Pharmacology Flashcards
(129 cards)
1
Q
Where do opioids act to reduce pain?
A
In the brain and spinal cord
2
Q
What does activation of opioid receptors cause?
A
inhibits the release of excitatory transmitters e.g. Substance P, NO and glutamate
3
Q
Main areas in the midbrain involved in inhibiting pain?
A
Periaqueductal grey
Nucleus raphe magnus
4
Q
Examples of places in the brain where opioids act?
A
Increases transmission to the nucleus accumbens (associated with euphoria)
Decreases transmission to locus coeruleus (anxiety)
Increases transmission from Periaqueductal grey and nucleus raphe magnus
5
Q
Three main types of opioid receptors?
A
Mu (μ)
Kappa (κ)
Delta (δ)
6
Q
Two main pathways for pain? (type of pain they transmit?)
A
Paleospinothalamic - Blunt visceral pain
Neospinothalamic - sharp somatic pain
7
Q
What four opiates might you use for short pain (and their features)?
A
Alfentanil: very short acting (orthopaedics)
Morphine: Poorly absorbed orally, very potent
Codeine: Less potent, better oral absorption
Pethidine: Rapid acting, less effect on respiration and uterus
8
Q
Three steps of the WHO analgesic ladder?
A
Step 1: simple analgesics e.g. paracetamol/NSAIDS
Step 2: Moderate opioid e.g. mixed action opiate, dihydrocodeine
+ simple analgesics
Step 3: Strong opioid e.g. morphine, codeine heroin
+ simple analgesics
+ other psychoactive drugs
9
Q
Non-analgesic affects of opioids?
A
Sedation and respiratory depression
Nausea and vomiting
Cough suppression
Miosis
Constipation (decreased gut motility)
10
Q
What do you use to combat the withdrawal symptoms of opioids?
A
Methadone
11
Q
Why is there no upper limit to opioid prescription?
A
Tolerance will build up and this is natural, can be combatted by increasing the dose
Opioids are not toxic and so upping the dose has no draw-backs
12
Q
Is dependence on opioids common or rare in pain patients?
A
Very rare
13
Q
Why is loperamide used to treat diarrhoea?
A
Causes decreased gut motility
Can’t get into the brain
14
Q
What do NSAIDS inhibit?
A
COX-1 and COX-2
15
Q
What does COX go on to do?
A
Catalyse the reaction from arachidonic acid to prostaglandins and thromboxane
16
Q
What do prostaglandins do?
A
Cause:
Pain
Inflammation
Fever
17
Q
What are the roles of prostaglandins and thromboxane on platelet aggregation?
A
Prostacyclin (PGI2) inhibits
TxA2 promotes aggregation
18
Q
What do prostaglandins do to increase pain?
A
Sensitise pain nerve endings inducing substance P
19
Q
Difference in COX-1 and COX-2?
A
COX-1 is constitutively expressed
COX-2 is expressed in inflammation
20
Q
Effects of COX-1?
A
GI protection: Less acid, more mucus
Increase renal blood flow
Platelet aggregation effects
21
Q
Effects of COX-2?
A
Pain
Inflammation
Fever
22
Q
The adverse effects of NSAIDS are usually due to what?
A
COX-1 inhibition
23
Q
What GI side effects are particularly bad in NSAIDS?
A
Gastric ulceration/bleeding
24
Q
What side-effects can NSAIDS have on renal function, who should not receive them due to this?
A
Reduced renal blood flow and GFR, due to constricted afferent arteriole at the glomerulus
25
Actions of local anaesthetics?
They prevent action potentials on all nerves through sodium channel blockade
26
Why do local anaesthetics, such as lidocaine need to have both a ionised and non-ionised form?
The non-ionised form needs to cross the membrane and work from within
27
Do myelinated or non-myelinated fibres get blocked by local anaesthetics more? why?
Myelinated fibres (as they only have to block the nodes of ranvier)
28
benefits to local anaesthetics?
- reversible impairment of conduction
- non-irritant
- low toxicity
- readily metabolised + eliminated
29
What 4 things does the duration of action of local anaesthetics depend on? will these things increase or decrease duration?
Structure - water soluble will decrease duration
Site - well perfused sited will decrease duration
Actions - Vasodilators will decrease duration (cocaine a vasoconstrictor)
Co-administration: administration of vasoconstrictors will increase duration
30
Most widely used local anaesthetic?
Lidocaine
31
3 routes to administer lidocaine?
Infiltration as injection
Epidural
Spinal
32
Differences/similarities in epidural and spinal administrations?
Epidural
- Larger doses
- outside dural membranes
- very precise
Spinal
- into subarachnoid
- Small dose
- High precision
33
Main systemic S/E of local anaesthetics?
Respiratory depression
| CVS collapse
34
What nervous system innervates the radial and the circular muscles of the eye?
