Top 100 drugs

Question 1

MAO of ACEI

Answer 1

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

Question 2

The effects of ACEi on the body

Answer 2

1. 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
2. Dilate arteries and veins by blocking angiotensin II formation and inhibiting bradykinin metabolism. This vasodilation reduces arterial pressure, preload and afterload on the heart
3. Down regulate sympathetic adrenergic activity by blocking the facilitating effects of angiotensin II on sympathetic nerve release and reuptake of norepinephrine.

Question 3

4 big adverse effects of ACEi

Answer 3

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

Question 4

Lifestyle advice for ACEi

Answer 4

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

Question 5

INDICATION for ACEi (esp. ramipril)

Answer 5

1. Heart Failure
2. hypertension
3. myocardial infarction

Question 6

why is ACEi an effective treatment for HEART FAILURE ?

Answer 6

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:

1. Reduced afterload, which enhances ventricular stroke volume and improves ejection fraction.
2. Reduced preload, which decreases pulmonary and systemic congestion and edema.
3. Reduced sympathetic activation, which has been shown to be deleterious in heart failure.
4. Improving the oxygen supply/demand ratio primarily by decreasing demand through the reductions in afterload and preload.
5. Prevents angiotensin II from triggering deleterious cardiac remodeling

Question 7

MAO of CCB

Answer 7

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

Question 8

what are the 3 indications for CCB? explain how CCB can be helpful for those indications

Answer 8

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.

Question 9

what are the 2 classes of CCB?

Answer 9

dihydropyridines & non dihydropyridines

Question 10

what are the differences between dihydropyridines and non dihydropyridines CCB?

Answer 10

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.

Question 11

what are the side effects of dihydropyridines CCB

Answer 11

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.

Question 12

what are the side effects of non - dihydropyridines CCB

Answer 12

The cardiac selective, non-dihydropyridine CCBs can cause excessive bradycardia, constipation, impaired electrical conduction (e.g., atrioventricular nodal block), and depressed cardiac contractility.

Question 13

what are the contraindications for non - dihydropyridines CCB

Answer 13

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.

Question 14

drug interactions for CCB

Answer 14

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.

Question 15

explain the MAO Loop diuretics

Answer 15

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

Question 16

explain the MAO Thiazide diuretics

Answer 16

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.

Question 17

how can the use of thiazide and loop diuretics cause hypokalemia ?

Answer 17

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.

Question 18

explain the MAO of potassium-sparing diuretics

Answer 18

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.

Question 19

what drug class is amiodarone and explain mao

Answer 19

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.

Question 20

what are the monitoring requirements for amiodarone?

Answer 20

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

Question 21

drug interactions for amiodarone

Answer 21

Amiodarone increases the plasma concentration of warfarin, digoxin and phenytoin

Question 22

what drug class is digoxin and explain mao

Answer 22

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.

Question 23

what are the cautions and contraindications for digoxin

Answer 23

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.

Question 24

what are the monitoring requirements for digoxin

Answer 24

• 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

Question 25

what are the drug interactions for digoxin

Answer 25

Drug interactions

• Many commonly used drugs interact with digoxin. The Class IA antiarrhythmic, quinidine competes with digoxin for binding sites and depresses renal clearance of digoxin. These effects increase digoxin levels and can produce toxicity. Similar interactions occur withcalcium-channel blockers andnonsteroidal anti-inflammatory drugs
• Other drugs that interact with digoxin areamiodarone (Class III antiarrhythmic) andbeta blockers
  -Diuretics can indirectly interact with digoxin because of their potential for decreasing plasma potassium levels (i.e., producing hypokalemia).
  
  • In states of hypokalemia, or low potassium, digoxin toxicity is actually worsened becausedigoxin normally binds to the ATPase pump on the same site as potassium
    When potassium levels are low, digoxin can more easily bind to the ATPase pump, exerting the inhibitory effects

Question 26

what are the counselling points for digoxin ?

Answer 26

Observe for signs and symptoms of toxicity. In adults and older children, first symptoms of toxicity usually include abdominal pain, anorexia, nausea, vomiting, visual disturbances, bradycardia, and other arrhythmias. stop taking and notify a healthcare professionals

Advise patient to notify health care professional of this medication regimen before treatment.

Your doctor will want you to have some blood tests from time to time during this treatment, to check levels of the salts (electrolytes) in your blood and to make sure your kidneys are working well. You will be required to have blood tests occasionally to check the digoxin level in
your body.

Before you buy any medicines check with a pharmacist that they are suitable to take with digoxin. This is because some medicines and herbal remedies can interfere with digoxin levels.

