ICS pharmacology Flashcards
1
Q
What is pharmacology?
A
The study of the effects of drugs
2
Q
What is pharmokinetics?
A
- How the body affects the drug:
- Absorbtion,
- Distribution,
- Metabolism
- Excretion
ADME
3
Q
What is pharmacodynamics?
A
How the drug affects the body
4
Q
What is the main target for drugs?
A
Receptors
5
Q
What are 3 things that naturally target receptors?
A
- Neurotransmitters e.g., acetylcholine, serotonin
- Autoacids (local hormones) e.g., cytokines, histamine
- Hormones e.g., testosterone hydrocortisone
6
Q
What are the different types of receptors?
A
- Ligand-gated ion channels
- G protein coupled receptors (most common)
- Kinase-linked receptors
- Cytosolic/nuclear receptors
7
Q
Name some drug targets that aren’t receptors?
A
- Enzymes
- Transporters
- Ion channels
Most drug targets are proteins
8
Q
What receptors do ligand-gated ion channels have?
A
Nicotinic ACh receptors
9
Q
What receptors do G protein coupled receptors have?
A
- M3R (muscarinic receptor)
- Beta-2-adrenorecepto. Produces second messenger cyclic-AMP
10
Q
What are kinase-linked receptors targets for?
A
Growth factors
11
Q
What are cytosolic receptors targets for?
A
Steroids
12
Q
What disease is the loss of nicotinic ACh receptors implicated in?
A
Myasthenia gravis
13
Q
Define potency?
A
Measure of how well a drug works
14
Q
What is a drug agonist?
A
A compound that binds to a receptor and ACTIVATES IT
15
Q
What is intrinsic activity?
A
- Emax of partial agonist/Emax of full agonist
- Basically, how well a drug works against something that fully works
16
Q
What is the difference between potency and efficacy?
A
- Potency is which drug is more effective at the same concentration
- Efficacy is with unlimited concentration which drug will be more effective
17
Q
What is an antagonist?
A
A compound that reduces the effect of an agonist
18
Q
How do competitive antagonism work?
A
- The reverse the effects of agonists by competing with them to bind with receptors.
- This therefore prevents agonists from having as strong of an effect
- They shift the curve to the right meaning more agonist is required for the same response
19
Q
How does non-competitive antagonism work?
A
- It binds to a receptor and prevents activation of the receptor. The same amount of agonist can still bind it will just be less effective
- It shifts the curve right and down meaning even more agonist is required to illicit the same response
20
Q
What is affinity?
A
How well a ligand/drug binds to the receptor
- Property shown by both agonists and antagonists
21
Q
What is efficacy?
A
Describes how well a ligand/drug activates the receptor
- Only agonists show efficacy
22
Q
What is allosteric modulation?
A
- Binding of an allosteric ligand to a receptor can affect an agonists effect
- Can change affinity and efficacy
- Can be positive or negative
23
Q
What is tolerance?
A
- The reduction in drug effect over time
- Seen with continuous, repeated high concentration of drug over time
24
Q
How does tolerance occur?
A
- Receptor can’t interact with G-protein
- Receptor becomes internalised in vesicle of the cell
- Receptor becomes degraded
25
Why is selectivity used to describe drug targeting than specificity?
Because no compound is truly specific
26
Give an example of a drug that is highly selective and one that is not?
- Isoprenaline is a non-selective B-adrenoreceptor agonist it activates both heart (B1) and lung (B2) receptors
- Salbutamol is a selective B"-adrenoreceptor and only activates lung (B2) receptors
27
Name a drug that targets enzymes?
NSAIDs
28
What are the actions of NSAIDs?
- Analgesic
- Anti-pyretic (reduces fever)
- Anti-inflammatory
29
What is the action of NSAIDs?
- They inhibit the COX enzyme
- COX is responsible for the breakdown of arachidonic acid to prostaglandin H2 (PGH2)
30
How do NSAIDs inhibit COX?
- They prevent arachidonic acid from reaching the active site of COX
- They are antagonists, so they bind to the active site of COX
- NSAIDs are competitive inhibitors
31
How is Aspirin different to other NSAIDs?
It irreversibly blocks the active site of COX resulting in irreversible inactivation
32
What are the two COX isomers and what do they do?
- COX-1 found normally and widely around the body
- COX-2 induced and found mainly in inflammation
33
Give an example of a selective and non-selective NSAID?
- Aspirin is non-selective inhibits COX-1,2.
- Celecoxib is COX-2 selective
34
What are ACE inhibitors?
- They are angiotensin-converting-enzyme inhibitors
- They are anti-hypertensive
35
How do ACE inhibitors work?
