Pharmacology -Part 2 Flashcards
1
Q
Give examples of patient risk factors that increase their chance of drug interactions
A
Poly-pharmacy Old age Genetics e.g. slow/fast metabolism Hepatic disease Renal disease
2
Q
What is the therapeutic index of a drug?
A
A comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity
3
Q
Give examples of drug related risk factors that increase their chance of drug interactions
A
NARROW Therapeutic index
Steep dose/response curve
Saturable metabolism
4
Q
Give example of saturable metabolism
A
Paracetamol and alcohol are metabolised at a SET RATE
5
Q
What 4 factors make up the pharmacokinetics of a drug
A
Absorption
Distribution
Metabolism
Elimination
6
Q
What factors can be influenced Absorption in pharmacokinetics of drug metabolism?
A
Motility Acidity Solubility Non-absorbed complex formation Direct action on enterocytes
7
Q
How does Erythromycin influence Motility in absorption in pharmacokinetics
A
Increases Gut Motility
8
Q
What 2 drugs have the commonest interaction causing motility changes?
A
Oral contraceptive pill
Antibiotics
9
Q
What drugs can influence the pH/acidity of the stomach and thus affect absorption in pharmacokinetics
A
Antacids and Proton Pump Inhibitors
These change pH of the stomach so if take with another medication, the absorption of the drug can be altered
10
Q
Give example of solubility being affected in drug metabolism due to interaction.
A
Eating avocado (high in fat) and taking a fat soluble drug e.g. anti-coagulant
Drug will dissolve meaning there will be less or no drug absorption
11
Q
Give example of a fat soluble drug
A
Anti-coagulant
12
Q
What would be effect on drug absorption if took a fat soluble drug with high fat food such as avocado
A
Drug will dissolve meaning there will be less or no drug absorption
13
Q
Give example of drug not being absorbed due to formation of a large complex in body
A
Cholestyramine +
Thyroxin, Warfarin or Digoxin
(large complexes formed in intestinal lumen)
14
Q
What are enterocytes
A
Intestinal absorptive cells
15
Q
What is effect of Grapefruit juice on uptake of certain drugs?
A
Grapefruit juice inhibits P-glycoprotein resulting in increased uptake of certain drugs
16
Q
What can cause a decrease in distribution of drug concentration in plasma (not including being use by target cells)
A
Drug can bind to proteins in plasma, thus reducing distribution and meaning effect is lowered.
17
Q
What drugs can have a reduced distribution due to protein binding in the plasma
A
Sulphonamide antibiotics
Warfarin
18
Q
What wavelength of light is absorbed by CYP450?
A
450nm
19
Q
What can be metabolised by CYP450?
A
Haemoproteins
Many other substrates, including Endogenous (body products) and Exogenous (durugs, toxins and food) products
20
Q
What classes of CYP450 are found in humans
A
Classes 1, 2, 3
21
Q
When would you give drug to inhibit CYP450
A
To block metabolism of drug (that would usually be metabolised by CYP450), leaving more of the drug free in plasma and Increasing its effects.
22
Q
When would you not inhibit CYP450, even if drug is metabolised by CYP450
A
If pro-drug
If block metabolism then effects of it will be decreased
23
Q
What is effect of drug of CYP450 induction?
A
Increased metabolism of drug causing decreased therapeutic effects
24
Q
When would CYP450 induction increase effects of a drug?
A
Pro-drug
Increase in metabolism leads to more of active form so increased effects
25
What CYP is affected by grapefruit juice?
Grapefruit juice affects CYP3A4
| Results in increased bioavailability and can therefore make a drug more effective.
26
What makes up the majority and minority of drug excretion
Renal excretion is majority
| Biliary excretion is minority
27
True or False:
| Renal excretion is not pH dependent
False
| Renal excretion is pH dependent
28
In what circumstance would a weak base be excreted faster?
If the urine is acidic
29
In what circumstance would a weak acid be excreted faster?
If urine is alkaline
30
How can you alter the excretion of a weak acid or weak base
By altering pH of urine
31
Give examples of weak acids that are drugs
Aspirin
Ibuprofen
Paracetamol
Warfarin
32
What can be done to increase excretion of aspirin if given an overdose?
