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Pharm 2.1 Flashcards

1
Q
A
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2
Q

Where do CA inhibitors have action? How do they work?

A

Work in proximal tubules of kidney as diuretics. Also in eye and brain (glaucoma and cerebral edema)Inhibition of CA in kidney -> diuresis by increasing passage of H2CO3 in urine (no water is freed in CA rxn). Also, reduced bicarb resorption -> metabolic acidosis.(review CA function)

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3
Q

Dorzolamide

A

CA inhibitor used in treatment of glaucoma. Topical ap to eye.

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4
Q

Why must mannitol be administered IV?

A

It does not permeate the luminal membrane (no reabsorption)If given orally -> osmotic diarrheaIV produces profound diuresis (osmotic diuresis)

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5
Q

Describe the action of furosemide

A

Loop diuretic. It directly inhibits NKCC2 symporter in the thick ascending limb of the Loop of Henley.Results in decreased reabsorption of Na (higher luminal [Na]) and increased water loss.**Increased Na+ delivery to the collecting tubule -> increased K+ loss and can lead to hypokalemia

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6
Q

Where are juxtaglomerular cells located and what do they do?

A

In afferent arteriole to glomerulus.Secrete renin in response to:-Decreased renal perfusion pressure-B1 adrenergic stimulation-Decreased Na+ load in distal tubule

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7
Q

Why are loop diuretics often administered with an ACE inhibitor?

A

Macula densa cells are sensitve to intracellular [Na] and use the furosemide sensitive NKCC2 symporter.Loop diuretic -> lowered intracellular [Na] -> increased renin secretion via juxtaglomerular cells.ACE inhibitor counteracts this effect by preventing formation of Angiotensin-II

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8
Q

What are examples of thiazide diuretics, how and where do they work?

A

Hydrochlorothiazide and ChlorthalidoneInhibit the Na/Cl symporter (NCC) in the distal convoluted tubule. **Increased Na+ load in collecting duct -> Increased K+ loss

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9
Q

Where does PTH have action and what is its effect?

A

Works in the distal convoluted tubule to increase Ca++ reabsorption. Increases activity of the Na+/Ca++ transporter

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10
Q

What are examples of potassium sparing diuretics and what are their mechanisms of action?

A

Amiloride: Inhibits ENaC (Na+ channel of collecting duct)Spironolactone: Competitive antagonist of aldosterone (prevent up-regulation of Na/K ATPase in distal tubule and collecting duct.Both reduce loss of K+ while increasing loss of Na+ and H2OMild diuresis. May be used to blunt K+ diminishing effects of loop and thiazided diuretics.

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11
Q

What effect does Lithium have on the kidney?

A

Decreases expression of Aquaporin 2 in response to ADH -> Nephrogenic Diabetes Insipidus

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12
Q

Bumetanide, Ethacrynic acid, Torsemide

A

Loop diuretics

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13
Q

What is furosemides half-life and how is it eliminated?

A

t1/2 = ~1.5 hrRenal elimination- tubular secretion and filtration

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14
Q

How is furosemide useful in treatment of CHF?

A

Reduction of preload (decrease fluid volume)Direct effect on reducing pulmonary congestionIncrease renal blood flow** reduces LV pressure and pulmonary congestion before diuretic action**

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15
Q

What are loop diuretic side effects?

A

Hypokalemia and alkalosisHypomagnesemiaHyperuricemia (hypovolemia induced reabsorption of urea in prox tubule) and gouty attacksDose-related hearing loss, allergic reactions

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16
Q

What is the effect of NSAID use on loop diuretic effectiveness?

A

Decreases effectiveness of loop diureticsInhibition of COX1 / COX2 -> decreased PGE expression in kidney where there are many dependent mechanismsNSAIDs can -> kidney failure, esp. in elderly population

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17
Q

What are the short / long term effects of thiazide diuretic use?

A

Initially: ECV decrease, decrease in COLong term: reduction in peripheral resistance - decrease in intracellular Na -> decreased in intracellular Ca++ (transport by Na/Ca exchanger) -> smooth muscle more refractory to contractile stimuli

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18
Q

How does chlorthalidone differ from hydrochlorothiazide?

A

It is more potent and has a longer half-life (40 hr. vs. 15hr.)

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19
Q

What conditions other than hypertension are thiazide diuretics helpful in treating?

