2 - Pharmacology

Question 1

What are the two main approaches to pharmaco treatment of asthma?

Answer 1

1) Tx the symptoms - bronchodilators - rescue inhalers

2) Tx the cause - anti-inflammatories - control meds

Question 2

What is the mechanism of B-adrenergic agonists for asthma tx? What is an example drug? Side effects?

Answer 2

Albuterol - immediately effective for acute, severe asthma
-acts within the sympathetic system at B2 receptors to cause airway smooth muscle to relax -> bronchodilation
-inhibits mast cell action to cause constriction
-inhibits microvascular leakage (edema)
-inhibits mucociliary transport (mucous build up)
Side Effects -> mostly safe, potentially makes lungs susceptible to more severe attacks; increased potential for B1 stimulation (arrhythmia)

Question 3

What is the mechanism of muscarinic anatagonists for asthma tx? What is an example drug? Side effects?

Answer 3

Tiotropium - less effective, but good for those intolerant of B agonists
-competitive inhibition of ACh at bronchi smooth muscle -> blocks bronchoconstriction and mucous secreting
Side Effects - systemic effects on parasympathetics limits doses that can be given (urinary retardation, tachycardia, vision); slow acting

Question 4

What is the mechanism of methylxanthines for asthma tx? What is an example drug? Side effects?

Answer 4

Theophylline - low cost/high compliance; not as effective
-antagonism of androgenic (a2) receptors -> block bronchoconstriction
- inhibition of PDE -> elevate cAMP -> dilation
-CNS/cardiac stimulant; kidney -> diuretic
Side Effects - arousal, tremor, convulsions, tachycardia, arrhythmias, weak diuretic
-LOTS of drug interactions -> macrolide antibiotics(erythromycin, azithromycin)

Question 5

What is the mechanism of corticosteroids for asthma tx? What is an example drug? Side effects?

Answer 5

Fluticasone - long, lasting anti-inflammatory -> prophylactic
-inhibits eosinophil-induced inflammation (allergy)
-inhibits cytokine production
-inhibit Phospholipidase A -> arachidonic acid -> prostaglandin, leukotriene
Side Effects - inhaled(mild) -> cataracts, decreased bone density
-oral(severe) -> wight gain, bone loss, cushing’s, adrenal supression

Question 6

What is the mechanism of leukotriene pathway modifiers for asthma tx? What is an example drug? Side effects?

Answer 6

Montelukast - alternative for corticosteroids; good for aspirin/exercise asthma
-competes for leukotriene receptor -> blocks several LT’s
-lasts 24hrs, but takes 2hrs to be effective
Side effects - hepatic injury - abdominal pain, nausea, jaundice, itching, lethargy

Question 7

What is the mechanism of Anti-IgE therapy for asthma tx? What is an example drug? Side effects?

Answer 7

Omalizumab - reserved for severe patients unresponsive to steroid
-anti-IgE monoclonal antibody -> blocks IgE-dependent activation of mast cells
Side effects - potential for anaphylaxis; observe patient for 2-4h after injection; IV or subcutaneous injection 2-4wks

Question 8

What is the standard pharmaco approach to tx of COPD?

Answer 8

Nothing is curative, so focus on tx symptoms. Very similar to asthma:

• bronchodilation -> albuterol, tiotropium
• anti-inflammatory -> fluticasone

Question 9

What are some notable diuretics that work at the Proximal Tubule?

Answer 9

Acetazolamide

Mannitol

Question 10

What are some notable diuretics that work at the Loop of Henle/TAL?

Answer 10

Furosemide
Bumetanide
Torsemide
Ethacrynic Acid

Question 11

What are some notable diuretics that work at the Distal Tubule?

Answer 11

Thiazides
Metolazone
Chlorthalidone
Indapamide

Question 12

What are some notable diuretics that work at the Collecting Tubule?

Answer 12

Spironolactone
Eplerenone
Amiloride
Triamterene

Question 13

For acetazolamide, what is the:

1) mechanism
2) therapeutic uses
3) timing
4) side effects/contraindications?

Answer 13

1) Inhibition of renal carbonic anhydrase to prevent “new” HCO3- production -> increase pH/HCO3- in urine and mild diuresis(4%)
2) endema w/ metabolic acidosis; Acute Mountain Sickness (CFS pH), glaucoma
3) peak +2hr; gone ~+12hr
4) hepatic cirrhosis; (SE) hypechloremic metabolic acidosis, stones, K+ loss

Question 14

For mannitol, what is the:

1) mechanism
2) therapeutic uses
3) side effects/contraindications?

Answer 14

1) freely filtered, but not completely reabsorbed, induces diuresis via osmotic pressure
2) increased urine volume(ARF), reduce intracranial/intraocular pressure
3) dehydration, hypernatremia

Question 15

For furosemide, what is the:

1) mechanism
2) therapeutic uses
3) timing
4) side effects/contraindications?

Answer 15

1) inhibit active chloride transport in TAL causing an increase in FeNa (1-20%)
2) ARF, CRF, refractory edema, acute PE, hypertensive crisis
3) PO -> onset: 30-60min, pk: 1-2hr, gone:4-8hr
IV-> onset: 5min, pk:15-45min, gone-2-3hr
4) Drug interaction- amino glycoside, wafarin
SE- dehydration, Low K, Na, Mg, urea, glucose (less than thiazides)

Question 16

For thiazides, what is the:

1) mechanism
2) therapeutic uses
3) timing
4) side effects/contraindications?

Answer 16

1) competitively inhibit Cl- on the NCC in the distal tubule AND increase Ca resorption
2) essential hypertension, CHF, edema, nephrogenic diabetes
3) onset:1-2hr, pk:2-4hr
4) CROSS Placenta; hypokalemia,-natriemia (high dose), Hyper-uricemia, -glycemia, -calcemia

Question 17

For a) sprironolactone, b) amiloride what is the:

1) mechanism
2) therapeutic uses
3) side effects/contraindications?

Answer 17

1a) aldosterone antagonist in Collecting Duct
1b) block Na resorption at ENaC; both mild K-SPARING diuresis (FeNa~2%) due to interruption with the electrogradient required to diffuse K+ into the lumen
2)good addition to other diuretics to preserve K+; spironolactone -> CHF!, lower proteinuria
3)hyperkalemia, azotemia, gynocomastia, glucose intolerance in diabetes
Drug int: ACE inhibitors, ARB, penecillin -> hypekalemia especially in patients with poor renal function

Question 18

What is diuretic resistance?

Answer 18

Decrease in effectiveness of Loop Diuretics (furosemide)
Acute Tolerance-> marked increase in Na resorption in PCT
Rebound Na Retention-> due to short duration of drug, marked Na resorption between doses
Chronic-> long term therapy can cause compensatory resorption in distal nephron, leading to hypertrophy and decreased efficacy