Pharma Flashcards
Identify the consequences of cholinoceptor blockade and list the main clinical uses and unwanted effects of muscarinic cholinoceptor antagonists
Clinical use: to treat hypertension
Unwanted effects: dilate pupils, constipation as gut motility is reduced, issues with emptying bladder, difficulty producing saliva.
Current use is to control blood flow during surgery.
Atropine poisoning: identify the signs and symptoms of atropine poisoning and explain how it may be treated
Signs: CNS agitation, restlessness, dry mouth, increased heartrate
Treat with anti-cholinesterase which will prevent Ach from breaking down in synapse, and Ach will build up and out-compete the atropine.
Why are nicotinic receptor agonists called ganglion blocking drugs?
Because nicotinic cholinergic receptors are present at all ganglia - both in sympathetic and parasympathetic nervous system.
What are two examples of nicotinic cholinoceptor antagonists?
Hexamethonium and trimetaphan.
What do we mean by use-dependent block?
There are two types of antagonists; true antagonists and ion channel blockers. In terms of our nicotinic cholinoceptor antagonists, trimetaphan is an ion channel blocker. This means the more open the channel is, the easier it is for the drug to enter the channel and block it. This means the more agonist is present, the more effective trimetaphan is = use-dependent block.
With hexamethonium and other true antagonists, the opposite is true; the more agonist is present the more competition there is and the less effective the antagonist is.
If a general nicotinic cholinoceptor antagonist affects both parasympathetic and sympathetic nervous system, what would be the observable effects of administering it?
Loss of function of whatever system was dominant at the time of administration.
Why do nicotinic cholinoceptor antagonists such as hexamethonium cause hypotension?
Because blood tends to be diverted away from the gut, when the sympathetic nervous system is suppressed at rest as a result of taking one of these drugs, Total Peripheral Resistance goes down and so does blood pressure. (The blood flow to the gut is under sympathetic control)
Muscarinic receptor antagonists: identify and explain the pharmacokinetic properties of muscarinic receptor antagonists
As muscarinic cholinoceptors are mostly present at parasympathetic end-organs, they are for blocking parasympathetic function.
Atropine and hyoscine: atropine no therapeutic effects at low dose but toxic at high dose, hyoscine therapeutic (sedative, probably due to higher M1 selectiveness) at low dose and toxic at high.
What is tropicamide and what is its clinical use?
It’s a muscarinic cholinoceptor antagonist that blocks parasympathetic constriction of the eye and therefore allows for observation of the back of the eye.
Identify and explain the clinical uses of muscarinic receptor antagonists
Clinical use: anaesthetic premedication: dilates airways before administration of anaesthetic.
Hyoscine patches are used for motion sickness. (Cholinergic nerve relays vision-balance mismatch to the vomiting centre)
Parkinson’s as M4 targeting antagonists because M4 receptors inhibit the little few
remaining D1 neurones in the basal ganglia, so this helps to alleviate some of the symptoms.
Asthma; rather than using salbutamol as an agonist for adrenoceptors, you can use an antagonist for muscarinic cholinoceptors.
Explain the unwanted side effects of muscarinic cholinoceptor antagonists.
Hot as hell – no sweating
Dry as bone – no secretions
Mad as a hatter – CNS disturbance
Blind as a bat – Cycloplegia (paralysis of ciliary muscle of eye therefore lack of
accommodation)
Poisoning – treat with anticholinesterases
Which receptors are adrenaline and noradrenaline selective for?
Noradrenaline is more alpha selective and adrenaline is more beta selective. However, they can both act on both receptors, they are just slightly more selective for one or the other.
Explain the clinical uses of selective and non-selective alpha and beta adrenoceptor agonists.
In epipens for anaphylactic shock. (Binds to beta2 and causes bronchodilation, beta1 and causes tachycardia and alpha1 for vasoconstriction.)
Also, for asthma and other types of bronchospasm (beta2).
Cardiogenic shock - sudden inability for heart to pump ¨ sufficient oxygen-rich blood.
For maintaining blood pressure during general anaesthesia, or keeping local anaesthesia local by restricting surrounding vessels.
Treating glaucoma (alpha2 agonist or alpha 1 agonist , as alpha2 is negative feedback receptor and alpha1 is vasoconstrictor for blood supply to ciliary bodies).
Explain the unwanted side effects of selective and non-selective alpha and beta adrenoceptor agonists.
Reduced and thickened secretions.
Not a lot of CNS effects.
Cardiovascular effects - may worsen or give arrhythmias.
What is the unusual property of an alpha2 adrenoceptor agonist?
As the alpha2 sits on the presynaptic membrane and acts as a negative feedback control, NA or an agonist binding here has a suppressive effect.
What are the examples of selective SNS agonists for alpha1, alpha2, beta1 and beta2 receptors?
alpha1: phenylephrine
alpha2: clonidine
beta1: dobutamine
beta2: salbutamol
Why might phenylephrine be used as a decongestant?
(Recap: phenylephrine is an alpha1 selective agonist)
Main effect of phenylephrine is vasoconstriction.
This will cause white blood cell build-up to leave nasal sinus
What is glaucoma?
Raised intraocular pressure due to poor drainage of aqueous humour.
Where is the aqueous humour produced?
In the ciliary bodies
How is clonidine used to treat migraines and headaches?
As it is mostly alpha2 selective (negative feedback receptor on presynaptic membrane) and inhibits NA release.
Also a bit alpha1 selective so will vasoconstrict (and migraine associated with vasodilation). Although the vasoconstriction does not occur in the brain, vasoconstriction in the brain is mostly b2 controlled rather than alpha1.
What is the possible complication related to using isoprenaline for cardiovascular problems such as heart failure or cardiogenic shock? And how is this overcome clinically?
Although isoprenaline is beta1 selective and will have an effect on the heart (increase cardiac output), it is equally selective for beta2 which in turn causes vasodilation and hypotension.
So, instead we use dobutamine which is far more beta1 selective.
What is the main pharmacological difference between adrenaline and salbutamol?
Salbutamol is more resistant to MAO, and therefore has a longer half-life.
What is the equation for a drug getting oxidised by Cytochrome P450?
RH + NADPH + O2 + H+ ——–> ROH + NADP+ + H2O
Î___ Cytochrome P450
Outline the Phase 1 reactions that can occur.
A hydroxyl group can be added (oxidation): paracetamol is activated by having a OH group added to the aromatic ring itself.
Methyl group removed (oxidation): codeine (prodrug) is activated into morphine by having methyl group removed.
Nitrogen can become oxidised: second carbon in ethanol has oxygen added to it to become acetylaldehyde.
Reduction and hydrolysis are far less common than oxidation. They both break the molecule in two.