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268 Cards in this Set
- Front
- Back
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Phenoxybenzamine molecular target?
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Blocks α1 and α2 “irreversibly” by a covalent modification of the receptors
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Phenoxybenzamine major CV effects?
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Block of α receptors in SMCs = progressive ↓ PR, which leads to an enhanced baroreflex response
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Phenoxybenzamine other effects?
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At higher doses, PBZ irreversibly inhibits serotonin, histamine and ACh
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What's required for restoration of function after a patient is given Phenoxybenzamine?
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the synthesis of new receptors
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What accentuates the tachycardia in the case of Phenoxybenzamine?
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Block of α2 receptors in the CNS = ↑ Σ outflow → β1 adrenergic receptor activation, especially in the heart
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Why do you get hypotension when standing if you take Phenoxybenzamine?
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Due to absence of a vasomotor response elicited by baroreceptor reflex
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What happens if you give epinephrine and Phenoxybenzamine?
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May produce a severe hypotension due to unopposed β receptors (especially β2)
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Phenoxybenzamine pharmacokinetics?
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Not well understood.
½ Life is probably less than 24 hours but impact lasts until receptor number returns to baseline (takes several days) |
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Phenoxybenzamine therapeutic uses?
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Pheochromocytoma (especially in surgical prep for these patients, not used long term unless the patient is inoperable)
Off label for BPH |
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Phenoxybenzamine dosage?
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10 mg BID X 1 to 3 weeks; increased until BP is controlled
Normal dose: 40 to 120 mg divided BID/TID |
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Phenoxybenzamine adverse effects?
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*Postural hypotension → reflex tachycardias and arrhythmias
*Nasal stuffiness; miosis *Impaired ejaculation due to inhibition of vas deferens SM |
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Phentolamine molecular target?
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Blocks α1 and α2 with a similar affinity
competitive and reversible |
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Phentolamine major CV effects?
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similar to PBZ (↓PR leads to ↓BP and ↑HR)
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Phentolamine other effects?
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Stimulates GI smooth muscles and enhances gastric acid secretion
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Phentolamine pharmacokinetics?
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Unknown. Extensively metabolized
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Phentolamine therapeutic uses?
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*Pheochromocytoma: short term HTN; may relieve pseudo-obstruction of the bowel by suppressing catecholamine inhibition of GI SM
*Can be rapidly infused to alleviate a severe hypertensive episode |
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Phentolamine other therapeutics?
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*May limit dental necrosis after extravasation of α agonist (e.g. Phenylephrine- used to limit local anesthetic loss)
*Raynaud’s disease *After rapid withdrawal of Clonidine *Following ingestion of Tyramine-rich food for MAO inhibitor pts *ED via direct penile injections |
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What are the “Classical” α blockers?
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Phentolamine and PBZ
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Phentolamine adverse effects?
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Hypotension, reflex tachycardia, arrhythmias, ischemic cardiac events, MI
GI: abdominal pain, nausea, peptic ulcer exacerbation |
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Phentolamine precautions?
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Patients with coronary artery disease or a history of peptic ulcers
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Prazosin molecular target?
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α1-selective antagonists (α1 v. α2 affinity ~ 1000 –fold)
α1A ≈ α1B ≈ α1D Also a potent inhibitor of cyclic nucleotide phosphodiesterases (PDE) |
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Prazosin major CV effects?
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↓ PR = ↓ BP = ↓ venous return
*Does not generally increase HR ↓ baroreflex mechanisms in HTN |
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Prazosin other effects?
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May also decrease ↓ sympathetic outflow in the CNS
Favorable effects on lipids: ↓ LDL, ↓ TG and ↑ HDL |
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Prazosin pharmacokinetics?
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Well absorbed; 50-70% bioavail
Tightly bound to plasma proteins Extensively metabolized by the liver ½ Life = 2-3 hrs (6-8 hrs in CHF) |
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Prazosin therapeutic uses?
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Essential Hypertension (mild-mod)
Vasodilator used in CHF BPH |
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Prazosin dosage?
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HTN: initial: 1 mg HS; 1 mg BID/TID; dose titrated until nl BP
Maximal effect with ~ 20 mg/day BPH: 1 to 5 mg BID |
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Newer generation selective α1 receptor antagonists effects on prostate? Examples of drugs?
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↑ apoptosis of prosthatic smooth muscle cells = blocks proliferation and alleviate BPH symptoms
Terazosin and Doxazosin |
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Prazosin Adverse Effects?
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Marked postural hypotension and syncope 30-90 min after the initial dose (check both supine and standing BP)
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Tamsulosin molecular target?
