ICS Pharmacology Flashcards
1
Q
Give an example of a proton pump inhibitor.
A
Omeprazole.
2
Q
Give an example of a statin.
A
Simvastatin.
3
Q
Give an example of an ACE inhibitor.
A
Enalapril.
4
Q
Give an example of a COX inhibitor.
A
Aspirin and paracetamol.
5
Q
Give an example of a β2 adrenoceptor agonist.
A
Salbutamol.
6
Q
Give an example of a β1 adrenoceptor blocker.
A
Atenolol.
7
Q
Give an example of a Ca2+ channel blocker.
A
Amlodipine.
8
Q
Give an example of a broad spectrum antibiotic.
A
Amoxicillin.
9
Q
Give an example of an opiate analgesic.
A
Tramadol.
10
Q
What do most drugs target?
A
Proteins!
11
Q
Name 4 receptors that drugs target.
A
- Ligand gated ion channels.
- GPCR.
- Kinase linked.
- Cytosolic/nuclear.
12
Q
Give an example of a ligand gated ion channel.
A
Nicotinic Ach receptor.
13
Q
Give an example of a GPCR.
A
Muscarinic and β2 adrenoceptor.
GPCR’s usually interact with adenylate cyclase or phospholipase C
14
Q
Give an example of a kinase linked receptor.
A
Receptors for growth factors.
15
Q
Give an example of a cytosolic/nuclear receptor.
A
Steroid receptors; steroids affect transcription.
16
Q
What are agonists?
A
Agonists bind to a receptor and to activate it.
17
Q
What are antagonists?
A
Antagonists decrease the effect of an agonist. They show no response at a receptor.
18
Q
Describe the shape of a log dose-response curve.
A
Sigmoidal.
19
Q
What does EC50 tell us about a drug?
A
Its potency!
20
Q
What is EC50?
A
The concentration of drug that gives half the maximal response.
21
Q
Would a drug with a lower EC50 have a lower or greater potency?
A
Greater potency.
22
Q
What does Emax tell us about a drug?
A
Efficacy.
23
Q
Which is more efficacious, a full agonist or partial agonist?
A
A full agonist is more efficacious because a full agonist can give a 100% response.
24
Q
Would an antagonist shift a dose-response curve to the left or right?
A
The antagonist would shift the dose-response curve to the RHS. The drug therefore becomes less potent.
25
Drug action: define affinity.
How well a ligand binds to a receptor.
26
Drug action: define efficacy.
How well a ligand activates a receptor; how well it induces a conformational change.
27
What is the effect of fewer receptors on drug potency?
Fewer receptors will shift the dose-response curve to the RHS, this means drug potency will be reduced.
28
What is the effect of fewer receptors on receptor response?
Receptor response is still 100% due to receptor reserve. (Partial agonists don't have receptor reserve).
29
What is the affect of less signal amplification on drug response?
Less signal amplification gives a reduced drug response.
30
Describe allosteric modulation.
An allosteric modulator binds to a different site on a receptor and influences the role of an agonist.
31
What is inverse agonism?
Where an agonist has a negative effect at a receptor.
32
Does an antagonist show efficacy?
No. An antagonist has affinity but zero efficacy. An agonist however demonstrates affinity and efficacy.
33
Pharmacology: define tolerance.
A reduction in the effect of a drug overtime. This can be due to continuous use of repeatedly high concentrations.
34
What 3 ways can a receptor be desensitised?
1. Uncoupled (an agonist would be unable to interact with a GPCR).
2. Internalised (endocytosis, the receptor is taken into vesicles in the cell).
3. Degraded.
35
Can aspirin be described as a selective drug?
No. Aspirin is non-selective, it acts on COX1 and COX2.
36
What is the function of COX1 and COX2?
They cyclise and oxygenate arachidonic acid and produce prostaglandin H2.
37
What does prostaglandin H2 form when it interacts with synthases?
Prostanoids.
38
Define pro-drugs and give an example of one.
