1
Q
Paracetamol - Indications
A
1) Acute and Chronic pain
2) Antipyretic
2
Q
Paracetamol - MOA
A
- Poorly understood
- Weak inhibitor of cyclo-oxygenase (COX) : enzyme involved in prostaglandin metabolism
- COX inhibition, increase pain threshold and reduce prostaglandin concentration s in thermoregulation pathway –> controlling fever
3
Q
Paracetamol - Side Effects
A
Few SE
Overdose : causes liver failure
4
Q
Paracetamol - Contraindication
A
None
5
Q
Paracetamol - Caution
A
- Chronic excessive alcohol use
- Liver toxicity, Hepatic impairment
6
Q
Paracetamol - Interactions
A
CYP inducers - increase risk of liver toxicity after overdose
7
Q
Paracetamol - Max dose
A
4g / day
8
Q
Weak/ Moderate Opioids - Examples
A
Tramadol
Codeine
Dihydrocodeine
9
Q
Weak/ Moderate Opioids - Indication
A
1) Mild - to - Moderate pain
- -> 2nd line
10
Q
Weak/ Moderate Opioids - MOA
A
They are metabolised by the liver to produce small amounts of morphine.
- These are agonists of opioid µ (mu) receptors. Thus have an analgesic effect
11
Q
Weak/ Moderate Opioids - Side Effects
A
- Nausea
- Constipation
- dizziness
- drowsiness
- Neurological and respiratory depression in overdose
12
Q
Weak/ Moderate Opioids - Contraindications
A
- Avoided in epilepsy and controlled epilepsy
13
Q
Weak/ Moderate Opioids - Caution
A
- Respiratory disease
- Reduced dose in renal and hepatic impairment + elderly
14
Q
Weak/ Moderate Opioids - Interactions
A
-Should not be used with other sedating drugs : antipsychotic, benzodiazepine, tricyclic antidepressants
15
Q
Weak/ Moderate Opioids - Patient education
A
Avoid driving or operating heavy machinery if they become drowsy or confused
16
Q
Strong Opioids - Examples
A
- Morphine
- Oxycodone
17
Q
Strong Opioids - Indications
A
1) Rapid relief of acute sever pain
2) Relief of chronic pain
3) Relief of SOB in end-of-life care & acute pulmonary oedema
18
Q
Strong Opioids - MOA
A
- The therapeutic action of opioids arises from activation of opioid µ receptors in the central nervous system (CNS).
- Activation of these G protein-coupled receptors has several effects that, overall, reduce neuronal excitability and pain
19
Q
Strong Opioids - Side Effects
A
- Euphoria & detachment
- Nausea & vomiting
- Constipation
- Itching, urticaria, sweating
- Tolerance & dependence
20
Q
Strong Opioids - Contraindications
A
- Respiratory Failure
- Biliary colic
21
Q
Strong Opioids - Caution
A
- Hepatic + Liver Failure
- Elderly
22
Q
Strong Opioids - Interactions
A
- Should not be used with other sedating drugs (e.g. antipsychotics, benzodiazepines & tricyclic antidepressants)
23
Q
Carbamazepine - Indications
A
1) Epilepsy = seizure prophylaxis
2) Trigeminal neuralgia –> 1st line
24
Q
Carbamazepine - MOA
A
- Inhibits neuronal sodium channels.
- This stabilises RMP and reduces neuronal excitability
25
Carbamazepine - Side Effects
- GI Upset : N & V
- Neuro effects : dizziness & ataxia
- Carbamazepine hypersensitivity
- Oedema + Hyponatraemia
26
Carbamazepine - Contraindications
- Prior antiepileptic hypersensitivity syndrome
27
Carbamazepine - Caution
Hepatic + renal or cardiac disease --> due to increased toxicity
28
Carbamazepine - Interactions
- Carbamazepine induces CYP enzyme which reduces plasma conc and efficacy of drugs that are metabolised by CYP enzymes (e.g. warfarin + oestrogen)
- CYP inhibitors : increased conc and adverse effects as carbamazepine is metabolised by CYP enzymes.
29
Carbamazepine - Patient Education
- Started at low dose (100-200mg) and then increased as tolerance to SE develops.
