Top 100 drugs Flashcards
(33 cards)
MAO of ACEI
ACE inhibitors produce vasodilation by inhibiting the formation of angiotensin II by inhibiting ACE enzyme.
ACE also breaks down bradykinin (a vasodilator substance). Therefore, ACE inhibitors, by blocking the breakdown of bradykinin, increase bradykinin levels contributing to dry tickly cough
angiotensin II stimulates the adrenal cortex to release aldosterone, which acts on the kidneys to increase sodium and water reabsorption leading to increased blood volume and arterial pressure.
angiotensin II also works by stimulating pituitary release of antidiuretic hormone (ADH; vasopressin), water renal reabsorption is increased, which increases blood volume and arterial pressure. ADH can also directly constrict blood vessels
The effects of ACEi on the body
- Promote renal excretion of sodium and water, and potassium retention (natriuretic and diuretic effects) by blocking the effects of angiotensin II in the kidney, blocking angiotensin II stimulation of aldosterone secretion, and by blocking angiotensin II stimulated ADH release. These actions blood volume, venous pressure and arterial pressure
- Dilate arteries and veins by blocking angiotensin II formation and inhibiting bradykinin metabolism. This vasodilation reduces arterial pressure, preload and afterload on the heart
- Down regulate sympathetic adrenergic activity by blocking the facilitating effects of angiotensin II on sympathetic nerve release and reuptake of norepinephrine.
4 big adverse effects of ACEi
Increased serum creatinine: The decrease in angiotensin II leads to preferential vasodilation of the kidney’s efferent arteriole compared to the afferent arteriole. That means the blood vessel carrying blood away from the glomerulus is more dilated than the blood vessel carrying blood to the glomerulus. the pressure in the glomerulus decreases. mean filtration of substances within the glomerulus (from the blood into the nephron) also decreases. So things…like serum creatinine…that are normally filtered out of the blood into the nephron may not be filtered as efficiently, leaving higher levels in the blood
Hyperkalemia (increased serum potassium): This adverse effect of ACE-Is is a result of these medications’ effects on aldosterone activity. Remember that angiotensin II usually stimulates release of aldosterone from the adrenal cortex, which leads to sodium and water retention in the kidney. Well this sodium and water retention occurs in tandem with excretion of potassium via the action of a Na/K ATPase. when we block (at least some of) the activity of aldosterone with the use of ACE-Is, there is less excretion of potassium within the renal tubule.
Hyperkalemia with ACE-Is isn’t usually something that happens in just any patient out of the blue (although it can). Most of the time, patients have some underlying (perhaps as yet undiagnosed) kidney disease, are taking in extra potassium through diet or supplements, or are taking other medications that contribute to potassium retention.
Dry, hacking cough
Angioedema: ACE-I angioedema is bradykinin-mediated, much like the dry, hacking cough. Can be life threatening
Lifestyle advice for ACEi
Ramipril is a medicine that can be used to treat high blood pressure, heart failure this is when your heart is not functioning as well and to protect your heart and blood vessel from further damage. 2
Take the amount of ramipril your doctor has told you to. The patient is advised to take their first dose at bedtime because people can often feel dizzy when they take their first dose of ramipril. With exception to the first dose, you can take it at any time of the day. 2
Try to take your medicine at the same time each day because it will stop you from forgetting to take your medicine. Swallow the tablet with water with or without food. 2
Ramipril can give you some side effects but not everyone gets them. The most common side effect includes dry cough, feeling dizzy, headaches and nausea. More serious but rare side effects like difficulty breathing, swelling of the face, mouth or tongue, skin rash and yellowing of your skin or the white of your eyes stop taking your medicine immediately and contact your doctor. 2
Ramipril is taken long term, do not stop taking it without speaking to your doctor because stop taking this drug suddenly can cause your blood pressure to spike. 6
Make sure you are keeping a balanced diet and avoid food with lots of salt because salt can raise your blood pressure. To cut down your salt intake, make sure you eat lots of fiber such as whole grain rice and have plenty of fruit and vegetable. 3
Limit your alcohol intake, because alcohol can raise your blood pressure and make you gain weight which can further increase your blood pressure. An adult is recommended not to drink more than 14 units of alcohol a week. 3
Doing regular exercise can lower blood pressure, by keeping the heart and blood vessel health. Regular exercise can help you lose weight that helps with lowering blood pressure. It is recommended that you do 30 mins of exercise 5 times a week. 3
If you forgot to take a dose of your medicine take it as soon as you remember, unless it is time for your next dose, in that case, forget the missed dose and take the next dose. Do not take two doses together to make up for a missed dose. 2
INDICATION for ACEi (esp. ramipril)
- Heart Failure
- hypertension
- myocardial infarction
why is ACEi an effective treatment for HEART FAILURE ?
