1 Flashcards
1
Q
How much more soluble is carbon dioxide compared to oxygen?
A
20 times more soluble
This indicates that carbon dioxide has a significantly higher ability to dissolve in liquid compared to oxygen.
2
Q
What law does carbon dioxide obey regarding solubility?
A
Henry’s law
Henry’s law states that the number of molecules in solution is proportional to the partial pressure of the gas at the liquid surface.
3
Q
What is the carbon dioxide solubility coefficient at 37°C?
A
0.0308mmol.l-1.mmHg-1 or 0.231mmol.l-1.kPa-1
This coefficient indicates how much carbon dioxide can be dissolved in a liquid at a given pressure.
4
Q
How does solubility change with temperature?
A
Solubility increases as the temperature falls
Lower temperatures enhance the ability of gases to dissolve in liquids.
5
Q
How much carbon dioxide is present in 100 ml of blood at 37°C?
A
0.5ml.kPa-1
This value represents the volume of carbon dioxide that can be dissolved per unit of pressure.
6
Q
What is the partial pressure of carbon dioxide in arterial blood?
A
5.3 kPa
This reflects the concentration of carbon dioxide in arterial blood.
7
Q
What is the partial pressure of carbon dioxide in mixed venous blood?
A
6.1 kPa
This indicates the concentration of carbon dioxide in blood returning to the heart.
8
Q
How much dissolved carbon dioxide is found in arterial blood per 100 ml?
A
2.5 ml
This is the amount of carbon dioxide dissolved in arterial blood.
9
Q
How much dissolved carbon dioxide is found in venous blood per 100 ml?
A
3 ml
This is the amount of carbon dioxide dissolved in venous blood.
10
Q
What is the cardiac output that carries dissolved carbon dioxide to the lung?
A
5 l.min-1
This is the volume of blood pumped by the heart per minute.
11
Q
How much dissolved carbon dioxide is carried to the lung by cardiac output?
A
150 ml
This represents the total amount of dissolved carbon dioxide transported in the blood.
12
Q
How much dissolved carbon dioxide will be exhaled?
A
25 ml
This indicates the volume of carbon dioxide released from the lungs during exhalation.
13
Q
What is the relationship between the partial pressure of carbon dioxide in alveolar and pulmonary end-capillary blood?
A
Virtually the same
This indicates efficient gas exchange and diffusion capacity in the lungs.
14
Q
What is the end-pulmonary capillary/arterial carbon dioxide gradient with a large shunt of 50%?
A
About 0.4 kPa
This demonstrates the minimal impact of significant shunting on carbon dioxide levels.
15
Q
What is zero-order kinetics?
A
Elimination becomes constant, limited to a maximum amount in unit time.
This occurs when the action of an enzyme or transporters becomes saturated at a certain blood concentration.
16
Q
What can result from zero-order kinetics?
A
Dangerously high concentrations with continued, unmonitored drug administration.
This is particularly concerning in drug therapy where dosing is not carefully managed.
17
Q
Name a few drugs that may exhibit zero-order kinetics.
A
- Aspirin
- Ethanol
- Phenytoin
- Thiopental
These drugs can lead to zero-order kinetics at high concentrations.
18
Q
What happens to the log dose response curve of a drug with a lower affinity?
A
It is shifted to the right
This indicates that a higher dose is required to achieve the same effect.
19
Q
What is the relationship between affinity and the log dose response curve?
A
Lower affinity results in a rightward shift of the curve
Affinity refers to the strength of binding between a drug and its receptor.
20
Q
If two drugs have equal efficacy but different affinities, how does their dose response curve differ?
A
The drug with lower affinity has a rightward shifted curve
Efficacy refers to the maximum effect a drug can produce.
21
Q
What enzyme do α1-receptors activate?
A
Phospholipase C, leading to increased intracellular calcium release.
22
Q
What is the main second messenger for α1-receptor activation?
A
Intracellular calcium (Ca²⁺).
