Pharmacology Flashcards
What is the MOA of Calcium channel blockers?
Blocks entry of calcium into muscle cells, causing vasodilation. This leads to decreased myocardial force generation (negative inotropy), decrease in heart rate (negative chronotropic) and decrease in conduction velocity within the heart (negative dromotropic)
List 2 examples of non-dihydropyridines CCBs
Diltiazem & verapamil
List 3 examples of dihydropyridines CCBs
1) Amlodipine
2) Felodipine
3) Nifedipine
4) Nicardipine
List 3 indications for verapamil
1) Supraventricular tachycardia
2) Hypertension
3) Angina
MOA of Beta blockers
Beta blockers inhibits activation of adenylyl cyclase -> decreased cAMP levels -> reduced activation of calcium channel -> reduced Ca conc. in cells -> reduction in contraction of muscle cells
List 3 non-selective beta-blockers
1) Propranolol
2) Pindolol
3) Carvedilol
List 3 beta-1 selective beta blockers
1) Atenolol
2) Bisprolol
3) Metoprolol
Beta-1 adrenergic receptors are predominantly found in?
Heart muscles
List 3 beta-blockers specifically approved to treat heart failure
1) Bisoprolol
2) Metoprolol
3) Carvedilol
List at least 3 indications for beta-blockers
1) Hypertension
2) Heart failure
3) Following myocardial infarction
4) Abnormal heart rhythm
5) Anxiety disorders
List 3 adverse effects of beta-blockers
1) Hypotension
2) Bradycardia
3) AV nodal block
4) Reduced exercise capacity
5) Bronchoconstriction (especially in asthmatics)
Explain why beta-blockers (especially non-selective) are contraindicated in asthmatics
B2 receptors are found in the bronchus to mediate bronchodilation. Use of beta-blockers, especially non-selective ones will lead to bronchoconstriction
MOA of ACE-I (hint: 3 pathways)
ACE-inhibitors inhibits ACE from converting angiotensin I to angiotensin II -> reduced angiotensin II leads to:
1) reduced vasoconstriction, hence reduced peripheral vascular resistance
2) reduced aldosterone secretion, hence reduced Na/water retention
3) reduces inactivation of bradykinin, which will activate nitric oxide and prostaglandins, causing vasodilation
=> overall reduces BP
List 3 examples of ACE-inhibitors
1) Captopril
2) Enalapril
3) Ramipril
4) Lisinopril
List 3 indications of ACE-inhibitors
1) Hypertension
2) Heart failure
3) Following myocardial infarction
4) Renal insufficiency- reduces aldosterone which provides kidney protective effects
List 5 adverse effects of ACE-inhibitors
1) Severe hypotension
2) Acute renal failure
3) Hyperkalemia
4) Angioedema
5) Dry cough - due to reduction of inactivation of bradykinin which leads to release of substance P -> causes airway smooth muscles to constrict leading to bronchoconstriction and cough
ACE-I/ARBs are contraindicated in which patient population?
Pregnancy
What are the advantages of ARBs over ACE-I?
Less/no dry cough; less angioedema
List 3 examples of ARBs
Losartan, valsartan, candesartan, irbesartan, telmisartan, eprosartan
Beta blockers are contraindicated in which patient populations?
1) Asthmatics
2) Diabetes - patients cannot recognize when they are in hypoglycemic state when taking BBs, unable to take action to restore glucose levels
CCBs are contraindicated in which patient population?
Congestive heart failure
How does prostaglandins affect renal blood flow?
It increases renal blood flow
Loop diuretics targets which part of the nephrons?
Loop of Henle
A unit of the kidney is known as?
Nephron
In the thin descending loop of henle, water is extracted by what force (1)? And how is it created (2)?
1) Osmostic force
2) Created in the hypertonic medullary interstitium
The thick ascending limb of the loop of henle actively reabsorbs what?
NaCl
For the following sections of the nephron, state whether they are permeable/impermeable to water:
1) Proximal convoluted tubule
2) Thin descending limb of loop of henle
3) Thick ascending limb of loop of henle
4) Distal convoluted tubue
1) Proximal convoluted tubule- permeable to water
2) Thin descending limb- permeable to water
3) Thick ascending limb - nearly impermeable to water
4) Distal convoluted tubule - relatively impermeable to water
Where does the bulk of water resorption occur in the nephrons?
At the collecting ducts
In the thick ascending limb of loop of henle, what is the cotransporter that transports NaCl?
Na/K/2Cl co-transporter
Which transporter does loop diuretics inhibit?
