Pharm Flashcards
Example of ligand-gated channel
nicotinic ACh receptors
Example of G protein-coupled receptor
adrenergic receptors
Example of Kinase-associated receptors
Insulin receptor
Example of Nuclear receptors
Steroid receptors
Explain the process of ‘No signalling’ for G protein-coupled receptor
- Receptor unoccupied
- G protein binds GDP
- Effector not modulated
Explain the process of ‘Turning on the signal’ for G protein- coupled receptor
- Agonist activates receptor
- G protein couples with receptor
- GDP dissociates from and GTP binds to the alpha subunit
- G protein dissociates from the receptor
- Alpha subunit combines with and modifies activity of the effector
- Agonist may dissociate from the receptor, but signalling persists
Explain the process of ‘Turning off the signal’ for G protein- coupled receptor
- Alpha subunit acts as an enzyme to hydrolyse GTP to GDP (GTPase)
- G protein alpha subunit recombines with the by subunit completing G protein cycle
Explain how Kinase associated receptors work
Work via autophosphorylation of tyrosine residues attached to the receptor inside the cell when agonist binds
Explain how Nuclear receptors work
- Diffuse across cell membrane
- Act as ligand gated transcription factors
- Bring about changes in transcription to bring about their effect
Where are nuclear receptors located?
Within the nucleus of cell
Explain the process of the sympathetic nervous system
Signal functions of fight or flight i.e. stress response
= (1) Outflow from central nervous system is throacolumbar
(2) Preganglionic neurotransmitter is ACh acting on nicotinic receptors (ligand gated)
(3) Postganglionic neurotransmitter is NA usually and act on alpha or beta adrenergic receptors which are G protein coupled
(4) Synapse at para/prevertebral ganglion and long secondary neuron to the effector organ. Exception being the adrenal medulla
Explain the process of the parasympathetic system
Signal functions of rest and digest
= (1) Outflow from central nervous system is cranial/sacral
(2) Both pre and postganglionic neurotransmitter is ACh
(3) Act at ganglion via nicotinic ACh receptors which are ligand gated
(4) Act at effector organ via muscarinic ACh receptors which are G protein coupled
(5) Long preganglionic neuron to a ganglion close to or within the effector organ then short postganglionic neuron to effector cell
Drugs confined to interstitial fluid and plasma: can get past capillaries, but are not lipid soluble so can’t get past cell membranes. Is an example of what antibiotic?
Amoxicillin
Drugs confined to plasma: too large to get past capillaries, or bound to plasma protein. Is an example of what?
heparin
What is zero-order kinetics?
A reaction where the rate of the reaction is independent of the concentration of the reactant(s)
What is first-order kinetics?
A reaction where the rate of the reaction is directly proportional to the concentration of only one reactant
How fast do ligand-gated channels go?
milliseconds
How fast do G protein-coupled receptors go?
seconds
How fast do Kinase linked go?
hours
How fast do nuclear receptors go?
days
Role of alpha 1 receptors
Cause salivary secretion and relaxation of GI smooth muscle
Role of alpha 2 receptors
Found presynaptically and acts to inhibit neurotransmitter release
Role of beta 1 receptors
Increase heart rate and force
Role of beta 2 receptors
Vasodilation, bronchodilation, and relaxation of GI smooth muscle
Role of beta 3 receptors
Induce lipolysis
Drugs exhibiting zero-order kinetics are what?
Phenytoin
Salicylates (e.g. high-dose aspirin)
Heparin
Ethanol
What Inhibits RNA synthesis?
Rifampicin
Electrical cardioversion is synchronised to what waves?
R
Which drugs lead to a decrease in the production of aldosterone?
Losartan - ARB blocker
Aspirin is derived from salicylic acid and acetic anhydride. How do NSAIDs (Non-steroidal anti-inflammatory drugs) exert their anti-inflammatory effect?
Inhibition of cyclooxygenase
A boy was diagnosed with Gitelman syndrome (a condition due to a defect in a transport protein in the kidneys).
What drug has the mechanism of action of inhibiting the transport protein providing a similar effect to those with Gitelman syndrome
thiazide diuretic
Mrs C, a 66-year-old woman attends with worsening shortness of breath and ankle swelling. She has a background in ischaemic heart disease. On examination, she has a raised jugular venous pressure. Which drug is most commonly used to acutely treat these symptoms?
Furosemide, a loop diuretic
In which tissues are b1-adrenoceptors found?
Cardiac muscle, sinoatrial and atrioventricular nodes, juxtaglomerular apparatus of kidney
Where are the hormones that spironolactone antagonises produced?
Zona glomerulosa of the adrenal cortex
Describe a partial agonist
Less effective than full agonists and cannot produce the maximal response even if they were to occupy the total receptor population
During the ‘cheese reaction’, elevated levels of tyramine increase sympathetic outflow, resulting in severe hypertension, tachycardia, and headache. Phentolamine, an alpha-adrenoceptor antagonist, may be given to lower the blood pressure in this instance. If tyramine is considered the agonist, what type of antagonism does phentolamine demonstrate?
Indirect antagonism
= The antagonist interferes with processes that link receptor activation by the agonist and tissue response, again without binding to the same receptor as the agonist
Drugs that are eliminated by zero-order kinetics include
salicylates, asprin, phenytoin, alcohol/ ethanol and omeprazole.