Radial muscles are sympathetic
Circular muscles are parasympathetic
35
What intrinsic muscles of the eye control the pupil size and what muscles control the lens size, what are they innervated by?
Pupil size - Radial and Circular muscles, both sympathetic and parasympathetic
Lens size - Ciliary muscles, only parasympathetic
36
Action of Tropicamide?
Muscarinic antagonist
37
Action of phenylephrine?
Alpha-1 adrenoreceptor agonist
38
Action of amethocaine?
Local anaesthetic (na+ channel blocker)
39
Action of cocaine?
Local anaesthetic and Nor Adrenaline reuptake inhibitor.
40
If the ciliary muscles contract they decrease or increase the size of the lens?
increase the size of the lens - make it bulge (near vision)
41
What effect will sympathetic and parasympathetic activation have on scleral blood vessels, if any?
Sympathetic - constrict them
Parasympathetic - no effect
42
What effects will tropicamide have on the eye?
Pupil will dilate (less PNS input)
Lens will relax and enlarge (less PNS input)
43
What effect will phenylephrine have on the eye?
Dilate pupil
Conjunctival vessels will constrict
44
What effect will amethocaine have on the eye?
less sensation
45
what effect will cocaine have on the eye?
Less corneal sensation
More constricted conjunctival vessels (NA reuptake inhibitor)
Larger pupil (NA re-uptake inhibitor)
46
What is pharmacological eye-patching?
When a drug such as cylclopentolate (muscarinic antagonist) is given to dilate the pupil and lens and cause a blur, this encourages the patient to use the other eye.
47
What is iritis?
Adhesions that formed between the lens and the iris, causing inflammation
48
What is glaucoma?
Syndrome with many causes that results in raised intraocular pressure, due to inadequate drainage of the aqueous humour which if left untreated results in optic nerve damage
49
What two areas are treated in glaucoma?
Reduce aqueous production
Improve drainage
50
What is open and closed angle glaucoma?
Open is when the angle between the iris and cornea is open (most cases)
Closed is when it is closed resulting in inadequate drainage
51
How do you treat closed angle glaucoma?
Stimulants such as pilocarpine/neostigmine constrict the sphincter pupillae and open the anterior angle
52
What's the canal of schlemm?
The canal where aqueous humour in the eye is drained
53
Where is aqueous humour formed?
Ciliary body
54
What drugs can be used to reduce aqueous production in glaucoma?
CA inhibitors e.g. acetazolamide, reduce production in ciliary epithelium
B2 blockers e.g. acetazolamide, reduce production in ciliary epithelium
Selective a-2 agonists do the same
55
What drugs can be used to improve aqueous drainage in glaucoma?
Cholinergic agonists e.g. pilocarpine, constrict the iris, increasing the anterior angle (mostly act on PNS)
Prostaglandins F2 agonists
56
Drugs used in prophylaxis of headaches?
| Examples?
B-blocker: propranolol
Anti-epileptic: gabapentin
TCA's amitryptyline
5HT agonist pizotifen
57
Drugs used to treat acute headaches?
NSAIDS
Antiemetics
5HT agonists
58
Two areas of the brainstem that contribute to vomiting and nausea?
Chemoreceptor Trigger Zone (CTZ)
Vomiting centre
59
What sends fibres to the CTZ?
Vestibular apparatus
Toxins in blood
Irritants of the stomach
60
What sends fibres to the vomiting centre in the brainstem?
Physical injury
Stomach irritants
61
Drugs used to treat/prevent Nausea/Vomiting?
Examples?
Anti-muscarinics: Hyoscine
Anti-histamines: cyclizines
D2 agonists: domperidone
5-HT agonists: ondansetron
NK1 receptor agonists: aprepitant
62
4 stages of anaesthesia?
1. Analgesia
2. Excitement
3. Surgical anaesthesia
4. Vital centre depression
63
What are the two main types of administrating General anaesthetics?
IV
Inhaled
64
2 examples of an IV general anaesthetic?
Thiopentone
| Propofol
65
2 examples of an inhaled general anaesthetic?
```
Nitrous oxide (N2O)
Isoflurane
```
66
What drugs are used to induce and maintain anaesthesia?
IV is used to induce anaesthesia
Inhalation is used to maintain anaesthesia
67
Features of thiopentone?
IV general anaesthetic:
- rapid onset
- short duration
- Cumulative (in muscle and fat)
- Highly alkaline (tissue necrosis if injected outside of vein)
68
Use of thiopentone
Induction of general anaesthesia
69
Features of propofol?
Use?
IV general anaesthetic
- Rapid onset
- Short duration
- Metabolised in the liver, so does not accumulate
Used for induction and maintenance in short procedures
70
Nitrous oxide features?
Use?
