Autonomic drugs Flashcards
Which is the correct property of the beta blocker?
A Atenolol B1-B2 antagonsit
B Propanolol B1 selective antagonist
C Labetalol B1-B2-A1 antagonist
D Pindolol B2 selective antagonist
C
Explanation
B1 selective antagonist:
Acebutolol, atenolol, betaxolol, bisoprolol, celiprolol, metoprolol, nevivolol, esmolol
Non selective beat blockers with alpha1 blocking abilities:
Labetalol, carvedilol, medroxalol and bucindolol
Non selective
Pindolol, propanolol, sotalol and timolol
Extra
Pindolol = Non selective (B1=B2) with moderate lipid solubility T1/2 = 3-4 hours
Propanolol = Non selective (B1=B2) with high lipid solubility T1/2 = 3.5=6 hours
Labetalol = Non selective (B1=B2 with some A1 effects) with low lipid solubility T1/2 = 5 hours
Atenolol = B1 selective (B1»>B2) with low lipid solubility T1/2 = 6-9 hours
Labetalol has the following pharmacodynamic effect
A Alpha 1 + B1 Antagonism
B Alpha 1 + B1 + B2 Antagonism
C B1 + B2 Antagonism
D Alpha 1+ Alpha 2 + B1 + B2 Antagonism
B
Explanation
Labetalol is a competitive selective alpha 1 antagonist and a competitive non selective beta 1 (B1) and 2 (B2) antagonist.
Note: in one of the tables in the prescribed TB, Labetalol seems to have some alpha 2 antagonism. However, in the section describing labetalol it reports that it is sea selective alpha 1 antagonist and a potent beta blocker .
The cholinesterase inhibitor with the shortest duration of action
A Ambenonium
B Physostigmine
C Echothiophate
D Pyridostigmine
B
Explanation
The different cholinesterase inhibitors and thier duration of action
Alcohols= Edrophonium- 5-15min
Carbamates= Neostigmine-0.5-2hrs, Pyridostigmine-3-6hrs, Physostigmine-0.5-2hrs, Ambenonium-4-8hrs, Demecarium-4-6hrs
Organophosphates= Echothiophate-100hrs
Which is true regarding Atropine?
A Atropine is a tertiary amine and does not cross the blood brain barrier
B Atropine’s effect on parasympathetic functions declines rapidly in all organs
C Atropine has a half life of 6 hours
D Atropine competitively antagonises ACH at muscarinic receptors
D
Explanation
Atropine causes reversible blockade of cholinomimetic actions at muscarininc receptors. Its block can be overcome with larger concentrations of ACH or muscarinic agonists. It is a tertiary amine. Significant levels are achieved in the CNS within 30min to one hr. Atropine’s effect on parasympathetic functions declines rapidly in all organs except the eye. Effects on the iris and the cillary muscle persist for >72hrs. Atropine disappears rapidly form the blood after administration, with a half life of 2 hours.
Note: There seems to be a slight discrepancy with the values given to atropine. Example-Atropine has been given a t1/2=4.3 hours. However in other sources its t1/2 is 2hours.
Extra: The elimination of atropine from the blood following administration, occurs in 2 phases (Fast and slow phases): Rapid phase half-life= 2hrs Slow phase is approximately 13hrs.
IprATROPium (a synthetic analogue of ATROPine) is a QUATERNARY amine, and is too large to pass through the blood brain barrier. Atropine is the smaller TERTIARY drug that is able to slip through.
Atropine
A It is predominantly metabolised by the liver
B Its mydriatic action lasts 12-24hrs
C Is a quaternary ammonium compound
D It may cause bradycardia
D
Explanation
Atropine is a tertiary compound and therefore crosses the blood brain barrier. The drug’s effect on parasympathetic function declines rapidly in all organs except the eye. The mydriatic effect on the iris and papillary muscles>72hrs. The effect of moderate to high therapeutic doses is a block of vagal activity and a tachycardia. However, lower doses often result in a bradycardia before the effects of peripheral vagal block become manifest. This effect (slowing) may be due to block pf presynaptic muscarinic receptors on vagal postganglionic fibres that normally limit ACH release in the sinus node and other tissue. The same mechanisms operate in the AV node. About 60%of the unchanged drug is excreted in the urine
Which of the following statements regarding receptor desensitization of adrenoreceptors in correct?