- They prevent the conversion of angiotensin I to angiotensin I
- This means there is less angiotensin II so less bind to angiotensin receptors (AT1)
- This results in reduced vasoconstriction and thus
hypertension as well as less aldosterone release further reducing
hypertension
36
Name two ACE inhibitors?
- Captopril
- Enalapril
- Both are competitive inhibitors and bind to ACE active site to prevent angiotensin I from binding
37
Give some examples of B-lactam antibiotics?
Penicillins, amoxicillin & cephalosporins
38
How do B-lactam antibiotics work?
- They inhibit the biosynthesis of peptidoglycan bacterial cell walls
- This is achieved by inhibiting the activity of certain enzymes
39
How are drugs inactivated?
-Most drugs are excreted by the kidneys
- Lipophilic drugs are not effectively removed
- Lipophilic drugs require Cytochrome P450 (addition of OH group) to make them soluble so they can be excreted by the kidneys
- Some drugs induce or inhibit cytochrome P450 to either be removed quickly or stay in the system for longer
40
What is summation?
When 2 drugs used at the same time both have the expected effect
41
What is synergism?
- When using two drugs together makes both of the drugs more effective
- For example, paracetamol and morphine
42
What is blockage
- When one drug blocks the action of another
- For example, salbutamol and non-selective beta blockers
43
What is potentiation?
When one drug makes the other more potent, but its potency stays the same
44
What is bioavailability?
How much of a drug taken is used. IV is always 100% but orally, this figure can change
45
Name some proton pump inhibitors (PPI)
- Omeprazole
- Lansoprazole
- Pantoprazole
- Rabeprazole
46
How do PPIs work?
- Activated in acidic conditions
- Inhibit acid secretion
- PPIs act to irreversibly inactivate the proton pump (H+/K+ ATPase)
47
Name a loop diuretic?
Furosemide
48
How does Furosemide work?
- It inhibits symporters
- It inhibits the NKCC2 pump on the thick ascending part of the loop of Henle
49
How do you treat a paracetamol overdose?
- If it has been less than 1 hour since OD give activated charcoal
- If longer than this give intravenous N-acetylcysteine
50
Name some calcium channel blockers
- Amlodipine
- Verapamil
- Diltiazem
All used in the treatment of hypertension
51
How does Amlodipine work?
- It blocks voltage dependant calcium channels found in cardiac muscle and vascular smooth muscle
- This means there is less vasoconstriction useful for hypertension
52
Name some local anaesthetics
- Lidocaine
- Procaine
They interrupt axonal neurotransmission.
53
How do local anaesthetics work?
- They block voltage dependant sodium channels thus preventing the neurons from depolarising.
- Therefore, there is no action potential, so no pain signal is sent to the brain
54
What is an adrenergic receptor?
Receptors that react to noradrenaline and adrenaline (sympathetic nervous system)
55
What is a cholinergic receptor?
Receptors that react to acetylcholine (parasympathetic nervous system)
56
Name 3 things that define the somatic nervous system
1. Single neuron between CNS and skeletal muscle
2. Innervates skeletal muscle
3. Leads to muscle excitation (not inhibition)
57
Name 3 things that define the autonomic nervous system
1. Two-neuron chain
2. Smooth muscle, cardiac muscle, glands, (GI neurons)
3. Leads to excitation or inhibiton
58
Is the postganglionic neuron closer to the effector organ in the sympathetic or parasympathetic nervous system
Parasympathetic
59
How are the sympathetic and parasympathetic nervous systems similar (in terms of neurotransmitters and receptors used)?
Acetylcholine acts on nicotinic receptors in preganglionic neurons
60
What receptors are acted on in postganglionic neurons in the parasympathetic system?
Acetylcholine acts on muscarinic receptors
61
What receptors are acted on in postganglionic neurons in the sympathetic system?
Noradrenaline acts on alpha and beta receptors
62
What are some exceptions to the usual receptors used in the parasympathetic and sympathetic systems
- Acetylcholine is released at sympathetic postganglionic termini (sweat glands)
- Nitric oxide is released from parasympathetic postganglionic termini in blood vessels
63
What are the 5 types of muscarinic receptors?
M1- Brain
M2 - Heart
M3- all organs with parasympathetic innervation
M4- mainly CNS
M5- mainly CNS
All are found outside the cell and activate intracellular processes through G-proteins
64
What do M3 receptors do when stimulated in the respiratory system?
- Produce mucus
- Induces smooth muscle contraction
65
What do M3 receptors do when stimulated in the GI tract?
- Increase saliva production
- Increase gut motility
- Stimulates biliary secretion
66
What do M3 receptors do when stimulated in the skin?
- Only place where sympathetic system releases ACh
- Stimulation causes sweating
67
What do M3 receptors do when stimulated in the urinary system?
