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Sketchy Pharma Flashcards

-Autoimmune Drugs -CV/renal drugs -Smooth muscle drugs

1
Q

What part of the kidney does mannitol act as?

A

Mannitol = osmotic diuretic
-works at proximal convoluted tubule and descending loop of Henle (both of which are freely permeable to water) to draw water out into the lumen and increase free water removal

Use to draw free water out of the CNS (transiently teat ICP) and eye (decrease intraocular pressure transiently)

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2
Q

General use for cholinomimetics

A

Cholinomimetics = parasympathomimetics

Stimulate parasympathetic tone: increase gastric motility (use to treat non-obstructive ileus), increase lacrimation and salivation (tx Sjogrens), decrease intraocular pressure (use pilocarpine in glaucoma)

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3
Q

What lab value must be monitored in 75 yo F on Bosentan for pulmonary HTN

A

Bosentan = endothelin antagonist that can cause fatal hepatotoxicty

Monitor monthly LFTs

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4
Q

Main beta2 adrenergic effect

A

Beta2 activates Gs that activates PKA to relax smooth muscle

Relaxes smooth muscles in bronchial tree => bronchodilation
Relaxes smooth muscle in venuoles (vasodilation) => decreased SVR = drop in diastolic pressure
On fat cells activate lipolysis and FA release, promotes gluconeogenesis and insulin release

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5
Q

Describe the effect on BP of

(a) Phenylephrine
(b) Norepi
(c) Dobutamine
(d) Isoproterenol
(e) Epinephrine

A

BP changes

(a) Phenylephrine (pure alpha1) increases both systolic and diastolic => increases MAP w/o change in pulse pressure
(b) Norepi: alpha1 vasoconstriction => increase in MAP, little beta1
(c) Dobutamine (mostly beta1) is an inoptrope => increases systolic BP, increases MAP but w/ an increase in pulse pressure

(d) Isoproterenol (both beta1 and beta2) decreased MAP b/c of beta2 (decrease SVR) and widened pulse pressure b/c of beta1 (systolic stays relatively unchanged)
- so systolic RTS and diastolic drops, so MAP drops

(e) Epi: dose dependent change in BP
- low dose epi, beta effects predominate: widened pulse pressure (beta1 increases systolic, beta2 drops diastolic)
- high dose, alpha predominates: vasoconstriction, increased SVR, increase BP

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6
Q

Side effects of ACEi

a) Electrolyte abnormality
(b) Clinically troubling side effect (what bothers the pts
(c) Interaction w/ NSAIDs

A

ACEi side effects

(a) Hyperkalemia
- ACEi decrease aldo release, aldo generally holds onto Na causing K+ dumping, so w/o aldo we hold onto K+
(b) Persistent dry cough
- avoid this by switching to ARB if it is that troubling to pt
(c) NSAIDs decrease PGE production (PGEs vasoconstrict efferent arteriole) => both NSAIDs and ACEi dilate efferent arteriole (decrease GFR) => using them together can precipitate AKI
- same reason NSAIDs decrease loop diuretic efficacy (inhibit PGE and PGE decrease Na+ reabsorption and increases GFR)

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7
Q

Main indications for the following

(a) oxybutynin
(b) benztropine

A

Both are antimuscarinics

(a) Oxybutynin works to relax smooth muscle in the ureters and bladder wall to treat overactive bladder
(b) Benztropine is a central M1 antagonist used to treat EPS (symptoms of antipsychotics) and to improve tremor and rigidity in Parkinsons

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8
Q

Which diuretics work at the

(a) PCT
(b) Ascending loop of henle
(c) DCT
(d) CD

A

Diuretics

(a) Proximal convoluted tubule = acetazolamide, mannitol
(b) Ascending loop of henle = loop diuretics (furosemide)
(c) DCT = thiazides (HCTZ, chlorthalidone)
(d) Collecting duct = K+ sparing diuretics: amiloride, spironolactone

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9
Q

Are thiazides or loop diuretics used for edematous vs. mild HTN?

A

Thiazides work at DCT (where about 10% of Na is reabsorbed), so much less potent then loop diuretics that work at ascending loop of henle (completely ruins medullary gradient)

=> use loop diuretics for edematous states to get rid of large amounts of excess fluid, while using thiazides for mild HTN

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10
Q

Explain the mechanism of reflexive bradycardia w/ certain sympathomimetics

A

Sympathetomimetics w/ alpha1 effects (phenylephrine, NE, epi at high doses) cause reflexive bradycardia b/c baroreceptors sense elevated BP and reflexively activate beta tone

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11
Q

Explain the pH disturbance caused by acetazolamide

A

Acetazolamide = carbonic anhydrase inhibitor, decreases bicarb reabsorption at the proximal convoluted tubule of the nephron
-in exchange you get Cl- in to balance ions

=> results in hyperchloremic non-anion gap metabolic acidosis

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12
Q

Explain how diphenhydramine can be helpful in treating side effects of Risperidone

A

Diphenhydramine (H1 receptor blocker) is lipophilic => has CNS activity and can help re-establish the dopmaine-cholinergic balance in the brain, therefore helping w/ acute dystonia or other extrapyramidal side effects of antipsychotics

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13
Q

2 side effects specific for Verapamil over other CCBs

A

CCBs frequent side effects: light-headedness, headache

Verapamil specifically- constipation (literally in 25% of pts) and gingival hypertrophy (ew)

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14
Q

Features of acetylcholinestrase inhibitor overdose

A

ACh-ase OD = parasympathomimetic OD = symptoms of too much parasympathetic innervation = DUMBBELS
-also caused by organophosphate poisoning

diarrhea
urination
miosis (pupils constricted)
bradycardia
bronchospasm
lacrimation
salivation
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15
Q

Mechanism of nitrates for angina

Be specific- what molecules mediate??

A

Nitrates: broken down by vascular smooth muscle to release NO. NO then activates guanyl cyclase to increase cGMP. cGMP (key modulator) stimulates dephosphorylation of myosin light chain which stops it from binding to actin => smooth muscle dilation

Venous smooth muscle dilation = decreased preload = decreased LVEDV and myocardial O2 demand

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16
Q

Indications for CCB

(a) First line for stable angina
(b) 2 vasospasm d/o
(c) Neuro ppx
(d) HA
(e) Which for antiarrhtyhmic

A

Calcium channel blockres

(a) Stable angina use vasodilators (dihydropyridines) to dilate coronary arteries and decrease afterload
(b) Treat prinzmetal angina and Raynaud’s phenomenon
(c) Ppx of vasospasm after subarachnoid hemorrhage (MC 2/2 rupture of berry aneurysm)
(d) Migraine ppx
(e) Non-dihydropyridine (cardiac selective) as anti-arrhythmic

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17
Q

3 contraindications for ACEi

A
  1. Hereditary angioedema (C1 estrase deficiency)
  2. Pregnancy- ACEi is teratogenic
  3. B/l renal artery stenosis- makes sense here b/c these pts need angiotensin II on board to maintain their GFR
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18
Q

Why do pts on extended release oral nitrates need a daily break?