A Multiple other receptors can still be desensitised by an agonist that only binds to its receptor
B Phosphorylation of G proteins is an example of heterologous desensitisation
C Receptor desensitisation occurs only after hours of repeated exposure to the agonist
D Secondary feedback mechanisms is an example of homologous desensitisation
A
Explanation
One of the best studied examples of receptor regulation is the desensitisation of adrenoreceptors that may occur after exposure to catecholamines and other sympathomimetic drugs. After a cell or tissue has been exposed to a drug for a period of time to an agonist, the tissue often becomes less responsive to further stimulation by that agent. Other terms for desensitisation include tachyphlaxis, refractoriness and tolerance.
Mechanisms of desensitisation occur within minutes, some over days.
There are two major categories of desensitisation
1-Homologous desensitisation: loss of responsiveness exclusively of the receptors that have been exposed to repeated or sustained activation by an agonist. E.g. phosphorylation of receptor members of the G protein coupled receptor kinase (GRK) family
2-Heterologous desensitisation: process by which desensitisation of one receptor by its agonist also results in desensitisation of another receptor that has not been directly activated by the agonist in question. E.g. secondary messenger feedback. cAMP leads to activation of protein kinase A which phosphorylates B receptor residues resulting in inhibition of receptor function. Protein kinase C works similarly. Both enzymes may phosphorylate any structurally similar receptors (not just their own receptors)
What is the effect of intravenous phenylephrine on heart rate and blood pressure?
A Increased blood pressure, decreased heart rate
B Decreased blood pressure, decreased heart rate
C Decreased blood pressure, stable heart rate
D Increased blood pressure, stable heart rate
A
Explanation
Phenylephrine increases both systolic and diastolic blood pressure, and decreases heart rate due to a vagal reflex.
Phenylephrine is a selective α1-adrenergic receptor agonist commonly used as a vasopressor to increase blood pressure in settings such as hypotension or shock. It works by causing vasoconstriction, which raises systemic vascular resistance and blood pressure.
Uses of Phenylephrine:
1. Hypotension:
Particularly in anesthesia (e.g., spinal or epidural-induced hypotension).
2. Nasal Congestion:
Topically as a decongestant due to vasoconstriction of nasal blood vessels.
3. Mydriasis:
Dilates pupils for ophthalmologic examinations.
4. Shock:
Used in distributive shock (e.g., septic shock) when tachycardia precludes the use of other vasopressors like norepinephrine.
Intravenous Side Effects of Phenylephrine:
1. Cardiovascular Effects:
- Hypertension: Excessive vasoconstriction can lead to a significant increase in blood pressure.
- Reflex Bradycardia: Stimulation of baroreceptors due to increased blood pressure leads to vagal-mediated slowing of the heart rate.
- Reduced Cardiac Output: Phenylephrine increases afterload (resistance against which the heart must pump), which can reduce cardiac output, especially in patients with left ventricular dysfunction.
- Ischemia:
- Peripheral vasoconstriction may reduce blood flow to extremities, leading to:
Skin mottling or cyanosis.
- Ischemia in extremities or organs (e.g., renal or mesenteric ischemia) in cases of overuse. - Extravasation and Local Effects:
Extravasation of phenylephrine can cause local tissue ischemia and necrosis due to intense vasoconstriction. - Central Nervous System Effects:
Anxiety, restlessness, or agitation may occur, though these are less common with intravenous use. - Rebound Hypotension:
Abrupt discontinuation after prolonged infusion may lead to rebound hypotension due to downregulation of adrenergic receptors.
Precautions:
Patients with Cardiac Conditions:
Use cautiously in patients with heart failure, coronary artery disease, or significant bradycardia.
Volume Status:
Phenylephrine should not be used as a substitute for volume resuscitation in hypovolemia.
Monitor Infusion Sites:
Avoid extravasation by using a central line for prolonged infusions or high doses.
Summary:
Phenylephrine is an effective α1-adrenergic agonist for treating hypotension, but its intravenous use can cause hypertension, reflex bradycardia, reduced cardiac output, ischemia, and extravasation injuries. Careful monitoring is essential to minimize these risks.
Noradrenaline reduces the production of cAMP via which adrenoreceptor?
A Beta 2
B Alpha 2
C Alpha 1
D Beta 1
B
Explanation
α1 = G-proteins to phospholipase C, formation of IP3 & DAG, increased intracellular Ca2+ & protein kinase C
α2 = G inhibitory proteins that inhibit adenylyl cyclase and decrease cAMP
β1 and β2= activate G protein à activate adenylyl and increase cAMP
Adrenaline causes skeletal muscle relaxation via which adrenoreceptor?
A Beta 2
B Alpha 2
C Alpha 1
D Beta 1
A
Explanation
Adrenaline dilates blood vessels in skeletal muscle and liver via β2 receptors. Noradrenaline and adrenaline both increase force and rate of contraction of the isolated heart via β1 receptors.