30
Valproate - Examples
Sodium valproate
| Valproic acid
31
Valproate - Indications
1) Epilepsy - seizure prophylaxis
2) Certain cases of established convulsive status epilepticus
3) Bipolar disorder
32
Valproate - MOA
- Weak inhibitor of neuronal sodium channels, stabilising RMP and reducing neuronal excitability
33
Valproate - Side Effects
Common:
- GI upset : Nausea, diarrhoea
- Neuro /psychiatric : tremor, behavioural disturbances
- Thrombocytopenia
Life-threatening:
- Severe liver injury, bone marrow failure
34
Valproate - Contraindications
- Women of child-bearing age
| - 1st trimester of pregnancy
35
Valproate - Caution
- Hepatic impairment
| - Severe renal impairment
36
Valproate - Interactions
- With Lamitrigine & drugs metabolised by CYP enzymes (warfarin) : inhibit liver enzymes, risk of toxicity and increase plasma conc
- CYP inducers (carbamezepine) : because valproate is metabolised by CYP enzymes, so inducers reduce conc and increase risk of seizures
37
Valproate - Patient Education
- Take tablets with food to reduce GI irritation
38
Lamotrigine - Indications
1) Epilepsy : seizure prophylaxis
- -> focal, tonic-clonic, absence
2) Bipolar disorder
39
Lamotrigine - MOA
- It binds to voltage-sensitive neuronal Na+ channels, interfering with Na+ influx into the neuron.
- This prevents repetitive neuronal firing, which is a characteristic of seizure activity
40
Lamotrigine - Side Effects
Common:
- headache
- drowsiness
- Irritability
- Blurred vision
- dizziness
- GI symptoms
RASH: urgent review and may need to discontinue due to severe hypersensitivity reaction
41
Lamotrigine - Contraindications
- Prior hypersensitivity to other anti-epileptic drugs
42
Lamotrigine - Caution
- Hepatic impairment - metabolised by liver
43
Lamotrigine - Interactions
- Carbamazepine, phenytoin, oestrogens, rifampicin --> reduce lamotrigine conc --> treatment failure
- Valproate --> increase conc to rise --> toxicity
44
Lamotrigine - Patient Education
- try not to miss dose
- do not stop treatment abruptly
- Driving is prohibited unless they have been seizure-free for 12 months, and for 6 months after changing or stopping treatment.
45
Levetiracetam - Indications
1) Epilepsy : seizure prophylaxis
| 2) Selected cases of established convulsive status epilepticus
46
Levetiracetam - MOA
- The molecular target of levetiracetam is synaptic vesicle protein 2A (SV2A).
- SV2A is expressed throughout the brain, in both excitatory and inhibitory synapses, as a glycoprotein located within the membranes of synaptic vesicles.
- It is presumably through interfering with synaptic vesicle function that levetiracetam modulates neuronal excitability and reduces the risk of seizures.
47
Levetiracetam - Side Effects
Most people usually have none.
- Drowsiness
- Weakness
- Dizziness
- Headache
Rare:
- Suicidal ideation
48
Levetiracetam - Caution
- Renal impairment
49
Levetiracetam - Interactions
Ver few
50
Levetiracetam - Patient Education
- try not to miss dose
- do not stop treatment abruptly
- Driving is prohibited unless they have been seizure-free for 12 months, and for 6 months after changing or stopping treatment.
51
Benzodiazepine - Examples
- Diazepam
- Temazepam
- Lorazepam
- Chlordiazepoxide
- Midazolam
52
Benzodiazepine - Indications
1) Seizure & SE : 1st line
2) Alcohol withdrawal : 1st line
3) Sedation for interventional procedures
4) Anxiety or insomnia : short-term
53
Benzodiazepine - MOA
- Benzodiazepines are gamma-aminobutyric acid (GABA) receptor agonists. They enhance the binding of GABA to the GABA receptor
- Benzodiazepine drugs increase the effects of GABA on your brain and body.
54
Benzodiazepine - Side Effects
- Drowsiness
- Coma
Overdose:
- airway obstruction & death
Repeated:
- dependence
55
Benzodiazepine - Contraindication
None
56
Benzodiazepine - Caution
- Elderly
Avoid in:
- Resp impairment
- Neuromuscular disease
- Liver failure
57
Benzodiazepine - Interactions
- Additive with other sedating drugs - alcohol & opioids
- CYP inhibitors - increase effects
- -> (e.g. amiodarone, diltiazem, macrolides, fluconazole, protease inhibitors)
58
CYP inhibitors
- amiodarone
- diltiazem
- macrolides
- fluconazole
- protease inhibitors
59
Benzodiazepine - Patient Education
- Should not drive or operate complex or heavy machinery after taking the drug
- caution them that sometimes sleepiness may persist the following day.
60
Benzodiazepine - Monitoring
- Pre-treatment: ECG, LFTs, U&Es
| - Ongoing: LFTs, U&Es Monitor potential for addiction – lowest possible dose for the shortest time should be given
61
Serotonin 5-HT1-receptor agonists - Examples
Sumatriptan
62
Triptan - Indications
1) Acute migraine with or without aura
63
Triptan - MOA
Triptans constrict cranial blood vessels and inhibit neurotransmission in the peripheral trigeminal nerve and in the trigeminocervical complex.
