PHARMACOLOGY Flashcards
1
Q
what are pharmacodynamics?
A
what the drug does to the body
i.e. what does the drug do once it is in the body?
2
Q
what factors affect the pharmacodynamics?
A
affinity
efficacy
potency
3
Q
what are pharmacokinetics?
A
what the body does to the drug
i.e. what does the body do once the drug is in it?
4
Q
what factors affect pharmacokinetics?
A
- absorption - gut vs parenteral
- distribution
- metabolism - first pass metabolism
- excretion - usually renal
5
Q
what is affinity?
A
it is how well a drug will bind to a receptor
high affinity = binds well
low affinity = binds less well
6
Q
what is efficacy?
A
it is the degree to how well a drug works on a specific receptor
it can be seen as the maximum effect a drug can have in the body
7
Q
what is potency?
A
it is the amount of the drug needed to achieve a response
8
Q
what is an agonist?
A
a molecule that attaches to a receptor, causing a reaction in the cell
- it stimulates the receptor
9
Q
what is a partial agonist?
A
a molecule that attaches to a receptor, causing the same reaction as a full agonist, to a lesser extent
10
Q
what are competitive inhibitors?
A
molecules that block other things from binding to the receptor by sitting in it’s action site
11
Q
what are non-competitive inhibitors?
A
- molecules that block other things from binding to the receptor but not by sitting in it’s action site
- it may attach to a different part of the receptor and cause the action site to change shape
12
Q
what factors affect distribution in pharmacokinetics?
A
- blood flow
- molecular weight/size
- how lipophilic/phobic a drug is
- blood brain barrier/blood testicle barrier
13
Q
where does first pass metabolism occur?
A
in the liver
14
Q
what is bioavailability?
A
the proportion of the drug given that enters circulation and so can exert an effect on the body
15
Q
why are different doses of the same drug prescribed when given orally vs IV?
A
- with oral medications, first pass metabolism via the liver will reduce how much enters circulation - reduces bioavailability
- giving mediations IV means drug enters straight into circulation - bioavailability = 100%
16
Q
what are the main routes of drug administration?
A
- oral
- IV
- subcutaneous
- intramuscular
- topical
- rectal
- intrathecal
- sublingual/buccal
- inhalation
17
Q
what does parenteral drug administration?
A
non-oral drug administration routes
18
Q
what is intrathecal drug administration?
A
into the spinal column for anaesthesia, chemotherapy or pain management
19
Q
what is oral drug administration?
A
drugs taken orally
undergoes first pass metabolism - reduced bioavailability
20
Q
what is IV drug administration?
A
drugs enter directly into circulation
21
Q
what is subcutaneous drug administration?
A
drugs have to diffuse through subcutaneous fat
- drug is absorbed more slowly
22
Q
what is intramuscular drug administration?
A
muscle tissue is vascular so it is rapidly absorbed
23
Q
what is topical drug administration?
A
- directly onto skin/mucosa
- avoids first pass metabolism
- slowly absorbs into circulation
24
Q
what is rectal drug administration?
A
can be used when patient is unable to tolerate oral route
highly vascular tissue so absorbs quickly
25
what is sublingual/buccal drug administration?
avoids first pass metabolism
| rapidly enters circulation
26
what is inhalation drug administration?
passes through trachea into the lungs
| good if target site is lungs
27
what is GFR used for?
- glomerular filtration rate is a test used to check how well the kidneys are working
- it estimates how much blood passes through the glomeruli each minute
- used in staging CKD
28
what is creatinine clearance (CrCl)?
volume of blood plasma cleared of creatinine per unit of time
29
what is creatinine clearance used for?
used to estimate GFR since glomeruli freely filter creatinine
this is done by comparing serum creatinine with urine creatinine
30
why is it important to know kidney function when prescribing drugs?
most drugs are excreted by kidneys
if kidneys are not functioning well, this can lead to reduced renal excretion and a build up of drug = toxicity
this can lead to further renal impairment
31
which drugs should be avoided/adjusted in renal impairment?
NSAIDs
PPIs
antibiotics
32
which conditions should you look out for before prescribing?
CKD
diabetes
hypertension
polycystic kidney disease
33
what do preganglionic neurones release at the autonomic ganglion in the sympathetic nervous system?
ACh
34
what do postganglionic neurones release at effector organs in the sympathetic nervous system?
catecholamines
- adrenaline
- noradrenaline
35
what happens in the sympathetic nervous system?
myelinated preganglionic neurones synapse with unmyelinated postganglionic neurones at the autonomic ganglia
36
what does the autonomic ganglia contain?
cell body clusters
37
what is a ganglion?
collection of neurone cell bodies in the PNS
38
which receptors does the sympathetic nervous system act on?
