Pharmacology Flashcards
What is the stepwise approach for asthma pharmacological management according to the Australian guidelines?
Step 1 - intermittent asthma (as-needed short-acting beta2 agonist (SABA))
Step 2 - mild persistent asthma (regular low-dose ICS)
Step 3 - moderate persistent asthma (low-dose ICS and additional therapy)
Step 4 - moderate to severe persistent asthma (medium-dose ICS and additional therapy)
Step 5 - severe persistent asthma (high-dose ICS and additional therapy).
When is it appropriate to add a long-acting beta2 agonist (LABA) to inhaled corticosteroid (ICS) therapy for asthma?
According to the Australian guidelines, a LABA may be added to ICS therapy for asthma when the patient has persistent asthma symptoms despite treatment with low-dose ICS, or when the patient has moderate to severe asthma.
What is the recommended treatment for acute asthma exacerbations?
The recommended treatment for acute asthma exacerbations includes a short-acting beta2 agonist (SABA) delivered via inhaler or nebulizer, along with oral or intravenous corticosteroids. Oxygen therapy may also be necessary for severe exacerbations.
How often should asthma control be assessed in patients receiving pharmacological therapy?
According to the Australian guidelines, asthma control should be assessed at every visit for patients receiving pharmacological therapy for asthma. This includes monitoring symptoms, medication use, lung function, and exacerbation history.
What are the potential side effects of inhaled corticosteroids (ICS) used for asthma management? How can they be minimized?
The potential side effects of ICS used for asthma management include hoarseness, oral thrush, and dysphonia. These side effects can be minimized by using a spacer and rinsing the mouth after inhalation.
What are the potential side effects of beta2 agonists used for asthma?
The most common adverse effects of beta2 agonists used for asthma include tremors, tachycardia, palpitations, headache, hyperactivity, and hypokalemia.
What is the first-line pharmacological treatment for primary hypertension?
Angiotensin-converting enzyme (ACE) inhibitors
Angiotensin receptor blockers (ARBs)
Calcium channel blockers (CCBs)
Thiazide diuretics
When would beta blockers be indicated for hypertension?
These medications may be preferred for patients with a history of myocardial infarction, heart failure with reduced ejection fraction, or atrial fibrillation. However, they should be avoided or used with caution in patients with asthma or chronic obstructive pulmonary disease.
What considerations are there for the use of calcium channel blockers for hypertension?
These medications may be preferred for patients with coronary artery disease, angina, or peripheral artery disease. However, they should be avoided or used with caution in patients with heart failure.
What considerations are there for the use of ACEi/ARBs for hypertension?
These medications may be preferred for patients with diabetes or chronic kidney disease, as they have shown to provide renal protection. However, caution should be taken in patients with bilateral renal artery stenosis or a history of angioedema
Which antihypertensives are recommended for diabetic patients?
ACEIs or ARBs (protective against diabetic nephropathy)
Difference between dihydropyridine and non-dihydropyridine CCBs. Mention examples of each.
Dihydropyridine CCBs primarily work by relaxing the smooth muscle cells in the walls of blood vessels, leading to vasodilation and a decrease in blood pressure. They have minimal effects on cardiac muscle cells and the electrical conduction system of the heart. Some examples of dihydropyridine CCBs include amlodipine, nifedipine, and felodipine.
Non-dihydropyridine CCBs have a greater effect on the heart and its electrical conduction system, and are therefore useful in treating certain arrhythmias such as atrial fibrillation. They also have some effect on blood vessels, but not as much as dihydropyridine CCBs. Some examples of non-dihydropyridine CCBs include verapamil and diltiazem.
Indications for nitrates
Angina pectoris
- Short-acting nitrates such as sublingual nitroglycerin, isosorbide dinitrate, or nitroglycerin spray for treatment of acute attacks
- Long-acting nitrates such as isosorbide mononitrate can be taken regularly (2–3 times daily) for anginal prophylaxis: unlike some other nitrates, isosorbide mononitrate does not undergo first-pass metabolism by the liver and thus has ∼100% bioavailability.
What are the effects of aspirin based on dosage?