In which of the following body compartments would pethidine (a weak base) most likely distribute itself?
Acidic enviornment
Drugs that are eliminated by first-order kinetics include what?
Statins, clopidogrel and candesartan.
A patient taking ramipril for heart failure develops a dry cough. What is the mechanism for the development of this side effect?
Increased bradykinin
Calcium channel blockers are the first line antihypertensive for who?
Non-diabetic patients >= 55 and patients of black African or African–Caribbean origin.
Diabetic + white - ACE regardless of age
You would like to prescribe long-term aspirin for one of your elderly patients. What is the most important side effect you should look out for when reviewing them in future?
Abdominal pain
Which medication is used to treat digoxin toxicity?
Digibind
For how long should a patient with atrial fibrillation be on warfarin for as primary prevention of stroke?
Life long
Which is an indication for flecainide
Atrial fibrillation
What is a distinguishing feature of the sympathetic nervous system?
A short pre-ganglionic axon and a long post-ganglionic axon
Warfarin is not readily filtered in the glomerulus, with only 2% of molecules found in the glomerular filtrate. Which characteristic of warfarin is the most likely explanation for the low concentration in the filtrate?
Albumin binding
Mr S, a 75-year-old man, presents to A&E with a recent history of intermittent blurry vision and seeing ‘halos’, nausea and vomiting, and periorbital pain. He is later diagnosed with acute angle-closure glaucoma. How can a drug that affects the parasympathetic nervous system be used to treat acute angle-closure glaucoma?
Causes pupillary constriction, improving drainage of aqueous humour
A male patient with heart failure starts to develop breast tissue. Which is the most likely causative medication?
Spironolactone
Which would require urgent medical attention in a patient who is on warfarin?
Black stools
An asthmatic patient was recently started on a new medication. They are now experiencing constipation, dizziness, dry mouth, confusion, urinary retention and blurred vision. Which drug is likely to have caused these side effects?
Ipratropium bromide - SAMA
Which diuretics decrease urinary calcium loss?
Bendroflumethiazide
What is the first-line anti-emetic used to prevent nausea and vomiting in a patient receiving chemotherapy?
Ondansetron
At which site within the kidneys does the greatest proportion of calcium reabsorption take place?
Proximal convoluted tubule
Which calcium channel antagonist is used to treat hypertension due to its effects on vascular smooth muscle?
Amlodipine
Which calcium channel antagonist is used to treat hypertension due to its effects in cardiac tissue?
Verapamil
A 36-year-old construction worker has presented with persistent back pain after bending down to lift a box. He has no red-flag symptoms. He is diagnosed with mechanical back pain and a decision to start him on ibuprofen and a proton pump inhibitor is made. Ibuprofen reversibly inhibits cyclooxygenase 1 which converts arachidonic acid into prostaglandin G2. Which enzyme is responsible for the formation of arachidonic acid?
Phospholipase A2
Name the enzyme that function is; involved in the conversion of prostaglandin G2 into prostaglandin H2
Peroxidase
Why are platelets are more sensitive to the effects of aspirin than other cell types?
Platelets lack the ability for protein synthesis
Which site accounts for the highest proportion of calcium excretion from the body?
Kidneys
Which laxatives should be avoided in an elderly patient suffering from chronic constipation who is frail with low mobility?
Bulk forming
A patient who is on long-term omeprazole presents with paraesthesia, tetany, seizures and arrhythmias. What is the main electrolyte imbalance that is likely to be causing their current presentation? and why?
Hypomagnesaemia
= Side effect of long-term PPI
A 65-year-old female was recently started on hydrochlorothiazide as a result of her hypertension which is poorly controlled by the maximum dose of amlodipine. She noticed that she had palpitations after taking the medication. An ABG is taken which shows hypokalaemia. Which is the main site of potassium excretion as a result of the use of thiazide diuretics?
Cortical collecting duct
A 38-year-old woman with known asthma presents to A&E with severe intractable vomiting, diarrhoea, palpitations, tachycardia and restlessness. Her serum theophylline levels are measured and found to be much higher than the therapeutic range. What would be the most appropriate therapy to administer next?
Activated charcoal because this woman has presented with signs of theophylline toxicity
What is the preferred direct oral anticoagulant (DOAC) for patients with chronic kidney disease?
Apixaban
Catabolic refers to what?
Phase 1
Anabolic refers to what?
Phase 2
Explain phase 1 metabolism in regards to prescribing in liver disease
Phase I metabolism is affected early
Affects metabolism of fat-soluble drugs opiates, calcium blockers, cyclosporin, metronidazole and others
Explain phase 2 metabolism in regards to prescribing in liver disease
Phase II metabolism is affected late
Explains why some drugs are better than others for patients with liver disease
What do you always prescribe with an NSAID?
PPI
Increased P450 whilst taking paracetamol can be stimulated by what?
Alcoholism
What antibiotics are not safe in established liver disease
Aminoglycosides - nephrotoxic
Quinolones - epileptogenic
Metronidazole metabolism reduced
ECG Changes in taking digoxin medication (this is not an indication of digoxin toxicity)
Downsloping ST depression - ‘Reverse Tick’
T wave changes (inversion)
Biphasic/flattened and shortened QT interval
Slight PR interval prolongation
