Week 2: Pharmacology
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- What is phase 1 block?
- overstimulation of Nicotinic (cholinergic)stimulation.
- What can block the nicotinic receptors at the skeletal muscle?
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1. Tubocurarine
2. Trimethaphan - 1. What is the mechanism of Vasodialation of endothelial cells by muscarinic cholinergic agonist?
- 1. Release of NO (activation EDRF)
- Alpha are always exciting except for?
- GI tract
- Location of alpha 1 and alpha 2?
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1. Mostly postjunctional
2. Mainly prejunctional (except postjunctional at plt, smooth muscle, and adipocytes) - what are the primary effects of Beta 1 adnergic receptors?
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1. Heart rate
2. Lipolysis
3. Renin secretion - Isoproterenol has a greater effect on what receptor over Epi and NE?
- Beta 1 (Iso also stimulates Beta 2)
- Function of Beta 2 adrenergic receptors?
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1.Vasodilation
2. Bronchial smooth muscle relaxation
3. GI relaxation -
Bethanechol, Carbachol and Pilocarpine are all what?
Which is the odd one out of the three? and why -
1.Muscarinic agonists
2. Carbachol- also stimulates both Muscarinic and Nicotinic - Effects of Parasympathetic in the Eyes?
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1. Miosis
2. Reduces intraocular pressure - Drugs that will cause Miosis and reduce intraocular pressure?
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Bethanechol, carbachol
most importantly Pilocarpine - What is the effects of alpha-adrenergic agonist on the cilliary muscle?
- None (it will contract just the iris radial m.causing mydrasis)
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What are the therapeutic effects of most Parasympathetic drugs?
Eyes
GI
Urinary tract -
1. Eyes - Glacoma (increase incidence of caratact)
2. GI - improves peristalsis (esp after surgery, gastric atony and postoperative abdominal distention)
3. Urinary tract - Improves urination
4. - What parasympathetic M. agonist can be used to diagonose Brochial hypersensitivity and asthmatic condition (constrict the bronchials)
- Methacholine
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What primary drug is used for the treatment of Open-angle glaucoma?
Any others used? -
1. Pilocarpine
2. Carbachol is used if pilocarpine is ineffective
3. B-adrenergic receptor antagonist (timolol and betaxolol)
Or CA inhibitor - Acetazolamide - Ach agonists are contraindicated in what conditions?
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1. Asthma
2. Heart disease
3. Peptic ulcer (increase secretions)
4. Parkinsonian disease (increase Ach) - What is Edrophonium?
- Short acting AchE inhibitor. Used in the Tensilon test for Mys. Gravis diagnosis
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Difference between Neostigmine and Physotigmine?
What are they? -
1.Neostigmine - poorly absorbed (GI, negligible in CNS)
Physotigmine - Well absorbed (GI,Enters CNS)
2. Reversible Long acting AchE - Name 2 irreversible Long acting AchE inhibitor?
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1. Echothiophate and Isoflurophate
Echo is poor absorbed
Isoflurophate is highly lipid solube and well absorbed even in skin - Name the antidote for insecticide or nerve gas poisoning (Ach E reactivator)?
- Pralidoxime (but ineffective in CNS)
- What parasympathetic drugs cause mydrasis (pupil dilation) and cycloplegia(loss of accomodation and paralysis of ciliary muscle)?
- Muscarinic -receptor antagonist e.g Atropine,Scopolamine et.c
- Is Atropine short or long acting - Muscarinic Receptor anatgonist?
- Long acting
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For each organ system list the therapeutic importance of Muscarinic Antagonist
Eye
Heart
Stomach
GI
Urinary
CNS (2 things) -
1. Eye - Opthalmoscopic exam
2. Heart- Acute MI with bradycardia
3. Stomach - Treat peptic ulcer (reduce acid) but there are better drugs now
4. GI - mild diarrhea
5. Treat Urinary Urgency
6. Parkinsonian and Motion Sickness -
what is difference between Tubocurarine, succinylcholine and Trimethaphan?
What do they all have in common? -
1. Succinylcholine is an Nictotinic depolorizing agonist
Tubocurarine and Trimethaphan are both Nicotininc antagonist
2. All are Neuromuscular blockers (Trimethaphan - blocks just the ganglionic nicotinic Receptors) - What is another drug you can use for Ach E inhibitor poisoning (aside from AchE regenrator Pralidoxime)?