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Newer well absorbed α1 antagonist with some subtype selectivity: α1A ≈ α1D > α1B
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Tamsulosin effects?
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Useful in BPH due to favorable blockade of α1A receptors with little undesirable effect on BP
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Tamsulosin pharmacokinetics? Dose?
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½ Life of 5 to 10 hours
Starting dose: 0.4-0.8 mg |
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Tamsulosin adverse effects?
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abnormal ejaculation
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Yohimbine molecular target?
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Selective α2 receptor antagonist
Structurally similar to reserpine |
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Yohimbine major CV effects?
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Readily enters the CNS: ↑ BP and HR
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Yohimbine other effects?
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↑ motor activity and produces tremors
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Yohimbine therapeutic uses?
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Historically: extensively used for ED but efficacy surpassed by the development of PDE5 inhibitors
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What is atropine?
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A naturally occurring muscarinic receptor antagonist (tropic acid + tropine)
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Where is atropine found naturally?
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Nightshade (Atropa belladonna)
Jimson weed (Datura stramonium) |
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What is scopolamine?
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A naturally occurring muscarinic receptor antagonist (tropic acid + scopine)
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Where is scopolamine found naturally?
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Henbane (Hyoscyamus niger)
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What is homatropine?
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A semisynthetic muscarinic receptor antagonist (mandelic acid + tropine)
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What are Synthetic Quaternary Ammonium Compounds? (Examples?)
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Muscarinic Receptor Antagonists that are chemical derivatives of atropine (ipratropium) and scolpolamine (tiotropium). (other = propantheline)
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What are ipra-/tio-tropiums?
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Synthetic Quaternary Ammonium Compounds (Muscarinic Receptor Antagonists)
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Examples of Synthetic Tertiary Ammonium Compounds?
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cyclpentolate, tropicamide, dicyclomine, triphenamil, flavoxate, oxybutynin, tolterodine
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What's special (with regards to distribution) with Synthetic Tertiary Ammonium Compounds?
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Cross the blood-brain barrier = can be used to treat conditions such as Parkinsonism
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What's a useful action of Flavoxate, oxybutynin and tolterodine?
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They have direct smooth muscle relaxing effects = used to treat bladder spasticity problems
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What's Prenezepine? What's it's main clinical use?
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A M1 selective Muscarinic Receptor Antagonist.
Used to treat gastric ulcers (equi-effective as cimetidine) |
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What's Otenzepad? What's it's main clinical use?
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A M2 selective Muscarinic Receptor Antagonist.
Investigated for it's use as an anti-arrhythmic |
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What're Enablex (darifenacin) & Vesicare (solifenacin)? What's are their main clinical use?
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M3 selective Muscarinic Receptor Antagonists.
Used to tx urinary bladder instability, incontinence & urgency |
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What drug is used in motion sickness prophylaxis? What's a caution with the use of this drug?
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Scopolamine
Due to its lipid solubility, can have significant CNS effects at therapeutic doses |
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What are the CNS effects seen with administration of Scopolamine?
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CNS depression
Amnesia Drowsiness Fatigue Dreamless sleep (↓REM sleep) Euphoria (with potential for abuse) |
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Which has greater CNS effects, scopolamine or atropine?
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Scopolamine
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What drugs are used to treat parkinsonism?
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Synthetic tertiary amine muscarinic antagonists.
Often in combination with levodopa and carbidopa (more effective) |
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What drugs are used in anti-psychotic therapy?
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Synthetic tertiary amine muscarinic antagonists.
Used for associated extrapyramidal symptoms |
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What drug is used to induce mydriasis? How?
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Atropine
Relaxes iris sphincter muscle by muscarinic antagonism |
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How are adhesions between the iris and lens treated?
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A muscarinic antagonist can be alternated with a miotic agent (like a muscarinic agonist)
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How does one induce cycloplegia (paralysis of accommodation)?
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Topical administration of muscarinic antagonists.
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What drugs are used to induce cycloplegia in children? adults?
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Topical atropine or scopolamine (= long lasting effects)
Synthetic tertiary amines (= shorter durations of actions) |
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Why must one be cautious with the systemic administration of atropine/scopolamine in glacoma patients?
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muscarinic antagonists can ↓aqueous humor outflow = ↑intraocular pressure
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What happens to heart rate with a low dose of atropine? Why?
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Paradoxical transient decrease HR due to:
Central effects Block of presynaptic muscarinics = ↑ACh release (↓negative feedback) |
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What happens to heart rate with higher doses of atropine? Why?
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Progressively ↑HR
Due to block of M2 receptors in SA node |
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Why are young adult's heart rates more affected by atropine? Who is least affected?