- Contracts detrusor muscle
- Relaxation of internal urethral sphincter
68
What do M3 receptors do when stimulated in the eye?
- Causes myosis
- Increases drainage of aqueous humour
- Secretion of tears
69
What do pilocarpine drops do?
- M3 agonists in the eye
- Increases drainage of aqueous humour
- Reduces ocular pressure
70
What is atropine used for?
- Is a muscarinic antagonist
- used to increase heart rate, treat bradyarrhythmias and AV node block
71
What are some direct-acting Cholinergic agonists, and how do they work?
- Carbachol (pupil constriction)
- Bethanechol (increases smooth muscle tone in the GI tract)
- Pilocarpine (stimulates saliva secretion)
Work by mimicking ACh and bind to receptors
72
What are some indirect-acting Cholinergic agonists, and how do they work?
- Neostigmine ( reverse anaesthesia, myasthenia gravis)
- Donepezil, Rivastigmine (Alzhimers)
They inhibit acetylcholine esterase, so it stays in the synapse for longer
73
Name some Muscarinic antagonists and how do they work?
- Atropine, Scopolamine, Belladonna alkaloids (treat bradycardia, diarrhoea, bladder spasms; dilate bronchi, reduce secretions, dilate pupils; as sedatives, respectively)
- Compete with ACh for binding to the muscarinic receptor
74
Name some Nicotinic antagonists and how they work
- Curare, Pancuronium (relax skeletal muscles during surgery)
- Compete with ACh for binding to the nicotinic receptor
75
What happens in Myasthenia Gravis?
- Antibody is produced that binds to ACh receptors
- Prevents ACh from binding at skeletal muscle
- Results in muscle weakness
- Treatment is anti-cholinesterase
76
What is the pathway from L-dopa to adrenaline?
L-dopa> Dopamine > Noradrenaline> Adrenaline
77
What do Alpha 1 adrenergic receptors do?
- Vasoconstriction
- Increase in peripheral resistance
- Increased blood pressure
- Increased closure of internal sphincter of the bladder
78
What do Alpha 2 adrenergic receptors do?
- Mixed effects on smooth muscle
- Inhibition of noradrenaline release
- Inhibition of ACh release
- Inhibition of insulin release
79
What do Beta 1 receptors do?
- Positively chronotropic (heart rate)
- Positively Ionotropic (force of contraction)
- Increased release of renin
- Increased lipolysis
80
What do Beta 2 receptors do?
- Vasodilation
- Decreased peripheral resistance
- Bronchodialtion
- Increased glycogenolysis in the liver and muscle
- Increased glucagon release
- Relaxation of uterine smooth muscle
81
When would Alpha 1 agonists be used?
- Noradrenaline is given IV for shock
- Also used to overcome anaesthetic agents
- Adrenaline can be used to overcome anaphylaxis
- Xylometazoline can be used as a nasal decongestion
82
Name an Alpha 2 agonist.
- Clonidine can be used in ADHD to help concentration`
83
Name some Alpha 1 antagonists.
- Doxazosin used to lower blood pressure (not commonly used)
- Phenoxybenzamine used to treat pheochromocytoma ( catecholamine secreting tumour)
84
What do Beta 1 agonists do?
- Tachycardia
- Increase in stroke volume
- Renin release
- Lipolysis and hyperglycemia
85
What do Beta 1 antagonists (Beta-blockers) do?
- Reduce heart rate
- Reduce stroke volume
E.g., Carvedilol, Bisoprolol, Atenolol
Caution in asthma if non-selective beta blocker
86
How can glucagon be useful in beta-blocker poisoning?
- It bypasses the beta-adrenergic receptor site and increases heart rate and myocardial contractility
87
What does Beta 2 agonism do in the bronchi?
Bronchodilation
88
What does Beta 2 agonism do in the bladder wall?
Inhibits micturtion
89
What does Beta 2 agonism do in the uterus?
Inhibits labour
90
What does Beta 2 agonism do in smooth muscle?
increases contraction speed
91
What does Beta 2 agonism do in the pancreas?
Insulin and glucagon secretion
92
When is a beta 2 agonist useful?
- Asthma/COPD (side effect hyperglycemia and tachyarrhythmia)
- Can be used to delay labour
Salbutamol is an example
93
What is the bioavailability of morphine taken orally?
50%
94
10mg of morphine is taken orally. What is the equivalent dose if given parenterally?
5mg
95
Give 5 side effects of opioid use
1. Respiratory depression.
2. Sedation.
3. Nausea.
4. Vomiting.
5. Constipation
96
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
97
What it do you give to reverse a morphine overdose
Naloxone - its an antagonist to morphine
98
What it do you give to reverse a morphine overdose
Naloxone - it's an antagonist to morphine
99
Briefly outline how opioids work.