A

Pts can develop nitrate tolerance, where vascular smooth muscle beds decrease metabolism to NO (active molecule to increase cGMP and venodilate)

W/ reduced metabolism, pt gets side effects of headaches and flushing, so give daily break from the medication to prevent tolerance build up

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19
Q

Describe the features of atropine overdose

A

Think of atropine (antimuscarinic) overdose as the opposite of dumbbels

“dry as a bat” (decreased lacrimation and salivation)
“hot as a hare” (can’t lose heat by sweat)
Tachy (can’t slow down HR)
“blind as a bad” b/c antimuscarinics cause mydriasis and cycloplegia (inability to accomodate lens to nearby objects)
“mad as a hatter”

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20
Q

Explain the mechanism by which ACEi help in tx of chronic HF

A
  • ACEi decrease SVR (by causing vasodilation) => decrease afterload
  • ACEi cause natruiresis => decreased preload
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21
Q

Mechanism by which nitroprusside is helpful in hypertensive emergency

A

Nitroprusside is broken down in NO, then NO increases intracellular cGMP which relaxes vascular smooth muscle => vasodilates

Decreases peripheral vascular resistance/afterload

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22
Q

ACEi’s effect on

(a) SVR
(b) GFR
(c) Diuresis

A

ACEi inhibit conversion of ATI to ATII

(a) SVR decreases b/c blocked vasoconstrictor (ATII vasoconstricts), so decreased afterload

(b) GRF decreased
- ACEi causes vasodilation all around, including vasodilation of efferent arteriole

(c) ACEi cause a natural diuresis

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23
Q

Use of the following antimuscarinic agents

(a) Atropine
(b) Scopolamine
(c) Ipratropium

A

Muscarinic antagonists = drugs that block muscarinic (parasympathetic) tone

(a) Atropine- reverse lethal bradyarrhtyhmias or AV block
(b) Scopolamine (patch) for motion sickness
(c) Ipratropium/tiotropium: inhaled muscarinic antagonists for bronchodilation and decreased airway secretion in COPD

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24
Q

Best initial HTN agent if pt has concomitant

(a) HF
(b) Diabetes
(c) African American
(d) Edlerly
(e) Previous MI

A

Try to hit two birds w/ one stone

(a,b,e) If pt has concomitant HF, diabetes, or h/o MI: start w/ ACEi b/c can reduce mortality

(c,d) African Americans and elderly do specifically well w/ CCBs

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25
Q

Why aged cheese and wine can be dangerous to ppl on certain antidepressants

(a) Tx

A

Aged cheese and red wines contain tyramine which is metabolized by MAO-A (degrades Epi and NE). MAO can be blocked by MAO-inhibitors (class of antidepressants) => tyramine not broken down and goes on to cause hypertensive crisis

(a) Treat this hypertensive crisis w/ phentolamine (nonselective alpha blocker)

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26
Q

Differentiate the two classes of CCB

A

CCB (all of which block L-type voltage gated calcium channels) divided into

  1. Dihydropyridine: more selective for smooth muscle in arteries => used as vasodilators
    - Nifedipine, Amlodipine, Nicardipine
  2. Non-dihydropyridines: more cardio-selective => best for decreasing HR and contractility => reducing CO and myocardial O2 demand
    - Verapamil = most cardiac selective
    - Diltiazem = cardiac mostly w/ some vasodilatory effect
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27
Q

Explain beta-blocker use in acute vs. chronic HF

A

Avoid beta-blockers in acute HF (b/c you need the compensatory tachycardia and inotropy)

But then beta-blockers reduce overall mortality s/p MI and in chronic HF
-potentially 2/2 reduced myocardial oxygen demand, anti-arrhythmic effects, or inhibition of catecholamine-induced remodeling

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28
Q

Which psych drug does thiazide diuretics alter excretion of?

A

Thiazides decrease the renal excretion of Lithium => be careful of lithium overdose/toxicity in pt on both Li and thiazide diuretics

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29
Q

Name the drug

(a) Alpha-2 agonist for hypertensive urgency
(b) Nonselective alpha-antagonist for cocaine induced HTN
(c) Alpha antagonist for PTSD

A

(a) Clonidine = alpha2 agonist that reduces BP quickly => use in HTN urgency
(b) Phentolamine = alpha1 and alph2 antagonist given for cocaine induced HTN
(c) Proazosin = alpha-1 selective antagonist that can help w/ the nightmares and sleep disturbance in PTSD

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30
Q

Why are ACEi especially good for pts w/ HTN and diabetes?

A

ACEi slow the progression of diabetic nephropathy => really good for pts w/ HTN and DM

-also ACEi can be started in a pt w/ borderling high pressures who have albuminuria: albumin (protein) in urine sign of impending nephropathy => want ACEi on board

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31
Q

How do thiazides help in tx of diabetes insipidus?

A

Thiazides (inhibit NaCl cotransporter at DCT) cause hypovolumeia induced increase in Na and Cl reabsorption in more proximal segments of the nephron

-this helps relieve some of the polyuria seen in nephrogenic DI b/c kidney is less dependent on collecting duct (ADH dependent) reabsorption of solutes/water

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32
Q

How does local phenylephrine act as

(a) Decongestant
(b) Pupillary dilator

A

(a) Local vasoconstriction in the nasal mucosa (lots of alpha1 receptors there) reduces edema of nasal mucosa
(b) Activates alpha-1 at pupillary dilator muscle => causes mydriasis

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33
Q

Main alpha2 adrenergic effect

A

Alpha2 = sympatholytic
(thru G1, decreases cAMP)

Decreases nt release (presynaptic inhibition) => decreased BP
Inhibits insulin release and lipolysis
Decreases aqueous humor production (esp. Brimonidine) so can be used for chronic open angle glaucoma tx

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34
Q

Why NSAIDs may reduce efficacy of furosemide

A

Furosemide inhibits NKCC at ascending loop of henle

PGE enhances furosemide’s effects by increasing GFR (by dilating afferent arteriole) and further reducing Na+ reabsorption

So NSAIDs (inhibit PGE production can interfere w/ loop diuretic efficacy

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35
Q

When combined w/ nitrates, which drug combo has a mortality benefit for diastolic HF pts