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They have significant vagal tone.
Infants and elderly |
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What situations warrant the use of atropine to prevent decreases in HR?
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Vagal-mediated reflexes that may be stimulated during surgery or catheterizations
Hyperactive carotid body reflex |
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What drugs can be used to treat bronchospasm? What's special about the route?
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Ipratropium and tiotropium
They aren't absorbed into systemic circulation when inhaled = can give large doses w/out side effects |
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Why isn't atropine used for treatment of bronchospams?
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Causes ↓ in mucociliary clearance
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What drugs can be used to treat asthma/COPD?
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Ipratropium and tiotropium in combination with beta agonists
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What are some examples of compounds that cause bronchoconstriction via muscarinic agonism?
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histamine
bradykinins prostaglandin F2alpha |
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Why is Tiotropium preferable to ipratropium?
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Longer acting and only Qdaily
More selective for M1 & M3 Less effects at M2 (M2 block = ↑ACh release, bronchioconstrict) |
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Is pirenzepine the primary treatment for gastric ulcers?
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Nope!
Primary tx = antibiotics against H.pylori |
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What are Ganglionic Blockers used to treat?
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Hypertensive crisis or controlled hypotension during surgery
Autonomic hyperreflexia- common result of spinal cord damage (↑BP, ↓HR, muscle convulsions) |
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How do ganglionic blocking agents work?
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Nn receptor antagonists
or Nn ion channel blockers |
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What type of drug is hexamethonium? What's the name of the clinically used derivative?
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One of the 1st ganglionic blockers developed (doesn't affect NM junctions, a relative (c10) does)
Pentolinium |
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What type of drug is trimethaphan? What's it's main clinical use?
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A short-acting ganglionic blocker
Used to produce a controlled hypotension during: surgery or hypertensive crisis |
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What are the side effects of high dose trimethaphan?
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histamine release
direct vasodilating effects long lasting N-M block |
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What type of drug is mecamylamine HCl? What's it's distribution pattern?
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Ganglionic blocker (secondary amine)
Crosses placenta and BBB Accumulates in liver & kidney (used infrequently due to side effects) |
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What are the CV adverse effects with ganglionic blocking agents?
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marked hypotension
severe postural hypotension anginal pain |
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What are the GI/GU adverse effects with ganglionic blocking agents?
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paralytic ileus
constipation or diarrhea urinary retention & hesitancy failure of ejaculation/erection |
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What are the eye/oral adverse effects with ganglionic blocking agents?
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mydriasis
paralysis of accommodation dry mouth |
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What class of drug is Dantrolene? How does it work?
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Muscle relaxant
↓Ca2+ release from the sarcoplasmic reticulum, preventing activation of contraction |
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What drug is used to treat malignant hyperthermia?
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Dantrolene
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What are examples of centrally acting Muscle relaxants?
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sedative-hypnotics and antianxiety drugs (GABA analogs)
**baclofen |
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What are centrally acting Muscle relaxants used for?
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Treatment of conditions involving muscle spasticity (ie cerebral palsy)
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What are the important features of neuromuscular blockers?
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They contain NH4+ groups so they can't enter cells or cross BBB
(**do not have CNS effects and have neither analgesic nor anesthetic actions***) |
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With what disorders are neuromuscular blockers used?
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Lagyngeal/muscle spasms
Multiple Sclerosis Blepharospasm and strabismus |
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What's the order of onset for competitive (nondepolarizing) N-M blockers?
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Small rapid muscles
Limb, neck and trunk muscles Intercostal muscles Diaphragm |
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What happens when competitive (nondepolarizing) N-M blockers are given IV?
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rapid block followed by a flaccid paralysis
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What's the order of recovery of movement for competitive (nondepolarizing) N-M blockers?
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Opposite of onset.
Breathing stops last and resumes first. |
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Examples of competitive (nondepolarizing) N-M blockers?
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d-tubocurarine, vecuronium, pancuronium and pipecuronium, atracurium, doxacurium and mivacurium, gallamine
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What is succinylcholine?
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dimer of 2 ACh molecules
Depolarizing NM blocker |
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How does succinylcholine work?
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Binding to Nm receptors results in prolonged channel activation and muscle depolarization producing a depolarizing block
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What's a phase I succinylcholine block?
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Occurs with low concentrations
Reverses within second Causes muscle fasiculations |
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What's a phase II succinylcholine block?
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Occurs with repeated & higher doses
Long lasting Involves desensitization of Nm receptors |
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Can the effects of succinylcholine be reversed or bypassed?
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Can't be reversed by increase ACh
Can't be bypassed by stimuli downstream of Nm receptor |
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What's the onset order of succinylcholine?