A

Idiopathic hypercalciuria with kidney stones - thiazides -> reduced intracellular Na+ in distal convoluted tubule cells. Na/Ca exchanger then pumps Na into cell and Ca out - driving Ca reabsorption from lumenNephrogenic Diabetes insipidus (including that caused by Li)- unknown mechanism

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20
Q

What are potential side effects of thiazide diuretics?

A

hypokalemic metabolic alkalosishyperuricemiahyperglycemiahypercholesterolemiahyponatremia - potentially fatal in predisposed individuals

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21
Q

What is spironolactone and what is it used for?

A

Competitive antagonist of aldosterone.Helpful in severe CHF - reduced morbidity and mortality when used with ACE inhibitor- antagonizes aldosterone’s pro-fibrosis effect on heartPotassium conservation when used in concert with loop and thiazide diuretics

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22
Q

What are the side effects of spironolactone?

A

HyperkalemiaEndocrine like effects: gynecomastia, impotence, peptic ulcersIncreased risk of breast cancer

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23
Q

What are the uses of Amiloride?

A

Limit diuretic induced hypokalemic alkalosisUsed in Li induced diabetes insipidus - limits Li’s ability to interfere w/ aquaporin 2 expression

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24
Q

What are the effects of Angiotensin II?

A

-increased arterial pressure-increased SS tone (via direct action on CNS - area posterna)-Na and fluid retention-Aldosterone release-Vascular and Cardiac remodeling-all via AT-1 receptor

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25
Q

Enalapril and Lisinopril are what class drugs?

A

ACE inhibitor-pril

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26
Q

What are the primary desirable effects of ACE inhibitors?

A

decrease peripheral resistance without increasing HRreduction of cardiac and vascular remodelingnatriuresisIn CHF patients - reduce preload and afterload -> increased CO and SV

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27
Q

How is use of an ACE inhibitor useful in chronic renal disease?

A

Decreases resistance in efferent glomerular arteriole -> decreased glomerular pressure (decrease GFR) and improves renal BFReduces proteinuria and improves renal function (natriuresis)

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28
Q

ACE inhibitor pharmacokinetics

A

taken as prodrug - metabolized to active state in the liver (ester bond cleavage)subject to first pass metabolismEnalapril and lisinopril - t1/2 = 12 hrs.

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29
Q

What are the side effects of ACE inhibitors?

A

Initial severe hypotension in patients w/ high renin activityPersistent dry cough (increased bradykinin and lung PGE)hyperkalemia (w/ NSAIDs, K-sparing diuretics, B-blockers)acute renal failure in pts w/ bilateral renal artery stenosisteratogenic

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30
Q

What is aliskiren? Uses and side effects?

A

Renin inhibitor - reduces angiotensin II syntheffective antihypertensive ( as good as thiazide + Ca channel blocker combo)Cough and GI disturbancesTeratogenicDecreases serum conc. of furosemideCyclosporin increases blood concentration of aliskiren

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31
Q

Losartan and Valsartan - what kind of drugs?

A

ARB- AT-1 receptor blockersSimilar properties to ACE inhibitorsDo not produce ACE inhibitor cough - may be used as a replacement optionshould not be used during pregnancy

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32
Q

What are 4 important effects of Beta Blockers?

A
  1. decreased cardiac excitability2. antihypertensive (reduced TPR by decreased renin release)3. reduced cardiac inotropy (force of contraction)4. reduced cardiac remodeling
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33
Q

Propanolol

A

Non-specific Beta 1 and 2 blockerUndergoes 1st pass metabolismnegative effects on serum lipid profiles

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34
Q

Metoprolol

A

Selective beta blockerLow dose: preferentially blocks B1CHF: increases longevity and decreases hospital admission timeContraindicated in COPD / asthma as it has some effect on B2 - risk of bronchospasm

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35
Q

Bisprolol

A

B1 selective blocker

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36
Q

Carvedilol

A

non-selective Beta and alpha-1 blockerblocks B1, B2 and a1

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37
Q

Atenolol

A

B1 selective antagonistDoes not undergo first pass metabolismNot for use in asthmatic patients

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38
Q

Pindolol

A

Non-selective Beta blockerB1 partial agonist - stimulation before blockade-less cardiodepression and less effect on serum lipidsNot for use in MI patients

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39
Q

Labetolol

A

Non-selective Beta antagonist, and alpha-1 antagonistHas beta sympathomimetic activityReduces TPR with less effect on HR and CO. Does not effect serum lipidsOnly B-blocker used in mgt. of simple HTN.Preferred drug for HTN in pregnant women.

