Angina + Diuretic Drugs

Question 1

Nitrates

Name [2], Indication
MOA
AE - of GTN
AE - of SNP - 3

Note these are used as antihypertensive too

Answer 1

Nitroglycerin GTN (glyceryl trinitrate)
Sodium Nitroprusside SNP - IV - use in hypertensive crises 

• releases NO
• NO increases cGMP, cGMP dephosphorylates MLC
• Vasodilation on arteries and vessels - decrease preload, decrease afterload, increases Coronary blood flow

Most effects are on periphery

AE: reflex TC; dilating meningeal artery - headache

SNP AE:
gives off NO, Cyanide, Met-HG

• methemoglobin - cellular hypoxia (pronounced MET-hemoglobin)
• hypotension
• Cyanide poisoning

Question 2

Glycosides

Use
MOA for Blood Pressure mechanism

AE from this mechanism

Answer 2

Digoxin, Digitoxin

block Na-K ATPase; - 3 sodium out 2 potassium in
[Na+] increase, less Na enter to exchange w Ca2+
- sodium calcium antiporter
- stronger systolic contractions
ALSO, parasympathetic effect, HR decrease, allowing SV increase, CO increase

• increases contractility, increases CO
• increases CO - body reflex decreases Preload, Afterload - renin + sympathetic decrease

AE: increase intracellular Ca2+ - automaticity increases, TC increases, Fibrillation

USE: arrhythmia!, HF no longer, but can

Question 3

Glycosides

MOA for ECG, Arrhythmia

AE

Answer 3

Digoxin increases parasympathetic activity through Vagus Nerve

• decreases AV conduction, increases PR interval, decreases ventricular rate

Used for AF

AE: AV block - AF, VF

Question 4

Glycosides all AE:

Answer 4

AV Block, AF, VF
TC: fibrillation

GI
CNS

Question 5

How to treat Digoxin toxicity [2]

Answer 5

Anti-arrhythmia: Lidocaine, Propranolol

Digoxin AB, Stop treatment

Question 6

Digoxin VS Digitoxin

Answer 6

Digitoxin

• more bind to protein,
• metab in liver VS Kidney
• longer OoA, Half-life

Liver metab, longer lasting vs Digoxin

Question 7

Loop Diuretic

• Class, Name
• MOA, location, transporter inhibited
• Actions [3] [2 electrolytes] [1 renal]

Answer 7

Sulfonamide derivative: Furosemide
- inhibits NKCC2 symporter @ THICK Ascending Limb
Actions
1: decrease reabsorption of Na, K, Cl; Decreasing water reabsorption at collecting duct
2: Normally, K diffuses out, increases + potential of lumen, driving Mg2+ and Ca2+ reabsorption paracellularly; w [K+] ICF decreases, + electric potential of lumen decreases, [Mg,Ca] urine increases
- as less ions reabsorbed, Renal Medulla tonicity decreases - less water pulled out at collecting duct!

RECALL function of TAL: site of maintaining Medulla osmolarity by accumulating salt in interstitium
Function of COLLECTING DUCT: W Vasopressin, Concentrates urine by reabsorption of water into osmotically active Medulla interstitium

3: Produce PGs
- PGE2 inhibit sodium reabsorption by blocking NKCC2
- increases renal blood flow by vasodilation

• note NSAIDs block PG production, less transporters inhibited, hence allowing Na reabsorption;
• NSAID also block PGI2 which stimulates renin - aldosterone blocked hence less Na reabsorbed but most is absorbed at ascending limb anyways but K+ retention occurs

Question 8

Loop Diuretic uses [4]

Answer 8

1: Edema
2: Renal Failure: Cirrhosis, Nephrotic syndrome
- diuretic lor, make urine

3: Anion Overdose
- Anions uses same pathway as chloride for reabsorption using K+ to drive it back
4: HypERkalaemia
- NKCC block
- plus aldosterone channels action in response to high Na in urine

Question 9

Loop Diuretic AE [5]

• explain HKMA
• explain triple whammy

Note calcium reabsorbed at DCT hence no Hypocalcemia

Answer 9

Hypokalemic Metabolic Alkalosis
- more sodium at Collecting duct, reabsorbed in exchange for potassium (response by aldosterone channels); H+ also secreted (to exchange for Na+)
- somemore secondary to hypovolemia - RAAS activated and hence aldosterone leads to K+, H+ excretion increase for Na+ reabsorption
ALSO
- hypovolemia trigger PCT to increase reabsorption of water and bicarbonate - alkalosis

Hypomagnesemia
Loop earrings hurt your ear: Ototoxicity - avoid Aminoglycosides

GOUT; Hyperuricemia (through diuretic effect)

Acute Renal Failure:

• ‘secondary’ to dropping BP, diuresis - the hypovolemia is a problem
• Triple whammy w ACEI/ARB due to lack of ANGII hence Efferent Vasodilation; w NSAIDs due to PG block and Afferent Vasoconstriction

Question 10

Thick vs Thin Ascending Limb

Answer 10

Thick ascending - where NaCl absorbed , H2O impermeable

Thin descending - where water absorbed

Question 11

Name all classes of CVS Drugs [7]

Answer 11

Positive Inotropes
- Glycosides @ Heart

Vasodilators

• Potassium Channel Opener @ Vessels - Minoxidil
• NO nitrates @ Heart, Peripheral Vessels - glyceryl trinitrate, SNP
• ACEI, ARB @ Renal
• Ca channel blockers - not used in CHF - @ Heart

Others

• Loop diuretics @ Renal
• Beta Blocker @ Heart