Drugs that need to be activated enzymatically e.g. ACE inhibitors, enalapril.
39
How do ACE inhibitors work?
Angiotensinogen is converted to angiotensin 1 via renin. Angiotensin 1 is then converted to angiotensin 2 via ACE. ACE inhibitors prevents angiotensin 1 binding and so you don't get angiotensin 2 formation.
(Angiotensin 2 is a vasoconstrictor and so ACEi can be used in the treatment of hypertension).
40
Give an example of a β lactam antibiotic.
Penicillin and amoxicillin.
41
How do β lactam antibiotics work?
The inhibit transpeptidase and so prevent bacterial cell wall synthesis.
42
How do diuretics work?
They inhibit 'synporters' in the loop of henle. This leads to increased H2O excretion and decreased salt reabsorption and so BP decreases.
43
Give an example of loop of henle diuretics.
- Furosemide, act on the ascending loop.
| - Thiazides, act on the distal tubule.
44
How can drugs be developed?
1. Serendipity, by chance. e.g. penicillin.
| 2. Rational drug design. e.g. propranolol.
45
Describe how rational drug design works.
Rational drug design is focused on developing an antagonist from an agonist. It looks at solubility, electrostatic charge and bulk.
46
How do you determine whether insulin is long or short acting?
Small changes in amino acid sequence will determine whether insulin is long or short lasting - RECOMBINANT PROTEIN!
47
Name 3 things that the chemical properties of a drug can influence?
1. Administration.
2. Distribution.
3. Elimination.
48
As the difference in concentration falls what happens to the rate of reaction?
The rate of reaction will slow down.
| Rate is proportional to the concentration of drug
49
What is the association between diffusion and concentration gradient?
Diffusion is proportional to concentration gradient; this is a first order process and represents an exponential function.
50
How many litres of water are there in the following body compartments:
a) Plasma.
b) Interstitial space.
c) Intracellular space.
a) 3L.
b) 11L.
c) 28L.
51
What are the 5 ways by which fluid can move between compartments?
1. Simple diffusion.
2. Facilitated diffusion.
3. Active transport.
4. Movement through extra-cellular spaces.
5. Non-ionic diffusion.
52
What can influence the degree of ionisation of weak acids and weak bases?
pH.
53
What equation can be used to determine the degree of ionisation at a specific pH?
Henderson Hasselbach.
| pH = log[A-]/[HA] + pKa.
54
What can enhance non ionic diffusion?
Non ionic diffusion can be enhanced if adjacent compartments have pH difference.
55
In terms of ionisation, what happens to Aspirin in the stomach?
Aspirin is a weak acid and so becomes less ionised in the stomach due to the low gastric pH.
56
What is the advantage of aspirin becoming less ionised in the stomach?
This allows rapid non-ionic diffusion across the gut membrane into the plasma. Once in the plasma aspirin becomes more ionised again.
57
What is the effect of an increase in pH on a weak acid?
The weak acid will become more ionised.
58
What is the effect of an increase in pH on a weak base?
The weak base will become less ionised.
59
What is the effect of a decrease in pH on a weak acid?
The weak acid will become less ionised.
60
What is the effect of a decrease in pH on a weak base?
The weak base will become more ionised.
61
Define bioavailability.
The amount of drug taken up as a proportion of the amount administered. It is a reflection of uptake.
62
What route of drug administration has a bioavailability of 1?
IV infusion, all the drug administered will go into the plasma.
63
Explain what would happen to the bioavailability of aspirin if gastric pH increased.
The bioavailability would decrease. Aspirin would be more ionised and so wouldn't diffuse across the gut into the plasma as rapidly this would mean aspirin uptake would decrease.
64
Give 2 factors that drug distribution in the plasma depends upon.
1. Chemical properties.
| 2. Molecular size.
65
Write an equation for the volume of distribution (Vd).
Vd = amount of drug administered/concentration of drug in plasma.
66
If a drug had a high Vd what would that tell us about the drug?