ACE inhibitors have proven to be very effective in the treatment of heart failure caused by systolic dysfunction (i.e., heart failure with reduced ejection fraction; HFrEF)). Beneficial effects of ACE inhibition in HFrEF include:
- Reduced afterload, which enhances ventricular stroke volume and improves ejection fraction.
- Reduced preload, which decreases pulmonary and systemic congestion and edema.
- Reduced sympathetic activation, which has been shown to be deleterious in heart failure.
- Improving the oxygen supply/demand ratio primarily by decreasing demand through the reductions in afterload and preload.
- Prevents angiotensin II from triggering deleterious cardiac remodeling
MAO of CCB
Currently approved calcium-channel blockers (CCBs) bind to L-type calcium channels located on vascular smooth muscle, cardiac myocytes, and cardiac nodal tissue (sinoatrial and atrioventricular nodes). These channels are responsible for regulating the influx of calcium into cells. In vascular smooth muscle, calcium influx stimulates smooth muscle contraction; in cardiac myocytes calcium influx stimulates muscle contraction; in nodal tissue calcium influx plays an important role in pacemaker currents and in phase 0 of action potentials. Therefore, by blocking calcium entry into the cell, CCBs cause vascular smooth muscle relaxation (vasodilation), decreased myocardial force generation (negative inotropy; decreased contractility), decreased heart rate (negative chronotropy), and decreased conduction velocity (negative dromotropy), particularly at the atrioventricular node
what are the 3 indications for CCB? explain how CCB can be helpful for those indications
Hypertension: By causing vascular smooth muscle relaxation, CCBs decrease systemic vascular resistance, which lowers arterial blood pressure. These drugs primarily affect arterial resistance vessels, with only minimal effects on venous capacitance vessels. Some CCBs also reduce heart rate and contractility, which can lead to a fall in cardiac output and thereby lower arterial pressure.
Angina: The anti-anginal effects of CCBs are derived from their vasodilator and cardiodepressant actions. Systemic vasodilation reduces arterial pressure, which reduces ventricular afterload (wall stress) thereby decreasing oxygen demand by the heart. The more cardioselective CCBs (verapamil and diltiazem) decrease heart rate and contractility, which leads to a reduction in myocardial oxygen demand. CCBs can also dilate coronary arteries and prevent or reverse coronary vasospasm (as occurs in Printzmetal’s variant angina), thereby increasing oxygen supply to the myocardium.
Arrhythmias: The antiarrhythmic properties (Class IV antiarrhythmics) of CCBs are related to their ability to suppress firing of aberrant pacemaker sites within the heart, and their ability to decrease conduction velocity and prolong repolarization, especially at the atrioventricular node. This latter action at the atrioventricular node helps to block reentry mechanisms, which can cause supraventricular tachycardia.
what are the 2 classes of CCB?
dihydropyridines & non dihydropyridines
what are the differences between dihydropyridines and non dihydropyridines CCB?
They differ not only in their basic chemical structure, but also in their relative selectivity for cardiac versus vascular L-type calcium channels. The most smooth muscle selective class of CCBs are the dihydropyridines. Because of their high vascular selectivity, these drugs are primarily used to reduce systemic vascular resistance and arterial pressure, and therefore are used to treat hypertension
Extended release formulations or long-acting compounds are used to treat angina and are particularly effecting for vasospastic angina (resting angina); however, their powerful systemic vasodilator and pressure lowering effects can lead to baroreflex cardiac stimulation (tachycardia and increased inotropy), which can offset the beneficial effects of afterload reduction on myocardial oxygen demand.