64
Triptan - Side Effects
Common:
- Pain or discomfort in the chest and throat
- -> intense but resolve quickly
- N & V
- Tiredness
- Dizziness
RARE: MI
65
Triptan - Contraindications
- Coronary Artery disease + Cerebrovasulcar disease due to its vasoconstrictor properties
- Hemiplegic or basilar migraines
66
Triptan - Caution
None
67
Triptan - Interactions
- Monoamine oxidase inhibitors (e.g. tramadol, SSRI, tricyclic antidepressants) increase the risk of serotonin toxicity
68
Triptan - Patient Education
- Can be taken with NSAIDs
| - Only works when taken after the start of migraine (no preventative of an attack)
69
Antiemetics, dopamine D2-receptor antagonists - Examples
- metoclopramide
| - domperidone
70
Dopamine D2-receptor antagonists - Indications
Prohpylaxis & treatment of N & V
| --> specifically regarding reduced gut motility
71
Dopamine D2-receptor antagonists - MOA
+ First, the D2 receptor is the main receptor in the chemoreceptor trigger zone (CTZ), which is the area responsible for sensing emetogenic substances in the blood.
+ D2-receptor antagonists are therefore effective in nausea and vomiting caused by CTZ stimulation (e.g. by emetogenic drugs).
+ Second, dopamine is an important neurotransmitter in the gut, where it promotes relaxation of the stomach and lower oesophageal sphincter and inhibits gastroduodenal coordination.
+ D2-receptor antagonists therefore have a prokinetic effect, promoting gastric emptying, which contributes to their antiemetic action in conditions associated with reduced gut motility
72
Dopamine D2-receptor antagonists - Side Effects
Common: Diarrhoea
-QT-interval prolongation & arrhythmias
73
Dopamine D2-receptor antagonists - Contraindications
Should not be prescribed for more than 5 days.
Avoid:
- neonates, children, young adults
- Intestinal obstruction
- perforation
Avoid metoclopramide:
- Parkinson's disease
Avoid Domperidone:
- cardiac conduction abnormalities
- severe hepatic impairmentt
74
Dopamine D2-receptor antagonists - Interaction
- Increased SE with antipsychotics.
- Avoid with dopaminergic agents for parkinson's
- Avoid with CYP inhibitors - increase SE.
75
Antiemetics, Histamine H1-receptor antagonists - Examples
- cyclizine
- cinnarizine
- promethazine
76
Histamine H1-receptor antagonists - Indications
Prohpylaxis & treatment of N & V.
| --> especially motion sickness or vertigo
77
Histamine H1-receptor antagonists - MOA
Nausea and vomiting are triggered by gut irritation, drugs, motion and vestibular disorders, as well as higher stimuli (sights, smells, emotions).
- The various pathways converge on a ‘vomiting centre’ in the medulla, which receives inputs from the chemoreceptor trigger zone (CTZ), & other centres.
- Histamine (H1) and acetylcholine (muscarinic) receptors predominate in the vomiting centre and in its communication with the vestibular system.
- Drugs such as cyclizine block both receptors.
- This makes them useful treatments for nausea and vomiting in a wide range of conditions, particularly when associated with motion or vertigo.
78
Histamine H1-receptor antagonists - Side Effects
Common: Drowsiness, dry throat and mouth.
- After IV tachycardia, palpitations
79
Histamine H1-receptor antagonists - Contraindications
- Hepatic encephalopathy
| - Prostatic enlargement
80
Histamine H1-receptor antagonists - Interaction
- Other sedative drugs (benzo , opioids)
| - Ipratropium or tiotropium
81
Antiemetics, serotonin 5-HT3-receptor antagonists - Examples
- ondansetron
| - granisetron
82
Serotonin 5-HT3-receptor antagonists - Indications
Prohpylaxis & treatment of N & V.
| --> especially in context of general anaesthesia and chemotherapy
83
Serotonin 5-HT3-receptor antagonists - MOA
- First, there is a high density of 5-HT3 receptors in the CTZ, which are responsible for sensing emetogenic substances in the blood (e.g. drugs).
- Second, 5-HT is the key neurotransmitter released by the gut in response to emetogenic stimuli.
- Acting on 5-HT3 receptors, it stimulates the vagus nerve, which in turn activates the vomiting centre.
- Thus 5-HT3 antagonists are effective against nausea and vomiting as a result of CTZ stimulation (e.g. drugs) and visceral stimuli (gut infection, radiotherapy).
84
Serotonin 5-HT3-receptor antagonists - Side Effects
SE are rare
- Constipation
- Diarrhoea
- Headaches
85
Serotonin 5-HT3-receptor antagonists - Contraindications
Avoid in pt with prolonged AT interval
86
Serotonin 5-HT3-receptor antagonists - Interactions
Drugs that prolong the QT interval : antipsychotics, quinine, SSRI
Applied Pharmacology
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