This would indicate that the drug was highly lipid soluble and that most of the drug had moved into the intracellular space, less was in the plasma.
67
What is the relationship between plasma concentration and Vd?
Plasma concentration is inversely proportional to Vd.
68
Give 3 factors that can increase gastric pH.
1. Ingesting alkaline foods.
2. Antacids.
3. Omeprazole (PPI).
69
Give the two definitions for clearance.
1. The volume of plasma from which a drug is completely removed per unit time.
2. The rate at which plasma drug is eliminated per unit plasma concentration.
70
Write an equation for renal clearance.
Renal clearance = Rate of appearance in urine / plasma concentration.
71
What are the two ways by which drugs can be eliminated in the kidneys?
1. Glomerular filtration.
| 2. Active secretion.
72
What are the possible dangers of kidney damage with regards to renal clearance?
Kidney damage results in decreased renal clearance and so there is danger of accumulation, over dosage and toxicity.
73
What compound do many lipid soluble drugs combine with to increase their hydrophilicity?
Glucuronic acid.
74
Define hepatic extraction ratio (HER).
The proportion of a drug removed by one passage through the liver.
75
What is the limiting factor when a drug has a high HER?
Hepatic blood flow, perfusion limited.
76
What is the limiting factor when a drug has a low HER?
Diffusion limited. A low HER is slow and not efficient.
77
What happens to high and low HER drugs when enzyme induction is increased?
The clearance of low HER drugs increases. There is minimal effect on high HER drugs.
78
Where do phase 1 hepatic metabolism reactions occur?
In the smooth endoplasmic reticulum.
79
What enzyme usually catalyses phase 1 reactions?
CYP450.
80
What is a phase 2 hepatic metabolism reaction?
Phase 2 reactions involve conjugation and glucuronidation etc.
They usually inactivate products and increase hydrophilicity for renal excretion.
81
Give 3 advantages of IV infusion.
1. Steady state plasma levels are maintained.
2. Highly accurate drug delivery.
3. IV infusion can be used for drugs that would be ineffective when administered via an alternative route.
82
Give 3 disadvantages of IV infusion.
1. Expensive.
2. Needs constant checking.
3. Calculation error likely.
83
Give an advantage of a drug having a low Vd.
It is easy to reach steady state and plasma concentration is ‘responsive’ to dose rate.
84
Give 4 properties of the 'ideal drug'.
1. Small Vd.
2. Drug broken down effectively by enzymes.
3. Predictable dose:response relationship.
4. Low risk of toxicity.
85
What are the advantages of pulsatile secretion as opposed to steady state?
1. Enhanced responsiveness.
| 2. More information can be conveyed.
86
What is the principal neurotransmitter in the body?
Acetylcholine.
87
What receptor does Ach interact with in the somatic nervous system?
Post-synaptic nicotinic receptors at the neuromuscular junction.
88
What type of receptor are nicotinic receptors?
Ligand gated ion channels.
89
Briefly describe how Ach is synthesised.
Acetyl CoA, choline and choline acetyl trasnferase combine to form acetylcholine. Ach is taken up into a vesicle in the presynpatic cleft and will be released following Ca2+ influx.
90
What enzyme is responsible for acetylcholine breakdown in the synaptic cleft?
Acetylcholinesterase.
91
Describe the action of botulinum toxin at the NMJ,
Botulinum toxin inhibits Ach release at the NMJ. Protease degrade vesicle proteins.
92
Describe the action of competitive antagonists at the NMJ.
They block Ach receptors. Competitive antagonists are muscle relaxants, adjuncts to general anaesthesia.
93
Describe the action of depolarising agonists (blockers) at the NMJ.
Depolarising agonists cause receptor desensitisation.
94
Describe the action of anticholinesterases at the NMJ.
There is increased Ach in the synaptic cleft. Ach can then compete with depolarising blockers.
95
What type of receptor are muscarinic receptors?
GPCR.