Inhaled general anaesthetic
- weak, so would require 95% to induce (would also asphyxiate)
- 70% for maintenance (possible)
- Can be used as a carrying agent
- Analgesic and amnestic effects
Maintenance, normally with isoflurane
71
Features of isoflurane?
Use?
Inhaled general anaesthetic
- Strong (need 5% for induction)
- Slow in onset
Maintenance (usually with N20)
72
S/E of isoflurane?
Cardiac dysarrhythmias
Harmless ectopic ventricular beats
Small chance of Ventricular fibrillation
73
S/E of opioids?
Constipation
Cough reflex reduced
Nausea and vomiting
74
Main receptors in the CTZ?
D2
5-HT
75
Main receptors in the vomiting centre?
Histamine
Muscarinic receptors
76
What is epilepsy?
Abnormal discharge pattern in a group of neurones, resulting in paroxysmal discharges
77
Main types of epilepsy?
Partial seizures - focal only, do not spread
Generalised seizures - spread from a focus:
2a) Tonic clonic (grand mal)
2b) Absences (petit mal)
78
4 stages of an epileptic fit?
1. Initiation
2. Spread
3. Maintenance
4. Collapse
79
What happens at each stage of an epileptic fit?
Initiation:
- excitation is more than inhibition, excessive glutamate, loss of GABA inhibition
Spread:
- by normal neuronal fibres
- also by adjacent fibres by ephaptic transmission
Maintenance:
- Positive feedback loops
- post-tetanic potentiation
Collapse
- Elevation of threshold
- Metabolic factors
- inhibition by other pathways
80
The two stages of a tonic clonic seizure?
Tonic (not long):
- intitial rigid extensor spasm
- defecation, micturation, salivation
- respiration stops
Clonic (longer, few minutes)
- violent synchronous jerks
81
4 Types of Na+ channel blockers used to treat epilepsy?
How do they treat the epilepsy?
Phenytoin
Lamotrigine
Carbamazide
Sodium valproate
stabilises Na+ channel in an inactivated state
82
uses of phenytoin, what drug is it given as?
Tonic clonic/partial
Given as fosphenytoin
83
S/E of phenytoin?
CNS:
- Diplopia
- Nystagmus
- Ataxia
- Sedation
Induction of p450
Allergies
84
Uses for carbmazepine? advantages?
Tonic clonic/partial seizures
Little sedation
85
Lamotrigine uses? advantages?
Tonic clonic
Long half life
Does not affect p450
Rare S/E
86
Sodium valproate uses? advantages/disadvantages?
Tonic clonic, partial and petit mal
- Best choice for petit mal
- Hepatotoxicity
87
Anti-epileptics that act on GABA pathways?
Phenobarbitone - only barbituate used, very long half-life
Benzodiazepines - diazepam (IV for staus epilepticus), or clonezepam (marked sedation)
Also sodium valproate
88
How does sodium valproate work?
Acts on Na+ channels and Ca2+ channels in the thalamus and GABA pathways
Enhances the production of GABA and inhibits its breakdown
89
What causes parkinsons?
Degeneration of dopaminergic neurones in nigrostriatal pathways
90
Symptoms of parkinsons?
Tremor, rigidity, bardykinesia, postural instability
91
The three dopaminergic pathways of the brain?
Nigrostriatal: Control of movement
Mesolimbic: Mood, emotion
Pituitary hormones
92
What parts of the nigrostriatal pathway are there?
Globus pallidus, striatum and substantia nigra
93
What do COMT and MAO do?
Breakdown L-dopa and Dopamine
94
What is levodopa, how's it work and what are the disadvantages, how are these solved?
A prodrug to treat parkinsons
Crosses the BBB and is converted to dopamine in dopminergic neurones by DOPA decarboxylase
Only 1% taken up by brain, means there is lots of dopamine in the periphery, given with a PDI (peripheral decarboxylase inhibitor)
Only works effectively for 2-5 years, bad in 50% of patients after 5 years (give other drugs)
95
An example of a PDI?
Carbidopa
96
Because Levodopa only works effectively for 2-5 years, what other drugs can be given?
COMT inhibitors e.g. entacapone
MAO-b inhibitors e.g selegiline
D2 receptor agonists e.g. ropinirole
Antimuscarinics e.g. benzehexol
97
red flags for parkinsons?
Early falls
Wheelchair
Postural hypotension
abnormal eye-movements
98
How do COMT inhibitors work to reduce parkinsons? e.g?
Entacapone
Inhibit peripheral COMT so there is more Levodopa to get into the brain
Can combine with l-dope and a PDI
99
How do MAO-b inhibitors work to reduce parkinsons? e.g?
Selegiline
Inhibit the breakdown of dopamine in the CNS, prolonging dopamine survival in the CNS
allows less L-dopa dose
100
How do D2 receptor agonists work to reduce parkinsons? e.g?