A

Hydralazine (potent arterial dilator) + nitrates (potent venous dilator) has a mortality benefit for diastolic HF

Hydralazine decreases afterload while nitrates decrease preload

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36
Q

Explain how digoxin acts as a inotrope

A

Digoxin = cardiac glycoside from the fox glove plant, NaK ATPase inhibitor

NaK ATPase inhibited => Na+ not transported out of the cell so intracellular Na increases which stimulates/reverses Na/Ca exchanger
-Na needs to get out of the cell somehow so it exchanges w/ Ca => increased intracellular and SR Ca which increases contractility

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37
Q

Explain use of tamsulosin in older men

A

Tamsulosin = selective alpha1 blocker- blocks smooth muscle contraction of urethra relieving the urinary retention seen in BPH

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38
Q

Which specific diuretic should be used in the tx of Liddle syndrome

A

Liddle syndrome = congenital overactivity of ENaC Na+ reabsorption channel in the collecting tubule

Use Amiloride, K+ sparing diuretic that directly inhibits ENaC channels

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39
Q

Which receptors are activated by the following sympathomimetics

(a) Phenylephrine
(b) Norepi
(c) Dobutamine
(d) Isoproterenol
(e) Epinephrine

A

(a) Phenylephrine = relatively pure alpha1 agonist (all about dat smooth muscle activation/contraction)
(b) NE: Primarily alpha (both alpah1/alpha2), bit of beta1
(c) Dobutamine = mostly beta1 (so increased CO) w/ a little beta2 (decrease in diastolic)
(d) Isoproterenol: both beta1 (HR and contractility) and beta2 (vasodilation- reduced diastolic 2/2 reduced SVR)

(e) Epi: potent beta and alpha, dose dependent
- low dose: beta predominates
- high dose: alpha predominates

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40
Q

Which of the 5 senses may be impaired by furosemide?

A

Hearing- furosemide can have a dose-dependent ototoxic effect

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41
Q

Misoprostol

(a) Main side effect
(b) Use as ppx
(c) OBGYN use

A

Misoprostol = PGE1 agonist

(a) Diarrhea b/c of increased gastric activity
(b) Use as ppx for NSAID-induced gastric ulcers b/c PGE1 increases mucin-production by GI tract
(c) Used to stimulate uterine contractions to hasten labor or terminate pregnancy

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42
Q

Digoxin

(a) Predictor of mortality in acute toxicity
(b) GI involvement
(c) Pathognomonic visual feature

A

Digoxin

(a) Degree of hyperkalemia = predictor of mortality
- recall if Na/K ATPase is inhibited, K+ can’t get into cells => hyperkalemia
(b) N/V/abdominal pain
(c) Color vision changes, xanthopsia = objects appear yellow

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43
Q

Main types of shock treated by

(a) Phenylephrine
(b) Norepi
(c) Dobutamine
(d) Epinephrine

A

(a,b) Phenylephrine and NE used in hypovolemic, distributive shock (b/c increase SVR/venous return) and septic shock

(c) Dobutamine = inotrope for acute decompensated heart failure or cardiogenic shock
(d) Epi in anaphylactic shock

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44
Q

Main effects of angiotensin II

(a) on GFR
(b) on Na reabsorption
(c) on aldo release

A

Angiotensin II = potent pressor (vasoconstrictor)

(a) Increases GFR via constriction of efferent arteriole
(b) Works at PCT to increase NaHCO3 reabsorption
(c) Increases aldo release from adrenal cortex

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45
Q

Suffix of

(a) ACEi
(b) ARBs
(c) Benefit of ARBs over ACEi

A

(a) ‘pril’ = Lisinopril, analapril = ACEi
(b) ‘sartan’ = Losaratn = ARB
(c) Same activity, use ACEi first then use ARB in ppl who can’t tolerate ACEi
- ex: ppl who get persistent dry cough from ACEi

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46
Q

Main indication for digoxin immune FAB

A

Digoxin immune FAB (antibody) for sympatomatic (aka arrhythmias) digoxin toxicity

-so pt on digoxin has arrhythmia => give Digoxin immune FAB

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47
Q

Danger when first starting ACEi

(a) Why start HF pts on low dose then increase gradually

A

When first starting ACEi look out for hypotension and syncope

(a) Esp in pts w/ existing HF (already have super high renin) b/c this sudden removal of the pressor effects of ATII can cause dangerous hypotension and syncope

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48
Q

Potential electrolyte abnormalities induced by furosemide

A

Furosemide inhibits NKCC in the thick ascending loop of henle

  • can cause hypokalemia (b/c not reabsorbing K+)
  • also can cause hypomagnesemia, b/c inhibiting NKCC reduces the lumen positive pressure that causes excretion of Mg, so furosemide stimulates secretion of Mg
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49
Q

Major thing to avoid when treating cocaine overdose

A

Mostly symptomatic/supportive therapy

But DONT give beta-blockers, b/c unopposed alpha activity will vasoconstrict and lead to end organ damage

Instead can give phentolamine (alpha antagonist) to reduce BP

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50
Q

Mechanism of cocaine that causes

(a) HTN/tachycardia
(b) agitation/seizures
(c) Nasal septum perforation

A

Cocaine = inhibits NET and DAT (NE and DA transporters responsible for reuptake of nts by the presynaptic neuron)

(a) Peripheral NET inhibition => increased NE peripherally = increased BP and HR (mainly alpha1)
(b) Central DAT inhibition => arousal, seizures, midriasis (dilated pupils), agitation
(c) Locally increases NE release in the nose = potent vasoconstrictor (alpha1) => ischemia locally

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51
Q

Name some unwanted side effects of diphenhydramine

A

Diphenhydramine = H1 receptor blocker, lipophilic so crosses BBB

  • has some 5-HT receptor antagonist effects => stimulates appetite = weight gain
  • antagonizes muscarinic receptors => can cause same pic as atropine overdose: pupillary dilation, urinary retention, dry mouth, constipation, delitium
  • also inhibits alpha1 receptors => dizziness and hypotension
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52
Q

Explain why dobutamine is used as a pharmacologic agent for cardiac stress test

A

Dobutamine = beta1 agonist = Gs receptor to increase intracellular cAMP in cardiac myocytes
-so increases HR and contractility (overall CO) which also increases myocardiac O2 demand => can reveal areas most sensitive to ischemia = use as pharmacologic stress test

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53
Q

Lab abnormalities seen on thiazide diuretics

(a) BMP changes
(b) Lipid panel

A

Thiazide induced lab abnormalities

(a) Hypokalemia (b/c more Na to the collecting duct, so more K+ pushed out while reabsorbing Na), hyperglycemia (thiazides impede insulin release and tissue glucose uptake)
- hyponatremia

