Pharmacology - CVS Flashcards
What is the mechanism, clinical effect and pharmacokinetics of GTN
**-mechanism:
converted to nitric oxide, taken up by smooth muscle (all types, including vascular), causes increased cGMP
prevents interaction between myosin and actin, leading to SMC relaxation
-clinical effect: reduces myocardial oxygen demand
vascular =** venodilation** at low concentration, causing reduced venous return–> reduced LVEDV/ventricular pre-load–> decreased LV wall tension–> reduced myocardial oxygen.
arteries dilated at high concentration, causing reduced BP and dilation of epicardial artery
overall effect: reduce CO and myocardial oxygen demand and improved delivery of oxygen to heart
other: relax bronchi, GI tract, GU tract, decrease platelet aggregation
-pharmacokinetics: Administration: SL/IV/Transdermal/Buccal
GTN rapidly absorbed but high first pass metabolism, bioavailability <10-20% (ISMN oral bioavailability of 100%)
SL route avoids hepatic metabolism,
onset 1-3 minutes, doa 10-30 minutes
excretion via kidneys
2/3; 2/3
What are the indications, side effects and contraindications of GTN
-indications:
angina, acs, hypertensive emergencies, APO, aortic dissection
-adverse effects:
orthostatic hypotension, tachycardia, headache, methaemoglobinaemia
-contraindications:
hypotension, inferior and posterior MI or right ventricular infarct, fixed cardiac output(Aortic stenosis, tamponade etc.); Raised ICP
What is tachyphylaxis as it relates to GTN
-continuous exposure to GTN causes SMC to develop tolerance, seen with continuous infusions
-require a drug free interval of at least 8 hours between doses
-theory: diminished release of nitric oxide and systemic compensation
When should GTN be used with caution
hypotension
inferior/posterior MI
raised ICP
significant tachycardia
What are the effects of nitric oxide
- smooth muscle relaxant
- platelet inhibition
- immune regulator
- neurotransmitter
(Nitro for a SPIN)
What are the therapeutic applications of nitric oxide
-vascular effects: angina
-hypertension associated with pregnancy
-respiratory disorders: newborns with pulmonary hypertension
-atherosclerosis: may act as an antioxidant and preventing foam cell formation in the vascular wall
-platelets: inhibitor of platelet aggregation
-CNS: may have a role in epileptic seizures
What drugs are used in hypertensive emergencies
GTN
nifedipine
diazoxide
hydralazine
nitroprusside
esmolol
labetalol
What is the mechanism of action, pharmackinetics and side effects of sodium nitroprusside?
Pharmacodynamics:
- release of NO leading to increased cGMP, causing smc relaxation
- affects arteries and veins equally
Pharmacokinetics:
- only parental form available
- onset 1 minute, half life 2 minutes, duration of action 5 minutes
- rapidly metabolised by uptake into RBC, release NO and cyanide
- sensitive to light
Side effects:
- accumulation of cyanide
- hypotension
- metabolic acidosis
- arrhythmia
What is the mechanism of action, pharmacokinetics, indications and adverse effects of Adenosine; Drug interactions
-mechanism:
Blocks AV conduction
act on the Adenosine receptor
activating inward rectifier K+ current and inhibit Ca+2 currents causing hyperpolarisation of AV node and suppresion of calcium dependent AP.
directly inhibits AV nodal conduction and increases AV nodal refractory period, less effect on SA node. Interrupts re-entry through AV node
-pharmacokinetics:
very rapid metabolism by adenosine deaminase in RBC and endothelial cells
t1/2 <10 seconds, doa 30 seconds, must be given by rapid IV bolus
-indications: conversion of SVT to sinus rythm
-adverse effects: flushing, Bronchospasm, chest tightness, sense of impending doom, Arrythmia
-contraindications: AV block, SSS, acute asthma
-Drug interactions: Theophylline inhibits adenosine rc
Dipyrridamole enhances;blocks adenosine re-uptake
How do you classify anti-arrhythmic drugs and give an example of each
-class 1 = Na+ channel blockers
a - procainamide, quinidine (prolongs AP)
b - lidocaine (shortens AP)
c - flecainide (minimal effect on AP)
-class 2 = beta blockers - propranolol
-class 3 = K+ channel blockers - amiodarone, sotalol
-class 4 = Ca+2 channel blockers - verapamil, diltiazem
What antiarrhythmic drugs can be used in the management of AF
class 1c (flecainide)
class 2 (metoprolol)
class 3 (amiodarone)
class 4 (verapamil)
unclassified (digoxin)
What is the mechanism of action and cardiac effects of Amiodarone?
-mechanism:
class 3 antiarrhythmic medication (potassium channel blocker)
blocks rapidly activating potassium current, causing markedly prolonged AP duration and QT interval
also: blocks Na+ channel, weak beta blocker, noncompetitive alpha blocker, weak Ca+ blocker
-effects:
prolongs AP duration, decreases HR and AV nodal automaticity, slows AV nodal conduction
Indications, side effects and drug interactions of Amiodarone
-indications: ventricular (vt) and supraventricular (af) arrhythmias
-adverse effects: heart block, pulmonary toxicity, hepatitis, hypo/hyperthyroidism, photodermatitis, torsades (rare)
-drug interactions:
amiodarone is a substrate for CYP3A4
inhibitors (cimetidine) - increase level of amiodarone
inducers (rifampicin) - decrease level of amiodarone
amiodarone inhibits several P450 enzymes, causing increased levels of - digoxin, warfarin, statin
What is the mechanism of action and pharmacokinetics of digoxin
-mechanism:
increases cardiac contractile force and decreases HR
mechanical =
inhibit Na+/K+ ATPase, causing increased intracellular Na+ and decreased intracellular K+
this causes decreased Ca+2 expulsion via Na+/Ca+2 exchange
increased concentration of Ca+2 causing increased contraction of cardiac sarcomere
electrical = indirectly modifies autonomic activity and increases efferent vagal activity
this causes decreased firing rate at SA node and increased refractory period at AV node
-pharmacokinetics:
well absorbed orally, moderate VOD, t1/2 36-40 hours, 2/3 excreted unchanged by kidneys
Are the parasympathetic effects of digoxin uniform throughout the heart
No
The atria and SA/AV node are more affected than purkinje or ventricular function
What are the features of toxicity of digoxin, antidote and why are patients in heart failure more prone
Features of Digoxin Toxicity:
- Cardiac: hyperkalaemia, enhanced automaticity + decreased AV nodal conduction -> arrhythmia (AVJR, PVC, VT, bigeminy, 2nd degree HB, bradycardia with R on T)
- Neurological: disorientation, hallucination, green and yellow vision
- Gastrointestinal: anorexia, nausea/vomiting/diarrhoea, abdominal pain
Antidote for Digoxin Toxicity: digoxin-specific antibody fragments (Digibind), 1 vial covers 500mcg digoxin
Predisposition:
- Reduced kidney function: renal clearance requires dose adjustment, patients in heart failure have poor renal perfusion from lower CO, K+ competes with binding of digoxin, so toxicity increased in setting of low K+ (may be on diuretics)
- Drug interaction: increased digoxin level by NSAIDs, (impairing renal clearance), thiazides and loop diuretics (depleting K), aitiarrhythmics (amiodarone, quinidine), verapamil (CCBs), macrolide antibiotics (increased bioavailability)
- Electrolyte disturbance: low K, low Mg, high Ca