96
Give examples of adverse muscarinic agonist effects.
1. Diarrhoea.
2. Urination.
3. Miosis.
4. Brachycardia.
5. Emesis (vomiting).
6. Lacrimation.
7. Salivation.
97
Give 2 examples of Ach action in the CNS.
1. Motion sickness; Ach stimulates the vomiting centre in the brain.
2. Ach leads to increase dopamine re-uptake and so can worsen the symptoms of Parkinson's.
98
Briefly describe catecholamine synthesis.
Tyrosine -> L-DOPA -> Dopamine -> Noradrenaline -> Adrenaline.
99
Where does the conversion from Dopamine to Noradrenaline happen?
In a vesicle in the pre-synpatic neurone.
100
Which enzymes inactivate catecholamines?
MAO and COMPT.
101
Which protein does α1 interact with to activate phospholipase C?
Gq.
102
What is the primary function of α1?
α1 leads to vasoconstriction.
103
Which protein does α2 interact with in order to inhibit adenylate cyclase synthesis?
Gi.
104
What is the primary function of α2?
α2 is responsible for pre-synaptic inhibition; it inhibits NAd release.
105
What protein does β1,2,3 interact with in order to activate adenylate cyclase?
Gs.
106
What is the role of adenylate cyclase?
It converts ATP to cyclic AMP, this then leads to PKA synthesis.
107
What are the primary functions of β1?
1. Increased cardiac effects e.g. force, rate and conduction.
2. Increased renin secretion.
108
What are the primary functions of β2?
1. Bronchodilation.
| 2. Vasodilation.
109
What are the primary functions of β3?
1. Increase lipolysis.
| 2. Bladder relaxation.
110
What would an α1 adrenergic antagonist do?
1. Vasodilation.
| 2. Relaxation of bladder neck = reduced resistance to bladder outflow.
111
What disease could an α1 adrenergic antagonist be used in the treatment of?
Benign prostatic hyperplasia.
112
What would a β1 adrenergic antagonist do?
1. Reduce CO.
| 2. Reduce renin secretion.
113
What diseases could an β1 adrenergic antagonist be used in the treatment of?
Hypertension, angina and arrhythmia.
114
Define pain.
An unpleasant sensory and emotional experience associated with actual or potential tissue damage.
115
Give 3 advantages of pain.
1. Gives a warning for tissue damage.
2. Immobilisation for healing.
3. Memory establishment.
116
Define acute pain.
Pain caused by nociceptor activation. It is of short duration,
117
Define chronic pain.
Pain that is on-going or persistent, it lasts for >3-6 months.
118
Define neuropathic pain.
Pain caused by a primary lesion or dysfunction of the nervous system.
119
Define nociceptive pain.
Pain caused by actual or potential damage to non neural tissue, it is due to nociceptor activation.
120
Are A delta fibres myelinated or unmyelinated?
Myelinated.
121
Are C fibres myelinated or unmyelinated?
Unmyelinated.
122
Describe the type of pain that A delta fibres conveys.
Quick, sharp, localised.
123
Describe the type of pain that C fibres conveys.
Slow, dull, spread out.
124
Describe pain wind up.
A perceived increase in pain intensity over time when a stimulus is repeatedly delivered. It is caused by C fibre stimulation.
125
Describe the gate control theory.
Non-noxious stimuli trigger larger A beta fibres, these override smaller pain fibres and 'close the gate' to pain transmissions to the CNS.
126
What is pain treatment focused on?
1. Reducing excitatory neurotransmitters and nerve excitation.
2. Enhancing inhibitory neurones.
127
What are released in the presence of pain?
Endorphines.
128
What is an adverse drug reaction?
A noxious and unintended response to a drug.
129
Rawlins-Thompson system: Describe a type A adverse drug reaction.
- Augmented.
- Very common.
- Predictable from physiological effects of the drug.
- Often dose related.
130
Rawlins-Thompson system: Describe a type B adverse drug reaction.