(b) Hyperlipidemia: increase LDL and TG

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54
Q

Indication for a selective NE transport inhibitor

A

NET inhibitor = Atomoxetine (straterra) = stimulant used to tx ADHD

-NET reuptakes NE at the presynaptic neuron => inhibition increases NE available in the synapse

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55
Q

2 indications of pilocarpine

A

Pilocarpine = parasympathomimetic
Tx dry mouth and glaucoma

-increases salivary secretions (M3 receptors on glands) and contracts ciliary muscle to increase aqueous humor outflow to high intra-ocular pressure

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56
Q

Go to 3 drug combo for treating primary hypertension

A

Primary HTN tx: thiazide diuretic (HCTZ) + ACEi (Lisinopril, ARB if dry cough) + CCB (long acting dihydropyridine to vasodilate)

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57
Q

Explain why some women may like spironolactone, and why some males may hate it

A

Spironolactone (K+ sparing diuretic) inhibits aldo receptor, but also has some cross reactivity, it’s an anti-androgen (both blocks testosterone synthesis and directly antagonizes androgen receptor)

=> spironolactone is used in tx for women w/ PCOS to decrease hirsuitism and symptoms of hyperandrogenism

=> spironolactone can cause low-T => gynecomastia, impotence, decrease in libido in men :-(

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58
Q

Which CCB is safest during pregnancy?

A

CCB during pregnancy = Nifedipine (dihydropyridine vasodilator)

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59
Q

Main side effects of nitrate therapy

A

Nitrate side effects: pounding headache, cutaneous flushing, tolerance (decreased metabolism to NO over time causing dizziness/HA- explains the need for daily breaks)

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60
Q

Differentiate Spironolactone and amiloride

A

Both are K+ sparing diuretics that work at the collecting duct

Spironolactone inhibits the aldo receptor, while amiloride inhibits ENaC (one of the main transporters aldo stimulates)
-but spironolactone is nonspecific => can block androgen receptors and block testosterone synthesis

Amiloride is more specific, doesn’t have any effects on androgens

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61
Q

Other indications for beta-blockers in addition to HF

A
  • migraine ppx
  • essential tremor (propranolol)
  • treating symptoms of thyroid storm
  • antiarrythmic (class II)
62
Q

Differentiate the mechanism of these two drugs in tx of acute HF:
Milrinone and Nesiritide

A

Milrinone = PDE inhibitor to decrease cAMP breakdown: increased cAMP increases cardiac contractility (intrope)

Nesiritide = synthetic BNP which increases cGMP in smooth muscle cells => arterial and venous dilation => decreased preload and afterload, also causes natriuresis

63
Q

Name some drugs used during hypertensive emergency

A

Drugs for hypertensive emergency: vasodilators!!! (decrease afterload)

  • beta blockers (esmolol, metoprolol)
  • labetalol (both beta and alpha blocker): beta blocker decreases HR/contractility, alpha blockade causes vasodilation

Other vasodilators

  • IV CCBs (Nicardipine)
  • Hydralazine
  • Nitroprusside
  • Fenoldopam (D1 receptor antagonist to vasodilate renal arterial bed)
64
Q

Alpha-methyl Dopa for use in HTN

(a) Side effect

A

Alpha-methyldopa = L-Dopa analogue (precursor to dopamine)
-dopamine activates alpha2 receptors centrally to decrease BP

Key here is that it’s safe for use during pregnancy
-so alpha-methyldopa as alpha2 agonist to tx HTN in pregnancy
Recall: labetolol = other anti-hypertensive useful in pregnancy

(a) Key side effect: Lupus like syndrome

65
Q

Name 2 RF for digoxin toxicity

A

RF for digoxin toxicity

  1. Hypokalemia- low serum K increases digoxin binding to NaK ATPase
  2. Renal insufficiency b/c then increased half life of digoxin
    - can be caused by drugs such as antiarrhythmics
66
Q

Dangerous side effect of nitroprusside

A

Nitroprusside can cause cyanide toxicity

-manifests as seizures, altered mental status

67
Q

Side effects of

(a) Beta1 blockade
(b) Beta2 blockade
(c) General beta-blockade in men

A

(a) b1 blockade => bradycardia and exacerbation of AV block
- so contraindicated in pt w/ existing heart block

(b) b2 blockade => can exacerbate COPD and asthma 2/2 bronchoconstriction
- so chose cardioselective (b1 selective) blockers to tx HF in pt w/ h/o ashtma

(c) Beta blockers can cause impotence in men

68
Q

Differentiate mechanism of cocaine and amphetamines

A

Cocaine inhibits NET and DAT to decrease catecholamine reuptake at synapse

Amphetamines increase catecholamine release by presynaptic neuron so more is available in the synapse

69
Q

Contraindications of cholinomimetics

A

Cholingeric tone works at both nicotinic and muscarinic receptors
-activation of muscarinic receptors (esp M3) => bradycardia, bronchospasm/bronchoconstriction, and increase rest/digest

Contraindications: asthma, peptic ulcer disease, COPD

70
Q

What is a contraction alkalosis?

(a) 2 ways by which thiazides and loop diuretics cause this

A

Contraction alkalosis = increase in pH due to volume loss

(a) Thiazides and loop diuretics:
increase fluid loss
increase aldo => increase H+ excretion
increase ATII => increase HCO3- reabsorption

71
Q

Signs of beta-blocker toxicity

(a) Reversal

A

Bradycardia, AV block, dyspnea
(overdose on beta blockade)

(a) Reversal agent = glucagon packets
- glucagon works directly on heart (not via adrenergic system, so not impacted by beta-blockade) to increase HR

72
Q

Use of pyridostigmine vs. edrophonium in tx for MG

A

Both are peripherally acting acetylcholinestrase inhibitors (increase ACh at nmj)
First line tx for MG is pyridostigmine

Edrophonium has super short half life (like only helps symptoms for 5 mins) so not used for tx, but good to use for distinguishing underdosed tx of MG from cholinergic crisis
If give edrophonium and symptoms improve- increase dose of pyridostigmine
If give edrophonium and symptoms don’t improve = cholinergic crisis and stop pyridostigmine

73
Q

Name 3 classes of vasodilatory agents used in the tx of pulmonary HTN

A

Tx of pulmonary HTN

  1. PGE1 agonists: Epoprostenol
  2. PDE5 inhibitors: Sildenafil (hence the old lady on Viagra)
  3. Endothelin antagonist: Bosentan
74
Q

Why are beta-blockers sometimes combined w/ nitrate therapy?