Low dose (below 300 mg/day): inhibition of platelet aggregation, cardiovascular prevention
Intermediate dose (300-2400 mg/day): antipyretic and analgesic effect
High dose (2400-4000 mg/day): anti-inflammatory effect
Adverse effects of aspirin
Gastrointestinal effects: Aspirin can irritate the lining of the stomach and cause ulcers and bleeding in the stomach and intestines.
Bleeding: Aspirin can interfere with blood clotting and increase the risk of bleeding, especially in people who are taking other medications that also affect blood clotting.
Allergic reactions: Some people may be allergic to aspirin and experience symptoms such as hives, swelling, and difficulty breathing.
Reye’s syndrome: Aspirin use in children and teenagers with viral illnesses such as the flu or chickenpox has been linked to Reye’s syndrome, a rare but serious condition that can cause liver and brain damage.
Kidney damage: Long-term use of high doses of aspirin can damage the kidneys.
When would clopidogrel be indicated?
Clopidogrel is indicated for the prevention of blood clots, particularly in people with a history of heart attack, stroke, peripheral arterial disease, or acute coronary syndrome. It is also used in combination with aspirin to prevent blood clots in people with acute coronary syndrome or those undergoing percutaneous coronary intervention (PCI).
Mention examples of parenteral and oral anticoagulants.
Examples of parenteral anticoagulants include:
- Heparin
- Enoxaparin
Examples of oral anticoagulants include:
- Warfarin
- Dabigatran
- Rivaroxaban
- Apixaban
What is the therapeutic range for activated partial thromboplastin time (aPTT) when using unfractionated heparin (UFH)?
The therapeutic range for aPTT when using UFH is typically 1.5 to 2.5 times the control value. However, the exact target range may vary depending on the clinical situation and the patient’s individual characteristics.
Which is the preferred agent for patients with severe renal impairment?
LMWH or UFH
While it is true that unfractionated heparin (UFH) is primarily cleared hepatically, both UFH and low molecular weight heparin (LMWH) can be used in patients with renal insufficiency. However, LMWH is generally preferred over UFH because it has a more predictable pharmacokinetic profile, a lower risk of bleeding complications, and does not require routine laboratory monitoring.
UFH may be preferred in certain situations such as patients with severe renal impairment or those requiring rapid anticoagulation reversal.
When would LMWH be indicated over UFH?
- DVT prophylaxis, outpatient care (longer half-life → fewer injections)
- Generally preferred to UFH (fewer side effects, easier handling) as long as there are no contraindication (preferred in pregnancy)
When would UFH be indicated over LMWH?
- Emergencies (more easily titrated, available as IV infusion)
- For patients with advanced renal failure (e.g., in patients with severe renal insufficiency (CrCl < 30mL/min) or the elderly)
- Pregnancies (does not cross placental barrier)
Advantages and disadvantages of UFH.
Advantages:
Short half-life, allowing for rapid reversal if necessary
Can be used in patients with renal failure or in situations where renal function is uncertain, as it is not primarily cleared by the kidneys
Disadvantages:
Requires frequent monitoring of activated partial thromboplastin time (aPTT) to adjust dose
Can cause bleeding, heparin-induced thrombocytopenia (HIT), and osteoporosis with long-term use
Requires continuous IV infusion or frequent subcutaneous injections
Advantages and disadvantages of LMWH.
Advantages:
More predictable anticoagulant effect, allowing for fixed dosing without routine monitoring
Lower risk of bleeding and HIT compared to UFH
Longer half-life, allowing for once or twice daily dosing
Does not require continuous IV infusion
Disadvantages:
Not easily reversible, with no specific antidote available
More expensive than UFH
May accumulate in patients with renal impairment and require dose adjustment
Indications of UFH
Atrial fibrillation
DVT, acute arterial thrombosis, pulmonary embolism
Acute coronary syndrome, myocardial infarction
Mechanical heart valve replacement
VTE prophylaxis for patients with hemodialysis, heart-lung machine, etc.
Commonly used oral anticoagulants
Warfarin (Coumadin)
Direct oral anticoagulants (DOACs), also known as non-vitamin K oral anticoagulants (NOACs):
Dabigatran (Pradaxa)
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Edoxaban (Savaysa/Lixiana)
Advantage and disadvantage of warfarin
Advantages:
- low costs
- reversible and can be easily managed in emergency situations (FFP or vitamin K)
Regular blood tests can help monitor the effects of warfarin and adjust the dose if needed.