They Inhibit the release of apin transmitters at the spinal cord and midbrain
They modulate the pain perception at higher centres, to create euphoria
100
What is the main opioid receptor, that all the drugs we currently use act on?
μ (Kappa) receptors
(MOP)
101
Name other receptors that morphine been found to bind to. Agonism of what receptor has been known to cause mental depression instead of euphoria?
after delta (DOP) and kappa (KOP) receptors.
Kappa agonists cause mental depression instead of euphoria
102
Where may you find kappa μ receptors (MOP) in the body?
- Midbrain
- Spine
- GI tract - can get constipated with opioid use
- Breathing centre - it communicates using opioid receptors, opioid use can cause respiratory depression
103
Why can giving Buprenorophine be safer?
Because it is only a partial agonist, so only reaches up to 50% response.
104
Outline the potentsies of Diamorphine and pethidine, relative to morphine.
Relative potencies:
- Diamorphine (Heroin)- 5mg (twice as potent as morphine)
- Morphine - 10mg
- Pethidine - 100mg (10 times weaker than morphine)
Diamorphine - Heroin:
- More potent and faster acting (crosses blood-brain barrier quickly)
105
Name some statistics regarding adverse drug reactions
- Account for 6-7% of hospital admissions
- 2% admitted will die
- 5th most common cause of hospital death
- 60% preventable
106
What are the 5 types of adverse drug reactions?
- Augmented
- Bizarre
- Chronic
- Delayed
- End of use
ABCDE (Rawlins-Thompson)
107
What is an augmented drug reaction?
- Most common
- An extension of the clinical effect
- Dose related
- Those with renal or hepatic impairment more at risk due to elimination difficulties
E.g., diuretic causing dehydration, anticoagulant causing bleeding
108
What is a bizarre drug reaction?
- Unexpected
- Not dose related and not from known pharmacological action
- Mostly immunological mechanisms
- Those with history of allergy's more at risk
E.g., Heparin causing hair loss
109
What is a chronic drug reaction?
- Occurs after long term therapy
- May not be immediately obvious with new medicines
E.g., Steroids predispose to hyperglycaemia may result in diabetes
110
What is a delayed drug reaction?
- Occurs a long time after the treatment (many years, common to be 20-30 years)
E.g., Neoplasia, Teratogenesis (congenital malformation in foetus) after taking thalidomide
111
What is an end of use drug reaction?
- Relatively long-term use (days/weeks)
- Withdrawal reactions
112
What are some important questions to ask when trying to identify what type of drug reaction has occured?
- Is it predictable? Does it seem dose related? (augmented)
- Is there a history of allergy in family or patient (bizarre)
- Has the patient been using the medication for a long time (chronic)
- What drugs has the patient taken in the past (delayed)
- Is the patient withdrawing from a medicine (end of use)
113
What are patient risk factors for an adverse drug reaction?
- Gender (women more at risk)
- Elderly
- Neonates
- Polypharmacy
- Genetic predisposition
- Allergies
- Hepatic/renal impairment
- Adherence problems
114
What are drug risk factors for an ADR?
- Steep-dose curve
- Low therapeutic index
115
What are the most common drugs to have ADR's?
- Antibiotics
- Anti-neoplastics
- Cardiovascular drugs
- Hypoglycaemics
- NSAIDS
- CNS drugs
116
What are the most common systems to be affetcetd?
- GI
- Renal
- Haemorrhagic
- Metabolic
- Endocrine
- Dermatologic
117
What is the yellow card scheme?
- Was introduced in 1964
- Collects spontaneous reports
- Collects suspected adverse reactions
118
When would you fill out a yellow card?
- All suspected reactions for, herbal medicine and black triangle drugs
- All serious suspected reactions for, established drugs, vaccines and drug interactions
119
What does a black triangle drug mean?
- A drug that contains a new active substance
- Is a biological medicine- a vaccine or medicine derived from plasma
- Has been given conditional approval
This means the company markets the medicine is required to carry out additional tests
120
What are the 4 pieces of information to include on a yellow card?
1. Suspected drugs/drugs
2. Suspected reaction
3. Patient details
4. Reporter details
121
Give an example of a proton pump inhibitor.
Omeprazole, lansoprazole
122
Give an example of a statin.
Simvastatin.
123
Give an example of an ACE inhibitor.
Enalapril.
124
Give an example of a COX inhibitor.
Aspirin and paracetamol
125
Give an example of a β2 adrenoceptor agonist.
Salbutamol.
126
Give an example of a β1 adrenoceptor blocker.
Atenolol.
127
Give an example of a Ca2+ channel blocker.
Amlodipine.
128
Give an example of a broad spectrum antibiotic.
Amoxicillin.
129
Give an example of an opiate analgesic.
Tramadol.