```
alpha 1
alpha 2
beta 1
beta 2
beta 3
```
39
what are the effects of stimulation of the sympathetic nervous system?
- fight or flight
- increased HR, increased CO
- vasoconstriction
- bronchodilation
- reduced GI motility and secretions
- reduced bladder detrusor activity
- increased sweating
- reduced salivation
40
where are beta 1 receptors found?
heart
| kidneys
41
what is the effect of beta 1 receptor stimulation?
increased CO
| increased renin production
42
where are beta 2 receptors found?
```
lungs
blood vessels
GI tract
bladder
uterus
liver
```
43
what are the effects of beta 2 receptor stimulation?
- bronchodilation
- vasodilation
- decreased peristalsis and digestion
- decreased urination
- conversion to glucose in liver
44
where are beta 3 receptors found?
adipose tissue
| bladder
45
what are the effects of beta 3 receptor stimulation?
increased lipolysis
| decreased urination
46
how do you remember where beta 1 and beta 2 receptors are found?
beta 1 = heart ( 1 x heart)
| beta 2 = lungs ( 2 x lungs)
47
where are alpha 1 receptors found?
```
blood vessels
pupils
pylorus
urinary sphincter
prostate
```
48
what are the effects of alpha 1 receptor stimulation?
- vasoconstriction
- pupil dilation
- urinary sphincter constriction
- pyloric sphincter constriction
49
where are alpha 2 receptors found?
presynaptic nerve terminals
50
what are the effects of alpha 2 receptor stimulation?
inhibitory
51
what do preganglionic neurones release at the autonomic ganglion in the parasympathetic nervous system?
ACh
52
what do postganglionic neurones release at effector organs in the parasympathetic nervous system?
ACh
53
which receptors does the parasympathetic nervous system act on?
muscarinic
54
what are the effects of parasympathetic nervous system stimulation?
- decreased HR
- decreased CO
- vasodilation
- bronchoconstriction
- increased bladder detrusor activity
- reduced sweating
55
how do ACE-inhibitors work?
- they block the action of ACE
- this prevents angiotensin I being converted to angiotensin II
- therefore no aldosterone is secreted so there is no vasodilation etc.
56
what do loop diuretics act on?
the ascending limb of the loop of henle
| Na+/K+/Cl- co-transporter
57
what is the effect of loop diuretics?
- inhibits Na+/K+/Cl- co-transporter
- usually all three get absorbed and water follows
- transportation blocked = less water reabsorbed and more excreted
58
what do thiazide diuretics act on?
distal convoluted tubule
| Na+/Cl- co-transporter
59
how do loop diuretics cause hypokalaemia?
less K+ is absorbed
60
what is the effect of thiazide diuretics?
less Na+ is reabsorbed, therefore less water follows
| - more water is excreted
61
how do thiazide diuretics cause hypokalaemia?
there is more Na+ in DCT where it can be exchanged for K+
| therefore more K+ is lost in urine
62
what do K+ sparing diuretics act on?
distal convoluted tubule
| ENaC channels
63
what are the effects of K+ sparing diuretics?
inhibits the reabsorption of Na+ and water in ENaC channels in DCT
this leads to Na+ and water excretion and K+ retention
64
what is the mechanism of action of NSAIDs?
- COX inhibitors - prevents the production of prostaglandins
| - COX-2 inhibition is useful but COX-1 inhibition causes adverse effects
65
what is the mechanism of action of antihistamines?
- H1 receptor antagonist
| - prevents the release of histamine from storage granules in mast cells which cause allergic reaction symptoms
66
what is the mechanism of action of proton pump inhibitors (PPIs)?
- irreversibly inhibits H+/K+ATPase pump in gastric parietal cells to reduce H+ (acid) secretion
67
what is the mechanism of action of opioids?
activation of mu receptors in CNS
68
what are the common side effects of NSAIDs?
GI upset
GI bleeding
renal impairment
69
what are the side effects of anti-histmines?
- older ones can corss BBB and cause sedation
| - there are many H1 receptors in vomiting centre - can act as anti-emetics
70
what are the side effects of ACE-inhibitors?
dry cough due to bradykinin!!!
| dilates afferent arteriole so worsens kidney function
71
what are the side effects of PPIs?
prolonged use in elderly can increase risk of fracture
72
what are the side effects of opioids?