Disadvantages:
- narrow therapeutic window - dose needs to be closely monitored and adjusted
- food and drug interactions
- takes several days to reach its full effect, so patients may need riding anticoagulation
- Regular blood tests are needed to monitor the international normalized ratio (INR) to ensure that the dose is appropriate, which can be inconvenient for patients.
Advantages and disadvantages of NOACs
Advantages of NOACs include:
- Predictable dosing with no need for regular monitoring of blood levels.
- Lower risk of bleeding in the brain compared to warfarin.
- Fewer drug interactions compared to warfarin.
- Rapid onset of action, with some NOACs starting to work within hours of the first dose.
Disadvantages of NOACs include:
- Shorter half-life, which means that missed doses can increase the risk of clots.
- Limited options for reversing the anticoagulant effect
- Higher cost compared to warfarin.
- Limited data on the use of NOACs in certain patient populations, such as those with severe kidney or liver disease, pregnant women, or patients with mechanical heart valves.
What is the therapeutic range for warfarin?
For most indications, the target INR range is between 2.0 and 3.0, although in some cases (such as in patients with mechanical heart valves), a higher target range of 2.5 to 3.5 may be used.
What are the main indication for warfarin and NOACs?
WARFARIN: Prophylaxis of thromboembolism (e.g., stroke) in patients with the following:
- Valvular atrial fibrillation and nonvalvular atrial fibrillation
- Heart valve replacement
- Heart failure
- DVT
- PE
NOACs:
- Nonvalvular atrial fibrillation
- DVT
- PE
Important drug interactions with warfarin.
Antibiotics: Antibiotics such as erythromycin, metronidazole, and fluconazole can increase warfarin levels and increase the risk of bleeding.
Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs such as ibuprofen, naproxen, and aspirin can increase the risk of bleeding when taken with warfarin.
Herbal supplements: Herbal supplements such as St. John’s wort, ginseng, and garlic can interfere with warfarin metabolism and increase the risk of bleeding.
Anticonvulsants: Anticonvulsants such as carbamazepine, phenytoin, and phenobarbital can increase warfarin metabolism and decrease its effectiveness.
Statins: Statins such as atorvastatin and simvastatin can increase warfarin levels and increase the risk of bleeding.
Side effects of loop diuretics
- Dehydration
- Electrolyte disturbances (hypokalemia, hypomagnesemia, hyponatremia, hypocalcemia)
- Metabolic alkalosis
- Ototoxicity (especially with high doses and rapid IV administration)
- Hyperuricemia and gout exacerbation
- Impaired glucose tolerance
- Hypotension
- Skin rashes and photosensitivity.
When would loop diuretics be preferred over thiazide or potassium-sparring diuretics?
When there is severe edema: Loop diuretics are more potent than other diuretics and can rapidly reduce fluid overload.
When there is impaired renal function: Loop diuretics are effective in patients with impaired renal function as they act on the loop of Henle in the kidney, which is less dependent on renal blood flow.
When there is a need for more rapid diuresis: Loop diuretics act more quickly than other diuretics and can produce a more rapid diuresis, which may be necessary in certain situations such as acute heart failure.
When would thiazide diuretics be preferred over loop diuretics?
In patients with hypertension and normal kidney function or mild to moderate kidney impairment, as they are effective at lowering blood pressure and have a lower risk of electrolyte disturbances compared to loop diuretics.
However, in patients with severe kidney impairment, thiazides may not be effective due to reduced renal excretion and loop diuretics may be preferred.
When would potassium-sparing diuretics be preferred over loop or thiazide diuretics?
Potassium-sparing diuretics may be preferred over loop or thiazide diuretics in patients who are at risk of hypokalemia (low blood potassium levels) or have a history of cardiac arrhythmias (irregular heartbeat) because they help to conserve potassium. They may also be used in combination with other diuretics to counteract the potassium-wasting effects of those medications.