A

Nitrates venodilate, which can cause venous pooling and hypotension. This hypotension can stimulate reflex sympathetic activity (tachycardia) which increases mO2 demand (ummm the opposite of what we want)

So give concomitant beta-blocker to block this reflex sympathetic activity

75
Q

Mechanism of action of the 4 sympathetic nervous system receptors

A

G proteins that function as transducers: QISS

alpha1: Gq (same as M1 and M3): activate IP3-DAG pathway to increased intracellular calcium
alpha2: Gi (inhibitory) decreases cAMP
beta1: Gs- increases cAMP to increase intracellular Ca
beta2: Gs- increases cAMP that activates PKA and relaxes smooth muscle

76
Q

Describe the involvement of ENaC and alpha intercalated cells at the collecting duct

A

Collecting duct:

  • ENaC channels on luminal surface for Na+ reabsorption
  • alpha intercalated cells contain H+ATPase for H+ secretion

ENaC reabsorbs Na+, creating a negative luminal pressure that draws out K+ and H+

77
Q

Name 2 states in which ACEi tx provides mortality benefit

A
  • chronic heart failure
  • after MI

Mechanism thought to be b/c of reduction of ATII mediated cardiac remodeling

78
Q

Main beta1 adrenergic effect

A

Beta1 activates Gs => increased intracellular cAMP and Ca2+

2 locations

  1. cardiac myocytes/nodal cells to increase HR and contractility => overall increase cardiac output
  2. on JGA cells to increase renin release- hold onto volume and maintain BP
79
Q

Which receptors are activated by dopamine at different doses

A

‘DBA’ order of activation

D1 (Gs activating PKA) at low dose (smooth muscle relaxation)
B1 (Gs increases cAMP) at medium dose (cardiac activation)
A1 (Gq for IP3-DAG) at high dose (pressor effects)

80
Q

Define hypertensive emergency

A

Hypertensive emergency = systolic over 180, diastolic over 120, with evidence of end-organ damage

E/o end organ damage: blurry vision, altered mental status etc

81
Q

Differentiate nicotinic and muscarinic receptors

(a) Location
(b) Mechanism of action

A

Receptors activated by ACh to stimulate parasympathetic innervation

Nicotinic receptors

(a) 3 places: ganglia, nmj of skeletal muscle, in the adrenal gland
(b) Ion channel activation

Muscarinic receptors
(a) At the effector organs
M1: nerves and CNS
M2: cardiac- atria, AV and SA node
M3: glands, smooth muscle organs
(b) Work via G-protein coupled receptors
-M1 and M3 work by activating IP3-DAG cascade to increase intracellular calcium
-M2 works by decreasing cAMP
82
Q

Main side effect of alpha blockers

A

Orthostatic hypotension w/ reflexive tachycardia

-b/c alpha1 tone is what causes the vasoconstriction that maintains BP when we stand

83
Q

Mechanism of furosemide

A

Furosemide = inhibits NKCC transporter at the thick ascending loop of Henle

  • thick ascending loop is impermeable to water (so only solutes are reabsorbed, this is used to dilute the interstitium)
  • so inhibit Na+ reabsorption here

Less Na+ reabsorption => diuresis, also ruins the medullary concentration gradient needed by collecting duct to concentrate urine

84
Q

Digoxin- describe the cardiac changes to look out for and involvement in arrhythmias

A

Digoxin (cardiac glycoside, NaK ATPase inhibitor) directly stimulates vagal innervation => can induce bradycardia and AV nodal block
-vagal stimulation makes Digoxin a second line agent for atria arrhythmias

Then Digoxin increases intracellular Ca and AV block => can cause almost any arrhythmia

-so ironic that it’s used both for treating certain arrhythmia, and it causes arrhythmias

85
Q

Briefly describe the amino acid precursor used in catecholamine synthesis

(a) Inhibitor

A

Tyrosine (AA precursor) transported to nerve terminal –> L-dopa –> DA –> NE

(a) Met-tyrosine can be used to prevent conversion of tyrosine to L-dopa

86
Q

Differentiate these beta-blockers: metoprolol, carvedilol, labetolol

A

Metoprolol is cardiac (b1) selective
Carvedilol is nonselective beta-blocker w/ some alpha1 blocking
Labetolol is also (like Cavedilol) a nonselective beta-blocker w/ some alpha1 blocking that is safe for use in pregnancy

87
Q

Fenoldopam

(a) Mechanism of action
(b) Key feature

A

(a) Fenoldopam = specific D1 receptor antagonist. Increases intracellular cGMP which vasodilates arterial beds
- vasodilates specifically: arterial, coronary, and renal arteries

(b) Key is that it dilates renal arterial bed => increases renal perfusion while decreasing BP (very unique feature)
- causes natruiersis

88
Q

Contraindications to nitrate therapy

(a) 2 cardiac conditions
(b) Simultaneous medication

A

Nitrate contraindications

(a) Right-sided MI and HOCM, both preload dependent d/o
(b) PDE5 inhibitors such as Sildenafil 2/2 dangerous drop in BP

89
Q

Clonidine

(a) Mechanism
(b) Indications

A

(a) Clonidine = alpha2 agonist

(b) Alpha1 = Gi, inhibitory, sympatholytic
- reduce HTN in hypertensive urgency
- ADHD refractory to stimulants
- First line for Tourette’s

90
Q

Expected BMP change after starting pt on ACEi

A

Expect a bump in creatinine

-b/c ACEi decrease GFR (by dilating efferent arteriole) => expected bump in creatinine when first start on ACEi

91
Q

Main alpha1 adrenergic effect

A

Alpha1 = sympathomimetic
(thru G1, activating IP3-DAG increasing intracellular Ca) causes smooth muscle contraction

Vasoconstriction of arterioles => increased BP
Vasoconstrictions of veins => increased venous return
Constriction of urethra and prostate => urinary retention
Constriction of ?? => pupillary dilation (but basically sympathomimetic so widen up eyes to see the bear)

92
Q

With epi on board: what effects would you see if the following were given

(a) alpha-blocker
(b) beta-blocker

A

Epi is dose dependent, low dose beta predominates and high dose alpha predominates
Both increase BP, w/ low dose dropping diastolic and widening pulse pressure

(a) Alpha blocker given: diastolic pressure drops (beta2), HR rises (beta1), pulse pressure widens
(b) Beta blocker given: Pulse pressure narrows (beta2 no longer dropping diastolic), MAP increases b/c of vasoconstriction causing increased SVR

93
Q

Digoxin

(a) 2 indications
(b) Mechanism of both indications

A

Digoxin

(a) Tx of refractory (to ACEi and diuretic) chronic heart failure, also antiarrhythmic