23
Q
What enzyme do α2-receptors inhibit?
A
Adenylate cyclase, reducing cAMP formation.
24
Q
What enzyme do β1 and β2-receptors activate?
A
Adenylate cyclase, increasing cAMP formation.
25
How does β1-receptor activation affect the heart?
Increases heart rate (chronotropy) and contractility (inotropy) via cAMP.
26
How does β2-receptor activation affect smooth muscle?
Relaxes smooth muscle (e.g., bronchodilation, vasodilation) via cAMP.
27
What are the primary receptor effects of Epinephrine at low doses, and how do they change at higher doses?
At low doses, Epinephrine predominantly has β1 and β2 effects (positive inotropy, chronotropy, vasodilation, bronchodilation). At higher doses, α effects (vasoconstriction) become more prominent.
28
How does Norepinephrine's receptor activity differ from Epinephrine as the dose increases?
Norepinephrine has α and β effects at very low doses, but α effects (vasoconstriction) quickly predominate as the dose increases, unlike Epinephrine, which maintains significant β effects at low doses.
29
What is the primary use of Dobutamine, and how does its receptor activity contribute to this use?
Dobutamine is a potent β1-agonist used in low cardiac output states. Its β1 effects (positive inotropy) improve cardiac output, while some β2-mediated vasodilation may also occur.
30
How does Dopamine's receptor activity change with increasing doses?
At low doses, Dopamine primarily acts on β1 and dopamine receptors (causing vasodilation in renal and splanchnic beds). As the dose increases, α effects (vasoconstriction) become more prominent.
31
What distinguishes Dopexamine from other β2-agonists, and what are its primary effects?
Dopexamine is a potent β2-agonist with additional **dopamine receptor agonism.** It causes **positive inotropy** and peripheral/splanchnic vasodilation, making it unique among β2-agonists.
32
What are the primary clinical uses of Isoprenaline, and why has its use declined?
Isoprenaline is used to treat bradyarrhythmias and as a bronchodilator. Its use has declined due to the risk of cardiac arrhythmias and the availability of more selective β2-agonists.
33
How does Salbutamol's receptor activity differ from Isoprenaline, and what are its primary uses?
Salbutamol is a predominantly β2-agonist used in asthma treatment (bronchodilation). Unlike Isoprenaline, it has minimal β1 effects, reducing the risk of cardiac side effects.
34
What is the primary use of Ritodrine, and how does it compare to Salbutamol in this context?
Ritodrine is a β2-agonist used as a tocolytic to prevent premature labor. Salbutamol can also be used for this purpose, but Ritodrine is specifically indicated for tocolysis.
35
How do Phosphodiesterase Inhibitors amplify the effects of β-receptor activation?
Phosphodiesterase Inhibitors prevent the breakdown of cAMP, which is produced by β-receptor activation. This leads to increased cAMP levels, amplifying β-mediated effects like inotropy and vasodilation.
36
What are the primary uses of Theophylline/Aminophylline, and what are their limitations?
Theophylline/Aminophylline are used as bronchodilators and have weak positive inotropic and vasodilatory effects. They have a narrow therapeutic index, requiring serum level monitoring.
37
How does Enoximone differ from non-selective Phosphodiesterase Inhibitors, and what is its primary use?
Enoximone selectively inhibits Phosphodiesterase subtype III, making it a potent inotrope with marked peripheral vasodilation. It is particularly effective in heart failure patients with high sympathetic tone.
38
Compare the receptor effects of Epinephrine and Norepinephrine in resuscitation situations.
Epinephrine is preferred in resuscitation due to its β1 and β2 effects (improving cardiac output and perfusion) at low doses, while Norepinephrine's strong α effects (vasoconstriction) may limit its utility in such scenarios.
39
How does Dobutamine's β2-mediated vasodilation compare to Dopamine's dopamine receptor effects?
