Smooth muscle of the renal vascular bed
D1,D5 signaling action
increases cAMP
D1, D5 effects on smooth muscle of the renal vascular bed
relaxation
Epinephrine action
Acts as a hormone, after release from the adrenal medulla into the blood it acts on distant cells.
-Agonist at both alpha and beta adrenoceptors
At low concentrations, epinephrine activates mainly [ ] receptors
beta-1 and beta-2
At higher concentrations, [ ] effects become more pronounced
alpha-1 effects
Isoproterenol
-May be used in emergencies to stimulate heart rate in patients with bradycardia or heart block
-Increases heart rate, force of contraction and cardiac output
-Dilates arterioles of skeletal muscle, resulting in a decrease in peripheral vascular resistance
Dobutamine
-Predominantly a beta-1 agonist.
-Given IV
-Potent inotrope, with comparatively mild chronotropic effects.
-Produces less increase in HR and less decrease in PVR than isoproterenol
-Increases myocardial O2 consumption
-Basis of the dobutamine stress echocardiogram
Albuterol
Causes bronchodilation
-Used in asthma
-DOC for acute asthma attacks
Phenylephrine
Causes vasoconstriction alpha-1 effect
Used for: Nasal decongestant (orally or topically)
-Mydriatic (dilation of pupils)
Clonidine
Partial alpha-2 agonist
-Centrally acting antihypertensive
-Reduces sympathetic outflow, reduces BP
Releasing agents
Amphetamine
Tyramine
Uses for amphetamine
Central stimulatory action
-Can increase BP by alpha-agonist action on vasculature as well as beta-stimulatory effects on the heart
Used for treatment of: ADHD, Narcolepsy
Tyramine
Found in fermented foods such as ripe cheese and Chianti wine
-MAO inhibitors (antidepressants)
Cocaine
Blocks monoamine reuptake
-Monoamines accumulate in synaptic space
Mixed acting adrenergic agonists
Ephedrine
Pseudoephedrine
Ephedrine
Penetrates the CNS
Used as: pressor agent, particularly during spinal anesthesia
Pseudoephedrine
One of 4 ephedrine enantiomers
-Sudafed over the counter component of many decongestant mixtures
Non-selective alpha-adrenergic blockers
Phenoxybenzamine
Phentolamine
Alpha-1 selective adrenergic blockers
Prazosin
Terazosin
Doxazosin
Tamsulosin
Phenoxybenzamine
Irreversible antagonist
Used to treat: Pheochromocytoma (pre-op surgical removal of a tumor)
-Chronic management of inoperable tumors
Phentolamine
Used to diagnose pheochromocytoma: control of hypertension during preoperative preparation and surgical excision
-Phentolamine blocking test
-Prevention of dermal necrosis after extravasation of norepinephrine
-Cocaine-induced acute coronary syndrome: to reverse coronary artery vasoconstriction
Treatment of hypertension and BPH
Terazosin
Doxazosin
Tamsulosin
Selective for alpha-1A receptors
-Approved for BPH
-Little effect on BP
-Less likely to cause orthostatic hypotension
Which kinds of drugs are contraindicated in patients with asthma?
beta-blockers
Non-selective beta-blockers
Propranolol
Nadolol
Timolol
Metabolic effects of beta blockers
1) Decreased glycogenolysis
2) Decreased glucagon secretion
Atenolol
Useful in hypertensive patients with impaired pulmonary function
Metoprolol
Useful in diabetic hypertensive patients who are receiving insulin or oral hypoglycemic agents
Esmolol
Ultra-short acting
-IV administration
-Used for rapid control of ventricular rate in patients with atrial fibrillation or atrial flutter
Pindolol
May be preferred in individuals with diminished cardiac reserve or a propensity to bradycardia
Labetalol
Competitive antagonist at beta and alpha-1 receptors
-Substantially more potent as a beta-antagonist than as an alpha-antagonist
-Used in hypertension
Carvedilol
Similar to labetalol
-Antioxidant properties
-Used in hypertension and CHF
Adverse effects of beta-blockers
1) Bronchoconstriction
2) Hypoglycemia
3) Lipid metabolism
CNS effects: Sedation, Dizziness, Lethargy, Fatigue