- respiratory depression - give naloxone
- nausea and vomiting
- constipation
- tolerance and withdrawal
73
what are the side effects of diuretics?
can cause hyperkalaemia
increased urinary frequency
dehydration
74
what is a side-effect?
a known, secondary and typically undesirable effect of a drug
75
what are adverse drug reactions?
unexpected
76
what are type A ADRs?
```
augmented
• Commonest
• An extension of the clinical effect
• Predictable
• Dose related
• Self-limiting
```
77
what are type B ADRs?
```
bizarre
• Unexpected
• Unrelated to dosage and not expected from known pharmacological
action
• Unpredictable
• Mostly immunological mechanisms
• Hypersensitivity
```
78
what is a type C ADR?
chronic
• Occurs after long term therapy
• May not be immediately obvious with new medicines
79
what is a type D ADR?
delayed
| • Also occurs after a long period of time after treatment - many years
80
what is a type E ADR?
end of use
• Relatively long term use (days/weeks)
• Withdrawal reactions
• Serious complication of stopping related to clinical effect
81
what are the different types of ADR according to Rawlins-Thompson classification
* A - Augmented
* B - Bizarre
* C - Chronic
* D - Delayed
* E - End of Use
82
what factors increase susceptibility of ADRs?
- Age - elderly
- Gender - more common in females
- Pregnancy - negative effect on baby etc.
- Disease - liver or renal in particular
- Drug interactions
- Diet or alcohol intake changes
- Genetics
- Hypersensitivity
83
how are ADRs reported?
using yellow card system
84
what is the equation for renal clearance?
clearance = rate of appearance in urine / plasma concentration
85
what is used as a marker substance in the kidney?
creatinine
86
what are the adult renal clearance values?
- Renal blood flow is 18% of cardiac output = 1L/min
- Renal plasma flow is 60% of blood flow = 600mls/min
- Glomerular filtration is 12% of renal blood flow = 130mls/min
87
what is the hepatic extraction ratio (HER)?
The proportion of drug removed by one passage through the liver
88
what is a high HER limited by?
hepatic blood flow - perfusion
89
what is a low HER limited by?
diffusion
90
what is pain?
Unpleasant sensory and emotional experience associated with actual or
potential tissue damage
91
what are c fibres, what information do they convey?
- Unmyelinated
| - Characterised by diffuse dull intense pain
92
what are a delta fibres and what information do they convey?
- Small and myelinated
| - Conduct localised sharp sensation
93
what is 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.
94
What can influence the degree of ionisation of weak acids and weak bases?
pH.
95
What equation can be used to determine the degree of ionisation at a specific pH?
Henderson Hasselbach.
| pH = log[A-]/[HA] + pKa.
96
What can enhance non ionic diffusion?
Non ionic diffusion can be enhanced if adjacent compartments have pH difference.
97
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.
98
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.
99
What is the effect of an increase in pH on a weak acid?
The weak acid will become more ionised.
100
What is the effect of an increase in pH on a weak base?
The weak base will become less ionised.
101
What is the effect of a decrease in pH on a weak acid?
The weak acid will become less ionised.
102
What is the effect of a decrease in pH on a weak base?
The weak base will become more ionised.
103
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.
104
Give 3 factors that can increase gastric pH.
1. Ingesting alkaline foods.
2. Antacids.
3. Omeprazole (PPI).
105
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.
106
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.
107
Where do phase 1 hepatic metabolism reactions occur?
liver
108
What enzyme usually catalyses phase 1 reactions?
CYP450
109
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.
110
Briefly describe catecholamine synthesis.
Tyrosine -> L-DOPA -> Dopamine -> Noradrenaline -> Adrenaline.
111
Which enzymes inactivate catecholamines?
MAO and COMPT.
112
what is specificity
the measure of a receptors ability to respond to a single ligand
113
what is selectivity
the ability of the receptor to distinguish between drugs
114
give an example of a local anaesthetic
lidocaine
115
what is the mechanism of action for local anaesthetics?
- interrupt axonal neurotransmission in sensory nerves
| - block voltage dependent Na channels -> this prevents depolarisation so no action potential
116
Give an example of a proton pump inhibitor.
Omeprazole.
117
Give an example of a statin.
Simvastatin.
118
Give an example of an ACE inhibitor.
ramipril
119
Give an example of a COX inhibitor.
Aspirin and paracetamol.
120
Give an example of a β2 adrenoceptor agonist.
Salbutamol.
121
Give an example of a β1 adrenoceptor blocker.