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40
Q

Carvedilol

A

Non-selective B-antagonist and a-1 antagonist (B-activity more prominent)Inhibits Oxygen radical mediated lipid peroxidation and reduces vascular smooth muscle mitogenesis - relevant to use in CHFQuinidine (anti-arrhythmic) and fluoxetine (Prozac) compete for metabolism by CYP2D6

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41
Q

Esmolol

A

Ultra short acting selective Beta-1 blocker (t1/2 = ~10min)IV admin for supraventricular arrhythmia, acute hypertension, and myocardial ischemia in acutely ill patients

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42
Q

Sotalol

A

non-selective Beta blockerK+ channel blockerUsed as anti-arrhythmic

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43
Q

Nebivolol

A

Selective B-1 antagonistMetabolized to B-2 AGONISTB2 activity: NO production, lower TPR3rd gen Beta blocker w/ secondary anti-hypertensive effects

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44
Q

Beta blocker untoward effects

A

Hypotension, bradycardia, heart failureB2 blockade - bronchospasm (esp. in asthmatics)CNS: depression, fatigue, insomnia, hallucinations, impotenceHypoglycemia (B2 blockade) - may mask symptoms (hunger, tremor, but not sweating)Lipids: elevate triglycerides, lower HDL, decrease HDL/LDLWithdrawal - remove slowly (upreg of receptors) - may precipitate hypertensive emergencyNSAIDs reduce anti-hypertensive effectsBBs may be less effective in African-Americans

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45
Q

Methyldopa

A

Selective alpha-2 agonistactive transport into brain, metabolism to methyl norepinepherineMost importantly active at NTS in medulla -> decreased sympathetic outflow, reduction of vasomotor toneEffect: reduction of peripheral resistance w/o effect on HR, CO, RBF, renin, or plasma volumeSide effects: hemolytic anemia (20% develop positive Coomb’s test, ~5% actual hemolytic anemia), sedation, drymouth, reduced libido, parkinsonian signsEffective anti-hypertensive, esp. when coupled w/ diuretic. May be used during pregnancy.

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46
Q

Clonidine

A

Selective A2 agonistInhibits central release of NE, reduction in SS outflow from NTS.Also activates imidazoline receptors in rostral ventrolateral medulla -> lowered BPNo effect on HR, CO, RBF, renin, or plasma volumeUsed transdermally to blunt SS activity caused by some vasodilatorsAnti-hypertensive activity potentiated w/ diuretic useDo not give to depressed patients, withdraw if depression occursSide effects: sedation, dry mouth, postural hypotension, impotence, bradycardia, sinus arrest in pts. w/ defect of SA node, AV block in pts. w/ AV node defect.Discontinue use slowly.

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47
Q

Phentolamine and Phenoxybenzamine

A

Non-selective Alpha blockersUsed to treat pheochromocytoma and impotence

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48
Q

Reserpine

A

Blocks vesicular storage of NE in nerve terminalsReduces peripheral resistance and COat high doses: depletion of central amine stores -> parkinson’s symptoms, depression, sedationInfrequently used. If used, often low dose coupled w/ diuretic for HTN.

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49
Q

Guanethidine

A

No central action (does not cross BBB). Peripherally: replaces NE in synaptic vessicles. Stabilizes membrane (anesthetic-like quality), impairing release of NE.Reduces peripheral resistance. Side effects: postural hypotension, bradycardia, depressed CO, diarrhea, impaired ejaculation.rarely used

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50
Q

Guanabenz and guanfacine

A

Similar to clonidineRarely used.

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51
Q

Prazosin

A

Selective alpha-1 antagonist (-osin drugs)Lowers BP by decreased arteriolar resistance, increased venous capacitanceInitial drop in TPR, increase in HR, CO and renin - this effect subsides in timeAlso used for prostatic urinary symptoms (esp. tamsulosin) - inhibit prostatic contraction. Side effects: orthostatic hypotension, doxazosin linked to HFNot recommended as monotherapy for HTN. Often given w/ diuretic or Beta blocker

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52
Q

What are the two main categories of Ca++ channel blockers and how do they differ?

A

Dihydropyridine (nifedipine and amlodipine)and Non-dihydropyridine (diltiazem, verapamil)Dihydropyridine: bind channel in open state - slow Ca++ entry, do not affect rate of recovery - preferential binding in arterial smooth muscle.Non-dihyrdopyridine: decrease both Ca++ entry and rate of recovery. Cardioselective - decrease inotropism and CW. Treatment of angina.

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53
Q

Do Ca++ channel blockers affect preload or afterload more prominently?