(b) Inhibits Na/K ATPase
- works at antiarrhythmic by direct vagal stimulation

94
Q

Differentiate HCTZ and chlorthalidone

A

Both are thiazide diuretics (inhibit NaCl cotransporter at DCT) but chlorthalidone has longer half life = longer duration of action

95
Q

Name two anti-epileptics used for migraine ppx

A

Topiramate (Topamax) and Valproic Acid (Valproate)

96
Q

Big distinguishing factor of low dose dopamine when used as pressor

A

Low dose dopamine activates D1 receptor (Gs => PKA => smooth muscle relaxation) which increases GFR and renal blood flow

While phenylephrine and other alpha1 agonists will decrease renal blood flow

97
Q

Relative contraindications to Verapamil and Diltiazem

A

Non-dihydropyridines decrease HR and contractility- decrease nodal activity => don’t give to pts w/ any heart block or conduction abnormalities

-don’t use w/ beta blockers which also decrease/block AV nodal conduction

98
Q

Differentiate mechanism of 1st and 2nd generation anti-histamines

(a) G-protein coupled
(b) Indications

A

Anti-histamines block H1 receptors (not talking H2 receptor blockers used for stomach acid reduction)

First generation anti-histamine = diphenhydramine, meclazine

(a) Gq coupled protein
(b) First line for acute allergy/hives (type I hypersensitivity), also can tx EPS symptoms from antipsychotics, can be used for insomnia (b/c cause drowsiness), tx motion sickness (b/c lipophilic and cross BBB)

Second generation = loratidine, fexofenadine, cetrizine

(a) Again inhibit H1 (Gq protein coupled)
(b) Tx allergic symptoms w/o the drowsiness and other CNS side effects (anti-muscarinic) b/c these are less liphophilic => don’t cross BBB

99
Q

Organophosphate poisoning

(a) Features
(b) 2 drugs for tx

A

Organophosphate binds (eventually bind becomes covalent and irreversible) to acetylcholinestrase, so organophosphate poisoning presents as

(a) Overdose of paraysmpthateic innervation = DUMBBELS: diarrhea, urination, miosis, bradycardia, bronchospasm, lacrimation, salivation

(b) Tx
- atropine to reverse the central muscarinic toxicity
- pralidoxime to block both muscarinic and nicotininic receptors, reverse the paralysis

100
Q

Mechanism of thiazide duiretics

A

Thiazides inhibit the NaCl cotransporter at the distal convoluted tubule

So decrease NaCl reabsorption at DCT

101
Q

Which diuretic may be beneficial in tx pt w/ HTN and osteoporosis?

A

Thiazide diuretics
-enhance calcium reabsorption => useful to help bone mineralization and potentially even prevenet fractures

NOT loop diuretics, furosemide actually increases Ca2+ excretion

102
Q

Tx of atropine overdose

A

Atropine (competitive muscarinic inhibitor) tx w/ physostigmine

Only pyridostigmine (and not other ACh-ase inhibitors) b/c pyridostigmine can cross BBB => CNS penetration (while pyridostigmine, neostigmine both can’t penetrate CNS)

103
Q

Use of methacholine challenge test

A

Methacholine = cholinomimetic that contracts smooth muscles of the bronchial tree => exacerbates asthma/COPD

104
Q

Main indication for azetazolamide

A

Decrease CSF production in pseudotumor cerebri (idiopathic intracranial hypertension)

105
Q

Aldosterone

(a) Location of receptor
(b) Action

A

Aldo

(a) Intracellular receptor (b/c aldo is a steroid hormone)- inside ENaC containing cells and alpha intercalated cells
(b) Aldo increases Na+ reabsorption (thru ENaC transporter) which increases negative transluminal pressure, increasing K+ excretion and activity of H+ATPase to secrete H+

106
Q

Mechanism of side effects seen in elderly who take diphenhydramine

A

Diphenhydramine (first generation histamine-1 receptor blocker) also has anti-muscarinic effects => can cause delirium and cognitive impairment, especially in the elderly

107
Q

Describe adrenergic effect on aqueous humor production and how this is targeted to treat glaucoma

A
  • beta2 activation increases aqueous humor production => use beta-blocking agents in glaucoma
  • alpha2 activation (specifically Brimonidine) decreases aqueous humor production => alpha2 agonist to tx glaucoma
108
Q

Explain etiologies of emesis when the irritant is in the

(a) GI tract
(b) Vestibular system
(c) Area postrema

A

Emesis from irritant in the

(a) GI tract = enteritis, gastritis, post-op (2/2 intra-op manipulation of vagal nerve)
- tx w/ Onadestron (5-HT3 inhibitor)

(b) Vestibular system from motion sickness
- tx w/ meclazine (H1 receptor blocker) or scopolamine (M1 receptor antagonist)

(c) Area postrema = just outside BBB in the 4th ventricle, chemotherapy-induced nausea
- Tx w/ Metoclopramide

109
Q

Name the 3 inputs to the nucleus solitarius

A

Nucleus solitarius = central nucleus that mediates vomiting reflex

3 inputs

  1. directly from GI tract from vagal afferents (CN X)
  2. vestibular system from CN VIII
  3. area postrema right outside the BBB in the 4th ventricle
110
Q

Mechanism by which GI irritation causes vomiting

A

GI irritation increases 5-HT (serotonin) release, activating the 5-HT3 receptors on vagal afferents that travel directly back to the nucleus solitarius

111
Q

Differentiate mechanism of anti-emetics

(a) Onadestron
(b) Meclazine
(c) Scopolamine
(d) Metoclopromide
(e) Aprepitant

A

(a) Onadestron (Zofran) inhibits 5-HT3 receptors on GI tract vagal afferents
(b) Meclazine = H1 receptor blocker to block nausea from vestibular system (motion sickness)
(c) Scopolamine = M1 antagonist (anti-muscarinic) to block nausea from vestibular system (motion sickness)
(d) Metoclopromide (Reglan) inhibits D2 receptors in the area postrema to block central vom-inducing substances (like chemo in the CSF)
(e) Aprepitant = NK1 receptor antagonist (neurokinin receptors on the area postrema) to treat chemotherapy induced vomiting w/o the side effects of reglan

112
Q

2 risks of of onadestron therapy

A

Onadestron (5-HT3 receptor antagonist) used as anti-emetic, risks:

  • serotonin syndrome: esp if used concomitantly w/ SSRI
  • prolonged QT (recall anti-ABCDEs for drug-induced prolonged QT)
113
Q