Possible side effects
 Loss of appetite and nausea
 Tiredness
 Confusion
 Palpitations
 Blurred vision
 Dizziness

Question 27

counselling points for amiodarone

Answer 27

Amiodarone patient counselling points: BITCH

* Advise patient about photosensitivity reactions;
	○ Its very common side effects and pay persist for months even after stopping treatment 
	○ Blue grey discolorations occurs in light exposed skin (goes away after stopping treatment)
	○ Counsel patients to use a wide spectrum sunscreen minimum SPF 30

* tell them that they are likely to experience side effects such as nausea vomiting, this is very common when patient its on high dose of amiodarone (i.e. the loading dose) -> side effect should go when dose is reduced

* Patient will get regular thyroid function tests;
	○  baseline is established when drug is started and they get a test every 6 months 
	○ Test is done 12 months after discontinuation of treatment


* Patient will get  regular liver functions test;
	○  baseline is established when drug is started and they get a test every 6 months
	○ make sure patients do know what the symptoms of jaundice are - eg yellowing of the skin, yellowing of the eyes itchiness developing --> make sure they know to report these to their Gp 

* Patient will get baseline urea test and every 6 months afterwards

* keep they should have an ECG every 12 months to see if there any conduction disturbances and any severe bradycardia which is associated with high doses of amiodarone, especially in elderly patient

* Patient should be aware the fact they may get pulmonary toxicity (signs of this includes pneumonitis, fibrosis), shortness of breath, nonproductive cough and just deterioration in general health (so any fatigue weight loss fever)

advised to have annual eye examinations, as visual disorder is quite common with amiodarone, they can also develop corneal microdeposits. This will rarely affect their vision but drivers may be dazzled by headlights at night

Question 28

MAO of warfarin

Answer 28

Liver which are responsible for synthesising coagulation factors X, IX, VII are vitamin K dependent - these factors are still being produced and release into blood but in a non functional form

Then an enzyme called gamma-glutamyl carboxylase which carries out that carboxylation step of the glutamic acid residues which allows these regulations factors to become functional

There is a separate enzyme called vitamin K reductase andwarfarin is an inhibitor of this enzyme- so it prevents the conversion of vitamin K epoxide back into reduce vitamin K which is an essential cofactor that’s needed for the paired reaction with gamma-glutamyl carboxylase for the carboxylation of the glutamic acid residues

Question 29

why is heparin given with warfarin ?

Answer 29

Takes several days to achieve anticoagulant effect - bc patient will already have fully functional coagulation factor in their blood before they started taking warfarin and it take several days for those to be completely cleared and be replaced by new non-functional coagulation Factor that were synthesised in the presence of warfarin - so before
warfarin starts to fully work patient is also given heparin

Question 30

what drugs increase the rate of warfarin metabolism ?

Answer 30

drugs that are able to increase the rate of metabolism of warfarin in the Liver can reduce the anticoagulant effect of warfarin such as (e.g. carbamazepine, primidone, phenytoin, rifamycins)

Question 31

what drug inhibit the metabolism of warfarin?

Answer 31

drugs that inhibit the metabolism of warfarin have can increase the anticoagulant effect of warfarin and predispose the patient to bleeding (e.g. cimetidine, amiodarone)

Question 32

what drug can displace warfarin from plasma albumin?

Answer 32

other drugs that are highly albumin bound have the potential to increase the anticoagulant effect of warfarin by potentially displacing it from plasma albumin (eg. NASAID) - thats why aspirin or nsaid should not be taken with warfarin as it increase the risk of bleeding

Question 33

counselling advice for warfarin

Answer 33

Side effects - What else did you doctor tell you to expect from this medication?

• Common = warfarin is increase risk of bleeding - your more likely to bleed easily bc this medicine thins out your blood - what this means is that your bleeding may take longer to stop if you hurt yourself, you may get occasional nose bleeds, you may get bruises more easily;
  
  • Nausea, vomiting, hairloss
• Serious but they are rare = skin necrosis is when bloodclots block blood vessels destroying areas of skin (signs to look out for - painful blister, black spots , skin redness)
• Calciphylaxis - caused by calcium accumulation under the skin (signs - painful skin rashes)
• Haemorrhage - warfarin can cause internal bleeding (signs - black/dark red stool, blood in the urine, very large unexplained bruises)

Medicinal advice

• Warfarin have extensive drug interactions so check with the pharmacist before you buy any over the counter medicines
• If you want to take painkillers, avoid ibuprofen, aspirin bc this can increase the risk of bleeding - just stick with paracetamol

Lifestyle advice - can I ask you few questions about your lifestyle just to see if there is any areas of improvement so that you get the full benefit from warfarin?

1. do you drink alcohol by any chance?

• Alcohol can affect how your warfarin works, so patient is advice to limit their alcohol intake
• If you do decide to drink, stay within the recommended limit of 14 units per week. You should spread the drink through the week , and avoid binge drinking bc that can have an effect your INR

1. How would you describe your diet ?

• The effectiveness of warfarin is affected by the amount of vitamin K in your diet - so Its important that you keep your diet consistent
• If your diet already consist of vitamin K rich food there is no need to make changes or restrict these food
• If you wish to change your diet in any way such as eating more dark leafy vegetables such as eating more kale, broccoli then discuss this with your doctor before you make these changes bc they may want to monitor your INR ratio

4) if you are getting a medical procedure done for example Dental procedure, let your dentist know you are taking warfarin

1. Avoid activity that could cause you to hurt your self for example avoiding contacts sports like ruby and football. Also wear gloves whilst using sharp knives to prevent cuts

1. Yellow book? - have you been given the yellow book and yellow card? - do you know what they are for?

• Remember to carry your yellow card with you at all times and always bring your yellow book to all your doctors appointments that is used to record your warfarin doses, indication of treatment and blood test results