Atenolol.
122
Give an example of a Ca2+ channel blocker.
Amlodipine.
123
Give an example of a broad spectrum antibiotic.
Amoxicillin.
124
Give an example of an opiate analgesic.
Tramadol.
125
What do most drugs target?
Proteins!
126
Name 4 receptors that drugs target.
1. Ligand gated ion channels.
2. GPCR.
3. Kinase linked.
4. Cytosolic/nuclear.
127
Give an example of a ligand gated ion channel.
Nicotinic Ach receptor.
128
Give an example of a GPCR.
Muscarinic and β2 adrenoceptor.
| GPCR's usually interact with adenylate cyclase or phospholipase C
129
Give an example of a kinase linked receptor.
Receptors for growth factors.
130
Give an example of a cytosolic/nuclear receptor.
Steroid receptors; steroids affect transcription.
131
Describe the shape of a log dose-response curve.
Sigmoidal.
132
What does EC50 tell us about a drug?
Its potency!
133
What is EC50?
The concentration of drug that gives half the maximal response.
134
Would a drug with a lower EC50 have a lower or greater potency?
Greater potency.
135
What does Emax tell us about a drug?
Efficacy.
136
Would an antagonist shift a dose-response curve to the left or right?
The antagonist would shift the dose-response curve to the RHS. The drug therefore becomes less potent.
137
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.
138
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).
139
What is the affect of less signal amplification on drug response?
Less signal amplification gives a reduced drug response.
140
Describe allosteric modulation.
An allosteric modulator binds to a different site on a receptor and influences the role of an agonist.
141
What is inverse agonism?
Where an agonist has a negative effect at a receptor.
142
Does an antagonist show efficacy?
No. An antagonist has affinity but zero efficacy. An agonist however demonstrates affinity and efficacy.
143
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.
144
Can aspirin be described as a selective drug?
No. Aspirin is non-selective, it acts on COX1 and COX2.
145
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.
146
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.
147
Write an equation for the volume of distribution (Vd).
Vd = amount of drug administered/concentration of drug in plasma.
148
Where do phase 1 hepatic metabolism reactions occur?
In the smooth endoplasmic reticulum.
149
What enzyme usually catalyses phase 1 reactions?
CYP450.
150
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.
151
Give 3 disadvantages of IV infusion.
1. Expensive.
2. Needs constant checking.
3. Calculation error likely.
152
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.
153
What type of receptor are muscarinic receptors?
GPCR.
154
Give examples of adverse muscarinic agonist effects.
1. Diarrhoea.
2. Urination.
3. Miosis.
4. Brachycardia.
5. Emesis (vomiting).
6. Lacrimation.
7. Salivation.
155
What would an α1 adrenergic antagonist do?
1. Vasodilation.
| 2. Relaxation of bladder neck = reduced resistance to bladder outflow.
156
What disease could an α1 adrenergic antagonist be used in the treatment of?
Benign prostatic hyperplasia.
157
What would a β1 adrenergic antagonist do?
1. Reduce CO.
| 2. Reduce renin secretion
158
What diseases could an β1 adrenergic antagonist be used in the treatment of?
Hypertension, angina and arrhythmia.
159
Give 5 patient risk factors for drug interactions.
1. Old age.
2. Polypharmacy.
3. Renal disease.
4. Hepatic disease.
5. Genetics.
160
Give 3 drug related risk factors for drug interactions.
1. Narrow therapeutic index.
2. Steep dose/response curve.
3. Saturable metabolism.
161
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.
162
How might drug interactions affect drug metabolism?
If a drug inhibits or induces CYP450 it might affect the metabolism of another drug.
163
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.
164
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.
165
Are weak acids cleared quicker if urine is more acidic or more alkali?
Weak acids are cleared quicker if urine is more alkali.
166
Are weak bases cleared quicker if urine is more acidic or more alkali?
Weak bases are cleared quicker if urine is more acidic.
167
What drug acts as an antagonist at the μ receptor?
Naloxone.
168
What is the bioavailability of morphine taken orally?
50%.
169
10mg of morphine is taken orally. What is the equivalent dose if given parenterally?
5mg.
170
What is morphine metabolised to?
Morphine 6 glucuronide.
171
Give 5 side effects of opioid use.
1. Respiratory depression.
2. Sedation.
3. Nausea.
4. Vomiting.
5. Constipation.
172
What drug inhibits ACh release at the NMJ?
Botulinum toxin.
| It is used to treat urinary incontinence and also cosmetically as a muscle relaxant.