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Neck, arm and leg muscles
Facial masticatory, lingual, pharyngeal & laryngeal muscles Respiratory muscles |
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What's a side effect of succinylcholine?
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muscle soreness due to sustained contraction
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What class of drugs is Botulinum toxins? How do they work?
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Neuromuscular blocker
Prevents muscle activation by ↓ACh release |
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When are Botulinum toxins used?
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Ocular disorders involving excessive muscle activity (like blepharospasm and strabismus)
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Which N-M blocker has ultrashort duration? Short duration?
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(< 5 min): succinylcholine
(10-15 min): mivacurium |
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Which N-M blocker has intermediate duration? Long duration?
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(15-30 min):atracurium, vecuronium, rocuronium, cis-atracurium
(> 30 min):d-tubcurarine, pancuronium |
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What are the primary side effects of NM blockers?
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Changes in BP
Changes in HR Stimulation of histamine release Others = ganglionic block/stimulation or muscarinic block |
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Beta Blockers major clinical use?
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HTN
CHF Ischemic heart diseases certain arrhythmias |
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What's the CV effect of β-receptor stimulation?
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↑ HR and contractility (prominant with stress/exercise)
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What's the CV effect of short-term β-blockers administration?
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↓ CO
↑ PR with β2 blocker potency and compensatory reflex mechanisms |
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What's the CV effect of long-term β-blockers administration?
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PR normal or ↓ in HTN patients
For β1 subclass or direct vasodilator subclass: CO maintained with ↓↓ PR |
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Most common Therapeutic Uses of β blockers?
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Essential Hypertension
Angina Pectoris Arrhythmias Glaucoma Post-MI Therapy Congestive Heart Failure (all grades) |
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Other Therapeutic Uses of β blockers?
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Pheochromocytoma
Acute dissecting aortic aneurysm Migraine as prophylactic agents Hyperthyroidism Anxiety states |
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Side effects of β blockers?
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Tiredness
Dizziness Vivid Dreams Insomnia Hallucinations Depression |
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Routes of administration for β blockers?
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All are orally available. Some are avail for ER IV use (esmolol) or opthalmic solutions (Timolol and Betaxolol)
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Bioavailability for β blockers?
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Many display prominent 1st passage metabolism through the portal system that ↓ their bioavailability
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General properties of 1st generation β antagonists?
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No subtype selectivity
No alpha blocking and no vasodilation |
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General properties of 2nd generation β antagonists?
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β1-selective
No alpha blocking and no vasodilation |
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General properties of 3rd generation β antagonists?
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Have additional vasodilation effects
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What generation is Propranolol? Special notes?
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1st
Has membrane stabilizing activity |
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What is Propranolol used for?
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HTN, angina, arrhythmias, MI, CHF, pheochromocytoma, migraine prophylaxis
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What generation is Timolol?
What is Timolol used for? |
1st
HTN, CHF, glacoma, migraine prophylaxis |
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What generation is Pindolol? Special notes?
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1st
Has intrinsic beta activity and slight membrane stabilizing activity |
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What is Pindolol used for?
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HTN (especially in pts with reduced cardiac reserve, bradycardia, or asthma)
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What generation is Metoprolol? What is it used for?
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2nd
HTN, angina, MI (given IV), heart failure |
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What generation is Atenolol? What is it used for?
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2nd
HTN (especially in the elderly, in combo with a diuretic) |
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What generation is Acebutolol? What is it used for?
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2nd - has intrinsic beta and membrane stabilizing activity
HTN, ventricular arrhythmias |
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What generation is Esmolol? What is it used for?
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2nd
IV in ER for compromised HTN pts - has rapid action and metabolism (1/2 life is 10 min) |
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What generation is Labetolol? What is it used for?
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3rd - also blocks alpha receptors but has 5-10 fold affinity for beta. Has intrinsic beta2 activity
Chronic HTN and IV for HTN emergencies |
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What generation is Carvedilol? What is it used for?
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3rd - blocks alpha with 1.5 fold affinity for beta. Has membrane stabilizing activity.
CHF, MI and post-MI, HTN (especially in elderly) |
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What compound inhibits tyrosine hydroxylase? (synthesis)
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α-methyltyrosine (htn tx)
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What compound inhibits the vesicular monoamine transporter? (Adrenergic storage)
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reserpine (old htn tx)
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What compounds inhibit catecholamine release?
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guanethadine and clonidine (mostly affect CNS)
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What's clonidine's mechanism of action?
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Inhibits catecholamine release by activating α2 receptors on the presynaptic nerve terminal
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What's guanethadine's mechanism of action?