A

Afterload. No effect on venous bed, so no effect on preload.

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54
Q

What class of calcium channel blocker is used in the treatment of hypertension?

A

Dihydropyridines - prominent reduction in smooth muscle tone -> decrease in TPR

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55
Q

What class of Ca++ channel blocker is more useful in treatment of SVT and why?

A

Supraventricular tachycardia: Non-dihydropyridines (verapamil and diltiazam) - affect both Ca++ flow and rate of recovery - strong impact on AV node conduction** because of decrease in contractility and AV conduction, do not pair non-dihydropyridines with Beta blockers. Can -> bradycardia, heart block, death

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56
Q

Nimodipine and application

A

Dihydropyridine - affects cerebral vessels more than other DHPs - decreases morbidity in subarachnoid hemorrhage patients.

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57
Q

What DHP drugs are best suited to treatment of emergency HTN?

A

Nicardipine and ClevidipineClevidipine has shorter half-life

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58
Q

What DHP is favored for use in a HF setting? Why?

A

Amlodipine - long acting, slow onset. 40 hr. half-life (vs. fast-action of nifedipine, 3 hr. half-life)reduces morbidity in patients w/ LV dysfunction

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59
Q

Calcium channel blocker metabolism and side effects

A

Metabolized in liver (P450) Rifampin (antibiotic) and phenytoin (anti-seizure) increase rate of metabolism, Azole antifungals decrease it.Side effects: flushing, peripheral edema, dizziness,

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60
Q

Nondihydropyridine specific side-effects

A

Heart failure, bradycardia, cardiac block, hypotensionVerapamil has a1 blocking property. If paired w/ other a1 blocker (quinidine) -> severe hypotension***Verapamil - decreases renal clearance of digoxin***

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61
Q

Describe the action of NO

A

NO activates guanylyl cyclase -> increased cGMP -> dephosphorylation of myosin light chains and smooth muscle relaxationVeins most sensitive, then arteries, arterioles, pre-capillary sphinctersEnd result is decreased filling pressure, decreased TPR, reduced afterload, improved cardiac perfusion, improved CO and decreased pulmonary congestion

62
Q

Describe 3 types of angina

A

Classic - due to atheromatous obstruction of coronary vesselsVariant - due to coronary vasospasmUnstable - increased coronary artery tone or non-occlusive platelet clots near atherosclerotic plaques

63
Q

What is the benefit of nitrate treatment in various types of angina?

A

Classic: reduction of myocardial O2 consumption: reduced filling pressure and ventricular radius; reduction in IVP, end diastolic VP -> increased perfusion; decreased afterloadVariant: dilation of epidural arteries, redistribution of coronary blood flow to endocardium, prevention of arterial spasmUnstable: decrease in platelet aggregation. Also, reduced myocardial O2 demand and coronary artery dilation

64
Q

What are side-effects of nitrates?

A

Throbbing headache (meningeal artery pulsation), hypotension and reflex tachycardia** action is potentiated w/ PDE-5 inhibitors (viagra) -> profound hypotension, MI***

65
Q

What is a PDE-5 inhibitor?

A

Seldenafil (viagra)inhibits degradation of cGMP by PDE-5 -> sustained action of NO, sustained smooth muscle relaxation

66
Q

Explain the concept of “coronary steal”

A

Coronary arterioles downstream from atherosclerotic plaques area maximally dilated to maximize perfusionAdministration of an arterial dilator has no effect on these, but dilates other, healthy coronary arterioles redirecting blood flow to those areas. This can induce anginal attacks or MI

67
Q

What is hydralazine, what is it used for?

A

Hydralazine relaxes arterial smooth muscle by unknown mechanism.Usually administered w/ a beta blocker and diuretic to treat complex hypertensionUseful in HF that is not responsive to standard treatment (ACE inhibitor, loop diuretic, beta blocker). Used in combo w/ nitrate (isosorbide dinitrate - reduce preload) in this setting to reduce afterload

68
Q

Hydralazine side effects

A

20% of patients develop lupus-like symptoms after ~6mosbecause of this, use is rare.

69
Q

Minoxidil

A

Activates ATP-modulated K+ channel in sm. muscle -> K+ efflux, hyperpolarization and sm. muscle relaxationAlways used w/ beta blocker and diureticRare use for complex HTN that is unresponsive to other therapyMay produce hypertrichosis - use in male pattern baldness

70
Q

Sodium nitroprusside

A

DOC for emergency HTN - arterial vasodilatorreduces preload and afterloadalso used in aortic dissection caseshigh dosing can lead to cyanide / thiocyanate poisoning

71
Q

What is the basic MOA of a local anisthetic?