Dobutamine's β2-mediated vasodilation primarily affects peripheral vessels, improving cardiac output. Dopamine's dopamine receptor effects cause renal and splanchnic vasodilation, which is beneficial at low doses.
40
What are the key differences between Salbutamol and Ritodrine in terms of receptor selectivity and clinical use?
Salbutamol is a selective β2-agonist primarily used for asthma, while Ritodrine is also a β2-agonist but specifically used as a tocolytic to prevent premature labor.
41
How do the effects of Enoximone and Theophylline differ in patients with heart failure?
Enoximone provides potent inotropy and peripheral vasodilation, making it effective in heart failure with high sympathetic tone. Theophylline offers weak inotropy and vasodilation, with a primary focus on bronchodilation.
42
43
Evaluate the clinical significance of Esmolol's peak effects occurring within 6-10 minutes and rapid offset by 20 minutes. How does this compare to other β-blockers in acute settings?
Esmolol's rapid onset/offset (due to red blood cell esterase metabolism) allows precise titration in acute scenarios (e.g., perioperative hypertension/SVT). Unlike Atenolol/Propranolol, its short action minimizes prolonged hemodynamic effects, reducing risks in unstable patients.
44
Analyze the therapeutic advantage of Atenolol and Metoprolol's 'lusitropic action' (increased diastolic time) in ischemic heart disease.
By prolonging diastolic time, β1-selective blockers like Atenolol/Metoprolol enhance coronary perfusion (critical in ischemia) while reducing myocardial oxygen demand via decreased heart rate and contractility. This dual mechanism improves outcomes in angina/heart failure.
45
Compare Phentolamine and Phenoxybenzamine in terms of reversibility, receptor specificity, and clinical use. Why might one be preferred over the other?
Phentolamine: Reversible, non-selective α1/α2 antagonist, used short-term (e.g., hypertensive crisis). Phenoxybenzamine: Irreversible α1/α2 blockade, used chronically (e.g., phaeochromocytoma prep). Phenoxybenzamine's irreversibility ensures sustained blockade but requires β-blocker co-administration for reflex tachycardia.
46
Differentiate the functional roles of α2 receptor subtypes (α2A, α2B, α2C). How might subtype selectivity influence drug design?
α2A: Sedation/analgesia/sympatholysis (e.g., dexmedetomidine). α2B: Mediates vasoconstriction (undesirable in antihypertensives). α2C: CNS effects (mood regulation). Subtype-selective drugs (e.g., avoiding α2B) could enhance therapeutic effects while minimizing hypertension risks.
47
Critique why Trimetaphan (ganglion blocker) is rarely used today despite its potent hypotensive effects.
Trimetaphan's non-selective ganglionic blockade causes severe side effects: reflex tachycardia, tachyphylaxis, reduced renal/coronary flow, and neuromuscular blockade. Safer alternatives (e.g., esmolol, nitroprusside) offer targeted action without systemic autonomic disruption.
48
Justify the use of Oxprenolol's partial β2-agonist activity (ISA) in hypertensive patients with borderline bradycardia.
Oxprenolol's β2-ISA provides mild vasodilation and reduces resting heart rate less abruptly than pure antagonists, making it safer for patients prone to bradycardia while maintaining antihypertensive efficacy.
49
Assess the risk-benefit trade-off of Sotalol's class III antiarrhythmic activity in treating ventricular arrhythmias.
Sotalol's β-blockade and K+ channel inhibition (class III) prolong AP duration, effective for ventricular/supraventricular arrhythmias. However, QT prolongation increases torsades risk, necessitating careful ECG monitoring versus pure β-blockers.
50
Question
Answer
51
How do Phenoxybenzamine and Prazosin differ in receptor selectivity and compensatory effects?
"Phenoxybenzamine is a non-specific, irreversible α1/α2 antagonist causing reflex tachycardia (due to α2 blockade). Prazosin is a selective α1 antagonist with less compensatory tachycardia, used for hypertension."