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Inhibits Na,K ATPase
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What does tyramine do?
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Causes NE release (found in aged cheese)
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What compound's an α1 and α2 agonist?
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oxymetazoline (used for local vasoconstriction)
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What compound's an α1 agonist?
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phenylephrine (systemic vasoconstriction, like in shock tx)
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What compound's an α2 agonist?
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clonidine
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What compound's an α1 and α2 antagonist?
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phentolamine
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What compound's an α1 antagonist?
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prazosin (tx htn)
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What compound's an α2 antagonist?
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yohimbine
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What compound's a β1 and β2 agonist?
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isoproterenol
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What compound's a β1 agonist?
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dobutamine (used to increase HR, contractility and cardiac output)
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What compound's a β2 agonist?
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terbutaline (used in asthmatics for vasodilation)
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What compound's a β1 and β2 antagonist?
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propranolol (htn tx)
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What compound's a β1 antagonist?
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metoprolol (htn tx)
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What compound inhibits catechol-O-methyl transferase (COMT)?
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entacapone
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What compound inhibits monoamine oxidase (MAO)?
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pargyline (used to tx depression)
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What compound inhibits neuronal reuptake of catecholamines?
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Cocaine (mostly CNS effects but OD sx cause by ANS effects)
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What are Muscarinic Receptor Agonists used for?
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GI system - stasis & inactivity
Bladder – retention & inactivity Salivary gland dysfunction Eye: Glaucoma and to produce miosis |
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What are AChE Inhibitors used for?
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Reversal of nondepolarizing NM blockers
Myasthenia gravis - ddx & tx Eye - strabismus Bladder/GI – smooth muscle atony Deadly anti-muscarinic activity Alzheimer’s disease |
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What drug blocks the uptake of choline?
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Hemicholinum
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What drug blocks the packaging of ACh into vesicles?
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vesamicol
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What drug blocks the release of ACh into the synaptic cleft? What stimulates this?
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botulinium toxin
black widow venom |
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What structural features are the same for all ACh and Synthetic Choline esters?
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quarternary N+
ester link |
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What's methacholine?
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Muscarinic agonist
beta-methyl analog of ACh |
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What's carbachol?
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Muscarinic agonist
the carbamyl ester of choline |
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What's bethanechol?
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Muscarinic agonist
beta-methyl analog of carbachol |
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What drug is a naturally occurring cholinomimetic alkaloid?
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Pilocarpine
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What 2 synthetic choline esters aren't susceptible to AChE?
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Carbachol
Bethanechol |
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When are Muscarinic Agonists used in GI disorders? Which drugs are used?
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Post-op stasis/distension
Gastric atony and retention Adynamic ileus Bethanechol Cl |
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When are Muscarinic Agonists used in urinary bladder disorders? Which drugs are used?
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Urinary retention: Acute (subq empty stomach) Chronic (orally with meals). Drug ↓slowly once voiding begins.
Bethanechol Cl |
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When are Muscarinic Agonists contraindicated in the treatment of GI or bladder disorders?
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Mechanical obstruction
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When are Muscarinic Agonists used in salivary gland dysfuction? Which drugs are used?
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Xerostomia
bethanechol, methacholine, or pilocarpine |
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When are Muscarinic Agonists used in narrow angle glacoma? Which drugs are used?
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Short term prior to surgery (iris contraction inc drainage through canal)
Choline esters and pilocarpine - topical |
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When are Muscarinic Agonists used in open angle glacoma? Which drugs are used?
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Chronically. As adjunctive with beta blockers, adrenergic agonsits, or prostaglandin analogs. May open spaces in trabeculum
Choline esters and pilocarpine |
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When are Muscarinic Agonists used in changing pupil size? Which drugs are used?
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To produce miosis.
Choline esters and pilocarpine |
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When is the use of Muscarinic Agonists contraindicated?
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Asthma
Hyperthyroidism (↑ atrial fibrillation) Coronary insufficiency Peptic ulcers |
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What are the side effects of Muscarinic Agonists?
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Flushing
Sweating Abdominal cramps Belching Feelings of bladder tightness Difficulty in visual accommodation Headache Salivation |
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What happens at low levels of AChE Inhibitors?
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↑ skeletal muscle activation and fasciculation
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What happens at high levels of AChE Inhibitors?
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Neuromuscular blockade due to persistent depolarization (Phase I) and subsequent desensitization of Nm receptors (Phase II)
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What are the effects of AChE Inhibitors?
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↑ activation of cholinergic receptors in exocrine glands, smooth muscle, heart, lung, etc.
↑ ganglionic transmission |
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CNS effects of AChE Inhibitors?