- Atropine (Muscarinic blocker)
- Reversibly what classes of drugs can be used to treat Muscarinic antagonist (Atropine, scopolamine) overdose?
- Physostigmine(tertiary, e.g atropine) and Neostigmine (quaternery)
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what ANS system does Ganglionic block drugs (ganglionic nicotinic antagonist)?
Can they be used for what? may cause what?
Name a drug with this properties? -
1. Non depolarizing blockade of both P-ANS and S-ANS
2. Decrease blood pressure (by reducing sympathetic tone in vasculature)
3. Trimethaphan -
Trimethaphan - is what kind of drug?
Simulates the release of ------ and causing -----, -----, ----. -
1. Peripheral ganglionic nicotinic blocker.
2. Histamine, and causes Flushing, dizzines and headaches - Name types of muscle relaxants and give a few drug examples?
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1. Neuromuscular junction blocker - Ach R antagonist
A. Depolarizing:Succinylcholine
B. Non-depolarizing: Tubocurarine
2. Spasmolytic drugs - mimic GABA in the CNS (Benzodiazapine) or some drugs interfere with release of Ca2+ in skeletal muscle (Dantrolene) - Tubocurarine, Atracurium, mivacurium, Pancuronium,Vecuronium and Rapacuronium are all -------- ?
- Non-depolarizing Neuromuscular blocking drugs (muscle paralysis)
- Name a drug - that will be great for muscle paralysis (but note they have to be on a mechanical ventilator or else respiratory failure)?
- Depolarizing or Non-depolaring neuromuscular blockers.
- What is the problem with Neuromuscular blocking drugs?(hint not at NMJ)
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1. Histamine release: may cause vasodialation and bronchospasms
2. Prolonged apnea (paralysis) - Name two drugs that may potentiate the effects of NMJ (nicotinic) blockers? (because they inhibiting Ach release)
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1. Aminoglycoside
2. Lincomycin - Is Succinylcholine broken down by AchE?
- 1. Yes but much slower.
- Describe the reversal of succinylcholine blockade
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1. Phase 1: due slow metabolization of succinylcholine
Muscle is depolarized(inital contraction), then flaccid paralysis
2. Phase 2: In repolarization, Ach still has no effect on the AchR. - Adverse effects of succinylcholine?
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1. Hyperkalemia
2. Malignant hyperthermia (likely to occur than succinylcholine than Halothane) - Tx of Malignant hyperthermia?
- Dantrolene
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1. Name a spasmolytic drugs?
2. Best used for?
3. Name their Mechanism and primary target site? -
1. Dantrolene and Baclofen
2. Spasms (seen in cerebral palsy, MS, stroke)
Muscle paralysis: Malignant hyperthermia
3. Ca2+ release in SR(dantrolene)and GABA-receptor (Baclofen)
Benzodiazepine also fall in this group (their main func is sedation and antianxiety) - Properties of beta 1 receptors?
- increase the rate and force of heart contractions (by increasing the conduction in the AV node and lowers refractory peroid).
- Name a spasmolytic drugs? Best used for? Name their primary target site?
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1. Dantrolene and Baclofen
2. Spasms (seen in cerebral palsy, MS, stroke)
Muscle paralysis: Malignant hyperthermia
3. Ca2+ release in SR(dantrolene)and GABA-receptor (Baclofen)
Benzodiazepine also fall in this group (their main func is sedation and antianxiety) - Name drugs used to reduce intraocular pressure by the reduction of aqueous humor production?
- Epinephrine and B-receptor antagonist
- Why at low doses of epinephrine do we not get reflexive tachycardia?
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1. Increase in Heart rate (Beta1) and vasodilation (Beta1 -reduction in TPR)
= No change in mean blood pressure
(HR increased, increased systolic, low diastolic) - Is NE used therapeutically?
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Nope - not really
(has less beta2 activity - so increase TPR and increase diastolic) - Name the main Beta1 agonist?
- Isoproterenol and Albuterol (same effect on Beta2)
- Name the main 3 Beta non-selective agonist drugs?
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1. Isoproterenol
2. Albuterol
3. Dobutamine -
Why is albuterol great for asthma?
Name other drugs like it? -
1.Because it works mostly on the Beta2 receptors (lungs and blood)
Beta 2agonist
2. Terbutaline (emergency drug for status asthmaticus), Albuterol -
Distinguish the potency of each drug on Beta 1 vs Beta 2
Dobutamine
Isoproterenol
Albuterol (Terbutamine) -
Dobutamine: B1>B2
Isoproterenol: B2=B1
Albuterol (Terbutamine): B2>B1 -
Name a common alpha-adrenegic agonist and function?