Note that dihydropyridines are easy to recognize because the drug name ends in “pine
Non-dihydropyridines, of which there are only two currently used clinically, comprise the other two classes of CCBs. Verapamil (phenylalkylamine class), is relatively selective for the myocardium, and is less effective as a systemic vasodilator drug. This drug has a very important role in treating angina (by reducing myocardial oxygen demand and reversing coronary vasospasm) and arrhythmias. Diltiazem (benzothiazepine class) is intermediate between verapamil and dihydropyridines in its selectivity for vascular calcium channels. By having both cardiac depressant and vasodilator actions, diltiazem is able to reduce arterial pressure without producing the same degree of reflex cardiac stimulation caused by dihydropyridines.
what are the side effects of dihydropyridines CCB
Dihydropyridine CCBs can cause flushing, headache, excessive hypotension, peripheral edema and reflex tachycardia. Baroreceptor reflex activation of sympathetic nerves and lack of direct negative cardiac effects can make dihydropyridines a less desirable choice for stable angina than diltiazem, verapamil or beta-blockers
Long-acting dihydropyridines (e.g., extended release nifedipine, amlodipine) have been shown to be safer anti-hypertensive drugs, in part, because of reduced reflex responses. This characteristic also makes them more suitable for angina than short-acting dihydropyridines.
what are the side effects of non - dihydropyridines CCB
The cardiac selective, non-dihydropyridine CCBs can cause excessive bradycardia, constipation, impaired electrical conduction (e.g., atrioventricular nodal block), and depressed cardiac contractility.
what are the contraindications for non - dihydropyridines CCB
Therefore, patients having preexistent bradycardia, conduction defects, or heart failure caused by systolic dysfunction (HFrEF) should not be given CCBs, especially the cardiac selective, non-dihydropyridines.
CCBs, especially non-dihydropyridines, should not be administered to patients being treated with a beta-blocker because beta-blockers also depress cardiac electrical and mechanical activity and therefore the addition of a CCB augments the effects of beta-blockade.
drug interactions for CCB
Some calcium channel blockers are affected by grapefruit juice — it is advised that patients on felodipine or lercanidipine do not consume grapefruit or grapefruit juice. Although with amlodipine any increased bioavailability caused by grapefruit appears to be minimal, there have been isolated reports of problems and some manufacturers still warn against grapefruit or grapefruit juice consumption.
Erythromycin is known to increase the bioavailability of felodipine substantially. A few interactions between other calcium channel blockers and macrolides have also been reported so manufacturers may advise against these combinations.
Azole antifungals can increase the levels of calcium channel blockers, resulting in greater adverse effects, so are best avoided if possible.
St John’s Wort is reported to reduce the bioavailability of some calcium channel blockers, but since this effect is due to induction of a cytochrome p450 enzyme relevant to the metabolism of all calcium channel blockers, it could affect the whole drug group. Either avoid the combination or ensure that extra blood pressure checks are in place.
explain the MAO Loop diuretics
inhibit the sodium-potassium-chloride cotransporter in the thick ascending limb . This transporter normally reabsorbs about 25% of the sodium load; therefore, inhibition of this pump can lead to a significant increase in the distal tubular concentration of sodium, reduced hypertonicity of the surrounding interstitium, and less water reabsorption in the collecting duct. This altered handling of sodium and water leads to both diuresis (increased water loss) and natriuresis (increased sodium loss).
By acting on the thick ascending limb, which handles a significant fraction of sodium reabsorption, loop diuretics are very powerful diuretics. These drugs also induce renal synthesis of prostaglandins, which contributes to their renal action including the increase in renal blood flow and redistribution of renal cortical blood flow.
Loop diuretics are the most effective diuretic class because their site of action has a very high capacity for sodium reabsorption. Note that efficacy is inversely related to renal function, which can be greatly impaired in heart failure
explain the MAO Thiazide diuretics
are the most commonly used diuretic, inhibit the sodium-chloride transporter in the distal tubule. Because this transporter normally only reabsorbs about 5% of filtered sodium, these diuretics are less efficacious than loop diuretics in producing diuresis and natriuresis. Nevertheless, they are sufficiently powerful to satisfy many therapeutic needs requiring a diuretic. Their mechanism depends on renal prostaglandin production.
how can the use of thiazide and loop diuretics cause hypokalemia ?