Alkalinise urine as aspirin is a weak acid
33
Give examples of weak bases that are drugs
Amphetamine
Atropine
Propranolol
Salbutamol
34
Give general examples of pharmacodynamic mechanisms of drug interaction
Receptor based
Signal Transduction
Physiological systems
35
Give example of agonist receptor based drug interaction
Alcohol and Benzodiazepine at GABA A receptor
| drugs bind to receptor
36
Give example of a partial agonist receptor based drug interaction
(Partial binding/activation at receptor)
| Buprenorphine for Opioid Addiction
37
Give example of a antagonist receptor based drug interaction
(blocks receptor -can be competitive or non-competitive)
| Beta-blockers and Asthma (competitive)
38
Why should you never give Beta-Blockers to Asthmatic
Asthmatics will be on B-agonists to help with bronchodilation
If using beta-blockers then will cause bronchoconstriction and increase risk of asthma attack
39
Why do you not give Beta-blockers to a diabetic
Beta-blockers in a diabetic:
Results in action at B3 receptor (in adipose tissue) which normally detect and alter blood glucose.
However action at B2 receptor can suppress hypoglycaemic awareness so they will not detect fall in glucose.
40
Why do you not give ACE inhibitors with NSAIDs?
High degree of nephrotoxicity
41
Can you give Ca channel antagonist and Beta-blocker?
No
Symptoms of heart failure may worsen because these drugs reduce the ability of the heart to pump blood.
(Also sexual function can be impaired)
42
*What is effect of giving Digoxin and Furosemide?
- Digoxin works on cardiac fibres and its effect is increased if there are low levels of potassium in blood plasma
- Furosemide is a diuretic that lowers arterial pressure but favours the loss of potassium
- This could lead to hypokalaemia, which could increase the toxicity of digoxin
43
How can you avoid prescribing drugs causing interactions
Prescribe rationally
BNF
Medicines infroamtion service
44
Effect of avocado and warfarin
Avocado reduces effectiveness of warfarin - could increase risk of blood clots
45
Effect of Grapefruit juice on Calcium channel blockers
Increases effectiveness of calcium channel blockers
46
Effect of Grapefruit juice on Anti-rejection medication
Increases effectiveness of anti-rejection medication
47
Effect of Garlic on Anti-platelet activity
Garlic increases anti-platelet activity so can increase risk of bleeding
48
Effect of Soya on NSAIDs or Warfarin
Soya increases effectiveness of NSAIDs and warfarin so can increase risk of bleeding
49
Effect of Ginger on Anticoagulants
Ginger reduces effectiveness of anticoagulants so increases risk of bleeding
50
What is a major interaction of antiarrhythmic agents
Amiodarone
51
What is major interaction of antihistamines
Terfenadine,
| Diphenhydramine
52
Name some minor interctions of Ca Channel Antagonists
Felodipine
Nifedipine
Nimodipine
Nicardipine
53
Give a major interaction of Statins
Simvastatin
54
Give a minor interaction of Statins
Atorvastatin
55
Give examples of minor interctions of immunosurpressants
Cyclosporin,
| Tacrolimus
56
What is side effect of Simvastatin
Rhabdomyolysis
| muscle pain/breakdown
57
What is side effect of Warfarin
Bleeding
58
What is side effect of SSRIs
Serotonin syndrome
59
What is side effect of Simvastatin + Warfarin + SSRIs
Renal failure
60
What is required for a safe prescription
```
Patient Name
Dose
Route
Frequency
Duration
Total number of tablets
Drug Name
Date and Signature
```
61
What needs to be kept in mind when deciding on a safe prescription
Diagnosis
Drug treatment
Indication and Contraindications
Others: does it require plasma monitoring or is there a risk of drug interaction?