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tremor, sleep disturbances, anxiety, restlessness,memory loss, confusion, convulsions, coma, dec ability to concentrate, circulatory and respiratory depression, desynchronization of the EEG
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How do Mono- or bis-quaternary amines work?
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Form noncovalent bonds with the anionic site of AChE and reversibly inhibit AChE.
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What's the difference in duration between the two Mono-/bis-quaternary amines?
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Mono-amines (edrophonium) inhibit for minutes
Bis-amines (ambenonium) inhibit for hours |
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How do the carbamates work?
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The carbonyl carbon interacts covalently with the esteratic site and a tertiary/quarternary amine binds noncovalently to the anionic site, forming a carbamylated intermediate = reversible inhibition that lasts for minutes to hours (inhibitor is destroyed during the reaction)
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Examples of Organophosphates?
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isofluorophate, echothiophate, pesticides
nerve gas |
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How do Organophosphates work?
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Primarily lipid soluble compounds that form a stable covalent phosphate ester bond with the esteratic site of AChE that requires days for spontaneous hydrolysis
= mostly irreversible inhibition |
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What drugs are used in the reversal of N-M junction block by nondepolarizing blockers during anesthesia?
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Neostigmine, pyridostimgine or edrophonium
A muscarinic antagonist (atropine) may be co-administered to prevent unwanted side effects of ↑ACh |
|
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How is myasthenia graves diagnosed?
|
a reversible short-acting AChE inhibitor (edrophonium) produces an ↑ in muscle strength
|
|
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How is myasthenia graves treated?
|
longer-acting AChE inhibitors
(pyridostigmine and neostigmine) |
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How is strabismus treated?
|
Long-acting AChE inhibitors (isofluorphate echothiophate) used to ↑ accommodation by ↑ ACh at the ciliary body
|
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What's a side effect to topical application of AChE inhibitors on the eye?
|
Cataracts may occur with an ↑ frequency
|
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What drug is used to treat smooth muscle atony?
|
Neostigmine (SC/IM) can be used to ↑ activity of GI or urinary tract smooth muscle
|
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What drugs can be used to treat Alzheimer's? How?
|
AChE inhibitors - Donepizil, Physostigmine, rivastigmine
Associated with ↓ ACh levels due to ↓CAT activity, so pts benefit from ↑ACh |
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Examples of Adrenergic Neuron Blockers?
|
Guanethidine
Bretylium |
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Examples of Synthesis Inhibitors?
|
Metyrosine
|
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Examples of Catecholamine Depleting Drugs?
|
Reserpine
|
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Examples of Centrally Acting Drugs?
|
α-Methyl-DOPA
Clonidine |
|
|
Guanethidine mechanism of action?
|
Substrate for neuronal re-uptake of NE → depletion of NE stores
Disrupts/uncouples triggering effect of the action potential on synaptic release |
|
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Guanethidine short-term effects?
|
Causes some release of NE = pro-hypertensive effect
|
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Guanethidine long-term effects?
|
↓ Sympathetic tone =
Cardiovascular system: ↓ BP, ↓HR and ↓ CO GI tract: ↑ Motility and causes diarrhea |
|
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Guanethidine adverse effects?
|
Unopposed parasympathetics = severe orthostatic hypotension
Nasal stuffiness Impaired ejaculation GI tract motility issues |
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|
Guanethidine pharmacokinetics?
|
Half-life: ~ 5 days
Plateau level: 20 to 25 days |
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Guanethidine therapeutic uses?
|
severe HTN (very effective)
|
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Guanethidine contraindications?
|
Should never be given to pheochromocytoma patients!
|
|
|
Guanethidine drug interactions?
|
Tricyclic antidepressants and phenothiazines due to competition for the uptake transporter
|
|
|
Bretylium mechanism of action?
|
Blocks the release of NE from peripheral adrenergic varicosities
|
|
|
Bretylium historical therapeutic uses?
|
Historically: severe HTN; no effect when supine but very active when standing = severe orthostatic hypotension
|
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Bretylium route?
|
IV
|
|
|
Bretylium current therapeutic uses?
|
Class III antiarrhythmic drug (in combination); last resort compound to terminate tachycardia and fibrillation
|
|
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Metyrosine mechanism of action?
|
Competitive inhibitor of tyrosine hydroxylase in the brain, periphery and adrenal medulla = ↓ NE stores because insufficient synthesis
|
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|
Metyrosine therapeutic uses?
|
Hypertension: inexpensive!