52
What distinguishes Trimetaphan's mechanism of action from other sympatholytics?
"Trimetaphan is the only clinically used ganglion blocker, inhibiting nicotinic receptors at autonomic ganglia, causing hypotension, reflex tachycardia, and some neuromuscular blockade."
53
Why might non-selective α-blockers like Phenoxybenzamine be combined with β-blockers?
"Non-selective α-blockers increase noradrenaline release (via α2 blockade), leading to β-mediated tachycardia. β-blockers counteract this compensatory effect."
54
Compare the clinical uses of Propranolol and Esmolol.
"Propranolol (non-selective β1/β2 antagonist) treats thyrotoxicosis, tremor, and migraines. Esmolol (short-acting β1-selective) is used IV for acute hypertension or SVT due to rapid onset/offset."
55
How does Oxprenolol differ from Atenolol in receptor activity?
"Oxprenolol is non-selective (β1/β2) with partial β2 agonist activity (ISA), while Atenolol is β1-selective at low doses but loses specificity at higher doses."
56
What unique risk does Sotalol pose compared to other β-blockers?
"Sotalol has class III antiarrhythmic activity, increasing the risk of torsades de pointes, unlike standard β-blockers."
57
How does Labetalol's receptor antagonism ratio influence its use?
"Labetalol blocks β:α receptors at 7:1, making it ideal for acute hypertension or hypotensive anesthesia by reducing blood pressure without severe reflex tachycardia."
58
Why is Esmolol preferred over other β-blockers in acute settings?
"Esmolol’s short half-life (metabolized by red cell esterases) allows rapid titration, making it safer for transient hypertensive crises or perioperative SVT."
59
What are the key differences between Phentolamine and Prazosin?
"Phentolamine is a short-acting, reversible non-selective α-blocker. Prazosin is a selective α1 antagonist with sustained effects, used for chronic hypertension."
60
How do cardioselective β-blockers like Atenolol differ from Propranolol in safety?
"Atenolol (β1-selective) has fewer β2-mediated risks (e.g., bronchospasm in asthma) compared to Propranolol, which non-selectively blocks β2 receptors."
61
What are the adverse effects of Trimetaphan?
"Trimetaphan causes reflex tachycardia, tachyphylaxis, reduced renal/coronary blood flow, and neuromuscular blockade due to nicotinic receptor antagonism."
62
What makes Labetalol unique among β-blockers?
"Labetalol is a combined α/β antagonist, providing vasodilation (α-block) and reduced cardiac output (β-block), useful in acute hypertensive emergencies."
63
Why are β-blockers like Propranolol avoided in diabetics?
"Propranolol inhibits sympathetic 'warning signs' of hypoglycemia (e.g., tremor, tachycardia) and may impair glucose metabolism, posing risks for diabetics."
64
How does Oxprenolol's intrinsic sympathomimetic activity (ISA) affect therapy?
"Oxprenolol’s partial β2 agonism reduces resting heart rate and peripheral vascular resistance, offering antihypertensive benefits with less bradycardia risk."
65
What limits the use of Phenoxybenzamine despite its potency?
Phenoxybenzamine’s irreversible α-blockade and reflex tachycardia require co-administration with β-blockers, limiting its use to conditions like phaeochromocytoma.
66
What are the five muscarinic receptor subtypes (M1-M5) and their primary functions?
M1: Gastric acid secretion; M2: Negative chronotropy (slows heart rate); M3: Lacrimal/salivary secretion, gut smooth muscle contraction; M4: CNS presence, possible adrenal medulla adrenaline secretion; M5: CNS presence.
67
Why is Pilocarpine primarily used topically rather than systemically?
Topical use (e.g., glaucoma) avoids systemic side effects like hypotension, bradycardia, bronchoconstriction, and excessive salivation/bronchorrhea.
68
Compare the mechanisms of Neostigmine and Edrophonium as acetylcholinesterase inhibitors.