62
Where can errors arise that affect prescription given
Home: Drug history & Pharmacy printout
Hospital admission: In patient prescription chart
In patient: Multi disciplinary prescribing
Discharge from hospital: Take home medication or not & discharge summary to GP
63
What are potential causes of prescribing error
- The number of different times the same information is translated or transposed
- Inadequate information on admission
- Duplication; paper, different teams
- Clerical/legibility/ administration errors
- Emergency situations
64
True or False:
| Prescribing errors are avoidable and thus a form of neglect
True
65
If drug name has prefix co- and suffix -amol, what does this mean
Drug contains paracetamol
66
Why is it important to specify route of administration of morphine
Since only a 1/3 of this dose will actually be absorbed due to high liver metabolism if administering orally - thus will be less effective
67
What is intrathecal
Via spinal cord
| careful not to confuse with IV, to prevent unnecessary spinal cord damage
68
What drugs can have withdrawal reactions if stopped after long term use
Analgesics
Anti-hypertensives
Anti-depressants
(but only stop if important reason or complaint)
69
What is policy of fluid use before surgery
Nil by mouth for fluid is 2 hours
This is due to fear of aspiration under anaesthesia
(sip of water with tablet OK tho)
70
What drugs should be discontinued prior to surgery
Ace inhibitors, Losartan (Angiotensin receptor blocker)
Warfarin (since should be rbidged to heparin -easier to manage dosage since injected)
Diabetes drugs
71
What drugs would you find at Step 1 on WHO analgesic ladder
Non-opioid analgesics
| NSAIDs
72
What drugs would you find at Step 2 on WHO analgesic ladder
Weak Opioids
73
What drugs would you find at Step 3 on WHO analgesic ladder
Strong opioids
Methadone (PO administration)
Transdermal patches
74
What drugs would you find at Step 4 on WHO analgesic ladder
```
Nerve block
Epidurals
PCA pump
Neurolytic therapy
Spinal stimulators
```
75
When would you use drugs higher on the analgesic ladder (e.g. step 3 or 4)
Chronic pain
Some Non-malignant pain
Cancer pain
76
When would you use drugs lower on the analgesic ladder (e.g. step 1 or 2)
Acute pain
Chronic pain without control
Acute crises of chronic pain
77
Where is tramadol on analgesic ladder
Weak opioid so Step 2
| do other examples
78
Where is diamorphine on analgesic ladder
Step 3
| Strong opioid
79
Why are intravenous IV infusions used>
- Enables steady state plasma (where drug intake is in equilibrium with its elimination) levels to be maintained for as long as possible
- Enables highly accurate drug delivery
- Useful for drugs that are ineffective administered by other routes or those who cannot absorb oral medication
- Is the quickest administration route
- Guarantees 100% bioavailability (the gold standard)
80
Describe chemicals that lead to synthesis of adrenaline
Tyrosine > DOPA > dopamine > noradrenaline >adrenaline
81
What type of chemical is DOPA, dopamine, noradrenaline or adrenaline?
Catecholamines
82
Give examples of chemicals that can metabolise/inactive adrenaline by metabolising it and thus reducing its stimulant effect
```
MonoAmine Oxidase (MAO)
Catechol-O-Methyl Transferase (COMT)
```
83
Describe characteristics of C fibres (pain transmission)
Unmyelinated
| Diffuse dull intense pain
84
Describe characteristics of A delta fibres (pain transmission)
Small and myelinated
| Conduct localised sharp sensation
85
Describe gate control theory
There is a balance of activity between large (A beta fibres) and small (A delta fibres & C fibres) fibres
Interneurons of the substansia gelatinosa regulate the input in Lamina V (dorsal horn of spinal cord)
If A beta fibres are NOT stimulated by nociceptive stimulus then the pain signal goes through to the brain and is perceived
If A beta fibres ARE stimulated then the pain signal is halted and does not reach the brain and is thus not perceived
This means that low intensity stimulation of the skin or peripheral nerves or vibration in order to stimulate the A beta fibres will generate analgesia
86
Applying gate control theory, how can you relieve pain?
Rubbing site of injury
Application of heat
Spinal cord stimulaiton
TENS - trans cutaneous nerve stimulation of A beta fibres
87
What is effect of prosaglandins
Act directly on the nociceptors and reduce their threshold meaning normal stimuli can activate them resulting in a sensation of pain (peripheral sensitisation)
(used by NSAIDs and paracetamol possibly) - add flashcard
88
What is main inhibitory neurotransmitter?
GABA
89
What is role of peri-aqueductal grey and locus cerulus in endogenous pain system
They inhibit the firing of the dorsal horn neutron that responds to noxious stimulus (gate control theory).
This can be done by changing the levels of neurotransmitters at the level of synapses meaning less pain is transmitted.