Name some side effects of Metoclopramide

A

Metoclopramide = D2 receptor blocker

  • can cause EPS b/c of dopamine blockade
  • can cause hyperprolactinemia (gynecomastia, galactorrhea, decreased libido, oligomenorrhea) due to loss of prolactin inhibition by dopamine
  • risk of NMS at high dose
  • prolonged QT
114
Q

2 indications of metoclopramide

A

Metoclopramide = D2 receptor blocker

  1. Used as anti-emetic b/c blocks D2 receptors on area postrema
  2. Used as pro-kinetic of upper GI tract (tx delayed gastric emptying post-op or in diabetics) b/c blocks D2 receptors in GI tract
115
Q

Benefit of aprepitant over metoclopramide

A

Area postrema (vomiting center) has both D2 receptors and NK1 (neurokinin receptors)

Metoclopramide antagonizes D2 receptors to act as anti-emetic, but this comes w/ a hole host of side effects

  • EPS, tardive dyskinesia
  • hyperprolactinemia
  • risk of NMS
  • QT prolongation
  • depression, drowsiness (esp in elderly)

While Aprepitant (NK1 receptor antagonist) doesn’t have any of these side effects…

116
Q

Insulin receptor

(a) Pathway signaling molecule
(b) Effect of ligand binding

A

Insulin receptor

(a) Intracellular tyrosine kinase
(b) Insulin binding to its receptor activates tyrosine kinase that causes:
1. increase of GLUT4 translocation onto plasma membrane
2. stimulates anabolic processess (lipolysis, glucogenlysis)

117
Q

How does insulin change serum K+

A

Insulin stimulates NaK ATPase => draws K+ into cells (in exchange for Na out)

So insulin can be used to tx hyperkalemia, also means when giving insulin in DKA you should co-administer K+ to prevent hypokalemia

118
Q

Which insulin form can be given intravenously?

(a) Clinical significance

A

Only regular insulin (intermediate acting) can be given IV

(a) Rapid acting, IV- this is the form given during DKA

119
Q

Give the names of

(a) Rapid acting insulin preparations
(b) Intermediate acting
(c) Long acting

A

Names of the drugs

(a) Rapid acting preparations: Glulisine, Aspart, Lispro
(‘girls and lads’)

(b) Regular insulin, NPH
‘rest now’

(c) Detamir, Glargine
‘don’t go’

120
Q

Give the names of the drugs

(a) Sulfonylureas
(b) Meglitinide

A

(a) Sulfonyulreas = sulfa drugs that bind to ATP-dependent K+ channel to close it, depolarizing beta-islet cell membrane and causing insulin release
Names = Glipizide, Glyburide

(C) Meglitinide = non-sulfa drugs (so can be used in ppl w/ sulfa allergies) w/ the same mechanism as sulfonylureas
Names = Repaglinide, Nateglinide ‘glinide’

121
Q

What type of drugs are the following:

(a) Glipizide
(b) Repaglinide
(c) Exanatide

A

(a) Glipizide = sulfonyurea = secretagogue, binds ATP-dependent K+ channel to depolarize beta-cell and cause insulin release
(b) Repaglinide = Meglitinide = secretagogue w/ same mechansim as sulfonyulrea but is a non-sulfa drug (can be used in ppl w/ sulfa allergy)
(c) Exanatide = GLP-1 (glucagon-like peptide 1, usually secreted by intestinal L-cell in response to food load) agonist: increases insulin release, decreases glucagon release, delays gastric empting

122
Q

What kind of drugs are the following:

(a) Glyburide
(b) Sitagliptin

A

(a) Glyburide = sulfonyurea = binds ATP-dependent K+ channel to depolarize beta islet cell and cause insulin release

(b) Sitagliptin = DPP-4 inhibitor, DPP-4 breaks down GLP-1 (glucagon-like peptide 1). So inhibiting DPP4 allows more GLP1 to be around.
GLP-1 increases insulin release, decreases glucagon release, and delays gastric emptying

123
Q

Insulin secretagogue drugs

(a) Name the two classes
(b) Weight change in pts
(c) Side effect

A

Insulin secretagogues

(a) Sulfonyulrea and Meglitinides
(b) Can cause weight increase b/c these drugs stimulate insulin release and insulin is an anabolic hormone
- stimulates nutrient storage
(c) High risk of hypoglycemia since stimulate insulin release regardless of food intake

124
Q

Side effects of Sitagliptin

A

Sitagliptin = DPP4 inhibitor (inhibits breakdown of GLP-1), more GLP-1 around to increase insulin release, decrease glucagon release, delay gastric emptying

Side effect = increased risk of URI and nasopharyngitis

125
Q

Benefit of GLP-1 agonists over sulfonyulrea

A

GLP-1 agonists do not carry a risk of hypoglycemia b/c activity is glucose dependent, so effects diminish as glucose levels approach normal

Sulfonylureas have high risk of insulin since stimulate insulin release regardless of oral intake

126
Q

Contraindication to metformin use

A

Renal failure- kidneys excrete metformin essentially unchanged, if not excreted then increased risk of lactic acidosis

Metformin already poses risk of lactic acidosis, then further increased if kidneys not metabolizing

127
Q

3 activities of metformin

A

Metformin

  1. decreases gluconeogenesis in the liver
  2. increases peripheral uptake of glucose
  3. increases peripheral sensitivity to insulin
128
Q

Metformin side effect

(a) MC
(b) Most dangerous

A

Side effects of metformin (inhibits gluconeogenesis and improves insulin sensitivity)

(a) MC = GI upset: N/V/D
(b) Most dangerous = lactic acidosis
- increased risk in renal insufficiency (less renal fxn to excrete metformin) or tissue hypoxia (higher load of lactate produced)

129
Q

Mechanism of piolitazone

A

Pioglitazone = PPARgamma ligand, PPARgamma is an intracellular nuclear receptor that regulates transcription of certain genes
-specifically activation of PPARgamma ligand upregulates adipnectin which increases insulin sensitivity and fatty acid oxidation

130
Q

Oral diabetes drug that

a) Can cause wt loss
(b) Can have delayed onset (takes days-weeks for full effect

A

Oral diabetic agents

(a) Cause wt loss: metformin
(b) Delayed onset = pioglitazone = PPARgamma agonist, PPARgamma is

131
Q

Side effect of pioglitazone

A

Pioglitazone = PPARgamma ligand that activates adiponectin production to increase insulin sensitivity and increase fatty acid oxidation

-stimulates TG uptake => reduces serum TG but can also lead to weight gain

Main side effect = fluid retention and peripheral edema => contraindicated in heart failure

132
Q

Mechanism of dapaglifloxin

A

Dapaglifloxin and canaglifloxin are SGLUT2 inhibitors- => decrease glucose reabsorption at the proximal convoluted tubule