Because loop and thiazide diuretics increase sodium delivery to the distal segment of the distal tubule, this increases potassium loss (potentially causing hypokalemia) because the increase in distal tubular sodium concentration stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium and hydrogen ion, which are lost to the urine. The increased hydrogen ion loss can lead to metabolic alkalosis.
the loss of potassium and hydrogen ion by loop and thiazide diuretics also due to the from activation of the renin-angiotensin-aldosterone system that occurs because of reduced blood volume and arterial pressure. Increased aldosterone stimulates sodium reabsorption and increases potassium and hydrogen ion excretion into the urine.
explain the MAO of potassium-sparing diuretics
Unlike loop and thiazide diuretics, some of these drugs do not act directly on sodium transport. Some drugs in this class antagonize the actions of aldosterone (aldosterone receptor antagonists) at the distal segment of the distal tubule. This causes more sodium (and water) to pass into the collecting duct and be excreted in the urine. They are called K+-sparing diuretics because they do not produce hypokalemia like the loop and thiazide diuretics.
The reason for this is that by inhibiting aldosterone-sensitive sodium reabsorption, less potassium and hydrogen ion are exchanged for sodium by this transporter and therefore less potassium and hydrogen are lost to the urine.
Other potassium-sparing diuretics directly inhibit sodium channels associated with the aldosterone-sensitive sodium pump, and therefore have similar effects on potassium and hydrogen ion as the aldosterone antagonists
Because this class of diuretic has relatively weak effects on overall sodium balance, they are often used in conjunction with thiazide or loop diuretics to help prevent hypokalemia.
what drug class is amiodarone and explain mao
Class III antiarrhythmic compounds which bind to and block potassium channels that are responsible for phase 3 repolarization. Byblocking these channels, action potential repolarization is delayed, which leads to an increase in action potential duration and an increase the refractory period
By increasing the refractory period, these drugs are very useful in suppressing tachyarrhythmias caused byreentry mechanisms. Reentry occurs when an action potential reemerges into normal tissue that is no longer refractory. When this happens, a new action potential is generated prematurely (before normal activation) and a circular, repeating pattern of early and rapid activation can develop, which leads totachycardia.
what are the monitoring requirements for amiodarone?
Liver toxicity can also occur, so liver biochemistry should be measured before and then every 6 months of treatment.
Amiodarone contains iodine and can cause both hyper- and hypothyroidism. Thyroid function should be carried before treatment and monitored every 6 months.
serum potassium levels should be measured before treatment.
Liver function - bc amiodarone is highly lipophilic, is concentrated in many tissues and cells, including hepatocytes in the liver which can cause liver damage
drug interactions for amiodarone
Amiodarone increases the plasma concentration of warfarin, digoxin and phenytoin
what drug class is digoxin and explain mao
Digitalis compounds are potent inhibitors of cellular Na+/K+-ATPase. This ion transport system moves sodium ions out of the cardiac myocytes and brings potassium ions into the cell. By inhibiting the Na+ /K+- ATPase, cardiac glycosides cause intracellular sodium concentration to increase. As a result this inactivate the Na+- Ca++ exchanger, thereby preventing Ca2+ from leaving the myocytes. In the heart, increased intracellular calcium, leads to increased in heart contraction.
By mechanisms that are not fully understood, activates the parasympathetic nervous system leading to decrease in Heart rate and conduction velocity in the AV node. Digoxin also increases the effective refractory period within the atrioventricular node.
what are the cautions and contraindications for digoxin
Contraindications
Digoxin is contraindicated in patients who are hypokalemic, or who have atrioventricular block or Wolff-Parkinson-White (WPW) syndrome
Cautions
- Impaired renal function leads to enhanced plasma levels of digoxin because digoxin is eliminated by the kidneys
- elderly has reduced muscle mass so are more susceptible to digoxin toxicity because they often have reduced renal function, and their reduced muscle mass increases plasma digoxin levels at a given dose because muscle Na+/K+ -ATPase acts as a large binding reservoir for digoxin
- Hypercalcaemia bc The end-point of digoxin’s effect is toopen membrane calcium channels, resulting in an increased calcium influx into cells**. When the calcium levels are high, in the setting of digoxin toxicity, the result is an increase in calcium influx and enhanced toxicity.
what are the monitoring requirements for digoxin
- Symptoms of digoxin toxicity can be hard to identify as they are clinically similar to deterioration of heart disease. Monitoring plasma- digoxin is not necessary during maintenance treatment. If blood monitoring is required a sample should be taken at least 6 hours after a dose
- monitor renal function
- monitor electrolyte levels bc electrolyte disturbances can increase toxicity eg. increase in ca2+ levels and decrease in K+ levels