90
What happens in peri-aqueductal grey after modulation of afferent noxious transmission from extreme stress (as example)?
Once activated, opioid receptors are activated resulting in a reduction in PRE-SYNAPTIC neuronal sensitivity (thereby reducing Substance P release) which in turn results in reduced pain sensation
91
Give examples of Endogenous opioid peptides
Enkephalin
Dynorphine
Beta endorphine: effect similar to morphine
92
*How do opioids work
Bind to opioid receptors in periaqueductal grey, thereby conferring profound analgesia
93
Give examples of opioids
Morphine
Methadone
Codeine
Oxycodone
94
Give example of excitatory neurotransmitter
Glutamate
95
What are the 2 types of basis for pain treatment/transmission?
Reducing excitatory neurotransmitters (glutamate) and excitation of the nerve.
Enhancing inhibitory neurotransmitters.
96
What is the basis for anti-epileptics
Reducing excitatory neurotransmitters (glutamate) and excitation of the nerve (with respect to pain transmission)
97
Other than GABA, give examples of inhibitory neurotransmitters
Noradrenaline
Serotonin
(used as basis for anti-depressants)
98
*How do local anaesthetics work?
Na+ channel blockers
| Prevent depolarisation of nerve and propagation of an action potential
99
What is effect of prostaglandins in pain snesation
Prostaglandins act directly on the nociceptors and reduce their threshold meaning normal stimuli can activate them resulting in a sensation of pain (peripheral sensitisation)
Ultisied by NSAIDs and possibly paracetamol
100
Define chronic pain
Ongoing persistent pain greater than 3-6 months
101
What are principles of treating chronic pain
```
Improve pain perception
Improve function/mobility
Improve sleep
Improve emotional and psychological consequences of pain
Improve quality of life
```
102
What % of the population can not metabolise morphine?
10%
103
Give examples of naturally occurring opioids
Morphine
Codeine
(from opium)
104
Is codeine a strong or weak opioid?
Weak
105
Give examples of simple chemical modified opioids
Diamorphine (heroin)
Oxycodone
Dihydrocodeine (more predictable than codiene)
106
Give examples of synthetic opioids
Pethidine
Fentanyl (v potent)
Alfentanil (v potent)
Remifentanil (v potent)
107
Give example of opioid antagonist
Naloxone
| give to reverse overdose
108
You start a patient on a new commonly used medication. Unfortunately they develop an unusual adverse drug reaction (ADR) that you have never seen before which results in their hospitalisation. Which of the following is the correct course of action after stopping the drug and informing the patient?
Report the adverse drug event on a ‘yellow card’
Contact the pharmaceutical company that makes the drug to inform them of the ADR
Write the case up as a case report to ensure that other doctors are educated
Contact the local pharmacist to inform them of the ADR
Stop prescribing the drug for all patients
Report the adverse drug event on a ‘yellow card'
As the patient has been hospitalised due to the ADR you should fill in a ‘yellow card’.
109
```
A 53-year old woman presents to her G.P. with symptoms of an over-active bladder, she is given an anti-cholinergic drug to help with her symptoms. Which of these symptoms is NOT a side effect of the anti-cholinergic drug she has been prescribed.
Constipation
Constricted pupils
Dry mouth
Reduction in sweating
Tachycardia
```
Constricted pupils
Anticholinergics will cause dilated pupils and all the rest are common side effects of anticholinergics
110
```
A 65-year old man has lower urinary tract symptoms and also suffers from narrow angle glaucoma. Which of the following drugs may help his lower urinary tract symptoms but would be contra-indicated due to his narrow angle glaucoma?
5-alpha-reductase inhibitor
Alpha-1 receptor antagonist
Anticholinergic
Beta-3 receptor agonist
Intra-vesical botulinum toxin
```
Anticholinergic
| Contra-indiated in narrow angle glaucoma
none of others are contraindicated
111
```
An 18-year old man who is known to be an iv drug abuser is admitted to the emergency department unconscious with reduced respiratory rate and pin-point pupils. Which one of the following drugs is most appropriate to reverse his opioid overdose?
intravenous flumazenil
intravenous fentanyl
intravenous glucagon
intravenous naloxone
intravenous neostigmine
```
intravenous naloxone
Flumazenil will reverse a benzodiazepine overdose,
fentanyl is an opioid and so would compound the situation,
glucagon is used in hypoglycaemia,
neostigmine will reverse the effects of non-depolarizing muscle relaxants
112
What can be used to reverse a benzodiazepine overdose?