Ropinirole
agonise dopamine receptors in the CNS, can be used in combination with l-dopa + PDI
101
How do antimuscarinics work to reduce parkinsons? e.g?
Useful in treating symptoms e.g. tremor/rigidity
102
What's the monoamine theory for depression?
The theory that depression is associated with decreased activity in central NA and/or 5HT synthesis
103
All antidepressant drugs? examples?
MAIN
SSRI's - citalopram
SNRIs - venlafaxine
TCAs - clomipramine
MAO inhibitors - pheneteine
OTHERS
antipsychotics - quetiapine
anticonvulsants - lamotrigine
Lithium
104
What advantage do SSRI's and SNRI's have over older TCAs?
TCAs are unsafe in overdose and have troublesome S/E's
105
What do MAO inhibitors do?
What can't you do on MAOIs?
Inhibit both MAO-B and A
Can't eat tyramine rich foods e.g. cheese/game/wine
106
Issues with SSRIs?
Increased nervousness in 1st week
worsened sexual function (40%)
107
S/E of TCAs?
weight gain/drowsiness
108
What are the two categories of sleep disorder?
Dyssomnias: interruption to timing/quality or amount of sleep
Parasomnias: abnormalities during sleep
109
Drugs to treat anxiety (anxiolytics)?
SSRIs - citalopram
SNRI's - venlafaxine
Pregabalin
Benzodiazepine - diazepam
TCAs - clomipramine
MAOIs - phenelzine
Antipsychotic - quetiapine
B-Blockers - propranolol
5-HT partial agonists - buspirone
110
What drugs are used to insomnias? (hypnotics)
Barbituates - phenobarbitol
Benzodiazepines - diazepam
Z drugs - zaleplon
111
Positives/negatives of barbituates? Mechanism?
Increase the duration of Cl- channel opening
significant risk of dependence
Highly dangerous in overdose and in combination with alcohol
Used only in severe insomnia
112
Positives/negatives of benzodiazepines? Mechanism?
Safer alternative to barbituates
increase in the frequency of Cl- channel opening
will only bind to site if GABA has already bound to the site
Metobolites will accumulate
Risk of dependence
Dangerous if combined with alcohol
Only recommended for short term treatment (4 weeks)
113
How does pregabalin work, what is it good for?
Reduces release of excitatory neurotransmitters e.g. glutamate
Good in GAD/SAD (generalised and social anxiety disorder)
114
What is mania and hypomania?
Mania - highly elevated mood/irritable mood/quickness of thought
Hypomania - less severe elations, lower levels of disturbances
115
What is bipolar I and II?
Bipolar I - mania
Bipolar II - hypomania
116
When is bipolar diagnosed (conditions for diagnosis)?
Two or more episodes in which the patients mood/activity levels are significantly altered for a significant length of time
117
pharmacological treatment for bipolar?
Lithium
Sodium valproate
Carbamazepine
Lamotrigine
118
Cause of schizophrenia?
Increased dopaminergic activity in mesolimbic system, and mesocortical system
119
What is the main class of drugs used in antipsychotic treatment? main receptors?
Dopamine receptor antagonists
D2 is main receptor
some drugs also block D3/4 and 5-HT receptors
120
S/E of Dopamine receptor antagonist antipsychotics?
Blockade of dopamine in the nigrostriatal pathway:
- Parkinsonian symptoms
Hypothalamus blockade (Dopamine receptors)
- decreased Growth Hormone in children
- Increased cortisol leading to cushings
Muscarinic receptors:
- Dry mouth
- Constipation
- blurred vision
Histamine receptors:
- Sedation
a-adrenoceptors
- hypotension
- hypothermia
121
Three main classes of antipsychotic?
Phenothiazine (classical)
non-phenothaizine (classical)
Atypical
122
Newer classical antipsychotics effects, example?
Fluphenazine
less antihistamine/antimuscarinic effects
More movement affects
123
Older classical antipsychotics effects, example?
Chlorpromazine
less movement effects
more antimuscarinic/antihitsmine effects
124
When might you use an atypical drug, example of two?
In treatment of negative symptoms
In non-responders to classical drugs
Clozapine: no movement disorders but risk of agranulocytosis (named basis only)
Remoxipride: little sedation but risk of aplastic anaemia
125
Will phenylephrine have an effect on accommodation of the eye?
No, this is controlled by the lens which is parasympathetically innervated only
126
What is horners syndrome caused by?
Lack of sympathetic outflow to the face
127
What drugs will reduce aqueous humour production?
Alpa 2 adrenoceptor agonists
128
What enzymes mostly break down L-dopa in the gut and in the brain?
COMT in the gut
MAO-B in the brain
129
What is domperidone, why does it have an antiemetic effect?
A peripheral dopamine antagonist, exerts it's affect on the CTZ (technically outside the BBB)