Potency is greater for which alpha receptor? -
1.Phenylephrine
2. Increase TPR by vasoconstriction
2. a1>a2 - What is Clonidine? The clinical effect of this drug?
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1.alpha2 prejunctional agonist (reduces the release of NE)
2. Lower BP - What drug will you like to use in short-hypotensive emergencies?
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1. Norepinephrine
2.Epedrine - What drug will you like to use in Cardiogenic or septic shock? Why?
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1. Dobutamine
2. Dopamine
- Increases CO,HR (B1), low vasoconstrictive
- Dopamine especially for the renal perfusion (D1). - What Catecholamine might you use for the treatment of anaphylactic shock?Why
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1.Epinephrine
2. Reverse the hypotension and angioedema and maintain BP - What Drug might you use for Congestive heart failure?
- Dobutamine (apparently it stimulates B1 but the contractility property as opposed to the Heart Rate as seen with Isoproterenol)
- For Temp. emergency treatment of cardiac arrest and heart block (Stokes-Adams syndrome)? Why
- Isoproterenol and Epinephrine because they increase ventricular automaticity and rate and increase AV conduction via B1
- What drug is used for the diagnosis of Horner's syndrome?
- Hydroxyamphetamine (miosis, anhydrosis)
- What drug can be used to relax the Uterus and suppress premature labor?
- Terbutaline (beta2 agonist) and Ritodrine
- Name some alpha antagonist? Main therapies?
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1. Phentolamine (a1=a2)
2. Prazosin (a1)
3. Phenoxybenzamine (irreversible a1 antagonist)
A. Hypertension
B. Pheochromocytoma - Difference between Phentolamine, Phenoxybenzamine (a) and Prazosin, Terazosin,doxasin (b).
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a.The former are non-selective alpha antagonist
b. a1 selective antagonist - What drugs will you use to treat essential hypertension, urinary rentention in BPH and Raynaud's phenomenoma?
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Prazosin, Terazosin and Doxazosine
(all a1 selective antagonist)
Relax the bladder, vasodilated the blood vessels peripherally - What is a key side effect of prazosin, terazosin and doxazosin?
- Postural hypotension
- What are the cardiovascular effects of Beta-antagonist?
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1. Lower blood pressure
A. reduce HR
B. Shorten AV node time and supress automaticity
C. May Increase TPR
D. Reduce Renin release - What are the respiratory and ocular side effects of Beta antagonist?
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1. Increase airway resistance
2. Reduce intra ocular pressure (Timolol used for glaucoma) -
What are the Endocrine and metabolic side effects of Beta antagonist?
Why should we becareful with the use of propanolol in diabetics? -
1. Decrease lipolysis
2. Decrease Gluconeogenesis (may increase the hypoglycemic effects of insulin)
3.Propanolol should be used carefully with diabetics. May mask tachycardia due to hypoglycemia - What drug long-term treatment of hypertension?
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1. Propranolol (not useful for hypertensive crisis)
With other drugs -diuretics and low salt diet - What drug is used to treat Supraventricular and ventricular arrhythmias?
- Propanolol
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1.Hexamethonium is what type of drug?
2.Why would Hexamethonium not cause Reflex tachycardia? -
1. Nicotinic antagonist
2. Will cause vasodilation but also inhibit the baroreceptor functions. - What drug prevents the reuptake of choline in cholinergic cells?
- Hemicholinium
- What drug prevents the conversion and packaging of Dopamine to Norepinephrine - in noradrenergic nerves?
- Reserpine
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What drug inhibits the release of NE? What drug cause the release of NE?
What drugs (2) blocks the reuptake of NE? -
1. Guanethidine
2. Amphetamine
3. Cocaine and TCA (tricyclic antidepressants) - What the Si/Sx of AchE inhibitor poisioning? DUMBBELSS
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Diarrhea and Urination
Miosis and Bronchospasm
Bradycardia and Excitated skeletal m.
Lacrimation and Sweating and Salivation -
Which Diuretics cause
Acidosis?
Alkalosis? -
1. Acidosis: Loop diuretics and Thiazides
2. Alkalosis: Carbonic anhydrase and K+ sparing diuretics -
What drugs are similar in mechanism to Thiazides but are more potent?