A

Uncharged (deprotonated) particle must cross the Neuron’s plasma membrane, be protonated, then bind the open Na+ channel.Once bound the drug stabilizes the closed conformation of the channel - prevents AP.

72
Q

What is the basic structure of local anesthetics?

A

Aromatic ring connected by an ester or amide bond to an ionizable group, commonly a tertiary amine.

73
Q

Describe the MOA of local anesthetics

A

Diffuse through membrane in non-protonated state, protonated inside cell, block voltage gated ion channel.Only able to bind when the channel is in OPEN state.Stabilizes the INACTIVE state - no Na+ influx - blocks AP propogation

74
Q

Are local anesthetics weak acids or bases? pKa range? What does a drug’s pKa say about its activity?

A

Weak basespKa 8-9Lower pKa -> faster acting

75
Q

What determines a local anesthetic’s length of action?

A

Affinity for Na+ channel binding site.

76
Q

Why is epinepherine often administered with LA for a nerve block?

A

VasoconstrictionElevation of LA concentration around nerve, decrease amount released in systemic circulation

77
Q

Are ester or amide LA drugs longer lasting? why?

A

Amide Metabolism by hepatic P450 vs. Ester metabolism by plasma pseudocholinesterase. Ester short duration of action.

78
Q

What are side effects of local anesthetics?

A
  1. CNS stim: depression of cortical inhibition pathways -> activity of excitatory pathways. Unbalanced excitation, then depression, restlessness, dizzy, tremors, confusion, resp. depression. Benzodiazepine prophylaxis2. Myocardial depression: same Na+ channel blocked -> decreased conduction velocity, contraction, CO. Also vasodilation (sm. muscle relaxation by all except cocaine)3. Hypersensitivity mostly esters (PABA derivatives)
79
Q

Cocaine

A

Local anesthetic - ester linkage-vasoconstrictor -medium duration of action-high toxicity (reduce catecholamine uptake in CNS and PNS)-addictive (mesolimbic pathway)Topical use only (oral, laryngeal, nasal) - vasoconstrictive action decreases operative bleeding.

80
Q

Procaine (Novocaine)

A

Ester linked LApKa = 8.9 - slow onset (2-5 minutes)Short half-life (20 sec.), no toxicityPoor protein binding, low hydrophobicity - rapid dissociation**reduces effectiveness of sulfonamides - hydrolyzed to PABA**Infiltration and dental procedures

81
Q

Benzocaine (Americaine)

A

Ester LA - small - fits in pore in CLOSED state, stabilizes CLOSED statelacks tertiary amineshort acting (15-20 min), low potency, rapid onset (1min)Cream, aerosol, ointment - TOPICAL onlyIncreased risk of methemoglobinemia, esp. aerosol and smokers

82
Q

Tetracaine

A

Ester LAHigh potency, long durationButyl group -> highly hydrophobicPossibly increased systemic toxicity (slow release from tissue -> blood, slow metab)Spinal and topical anesthesia

83
Q

What is Minimum Alveolar Anesthetic Concentration?

A

Concentration (% alveolar gas mixture - partial pressue) resulting in immobility in 50% of patients when exposed to noxious stimulusAnalgesia ~0.3MACAmnesia ~0.5MACSurgical anesthesia >1MAC

84
Q

What is the oil:gas partition coefficient?

A

Lipid solubility. Equal to potency of an anesthetic.Potency =1/MACPotency of inhaled anesthetic = quantity required to produce desired effectPotency of IV anesthetic = free plasma conc. required for lack of response to pain stimulus in 50% of people

85
Q

What are the primary targets and general effect of general anesthetics?

A

Target: Ligand gated ion channelsEffect: potentiation of inhibitory NTs or inhibition of excitatory NTs

86
Q

What are the two modes of administration of General Anesthetics and what groups of drugs fall under each?

A

Inhaled GAs: Gasses and volatile liquidsIntravenous GAs: Barbituates, Benzodiazepines, Misc. (propofol), Dissociatives

87
Q

What is the general structure of IV general anesthetics?

A

Small, hydrophobic, substituted aromatic or heterocyclic compounds

88
Q

3 barbituates, mode of administration, and general characteristics

A

Sodium Thiopental, Thiamylal, MethohexitalGiven IVHighly lipid soluble, ultra-short acting (2-5 minutes)**Induction of surgical anesthesia w/in seconds**

89
Q

How are barbiturates metabolized and distributed in the body?