Inoperable Pheochromocytoma patients |
|
|
Metyrosine adverse effects?
|
Typical sympathetic depression (nasal congestion, postural hypotension, impotence)
Sedation |
|
|
Reserpine mechanism of action?
|
*Naturally occurring plant alkaloid from Rauwolfia serpentina
*Depletion amine stores via block of vesicular uptake transporters *Will also deplete dopaminergic and 5-HT synapses |
|
|
Reserpine contraindication?
|
Patients with a history of depression
|
|
|
Reserpine adverse effects?
|
Typical sympathetic depression (nasal congestion, postural hypotension, impotence)
Sedation Depression |
|
|
α- Methyl DOPA mechanism of action?
(possibles) |
1. Drug metabolite, α-Methyl-NE = α2-receptor agonist → ↓ symp outflow
2. L-Aromatic amino acid decarboxylase inhibitor |
|
|
α- Methyl DOPA pharmacokinetics?
|
Long acting because not metabolized by MAO
|
|
|
α- Methyl DOPA therapeutic uses?
|
Mild to moderate hypertension
HTN during pregnancy (pre-eclampsia) |
|
|
α- Methyl DOPA adverse effects?
|
Sedation, drowsiness
Typical sympathetic depression (nasal congestion, postural hypotension, dry mouth) |
|
|
Where do α2-receptor agonists decrease symp outflow?
|
Brain stem: Nucleus Tractus Solitarius and vasomotor center
|
|
|
α- Clonidine mechanism of action?
|
α2-Adrenergic Receptor Agonist → ↓ sympathetic outflow
|
|
|
α- Clonidine therapeutic uses?
|
Hypertension
|
|
|
α- Clonidine adverse effects?
|
Typical sympathetic nervous system depression (nasal congestion, postural hypotension, dry mouth)
|
|
|
What's a problem when stopping clonidine?
|
“rebound” hypertension
|
|
|
What's the therapeutic use of epinephrine?
|
Bronchospasms, anaphylactic shock, cardiac arrest, open angle glaucoma, local anesthetic (adjunct)
|
|
|
What's the CV response to epinephrine?
|
low doses – similar to isoproterenol (β1 and β2 = ↓periph resistance and diastolic BP with ↑HR and no change in MAP)
high doses – similar to norepinephrine (α1 and β1=↑ BP, esp systolic but ↓HR) |
|
|
What other responses occur with epinepherine?
|
airways – significant dilation (β2)
gut – transient ↓ motility (β2) bladder – relax detrusor muscle (β2), contract sphincter muscle (α1) uterus – relaxation (β2) |
|
|
What are the metabolic responses that occur with epinepherine?
|
increased glycogenolysis
increased lipolysis (due to beta1) |
|
|
Routes for epinepherine?
|
intravenous, subcutaneous, inhalation, intracardiac, topical
|
|
|
Epinepherine side effects?
|
fear, anxiety, restlessness, palpitations (secondary to cardiovascular effects)
cerebral hemorrhage, cardiac arrhythmias |
|
|
Therapeutic use of norepinephrine?
|
(limited) hypotension (shock)
|
|
|
What are the CV responses with norepinepherine?
|
↑CO from ↑contractility (β1)
↓HR from reflex ↑parasymp tone vasoconstriction (α1) ↑systolic/diastolic/pulse pressure ↑MAP |
|
|
What other responses occur with norepinepherine?
|
airways, gut, uterus - not much effect (not many α receptors).
iris – contract radial muscles = mydriasis bladder – contract sphincter muscle (promotes filling) |
|
|
What are the metabolic responses that occur with norepinepherine?
|
↑glycogenolysis (skeletal muscle)
↑lipolysis (adipose tissue) |
|
|
Routes for norepinepherine?
|
IV
|
|
|
Norepinephrine side effects?
|
fear, anxiety, restlessness, palpitations (secondary to cardiovascular effects)
cerebral hemorrhage, cardiac arrhythmias |
|
|
Therapeutic use of Dopamine?
|
cadiogenic shock, heart failure
|
|
|
What are the CV responses with Dopamine?
|
*Low doses activate D1/5= inc renal blood flow and urine product
*Intermed doses activate β1= inc CO *High doses activate α1= vasoconstriction and inc BP |
|
|
What other responses occur with Dopamine?
|
*Involved in controlling motor movement in the basal ganglia
*Inhibits prolactin secretion in the anterior pituitary |
|
|
Routes for Dopamine?
|
IV
|
|
|
Other dopamine agonists/mimetics?
|
fenoldopam, bromocriptine, levodopa
|
|
|
Therapeutic use of Isoproterenol?
|
bradycardia (heart block, cardiac arrest), bronchospasms
|
|
|
What are the CV responses with Isoproterenol?