- Bizarre.
- Unpredictable.
- Immunological mechanisms and hypersensitivity.
- Often there is a history of allergy.
131
Rawlins-Thompson system: Describe a type C adverse drug reaction.
- Chronic.
| - Occurs after long term therapy.
132
Rawlins-Thompson system: Describe a type D adverse drug reaction.
- Delayed.
| - Occurs many years after treatment.
133
Rawlins-Thompson system: Describe a type E adverse drug reaction.
- End of use.
| - Withdrawal reaction after long term use; complications of stopping medication.
134
What is the treatment for a type A adverse drug reaction?
Reduce the dose.
135
What is the treatment for a type B adverse drug reaction?
Withdraw drug immediately!
136
Why are drug interactions such a big problem today?
1. Ageing population.
2. Polypharmacy.
3. Increased use of over the counter drugs.
137
Give 5 patient risk factors for drug interactions.
1. Old age.
2. Polypharmacy.
3. Renal disease.
4. Hepatic disease.
5. Genetics.
138
Give 3 drug related risk factors for drug interactions.
1. Narrow therapeutic index.
2. Steep dose/response curve.
3. Saturable metabolism.
139
Name 3 types of drug interaction.
1. Synergy; interaction of 2 compounds leads to a greater combined effect.
2. Antagonism; one drug blocks another.
3. Other.
140
How might drug interactions affect drug metabolism?
If a drug inhibits or induces CYP450 it might affect the metabolism of another drug.
141
How does avocado affect CYP450? And what drug might this impact on?
Avocado is a CYP450 inductor. Warfarin is likely to be affected and the risk of blood clots will be increased.
142
How does grapefruit juice affect CYP450? And what drugs might this impact on?
Grapefruit juice is a CYP450 inhibitor, it affects CYP3A4 specifically and increases the bioavailability of some drugs e.g. Ca2+ channel blockers and immunosuppressants.
143
Are weak acids cleared quicker if urine is more acidic or more alkali?
Weak acids are cleared quicker if urine is more alkali.
144
Are weak bases cleared quicker if urine is more acidic or more alkali?
Weak bases are cleared quicker if urine is more acidic.
145
What drug acts as an antagonist at the μ receptor?
Naloxone.
146
What enzyme is needed to metabolise codeine?
Codeine is a pro drug and needs to be metabolised by CYP2D6.
147
What is the bioavailability of morphine taken orally?
50%.
148
10mg of morphine is taken orally. What is the equivalent dose if given parenterally?
5mg.
149
What is morphine metabolised to?
Morphine 6 glucuronide.
150
Where might μ receptors be found?
In the epidural space and CSF.
151
Give 5 side effects of opioid use.
1. Respiratory depression.
2. Sedation.
3. Nausea.
4. Vomiting.
5. Constipation.
152
Describe the dose-response curve for morphine.
As dose increases response increases. This association is initially rapidly and then the graph plateaus. It is not sigmoidal!
153
Name a protein that can inhibit apoptosis.
BCL-2; it inhibits pro-apoptotic proteins e.g. caspase and therefore inhibits apoptosis.
154
What disease might develop in someone with a non-functional BCL-2 protein?
Cancer.
155
Where are mast cells found?
They are only found in tissues, not in the blood!
156
What is dobutamine used in the treatment of and at what receptor is it an agonist?
Dobutamine is a beta 1 agonist. It is used in the treatment of heart failure.
157
Define physiological antagonism.
A substance that produces effects that counteract the effects of another substance.
158
What are the 3 actions of NSAIDS?
1. Anti-inflammatory.
2. Analgesic.
3. Anti-pyrexic.
(AAA).
159
Name a local anaesthetic.
Lidocaine.
160
How do local anaesthetics work?
They inhibit pain by stopping impulse conduction in sensory nerves.
161
What drug inhibits ACh release at the NMJ?
Botulinum toxin.
| It is used to treat urinary incontinence and also cosmetically as a muscle relaxant.
