Intro Pharm Flashcards
Alpha1 receptors
Sympathetic
Linked with Gq proteins
1) Increase vascular smooth muscle contraction
2) Increase pupillary dilator muscle contraction (mydriasis)
3) Increase intestinal and bladder sphincter muscle contraction
Alpha2 receptors
Sympathetic
Linked with Gi proteins
1) Lower sympathetic outflow
2) Lower insulin release
3) Lower lipolysis
4) Increase platelet aggregation
5) Lower aqueous humor production
B1 receptors
Sympathetic
Linked with Gs proteins
1) Increase HR
2) Increase Contractility
3) Increase renin release
4) Increase Lipolysis
B2 receptors
Sympathetic
Linked with Gs proteins
1) Vasodilation
2) Bronchodilation
3) Increase lipolysis
4) Increase insulin release
5) Lower uterine tone (tocolysis)
6) Ciliary muscle relaxation
7) Increase aqueous humor production
M1 receptors
Parasympathetic
Linked with Gq proteins
1) CNS
2) Enteric Nervous System
M2 receptors
Parasympathetic
Linked with Gi proteins
1) Lower HR
2) Lower contractility of atria
M3 receptors
Parasympathetic
Linked with Gq proteins
1) Increase exocrine gland secretions (lacrimal, salivary, gastric acid)
2) Increase gut peristalsis
3) Increase bladder contraction
4) Increase bronchoconstriction
5) Increase pupillary sphincter muscle contraction (miosis)
6) Increase ciliary muscle contraction (accommodation)
D1 receptor
Dopamine
Linked with Gs proteins
Relaxes renal vascular smooth muscle
D2 receptor
Dopamine
Linked with Gi proteins
Modulates transmitter release, esp in brain
H1 receptor
Histamine
Linked with Gq proteins
1) Increased nasal and bronchial mucus production
2) Increased vascular permeability, contraction of bronchioles, pruritis, and pain
H2 receptor
Histamine
Linked with Gs proteins
Increases gastric acid secretion
V1 receptor
Vasopressin
Linked with Gq proteins
Increase vascular smooth muscle contraction
V2 receptor
Vasopressin
Linked with Gs proteins
Increase H2O permeability and reabsorption in collecting tubules of kidney.
Bethanechol
Cholinomimetic Direct Muscarinic Agonist
Use: Postoperative ileus, neurogenic ileus, urinary retention
Activates bowel and bladder smooth muscle; resistant to AChE
Carbachol
Cholinomimetic - Direct Muscarinic agonist
Use: Constricts pupil and relieves intraocular pressure in glaucoma
Carbon copy of acetylcholine
Methacholine
Cholinomimetic - Direct Muscarinic agonist
Use: Challenge test for diagnosis of asthma
Stimulates muscarinic receptors in airway when inhaled
Pilocarpine
Cholinomimetic - Direct Muscarinic agonist
Use: Potent stimulator of sweat, tears, and saliva. Open angle and close-angle glaucoma
Contracts ciliary muscle of eye (open-angle glaucoma), pupillary sphincter (closed-angle glaucoma); resistant to AChE
Donepezil
Galantamine
Rivastigmine
Cholinomimetic - Indirect muscarinic agonist/ anticholinesterase
Use: Alzheimer
Increase ACh
Edrophonium
Cholinomimetic - Indirect muscarinic agonist/ anticholinesterase
Use: Historically, diagnosis of myasthenia gravis (extremely short acting). Myasthenia now diagnosed by anti-AChR Ab (anti-acetylcholine receptor antibody) test.
Increases ACh
Neostigmine
Cholinomimetic - Indirect muscarinic agonist/ anticholinesterase
Use: Postop and neurogenic ileus and urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade (postop)
Increases ACh
No CNS penetration
Physostigmine
Cholinomimetic - Indirect muscarinic agonist/ anticholinesterase
Use: Anticholinergic toxicity; crosses BBB into CNS
Increases ACh
For Atropine overdose
Pyridostigmine
Cholinomimetic - Indirect muscarinic agonist/ anticholinesterase
Use: Myasthenia gravis (long acting); does not penetrate CNS
Increases ACh
Increases muscle strength
Cholinomimetic (Muscarinic agonist) cautions
For all of these agents, look out for exacerbation of COPD, asthma, and peptic ulcers when giving to susceptible patients.