133
Q

2 side effects of dapaglifloxin/canaglifloxin

A
  1. Increased risk of UTI and vaginal candidiasis

2. Dehydration (glucose acts as osmotic solute to suck water out into urine)

134
Q

Mechanism of alendronate

A

Alendronate = bisphosphonate

  • inhibits binding of osteoclasts to bone => inhibits bone breakdown
  • also inhibits osteoclast differentiation and recruitment
135
Q

Name another indication for alendronate aside from osteoporosis tx

A

Alendronate = bisphosphonate = inhibits osteoclast binding to bone to decrease bone breakdown

  • can be used to acute treat hypercalcemia (ex: hypercalcemia of malignancy), b/c reduces bone breakdown therefore reduction of Ca2+ put into serum
  • can treat Paget’s disease = overactive osteoclasts that lead to disorganized bone growth
136
Q

Alendronate side effects

(a) MC
(b) Most dangerous

A

Side effects of bisphosphonates

(a) MC = upper GI side effects such as acid reflux, esophagitis, even esophageal ulcers
- explains why pts are told to take these meds w/ a lot of water and sit upright for 30 mins after taking

(b) Most dangerous = rare side effect of jaw osteonecrosis

137
Q

Benefit of Raloxifen over estrogen therapy for osteoporossi

A

Raloxifen = SERM = selective estrogen receptor modulator, so only is an agonist of estrogen receptors at specific tissues

Activates estrogen receptors at bone to decrease bone mineral loss, while antagonizing estrogen receptors on breast and uterine tissue => doesn’t increase risk of breast/uterine malignancy like endogenous estrogen

138
Q

How does PTH affect bone resorption

A

PTH stimulates osteobalsts to upregulate RANKL (RANK-ligand), RANKL binds to RANK on osteoclasts to activate bone breakdown

139
Q

How does calcitonin affect bone resorption

A

Calcitonin inhibits osteoclasts => reduces bone break down to ‘tone down calcium’

So calcitonin can be used in the tx of Paget’s disease where overactive osteoclasts resorption causes disorganized bone structure

140
Q

How does the monoclonal antibody Denosumab act compared to PTH

A

PTH stimulates RANKL expression on osteoblasts, which binds to RANK to activate osteoclasts to break down bone and release Ca2+ into serum

Denosumab = anti-RANKL monoclonal antibody that blocks the osteoblast’s ability to stimulate osteoclast bone breakdown => useful in tx of osteoporosis

141
Q

Differentiate ADH’s two receptors

(a) G-coupled protein
(b) Location

A

ADH receptors

V1

(a) Gq coupled => activates PLC (phospholipase C) to increase intracellular Ca2+
(b) On vascular smooth muscle cells to cause vasoconstriction (hence vasoPRESSIN)

V2
(a) Gs coupled => activates adenylyl cyclase to increase cAMP
(b) On collecting duct basolateral membrane to stimulate translocation of aquaporin2 onto apical surface
Extrarenal V2 also located on vascular endothelium to stimulate release of both vWF and factor VIII

142
Q

Name 3 drugs for the tx of nephrogenic DI

A
  1. Thiazide diuretics
  2. Amiloride (K+ sparing diuretic) specifically good for Li induced nephrogenic DI
  3. NSAIDs (ex: Indomethacin), reduces PGE production which antagonist ADH
143
Q

Indication of desmopressin in addition to central diabetes insipidus

A

Desmopressin = ADH analog
V2 receptors are present extrarenally on vascular smooth muscle, stimulation increases release of both vWF and factor VIII

So desmopressin can be used in the treatment of von Willebrand deficiency and Hemophilia A (factor VIII deficiency)

144
Q

Conivaptan use in tx of SIADH

A

Conivaptan (‘vaptans’) are ADH receptor antagonists

So use (along w/ free water restriction) in tx of SIADH to block ADH receptors on collecting tubules and prevent more water retention

145
Q

Explain how ADH can be useful in the treatment of bleeding varices

A

ADH is called vasoPRESSIN after all!!! V2 receptors on vascular endothelial smooth muscle cells cause vasoconstrictino => constrict the mesenteric arterioles to reduce portal pressure and aid in tx of bleeding esophageal varices

146
Q

Location of glucocorticoid receptor

(a) Mechanism of action

A

Glucocorticoid (steroids) are lipophilic so can enter the cell, glucocorticoid receptors are in the cytoplasm, then once bound to receptor the complex moves into the nucleus where it acts directly as a transcription regulator

(a) Receptor and ligand together bind to DNA to alter transcription

147
Q

Explain how glucocorticoids

(a) Reduce leukotrienes
(b) Inhibit lymphocyte attraction
(c) Inhibit neutrophil attraction

A

Glucocorticoids

(a) Reduce both PGE and leukotriene synthesis b/c glucocorticoids inhibit phospholipase A2 (PLA2) that is the first step in removing arachidonic acid (precursor molecule for PGE and leukotrienes) from the plasma membrane
(b) Glucocorticoids inhibit NF-kappaB which stimulates IL-2 and TNF-alpha which are needed to recruit and activate both T and B lymphocytes
(c) NF-kappaB (inhibited by glucocoritoicds) is responsible for producing neutrophil adhesion molecules needed for neutrophils to leave blood stream and exit to cause inflammation.

148
Q

CBC in pt on glucocorticoids: what will be elevated vs. reduced

A

Glucocorticoids
-inhibit NF-kappa B => decreased IL2/TNFalpha (activate T and B cells) and reduced neutrophil adhesion molecules => neutrophils can’t leave BV so get neutrophilia 2/2 marginalization of neutrophils

All other WBC cell lines (T-cells, B-cells, especially helper-T cells) are reduced

149
Q

Explain metabolic (glucose and fat) changes due to glucocorticoids

A

Glucocorticoids (think like cortisol, stress hormone)

  • stimulates gluconeogenesis
  • stimulate proteiolysis and lipolysis to provide substrate for gluconeogenesis
  • induces insulin resistance, which along w/ increased glucose production => hyperglycemia
150
Q

Explain the following findings in glucocorticoid tx

(a) Moon face
(b) Striae
(c) Fracture
(d) Hypokalemia
(e) Reactivation of Tb

A

Glucocorticoid side effects

(a) Moon facies 2/2 increased lipolysis to provide substrate for stimulated gluconeogenesis
(b) Striae b/c fibroblasts are inhibited
(c) Fracture b/c glucocorticoids stimulate osteoblasts
(d) Hypokalemia 2/2 crossover w/ mineralocorticoid activity
(e) Reactivation of Tb 2/2 immune suppressoin

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