Flumazenil
113
```
Which of the following drugs does NOT have a narrow therapeutic index?
Digoxin
Gentamicin
Lithium
Simvastatin
Warfarin
```
Simvastatin
| has a wide therapeutic index
114
Define therapeutic index
Comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity
115
```
An 80-year old lady with metastatic cancer has been taking oral morphine for pain at home. She is admitted to hospital as an emergency as she has accidentally taken a large overdose and is confused and hypoxic. Which of the following is the side effect that may be contributing to her hypoxia.
Constipation
Cough
Neuromuscular paralysis
Respiratory depression
Tachypnoea
```
Respiratory depression
116
A 22-year old woman is prescribed oral penicillin, an hour later she develops a rash, facial swelling and difficulty breathing. A diagnosis of anaphylaxis is made and she is treated appropriately.
Which type of adverse drug reaction is an anaphylactic reaction to penicillin?
```
Type A
Type B
Type C
Type D
Type E
```
Type B
| Bizarre or Idiosyncratic
117
A 50 year old male patient found to be at increased risk of cardiovascular disease mentions at a routine GP check-up that he has not been taking the statin prescribed at his last visit. He comments that he is “not anti-medication” but he “feels fine without it”. Which of the following seems to be the most pertinent reason for his non adherence?
```
Capacity and resources
Concerns about medication
Necessity beliefs about medication
Practical barriers to adherence
Specific beliefs about medication
```
Necessity beliefs about medication
The answers relate to various potential reasons for non adherence
a. Capacity and resources – a practical rather than perceptual barrier
b. Concerns about medication – perceptual barrier to adherence that relates to worries about a potential adverse consequences
c. Necessity beliefs about medication - relates to perceptions of personal need for treatment, in this case to reduce risk rather than make him feel better
d. Practical barriers to adherence - capacity and resource to adhere to treatment
e. Specific beliefs about medication – relates to beliefs about the specific treatment (statin), in this example it is implied that the patient doesn’t fully understand that this is not a treatment to make him ‘feel better’ at present.
118
A 44 year old man receives penicillin V from his general practitioner for tonsillitis. He becomes very unwell with a rash, flushing, wheezing and he collapses. He is told that he has had an anaphylactic reaction to penicillin. This type of allergic reaction is mediated by which one of the following antibodies?
```
IgA antibodies
IgD antibodies
IgE antibodies
IgG antibodies
IgM antibodies
```
IgE
IgA is found in mucosal areas, such as the gut, respiratory tract and urogenital tract, and prevents colonization by pathogens, it is also found in saliva, tears, and breast milk.
IgD is found on B cells that have not been exposed to antigens.
IgG is the most abundant antibody and responsible for the secondary response.
IgM is the most primitive antibody and eliminates pathogens in the early stages of B cell-mediated (humoral) immunity (primary response) before there are sufficient IgG.
IgE is in response to parasites and is responsible for anaphylaxis.
119
Where are IgA antibodies found and what is there function?
IgA is found in mucosal areas, such as the gut, respiratory tract and urogenital tract, and prevents colonization by pathogens, it is also found in saliva, tears, and breast milk.
120
Where would you find IgD antibodies?
IgD is found on B cells that have not been exposed to antigens.
121
What is purpose of IgG?
IgG is the most abundant antibody and responsible for the secondary response.
122
What is purpose of IgM?
IgM is the most primitive antibody and eliminates pathogens in the early stages of B cell-mediated (humoral) immunity (primary response) before there are sufficient IgG.
123
What is purpose of IgE?
IgE is in response to parasites and is responsible for anaphylaxis.
124
A 70 kg woman is prescribed digoxin for atrial fibrillation . The digoxin has a half life of 42 hours.
The half life is:
- the time taken for the plasma drug concentration to fall to half its original value
- the time to metabolise half the drug into its active metabolite
- the time to absorb half the drug
- the time to bind half the drug to plasma proteins
- the time to maximum plasma levels after a dose of the drug
the time taken for the plasma drug concentration to fall to half its original value