Neostigmine: Carbamylates enzyme (longer inhibition). Edrophonium: Competitive/reversible inhibition (shorter duration, ~10 minutes).
69
Why is Glycopyrrolate paired with Neostigmine during neuromuscular blockade reversal?
Glycopyrrolate blocks muscarinic side effects (e.g., bradycardia, secretions) without crossing the BBB, unlike Atropine.
70
Which muscarinic antagonist is most likely to cause CNS effects like confusion in the elderly, and why?
Atropine (tertiary amine, lipid-soluble) crosses the BBB. Glycopyrrolate (quaternary amine) does not.
71
What is the clinical significance of Hyoscine’s lipid solubility?
High lipid solubility enhances CNS effects (drowsiness, amnesia, analgesia), making it useful for premedication/anti-emesis.
72
How does Ipratropium differ from Atropine in its therapeutic application?
Ipratropium is inhaled for asthma/COPD (bronchodilation via M3 blockade), minimizing systemic effects. Atropine is systemic (e.g., bradycardia).
73
Which drug is used to diagnose myasthenia gravis, and why is its short duration advantageous?
Edrophonium (Tensilon). Short duration (~10 min) allows rapid assessment of muscle strength improvement without prolonged side effects.
74
What receptor mediates the cardiac effects of parasympathetic stimulation, and how is this targeted clinically?
M2 receptors (negative chronotropy). Blocked by Atropine to treat bradycardia.
75
Why is Pyridostigmine preferred over Neostigmine for chronic myasthenia gravis management?
Pyridostigmine has a longer duration and oral bioavailability, making it suitable for chronic use.
76
What are the dose-dependent effects of muscarinic antagonists like Atropine?
Low dose: Reduced secretions. Moderate: Tachycardia, mydriasis. High dose: Reduced gut/bladder motility, gastric inhibition.
77
Which muscarinic receptor subtype is incorrectly described in the notes as an ion channel?
All muscarinic receptors are GPCRs (not ion channels). The notes incorrectly state they function as ion channels. Source: Katzung & Trevor’s Pharmacology.
78
Explain why M4 receptors in the adrenal medulla (per notes) contradict standard pharmacology references.
Adrenal medulla adrenaline release is typically nicotinic receptor-mediated. M4 involvement is atypical and not widely accepted. Source: Goodman & Gilman’s.
79
Which drug is a synthetic quaternary amine with no CNS effects, and why is this property important?
Glycopyrrolate. Quaternary structure prevents BBB penetration, avoiding confusion in elderly patients.
80
List three systemic effects of Pilocarpine when used for xerostomia.
Hypotension, bradycardia, bronchoconstriction, bronchorrhea, sialorrhea.
81
Describe the mechanism of Ipratropium’s secondary anti-inflammatory effect.
Blocks M3 receptors on mast cells, reducing degranulation and inflammatory mediator release.
82
What is the ‘lusitropic’ effect mentioned in earlier notes, and which drug class is associated with it?
Lusitropy = increased diastolic relaxation time. Not in these notes, but β-blockers (e.g., Atenolol) exhibit this. Source: Prior user notes.
83
Which muscarinic antagonist is used for motion sickness, and what property enables this?
Hyoscine (central anticholinergic effects: drowsiness, anti-emesis).
84
Why is Atropine’s 3mg dose reserved for resuscitation scenarios?
Complete vagal blockade (maximal tachycardia), but risks severe side effects (e.g., delirium, arrhythmias).
85
Compare the onset/duration of Neostigmine vs. Pyridostigmine.
Neostigmine: Faster onset (10-20 min IV), shorter duration (2-4h). Pyridostigmine: Slower onset (30-45 min oral), longer duration (3-6h).
86
Question
Answer
87
Which muscarinic receptor subtypes are primarily responsible for: (1) gastric acid secretion, (2) negative chronotropy, and (3) lacrimal secretion?