Cholinesterase inhibitor poisoning
Often due to organophosphates such as parathion that irreversibly inhibit AChE.
Diarrhea Urination Miosis Bronchospasm Bradycardia Excitation of skeletal muscle and CNS Lacrimation Sweating Salivation
DUMBBELSS
Organophosphates are often components of insecticides; poisoning usually seen in farmers.
Antidote = atropine (competitive inhibitor) + pralidoxime (regenerates AChE if given early)
Atropine
Homatropine
Tropicamide
Muscarinic antagonists/anticholinergics
Act at Eye
Use: Produces mydriasis and cycloplegia
Benztropine
Muscarinic antagonists/anticholinergics
Act in CNS
Uses:
Parkinson Disease
Acute dystonia
Glycopyrrolate
Muscarinic antagonists/anticholinergics
Acts in GI, respiratory
Uses: Parenteral - preop use to reduce airway secretions
Oral - drooling, peptic ulcer
Hyoscyamine
Dicyclomine
Muscarinic antagonists/anticholinergics
GI
Uses:
Antispasmodic for IBS
Ipratropium
Tiotropium
Muscarinic antagonists/anticholinergics
Respiratory
Use:
COPD
Asthma
Oxybutynin
Solifenacin
Tolterodine
Muscarinic antagonists/anticholinergics
GU
Use:
Reduce bladder spasms and urge urinary incontinence (overactive bladder)
Scopolamine
Muscarinic antagonists/anticholinergics
CNS
Use for motion sickness
Atropine
Muscarinic antagonist/anticholinergic
Used to treat bradycardia and for ophthalmic applications
Eye: Increases pupil dilation, cycloplegia Airway: Lowers secretions Stomach: Lower acid secretion Gut: Lower motility Bladder: Lower urgency in cystitis
Toxicity: Increased body temp (due to less sweating); rapid pulse; dry mouth; dry, flushed skin; cycloplegia; constipation; disorientation
Can cause acute-angle closure glaucoma in elderly (due to mydriasis), urinary retention in men with prostatic hyperplasia and hyperthermia in infants
Hot as a hare Dry as a bone Red as a beet Blind as a bat Mad as a hatter
Jimson weed (datura) leads to gardener’s pupil (mydriasis due to plant alkaloids)
Tetrodotoxin
Highly potent toxin that binds fast voltage-gated Na channels in cardiac and nerve tissue, preventing depolarization (blocks action potential without changing resting potentials).
Causes nausea, diarrhea, paresthesias, weakness, dizziness, loss of reflexes
Tx is primarily supportive
Poisoning can come from ingestion of poorly prepared pufferfish (fugu), a Japanese delicacy
Ciguatoxin
Causes ciguatera fish poisoning. Opens Na channels causing depolarization
Symptoms easily confused with cholinergic poisoning
Temperature-related dysesthesia (cold feels hot; hot feels cold) is regarded as a specific finding of ciguatera
Tx is supportive
Comes from eating reef fish - barracuda, snapper, moray eel
Scombroid poisoning
Acute-onset burning sensation of the mouth, flushing of face, erythema, urticaria, pruritis, headache.
May cause anaphylaxis-like presentation (bronchospasm, angioedema, hypotension)
Tx supportively with antihistamines; if needed, antianaphylactics (bronchodilators, Epi)
Caused by consumption of dark-meat fish (bonito, mackerel, mahi-mahi, tuna) improperly stored at warm temps.
Bacterial histidine decarboxylase converts histidine to histamine. Histamine is not degraded by cooking.