A

Metabolized in plasma and liverDistributed from blood -> heart, brain, highly vascular tissues, lean tissue before fat.Drug may deposit in fat and produce “hangover” effect in patients w/ high % body fat.

90
Q

3 benzodiazepines, general characteristics and use

A

Diazepam, Lorazepam, MidazolamUsed for anxiolytic and anterograde amnesic propertiesAdmin 15-60 min before induction of GA, may be used as intraoperative sedatives

91
Q

How long does a single IV bolus of opioid analgesic typically last?

A

~30-60 minutes

92
Q

What are opioids used for in General Anesthesia and what are examples?

A

Analgesics. No amnesic effect. May be used in certain high-risk cases where a patient is not likely to survive full anesthesia.MorphineFentanyl

93
Q

Propofol

A

Most popular IV anesthetic - not analgesic.Used for induction and, with continuous infusion, maintenance.rapid recoverygood for outpatient surgeriesProlonged anesthesia in critical care settingsAntiemeticliver metabolism

94
Q

Etomidate

A

Used for general anesthesia - Not analgesicDoes not cause significant cardiovascular or respiratory depression - used where risk for hypotension or impaired ventricular functionHigh incidence of post-op N/VPain w/ injection - co-administer LidocaineLiver metabolism

95
Q

Ketamine

A

PCP analog - NMDA receptorDissociative agent, produces profound analgesia***Only IV anesthetic that produces dose-related cardiovascular stimulationLiver metabolism

96
Q

What inhalation anesthetic agents are used for induction of children?

A

Sevoflurane - expensive. sweet smell.Halothane - non-pungent

97
Q

What is the most widely used inhalation anesthetic agent?

A

Isoflurane - has pungent smell

98
Q

Nitrous Oxide

A

Inhalation anesthetic agent.Not used alone outside of dental proceduresAnalgesic - low potency

99
Q

Desflurane

A

Inhalation anesthetic - widely used in outpatient setting

100
Q

System effects of inhaled anestheticsCV, respiratory, brain, kidney, liver

A

CV: Decrease systemic BPResp: Reduce /eliminate respiratory drive (except NO)Brain: Increase cerebral blood flow, volume and ICPKidney: Conc. dependent - decrease GFR and RBF, increase filtration fractionLiver: Conc. dependent reduction in hepatic BF (15-45%)

101
Q

Compare effects of Ketamine, Etomidate, and Propofol on CV, Resp and Cerebral activity

A

CV Resp. Cereb. HR MAP Vent B.dill CBF CMO2 ICPKetamine ++ ++ - +++ +++ + +++Etomidate 0 - - 0 — — —Propofol 0 — — 0 — — —

102
Q

Describe Malignant Hyperthermia

A

Rare autosomal dominant disorderOccurs in susceptible individuals undergoing general anesthesia with volatile agents and muscle relaxants (succinylcholine)Increase in free Ca++ in skeletal muscle -> rapid and severe HTN, tachycardia, muscle rigidity, hyperthermia, hyperkalemia, acid/base imbalance w/ acidosis

103
Q

What does the blood:gas partition coefficient say about a drug’s ability to induce anesthesia?

A

Low coefficient = more rapid effectLow solubility -> lower coefficient. Lower solubility means faster equilibration and less drug has to be delivered for maximum effect.

104
Q

Does high pulmonary blood flow speed or slow equilibration of anesthesia (inhaled agent)?

A

High pulmonary blood flow (increased CO) slows equilibration. Larger volume of blood exposed to same conc. of agent per time unit, so slower equilibration

105
Q

What is the process of anesthetic emergence? What determines rate?

A

Anesthetic redistributes from brain -> blood and is eliminated through lungs or metabolism / excretionLow blood:gas partition coefficient -> faster emergenceRate is proportional to duration of anesthesia (muscle/ fat conc increases with time)Rate of respiration - higher rate -> faster emergence

106
Q

3 opioid receptors and associated activities

A

Mu: Primary site of action of opium and other drugs. (endogenous proteins less active here)Delta: Less potent, but can mediate analgesia. Enkephalin activatedKappa: Can mediate analgesia, but psychotomimetic effect.

107
Q

What is the molecular effect of opiate receptor activation? How does heterodimerization play a role?

A

Result is a decrease in nerve transmission. Closure of VGCC on presynaptic terminal and opening of K+ channel on postsynaptic.

