PHARM; Lecture 11, 12 and 13 - Autumn Term Quiz; Drugs and the cardiovascular system: the heart; Drugs and the vasculature Flashcards
Which of the following pharmacodynamic properties is a competitive receptor antagonist most likely to display? 1) High efficacy and zero affinity 2) High potency and moderate affinity 3) Zero efficacy and moderate affinity 4) Zero potency and zero affinity 5) Moderate efficacy and moderate affinity
Zero efficacy and moderate affinity
Which of the following forms of drug antagonism describes the ability of adrenaline to reduce the effects of mast cell derived histamine during an anaphylactic response. !) Receptor blockade 2) Physiological antagonism 3) Chemical antagonism 4) Pharmacokinetic antagonism 5) Irreversible antagonism
Physiological antagonism
A section of vascular smooth muscle is placed in an organ bath and stimulated with increasing doses of noradrenaline. A graph of the relationship between dose and response (effect) wherein all possible degrees of response between minimum detectable response and a maximum response is produced. From the list below, please select which possibility could NEVER induce a maximal response. 1) Noradrenaline plus Phentolamine (non selective alpha receptor antagonist) 2) Adrenaline (agonist with lower affinity for alpha receptors) 3) Clonidine (partial agonist) 4) Noradrenaline plus Propranolol (non-selective beta receptor antagonist) 5) Phenylephrine (1-selective agonist)
Clonidine
With respect to the distribution of a drug around the body; 1) Regional blood flow is an important factor 2) The distribution profile of a drug is determined by its carbon content 3) Capillary structure is unimportant 4) If a drug is highly plasma-protein bound it is not free to be distributed from the blood stream 5) Active transport into tissues does not influence this process
Regional blood flow is an important factor
Drug metabolism often reduces the lipid solubility of drugs and thus makes the drug easier to excrete. Why is this so? 1) Reduces distribution to the body fat 2) Reduces reabsorption in the kidney 3) Increases plasma protein binding 4) Reduces the potency of the drug 5) Enhances enterohepatic recycling
Reduces reabsorption in the kidney
Which of the following neurones is associated with noradrenaline neurosecretion? 1) Preganglionic sympathetic neurone innervating the sympathetic trunk 2) Postganglionic sympathetic neurone innervating the kidney 3) Sympathetic neurone innervating the adrenal medulla 4) Postganglionic parasymapthetic neurone innervating the heart 5) Postganglionic sympathetic neurone innervating the sweat gland
Postganglionic sympathetic neurone innervating the kidney
Which one of the following effects can be attributed to anti-cholinesterase poisoning? 1) Bronchodilation 2) Reduced gut motility 3) Increased secretions 4) Tachycardia 5) Mydriasis
Increased secretions. All others are SNS responses.
Why might a patient be prescribed a muscarinic receptor agonist following abdominal surgery? 1) To stimulate gastrointestinal activity 2) To reduce gastric acid production 3) To inhibit bladder emptying 4) To increase gastrointestinal blood flow 5) To increase wound healing
To stimulate GI activity
How do muscarinic receptor antagonists influence function within the striatum and thus improve the symptoms of Parkinson’s? 1) Reduced GABA receptor activation 2) Increased dopamine receptor activation 3) Inhibition of DOPA decarboxylase 4) Increased monoamine reuptake transporter function 5) Increased dopamine secretion from nigrostriatal neurones
Increased dopamine receptor activation. Blocks M4 receptor, blocking inhibition of DA receptor, so enhances the receptor activation not the increase of DA
A 54-year-old man is admitted to Accident & Emergency suffering an anaphylactic reaction after being stung by a wasp whilst out rambling. The registrar finds a bottle of beta-blocker tablets in his pocket. Which of the following clinical features of anaphylaxis could be worsened by these tablets? 1) Bronchospasm and Hypertension 2) Bronchospasm alone 3) Hypertension alone 4) Bronchospasm + Hyperglycaemia 5) Hypertension + Hyperglycaemia
Bronchospasm alone. Hypotension, bronchospasm are features of anaphylaxis, so beta blocker would exacerbate both, not causing HTN
A 75-year-old man is diagnosed with glaucoma and is treated with a α1 selective adrenoceptor agonist. The therapeutic effects of the drug are partly due to which of the following functions? 1) Dilation of the pupil 2) Activation of carbonic anhydrase 3) Accomodation for near vision 4) Opening of scleral spur 5) Ocular vasoconstriction
Ocular vasoconstriction. PSNS: angle of lens, opening of scleral spur (+ve glaucoma effect but not SNS). SNS: carbonic anhydrase (important to produce aqueous humour and beta-mediated); Dilation of pupil (alpha mediated but as lens pulls back it block the drainage of aqueous humour so -ve impact)
Neuromuscular blockade by tubocurarine is used as an adjunct to anaesthesia in surgery. How does tubocurarine bring about its effects at the motor end plate? 1) Inhibition of acetylcholine release from nerve endings. 2) Antagonism of the actions of acetylcholine at nicotinic receptors 3) Causes persistent depolarisation 4) Increases the rate of acetylcholine breakdown 5) Prevents opening of the voltage sensitive Na+ channels
Antagonism of actions of ACh at nAChR
How is HR regulated?