|
*↑CO due to ↑HR/contractility (β1)
*Vasodilation (β2) *↑systolic and pulse pressure, ↓diastolic = slight ↓MAP |
|
|
What other responses occur with Isoproterenol?
|
airways – significant dilation
gut – transient decrease in motility bladder – relaxation of detrusor muscle (promotes filling) uterus – relaxation |
|
|
What are the metabolic responses that occur with Isoproterenol?
|
increased glycogenolysis
increased lipolysis (beta 1 and 3) |
|
|
Routes for Isoproterenol?
|
IV, subcutaneous
|
|
|
Isoproterenol side effects?
|
fear, anxiety, restlessness, palpitations (secondary to cardiovascular effects)
cerebral hemorrhage, cardiac arrhythmias |
|
|
(±) Dobutamine mechanism of action?
|
(+) – selective activation of β1 receptors, α1 antagonist
(-) – α1 agonist |
|
|
(±) Dobutamine pharmacologic responses?
|
↑CO (β1) primarily through ↑contractility
↑systolic and pulse pressure (little change in diastolic pressure) = ↑MAP |
|
|
(±) Dobutamine route of administration?
|
IV
|
|
|
(±) Dobutamine therapeutic uses?
|
cardiogenic shock, acute heart failure
|
|
|
other selective β1 agonists?
|
prenalterol
|
|
|
terbutaline mechanism of action?
|
selective activation of β2 receptors
*not a substrate for COMT = long duration of action |
|
|
terbutaline pharmacologic responses?
|
smooth muscle relaxation, especially airways
|
|
|
terbutaline route of administration?
|
oral, subcutaneous, inhalation, intravenous
|
|
|
terbutaline therapeutic uses?
|
obstructive airway diseases, acute bronchospasms
|
|
|
other useful β2 selective agonists?
|
metaproterenol, albuterol, ritodrine
|
|
|
oxymetazoline mechanism of action?
|
selective activation of α receptors (α1 and α2)
|
|
|
oxymetazoline pharmacologic responses?
|
smooth muscle contraction, especially vascular
|
|
|
oxymetazoline route of administration?
|
topical (minimizes systemic effects)
|
|
|
oxymetazoline therapeutic uses?
|
nasal decongestant
|
|
|
other useful imidazolines?
|
tetrahydrozoline, naphazoline, xylometazoline
|
|
|
phenylephrine mechanism of action?
|
selective activation of α1 receptors
|
|
|
phenylephrine pharmacologic responses?
|
smooth muscle contraction
|
|
|
phenylephrine route of administration?
|
intravenous, topical (nasal, ophthalmic)
|
|
|
phenylephrine therapeutic uses?
|
vasopressor, nasal decongestant, mydriatic
|
|
|
other α1 selective agonists?
|
midodrine, methoxamine, metaraminol, mephentermine
|
|
|
clonidine mechanism of action?
|
selective activation of α2 receptors
|
|
|
clonidine pharmacologic responses?
|
reduced sympathetic tone (central effect), inhibits NE release
|
|
|
clonidine route of administration?
|
oral
|
|
|
clonidine therapeutic uses?
|
hypertension, reducing sympathetic responses associated with withdrawl, analgesic adjuvant
|
|
|
other α2 selective agonists?
|
α-methyldopa, guanfacine, guanabenz, dexmedetomidine
|
|
|
ephedrine mechanism of action?
|
mixed acting sympathomimetic: stimulates release of NE, also causes direct activation of α and β receptors
|
|
|
ephedrine pharmacologic responses?
|
vasoconstriction, positive inotropy, bronchodilation, CNS stimulation
|
|
|
ephedrine route of administration?
|
oral
|
|
|
ephedrine therapeutic uses?
|
bronchodilator, nasal decongestant, mydriatic, narcolepsy
|
|
|
other mixed acting sympathomimetics?
|
pseudoephedrine, phenylpropanolamine
|
|
|
amphetamine mechanism of action?
|
indirectly acting sympathomimetic; stimulates the release of neurotransmitters (central and peripheral)
|
|
|
amphetamine pharmacologic responses?
|
Inc cardiac output
vasoconstriction - inc systolic, diastolic, and MAP contract bladder sphincter CNS stimulation |
|
|
amphetamine toxicity?
|
*CNS effects - restlessness, dizziness, tremor, irritability, anxiety, delirium, paranoia, hallucinations
*CV effects – severe HTN |
|
|
amphetamine therapeutic uses?
|
narcolepsy, ADHD, appetite suppression, enuresis, incontinence
|
|
|
other indirectly acting sympathomimetics?
|
modafinil, dextroamphetamine, methampetamine, benzphetamine, methylphenidate, tyramine
|