108
Q

What is naltrexone?

A

Added to SR morphine capsules in embedded capsule (Embeda) - opioid antagonistIntended to discourage abuse

109
Q

What are morphine’s major metabolites? How are they eliminated?

A

Morphine-6-glucuronide: active analgesic effect, esp. w/ chronic useMorphine-3-glucuronide: neuroexcitatory effect - proconvulsantMetabolites renally excreted. Renal insufficiency - adverse effects from agitation - respiratory depression

110
Q

In what brain centers is morphine thought to exert effect on mood and cognition? What are the effects?

A

Locus coeruleus, mesolimbic DA, nucleus acumbens (pleasure ctr)Produces feelings of euphoria, tranquilityConfusion and sedation are common - esp. in elderly

111
Q

What is the important role of prompt morphine administration in combat wounded patients?

A

Reduction in PTSD incidence

112
Q

What is morphine’s effect on the eyes?

A

Miosis (pinpoint pupils)PS activation (atropine sensitive) - sign of abuse / toxicity

113
Q

What is morphine’s effect on respiration / cough reflex?

A

Respiration: Dose-related depression via brainstem ctrsdecreased response to CO2 (important in COPD setting and in combo w/ other CNS depressants)Cough: suppression via medullary ctr (easily dissociated from respiratory effect)

114
Q

What effect does morphine have on ICP and why?

A

Due to increased pCO2 -> cerebrovascular dilation -> increased ICP**head trauma**

115
Q

What effect does morphine have on the CV system?

A

Minimal CV depressionperipheral vasodilation, reduced resistance, inhibition of baroreceptor response**orthostatic hypotension**

116
Q

How is morphine used in the setting of CHF?

A

Direct relief of dyspnea associated with LV failureDecrease anxiety, venous tone, TPR

117
Q

What effect does morphine have on the GI system?

A

decrease in propulsionincreased water absorption-> constipation - QOL issue, esp w/ chronic use

118
Q

Oxycodone

A

Painkiller w/ morphing backboneMore orally active than morphine. Potent w/ same efficacyPopular drug of abuseCurrent formulations including additives -> upleasant effects if crushed or turns to gel - unusable

119
Q

Fentanyl

A

80-100x more potent than morphineShort duration of action, no active metabolitesSurgical anesthetic (often w/ droperidol)Trans-dermal patch for acute post-op pain***CYP3A4 metabolism***

120
Q

Meperidine

A

DemerolOpioid Painkiller of rapid onset and short durationIrritating to tissue if admin IMUnique toxicity: delerium, seizures, twitches, due to long-lived metabolite accumulationUse limited to moderate-severe pain, short duration (1-2 day post-surgical)NO OUTPATIENT USE

121
Q

Methadone

A

Opioid: Full Mu agonist w/ very long half-life (up to 5 days)High fat solubilityHepatic metabolism - no active metabolitesUsed for chronic pain and addiction management.Inovolved in 30-40% of opioid deaths

122
Q

Codeine

A

Prodrug - metabolized to morphine (CYP2D6 demethylation)High oral/parenteral potency ratio - largely avoids first pass metabolismWeak agonist - moderate analgesic activityUsually used in combo formulationNot for peds in minor procedures

123
Q

How is codeine metabolized and what variants exist in population?

A

Demethylated by CYP2D6 to morphine10% of pop lack CYP2D6 - poor responders1-7% of pop are ultra-rapid metabolizers, poss of OD

124
Q

Buprenorphine

A

OpiatePartial agonist at mu receptor - slow dissociation -> long activityModerate-severe pain and addiction managementIV, patch, sublingual (also w/ naloxone available)

125
Q

Tramadol

A

Ultram - synthetic codeine derivativeProdrug - O-desmethylated product is activeweak mu agonist and 5-HT / NE reuptake inhibitorpossible GABA mechanismNeeds slow titration - use for chronic painInhibition of CYP2D6 and 3A4 -> toxicity, decreased efficacySeizures reported, but unknown mechanism

126
Q

Tapentadol

A

Similar to TramadolWeak mu agonist and NE uptake inhibitor (not 5-HT)ER availableRisk of abuseShivering, diaphoresis, muscle pain

127
Q

Naloxone / Naltrexone

A

Naloxone = NarcanOpioid receptor antagonists (mu > kappa, delta)Naloxone: used in ED for opiate OD - also blocks antidiarrheal and antitussive effectsNaltrexone: Used to prevent relapse to heavy drinking in alcoholism -> hepatic damage at 3-4x normal dose