Na enters through channels; then Ca enters through the VGCS, activating the transient channels then the long acting ones. K channels cause the repolarisation of the heart.
What are the effects of the SNS and PSNS on the heart rate regulation?
B1 upregulate cAMP which has an effect on If chnnels, which speeds up depolarisation of the heart and on PKA which acts on Ica channels. PSNS: work the other way round, by downregulating cAMP and increasing the Ik channels
Which mechanisms regulate contractility?
- Electrical excitation of the cell from action potentials arising from the sino-atrial node induce membrane depolarization that promotes gating of Ca2+ channels, which open and cause a small release of Ca2+ into the cytoplasm.
- The small Ca2+ current induces a release of Ca2+ from the SR by a process called Ca-induced Ca-release, occurs through Ca2+ release channels (RyR).
- Depolarization-induced influx of Ca2+ current (ICa) through the L-type channels contributes approximately 20–25% of the free Ca2+ in a cardiac twitch.
- The release of Ca2+ through the RyRs contributes the remaining 75–80% of Ca2+ necessary for cardiac contraction.
- 20-25% of Ca come from outside via dihydropiridine receptor and the rest from the sarcoplasmic reticulum.
- Na/Ca exchange protein and Ca ATPase channel which are there to remove Ca from the cell after the contraction has taken place.
Which mechanisms regulate myocardial O2 supply and demand?
The balance needs to occur between the demand and supply to the myocardial O2 supply
Which drugs influence HR?
- Beta-blockers (decrease cAMP production, leaving the If channels decreased and the Ica are decreased)
- Ca channel antagonists (block Ca long receptors which decreases the Ca intake)
- Ivabradine (decrease If).
Prolong rate of depolarisation
Which drugs influence contractility?
B blockers reduce cross-bridge formation; Ca antagonists reduce Ca entry into cell
What are the 2 classes of Ca antagonists?
Which drugs influence myocardial O2 supply?
Organic nitrates, deliver NO to coronary vessels, involved in cGMP, which is involved in relaxation of coronary vessels; K channel opener: leading to hyperpolarization of coronary cells, which impair ability to contract. Overall, increase coronary blood flow
Summarise the drugs which can affect the HR, contractility nd myocardial O2 supply.
What are the side effect of beta blockers?
The red ones are the questioned for validity by RCTs
What are the side effects of Ca channel blockers?
Effects can be so substantial that they can affect compliance with these drugs
What are rhythm disturbances and what are the aims of treatment of these?
- May be associated with decreased HR or increased HR.
- Classifications based on site of origin:
- Supraventricular arrhythmias (e.g. amiodarone, verapamil)
- Ventricular arrhythmias (e.g. flecainide, lidocaine)
- Complex (supraventricular + ventricular arrhythmias) (e.g. disopyramide).
What is the Vaughan-Williams classification of anti-arrhythmic drugs?
Can have drugs which don’t fall into just one class
What is adenosine?
Has its own sub-type as it doesn’t fall into any class; increases If channels. Prolonging HR increases chances of arrhythmia decreasing and sorting itself out
What is Verapamil?
Class IV
What is Amiodarone?
Reentry rhythms cause arrhythmia, where the hyperpolarisation should occurs; prolong action potential and hyperpolarisation to reduce the action of reentry AP
What is Digoxin (cardiac glycosides) and how does it affect inotropy of cell?
- Inhibits NA/K ATPase
- Increases contractility
- reduces Na/K exchange so less Na outside the cell,
- so less Na/K exchange,
- so by decrease Ca export of cell,
- more stays in muscle so contractility increases.
- Used as anti-arrhytmic as it directly affects the PSNS to increase: central vagal stimulation causes increased refractory period and reduced rate of conduction through the AV node
What is digoxin used for and what are the adverse effects?
Less K means less competition for digoxin, so there is a lesser threshold for toxic effects; s need to take blood test for K levels before admin.
How is vascular tone/peripheral vascular resistance changed?
Varicosities aren’t synapses but when the nerve is activated, NA is released (as well as ATP and NPY) which leads to vasoconstriction. AngII acts on AT1 receptor and drugs affect the receptors to try to cause vasodilation. Most drugs used affect peripheral resistance specifically affecting arterioles.
How do arterioles contribute to BP?
What is hypertension: pathophysiology and physiology?
Although it isn’t a problem on its own, it increases the risk of many other diseases
How do you treat HTN?
ACEi/ARB/CCB’s main aim is to reduce TPR
What is the RAS system and what activates renin?
What are ACE inhibitors?
NB: ‘-pril’ is commonly ACE inhibitor ending
What are Ang receptor blockers?
How do you choose between ACE inhibitors and Ang receptor blockers?
Look at side effects which are caused by each drug and decide from there as they are both interchangeable otherwise
How do CCB affect smooth muscle contraction (vasoconstriction/dilation?
What are CCB?
Dihydropyridines used for HTN (inhibit Ca entry into VSM cells to decrease TPR and BP -> powerful vasodilation can lead to reflex tachycardia and increased inotropy thus increased myocardial O2 demand