How may they be better than thiazide? -
1.Quinazlinones and Indolines
2. May be effective in the presence of some renal impairment - Summary of the therapeutic benefits of thiazide?
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1. Prefered Tx: HTN in with nl renal func
2. Ca2+ stones: idiopathic hypercalciuria
3.Diabetes insipidus
4. Combo (edema,cirrhosis or nephrotic) -
What type of diet is recommended for a patient on thiazide?
To avoid what Six/Sx of hypo-K,Hypo-Na,Hypo-Cl? -
1. Diet high K+
2. CNS disturbances, cardiac arrhythmias
and increased sensitivity to digitalis - Does thiazide help with Gout Sx?
- No, may increase Urate serum levels
- What is the effect of thiazide in patients with diabetes?
- May cause hyperglycemia
- Give me an example of a "high ceiling diuretic"
- Loop diuretic
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1.What transporter is blocked by loop diuretics and location of action?
2. What key electrolytes are lost?
3.Clincially used for? -
1.Na+,K+,2Cl- of the Thick ascending limp of loop of henle.
2. Na,K,Cl and Ca2+ and Mg+
3. Edema,HTN,Hyper-Ca2+ - Loop diuretics causes dose -related ototoxicity - So with this property what will be a bad combination with loop diuretic?
- Loop diuretic(furosemide, erthacryin) and Aminoglycosides
- Name the 2 types of K+-sparing drugs and examples of them?
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1. Aldosterone inhibitor-spirolactone
2. non-Aldosterone inhibitor - Amiloride and Triamterene -
What are the adverse effects of all the K+ sparing agents?
Spirolactone-specific side effects? -
1. Hyper-K
2. Hyper-K, Endocrine effects (gynecomastia, antiandrogen efxs) -
Location of receptor of adolsterone and spirolactone?
Location of the receptor for Amiloride and Triamterene? - Both in the cortical collecting tubule.
- What electrolytes are involved when Spirolactone is used?
-
K and H secretion is prevented
Na reabsorption is prevented
Serum pic: Hyper-K, Metabolic acidosis, and Hypo-Na - Mechanism of Amiloride and Triamterene?
- Prevents just Na+ reabsorption and prevents K+ excretion
- Name the drug used for glaucoma, Urinary alkalinization, metabolic alkalosis and altitude sickness?
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Carbonic Anhydrase (sulfonamide derivatives)
CA prevents the exchange of H+, with Na+ and HCO3- -
Name an important Carbonic Anhydrase?
Side effects? -
1. Acetazolamide
2. M. Acidosis, NH3 toxicity, Hyper-Cl, sulfa allergy - Name a few Osmotic agents
- Mannitol, glycerin and isosorbide
- Mannitol contraindicated in what?
- Anuria and CHF (may cause pulmonary edema)
- Name an ADH analog
- Vassopressin and Desmopressin
- Clinical use of ADH?
- Central Diabetes insipidus and Nocturnal enuresis
- Name drugs that increase the release of ADH? and enhance the action of ADH?
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1.Clofibrate (increase ADH release centrally)
2.Chlorpropamide, Acetominophen, indomethacin(by reducing the production of PGE and enhance the action of ADH) - Name the alpha agonist used for glaucoma?
- Epinephrine (outflow, mydriasis) and Brimonidine (decrease synthesis)
- what family of drugs will cause decreased aqueous humor production?
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1. Bromonidine (alpha agonist)
2. Beta-blockers - Timolol, betaxolol, Carteolol - What will cause increase outflow of aqueous humor in glaucoma tx?
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1. Epinephrine (as an alpha agonist)
2. Cholinomimetics: Pilocarpine, Carbachol, Physostigmine,echothiophate
3. Prostagladin - Latanoprost (darkens the color of iris) - what is used for glaucoma by increasing outflow - it darkens the iris(browning)?
- Prostagladin - Latanoprost
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Amantadine is used for influenza but it is also used for another condition?
Mechanism? -
1. Parkinson
2. Increases the release of dopamine - Name an MAO type B inhibitor for the Tx of Parkinson?
- Selegiline
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Why use Benztropine in Parkinson?
What are the therapeutic effects? -
1.To inhibit Ach effect.
2. Improves tremor and rigidity ( no effect on bradykinesia- slow movement) - Aside from Malignant hyperthermia - what is Dantrolene is for clinically to treat? (also dopamine agonist)
- Neuroleptic malignant syndrome - rigidity, autonomic instability, hyperpyrexia