128
Q

Methylnaltrexone

A

Opiate receptor antagonist - does not cross BBBUsed to relieve opiate constipation - action in gut

129
Q

Diphenoxylate

A

Opiate - poor absorption from gutUsed for diarrhea

130
Q

Dextromethorphan

A

D-isomer of methylated levorphanol - no typical opioid effectUsed for antitussive effect in lower airway diseaseContraindicated in childrenCombo admin is discouragedNMDA receptor antagonist, sigma receptor agonistpotential for abuse

131
Q

Nalfurafine

A

Kappa receptor agonistreduces substance P-induced scratching in animalsapproved in Japan for uremic itching (dialysis related)

132
Q

How much acetaminophen may be included in an opiate combination drug?

A

325 mgFDA imposed max

133
Q

What are some non-prescription hypnotics?

A

diphenhydramine, doxylamine, L-tryptophan (serotonin precursor), and melatonin

134
Q

What are the two major classes of sedative-hypnotic drugs?

A

Benzodiazepines and barbiturates

135
Q

Describe benzodiazepine receptor function

A

Part of GABA-a receptor Cl- channelresults in increased frequency of opening in response to GABA, increased GABA potency and membrane hyperpolarization

136
Q

Flumazenil

A

BZ receptor antagonist - reversal of CNS effects of Benzos

137
Q

Describe the Barbiturate receptor

A

Barbiturates bind to a site on the GABA-a receptor (separate from BZ) -> prolongation of duration of opening and increased GABA efficacy

138
Q

What drugs are preferred for treatment of anxiety?

A

those w/ longer duration of actionEx. Diazepam

139
Q

What drugs are preferred for treatment of panic and phobic disorders?

A

Alprazolam and Clonazepam have higher efficacy than other drugs

140
Q

What drug is preferred for treatment of general anxiety in a patient with a hx of substance abuse?

A

Buspirone - does not have a sedative / cognitive impairment effect-may take a week or more for effects to develop

141
Q

What is standard treatment for status epilepticus?

A

IV diazepam or lorazepam, followed by IV fosphenytoin or phenobarbital-Watch for CNS depression

142
Q

What did the RAMPART study demonstrate?

A

Use of midazolam (EMS admin) better than IV lorazepam in treatment of status epilepticus

143
Q

What is a Ketogenic Diet and what is its use?

A

Non-pharmacological treatment of chronic seizures / epilepsyMimics fasting: High fat, low carb diet : 4gm fat / gm protein or carbCreates ketosis - brain uses ketones (acetone, acetoacetate, beta-hydroxybutyrate) for fuelRequires strict adherence and initial hospitalization

144
Q

What are the roles of monamine NTs in the brain?

A

NE and serotonin:Modulate behavioral stateRegulate how neurons function rather than produce rapid excitatory / inhibitory signals as in the periphery

145
Q

qualities of a migraine headache

A

pulsatileunilateralassoc. with N/VIntense enough to interrupt daily activities4-72 hrs if left untreated.

146
Q

What is thought to be the underlying cause of migraine headaches?

A

Neurogenic inflammationTrigeminal afferents to the brain release pro-inflammatory peptides -> vasodilation and inflammation

147
Q

What are 3 non-amphetimine treatments for ADHD?

A

Atomoxetine - NE reuptake inhibitorGuanfacine - Extended release a2 agonistClonidine - a2 agonist*none are first line drugs

148
Q

2 non-amphetamine drugs that can be used to treat daytime sleepiness (narcolepsy)

A

Modafinil - DA uptake inhibitor (Provigil)Sodium Oxybate - GHB - narcolepsy - condenses sleep so occurs in one stretch rather than multiple short periods through the day.

149
Q

How are migraines treated?

A

Mild, w/o vomiting: NSAID, acetaminophenSevere: Triptans - 5-HT agonists: block inflammatory peptide release. Best w/ NSAID Dihydroergotamine - old. can -> serotonin syndrome***Early treatment mandatory! As soon as prodrome is recognized

150
Q

What drugs can be used for migraine prophylaxis?

A

Beta blockerAntiepileptic (Valproic Acid, Topiramate)TCA (Amitriptiline) - SSRI/SNRI evidence lackingBehavioral therapy

151
Q

What is a CGRP antagonist?

A

future treatment of migraineblocks peptide believed to be responsible for neuro-vascular inflammationCurrent investigation: anti-CGRP Ab

M2 (19 decks)

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