Na/K/2Cl transporter in the thick ascending limb of loop of henle
Explain the function of the Na/K/2Cl co-transporter in the thick ascending loop of henle
1) Facilitates absorption of Na, K and Cl from the lumen (where the urine is formed) into the cell
2) This leads to excess K+ accumulation within the cell, causing back diffusion of K+ back into the lumen
3) Lumen now has a positive electric potential which drives the reabsorption of Mg and Ca via the paracellular pathway, into the blood
Explain the MOA of loop diuretics
1) Selectively inhibits luminal Na/K/2Cl transporter -> causing increase in Mg and Ca excretion in the urine
2) Induce renal prostaglandin synthesis
3) Furosemide increases renal blood flow
List 4 side effects of loop diuretics
1) Hypokalemic metabolic alkalosis
2) Ototoxicty - avoid using together with aminoglycoside antibiotic (due to ototoxicity S.E. as well)
3) Hyperuricemia - prevents urea from getting into the lumen, hence increase conc in blood
4) Hypomagnesemia - due to reduced reabsorption of Mg back into the blood
Which ion (1) is actively reabsorbed in the distal convoluted tubule and what facilitates its reabsorption (2)?
1) Ca ions
2) Apical Ca channel and basolateral Na/Ca exchanger
What transporter does thiazide diuretics inhibit?
Blocks Na/Cl transporter in the distal convoluted tubule
Explain the MOA of thiazide diuretics
1) Inhibits NaCl reabsorption in the distal convoluted tubule by blocking the Na/Cl transporter -> NaCl remains in the urine
2) Enhance Ca reabsorption in the distal convoluted tubule
Explain the relationship between thiazide diuretics and NSAIDs
Action of thiazides depend in part on renal prostaglandin synthesis. NSAIDs can interfere with the actions of thiazide diuretics by reducing prostaglandin synthesis -> DDI
Explain the relationship between NSAIDs and loop diuretics
Loop diuretics can induce renal prostaglandin synthesis. NSAIDs can interfere with the actions of loop diuretics by reducing prostaglandin synthesis -> DDI
List 3 examples of thiazide diuretics
1) Hydrochlorothiazide
2) Indapamide
3) Chlorthalidone
List 3 side effects of thiazide diuretics
1) Hypokalemic metabolic alkalosis
2) Hyperuricemia (due to upset of ionic balance, hence increased urea in blood)
3) Hyperglycemia
4) Hyperlipidemia
5) Hyponatremia
Explain the 3 main MOA of digoxin
1) Inhibits Na/K/ATPase pump in myocytes -> increase intracellular Na -> increase Ca influx -> increase contractility
2) Suppression of SA and AV nodal conductions -> increase refractory period and decrease conduction velocity -> decrease heart rate (direct effect)
3) Enhances vagal tone (i.e. increase parasympathetic activity), which slows down AV node conduction -> decrease heart rate
Comment on the volume of distribution of digoxin
1) Large volume of distribution as it is extensively distributed to peripheral tissues
2) Has a distinct distribution phase of 6-8h where pharmacologic effects are delayed and do not correlate well with serum concentrations during this phase
3) Volume of distribution is increased (i.e. increased toxicity) in scenarios like hypokalemia and hyperthyroidism
Does digoxin have a long or short half life?
Long half life of 36-48h in normal renal function, up to 5 days in severe renal impairment
List 5 characteristics of amiodarone
1) high affinity to tissues
2) Large volume of distribution
3) Long half-life of 40-60 days
4) Bears similar structure to thyroid hormones; deiodination during metabolism creates a source of iodine
5) High potential for DDIs (e.g. warfarin, digoxin, statins) - inhibits CYP 1A2, 2D6, 2C9, 3A4
List down 5 lab monitoring components required for amiodarone, and the monitoring intervals
1) Thyroid function test (think: iodine)
2) Liver function test
3) Chest X-ray
4) ECG
5) Physical exam
Monitoring intervals: at baseline & Q6 monthly or more often if deranged or if patient complains of symptoms
List down 7 different organs that amiodarone can cause side effects in
1) Opthalmic: hence eye exam is recommended if there is visual impairment at baseline, or if it develops during treatment
2) GI (PO route): n/v, abdominal discomfort; counsel to take after food
3) Dermatological: photosensitivity (counsel on sun protection), blue-gray skin discoloration
4) Thyroid: causes thyroid function derangements
5) Lungs: can cause pulmonary toxicity- routine chest x-rays required
6) Liver: deranged LFTs, hepatitis, cirrhosis
7) CNS: neuropathy, numbness, paraesthesias
Which classes of anti-arrhythmic drugs carries the risk of torsades de pointes?
Vaughan Williams Classification:
1) Class IA
2) Class III (amiodarone, sotalol)
Explain the role of sotalol in treatment of arrhythmias
1) Has both non-selective beta-blocking and Class III (vaughan williams classification) effects
2) Racemic mixture:
- L-isomer: class II and III effects
- D-isomer: only class III effects
List 3 lab monitoring parameters for sotalol (anti-arrhythmia lecture)
1) Renal function
2) QTc prolongation
3) Pulse rate and blood pressure