Frequently misdiagnosed as allergy to fish
Albuterol
Salmeterol
Sympathomimetics - Direct
B2 > B1
Albuterol for acute asthma
Salmeterol for long term asthma or COPD control
Dobutamine
Sympathomimetic - Direct
B1 > B2, Alpha
Heart failure (inotropic > chronotropic) Cardiac stress testing
Dopamine
Sympathomimetic - Direct
D1 = D2 > B > alpha
Unstable bradycardia
HF
Shock
Inotropic and chronotropic alpha effects predominate at high doses
Epinephrine
Sympathomimetic - Direct
B > alpha
Anaphylaxis
Asthma
Open-angle glaucoma
Alpha effects predominate at high doses
Significantly stronger effect at B2 receptor than NE
Isoproterenol
Sympathomimetic - Direct
B1 = B2
Electrophysiologic evaluation of tachyarrhythmias. Can worsen ischemia
Norepinephrine
Sympathomimetic - Direct
Alpha1 > alpha2 > B1
Hypotension (but lowers renal perfusion)
Significantly weaker effect at B2-receptor than Epi
Phenylephrine
Sympathomimetic - Direct
Alpha1 > alpha2
Hypotension (vasoconstrictor) Ocular procedures (mydriatic) Rhinitis (decongestant)
Amphetamine
Sympathomimetic - Indirect
Indirect general agonist, reuptake inhibiter, also releases stored catecholamines
For: Narcolepsy, obesity, ADHD
Cocaine
Sympathomimetic - Indirect
Indirect general agonist, reuptake inhibiter
Causes vasoconstriction and local anesthesia. Never give B-blockers if cocaine intoxication is suspected (can lead to unopposed alpha 1 activation and extreme hypertension)
Ephedrine
sympathomimetic - Indirect
Indirect general agonist, releases stored catecholamines
Nasal decongestion, urinary incontinence, hypotension
Clonidine
Alpha 2 agonist
For: hypertensive urgency (limited situations); does not decrease renal blood flow
ADHD
Tourette Syndrome
Toxicity: CNS depression, bradycardia, hypotension, respiratory depression, miosis
Alpha-methyldopa
Alpha 2 agonist
For: HTN during pregnancy
Toxicity: Direct Coombs (+) hemolysis
SLE-like syndrome
Nonselective alpha blockers
Phenoxybenzamine (irreversible)
Phentolamine (reversible)
Phenoxybenzamine
Nonselective alpha blocker (irreversible)
Uses:
Pheochromocytoma (used preop) to prevent catecholamine (hypertensive) crisis
Side effects:
Orthostatic hypotension, reflex tachycardia
Phentolamine
Nonselective alpha blocker (reversible)
Uses:
Give to patients on MAOIs who eat tyramine-containing foods
Side effects:
Orthostatic hypotension, reflex tachycardia
Alpha 1 selective alpha blockers
Prazosin
Terazosin
Doxazosin
Tamsulosin
Prazosin
Terazosin
Doxazosin
Tamsulosin
Alpha 1 selective alpha blockers
Uses:
Urinary symptoms of BPH; PTSD (prazosin); HTN (not tamsulosin)
Side effects:
1st dose orthostatic hypotension, dizziness, HA
Alpha 2 selective alpha blockers
Mirtazapine
Mirtazapine
Alpha 2 selective alpha blocker
Uses:
Depression
Side effects:
Sedation, high serum cholesterol, high appetite
B1 selective antagonists
B1 > B2
Acebutolol (partial agonist) Atenolol Betaxolol Esmolol Metoprolol
Nonselective Beta antagonists
B1 = B2
Nadolol
Pindolol (partial agonist)
Propranolol
Timolol
Nonselective Beta and Alpha antagonists
Carvedilol
Labetalol
Nebivolol
Combines cardiac-selective B1-adrenergic blockade with stimulation of B3 receptors, which activate NO synthase in the vasculature
Beta Blockers
Uses:
1) Angina pectoris - lower HR and contractility, resulting in lower O2 consumption
2) MI - B-blockers (metoprolol, carvedilol, bisoprolol) lower mortality
3) SVT (metoprolol, esmolol) - lower AV conduction velocity (class 2 antiarrhythmics)
4) HTN - lower Cardiac Output, lower renin secretion (due to B1 receptor blockade on JGA cells)
5) HF - lower mortality in chronic HF
6) Glaucoma (timolol) - lower secretion of aqueous humor
Toxicity:
Impotence
CV adverse effects (bradycardia, AV Block, HF)
CNS adverse effects (seizures, sedation, sleep alterations)
Dyslipidemia (metoprolol)
Asthma/COPD exacerbations
Avoid in cocaine users due to risk of unopposed alpha-adrenergic receptor agonist activity
Despite theoretical concern of masking hypoglycemia in diabetics, benefits likely outweigh risks; not contraindicated