Additionally, potassium-sparing diuretics may be used in patients with liver cirrhosis or ascites (accumulation of fluid in the abdomen) to help reduce fluid overload without causing electrolyte imbalances. However, they may not be as effective as other diuretics in reducing fluid volume.
Important drug interactions with loop diuretics and their effects.
- NSAIDs - can decrease the effectiveness of loop diuretics and risk of kidney damage
- Digoxin - can cause increased risk of digoxin toxicity due to hypokalemia
- Lithium - can increase lithium levels and cause toxicity
- Aminoglycoside antibiotics - can increase the risk of ototoxicity and nephrotoxicity
- Corticosteroids - can decrease the effectiveness of loop diuretics and increase the risk of hypokalemia
- ACE inhibitors and ARBs - can increase the risk of hyperkalemia when used with potassium-sparing diuretics.
Important drug interactions with thiazide diuretics and their effects.
NSAIDs: Can decrease the effectiveness of thiazides and increase the risk of kidney damage.
Lithium: Thiazides can increase the levels of lithium in the blood, leading to toxicity.
Digoxin: Thiazides can cause low potassium levels, which can increase the risk of digoxin toxicity.
Antidiabetic agents: Thiazides can increase blood sugar levels and reduce the effectiveness of antidiabetic medications.
Calcium supplements and vitamin D: Thiazides can increase calcium levels in the blood, and taking calcium supplements or vitamin D with thiazides can increase the risk of high calcium levels.
Examples of the different types of diuretics.
Loop diuretics: Examples include furosemide, bumetanide, and torsemide.
Thiazide diuretics: Examples include hydrochlorothiazide, chlorthalidone, and indapamide.
Potassium-sparing diuretics: Examples include spironolactone, eplerenone, and amiloride.
What is the different use for H1 and H2 antihistamines?
H1 antihistamines are mainly used for allergic conditions, such as hay fever and hives, and they work by blocking histamine receptors in the body.
On the other hand, H2 antihistamines are primarily used to treat conditions related to excess stomach acid production, such as gastroesophageal reflux disease (GERD), and they work by blocking histamine receptors in the stomach.
Side effects of H1 antihistamines
- Sedation (less pronounced with second-generation antihistamines)
- Anticholinergic effects (dry mouth and eyes, urinary retention, tachycardia, dizziness)
- Headaches
Indications for H2 antihistamines
Mainly for gastroesophageal reflux disease (GERD), peptic ulcers, and dyspepsia
Side effects of a short-term course of corticosteroids.
- Increased appetite and weight gain
- Insomnia or disrupted sleep
- Mood changes, such as irritability or restlessness
- Increased risk of infections, including fungal infections
- Increased blood sugar levels, which may be a concern for people with diabetes
Side effects of a long-term course of corticosteroids
- Osteoporosis and increased risk of fractures
- Diabetes and impaired glucose tolerance
- Hypertension and fluid retention
- Cataracts and glaucoma
- Increased risk of infections
- Mood changes and psychiatric symptoms.
Corticosteroids indications
- Inflammatory and autoimmune conditions such as asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, lupus, and inflammatory bowel disease (IBD)
- Allergic reactions and anaphylaxis
- Skin conditions such as eczema, psoriasis, and dermatitis
- Adrenal insufficiency
- Transplant rejection prophylaxis
- Cancer chemotherapy-induced nausea and vomiting.
How would you stop corticosteroid use?
Short-term administration (≤ 3 weeks): usually no tapering is necessary
Long-term administration (> 3 weeks): tapering regimen based on patient age and condition and on duration/dose of prior glucocorticoid administration → e.g., tapering over 2 months
Sudden discontinuation after chronic use should be avoided because of the risk of adrenal insufficiency (adrenal crisis) secondary to long-term hypothalamic-pituitary-adrenal axis suppression.
Adverse effects of PPIs
GI: nausea/diarrhea, abdominal pain, reduced absorption of iron and Vit B12, reduced absorption of calcium and magnesium (increased risk of osteoporosis)
Neuro: lightheadedness, headaches
Indications for PPI
Gastroesophageal reflux disease (GERD)
Peptic ulcer disease
Zollinger-Ellison syndrome
Dyspepsia
Barrett’s esophagus
Gastric prophylaxis in critically ill patients