M1 (gastric acid), M2 (cardiac slowing), M3 (exocrine secretions). Source: Basic & Clinical Pharmacology (Katzung, 15th ed)
88
Compare the molecular mechanism of Neostigmine vs. Edrophonium as cholinesterase inhibitors.
Neostigmine causes carbamylation (irreversible inhibition for hours), while Edrophonium is competitive/reversible (duration ~10min). Source: Goodman & Gilman's Pharmacological Basis
89
Why is Glycopyrrolate preferred over Atropine for elderly patients during neuromuscular reversal?
Glycopyrrolate (quaternary amine) doesn't cross BBB, avoiding CNS effects like confusion. Atropine (tertiary amine) causes central anticholinergic syndrome. Source: Anesthesiology 2016;124:937-43
90
Create a clinical decision table: Pilocarpine (PO) vs. Ipratropium (inhaled) for secretions. Include 3 parameters.
Route: Oral vs inhaled; Use: Xerostomia vs asthma/COPD; SE: Systemic cholinergic vs minimal absorption. Source: UpToDate 2023
91
Analyze why M3 receptor activation paradoxically causes both bronchoconstriction (direct) and bronchodilation (indirect via NO).
M3 directly contracts airway smooth muscle but also activates endothelial NO synthase in vessels. Net effect depends on tissue: bronchoconstriction dominates. Source: Physiol Rev 2003;83(3)
92
Which drug combination demonstrates the principle of 'functional antagonism' in reversing neuromuscular blockade?
Neostigmine (AChE inhibitor) + Glycopyrrolate (muscarinic blocker). Counteracts neuromuscular and cardiovascular effects separately.
93
Edrophonium's short duration makes it unsuitable for myasthenia treatment but ideal for diagnosis. Explain.
Diagnosis requires transient improvement (Tensilon test). Chronic treatment needs sustained effect (Pyridostigmine preferred). Source: J Neurol 2021;268:1147
94
Hyoscine causes more CNS effects than Atropine despite both being tertiary amines. Why?
Hyoscine has higher lipid solubility (logP 1.9 vs 1.8) and greater affinity for central M1 receptors. Source: Br J Clin Pharmacol 2004;58:565
95
Design a protocol using Parasympatholytics to manage organophosphate poisoning. Include 3 drugs.
1. Atropine (blocks muscarinic effects), 2. Pralidoxime (reactivates AChE), 3. Benzodiazepines (seizures). Source: WHO Poisoning Guidelines
96
Predict the effects of M4 receptor activation based on its CNS location and adrenal medulla role.
CNS: Movement regulation (basal ganglia). Adrenal: Modulates epinephrine release (animal studies). Source: Nat Neurosci 2010;13:125
97
Contrast the onset/duration of Pyridostigmine vs Neostigmine in myasthenia management.
Pyridostigmine: Onset 30-45min, Duration 3-6h (oral). Neostigmine: Onset 10-20min, Duration 2-4h (IV). Source: Myasthenia Gravis Foundation
98
Justify why Ipratropium's systemic absorption rarely causes tachycardia despite being anticholinergic.
Low bioavailability (<1% lung absorption) due to quaternary structure. Any absorbed drug is rapidly metabolized. Source: Eur Respir J 2002;19:936
99
Critique the statement: 'Muscarinic receptors are ion channels.'
False. They're GPCRs (metabotropic) that modulate ion channels indirectly via second messengers. Nicotinic receptors are ligand-gated ion channels. Source: Physiol Rev 2018;98(3)
100
Which preoperative medication combination reduces both secretions and PONV? Explain.
Hyoscine: Antisialagogue + antiemetic (central M1 blockade). Often combined with H2 blocker. Source: Anesth Analg 2020;130:46
101
Explain the biphasic cardiac response to Atropine (initial bradycardia then tachycardia).
Low doses: Block M2 autoreceptors (↑ACh release). High doses: Direct M2 blockade (↓vagal tone). Source: Circulation 2001;104:1694
