Billy’s Top drugs profiles & pharmacology
Opioid analgesics
MOA: mu-opioid agonist that can bind to glutamatergic NMDA receptor, thus acting as a receptor antagonist against glutamate
Classifications of opioid analgesics:
Strong opioid: morphine (drug of choice for PO severe pain in palliative care), buprenorphine, dipipanone, diamorphine, alfentanil, fentanyl, remifentanil, methadone, papaveretum, pentazocine (partial
agonist), pethidine (very short action), tapentadol, tramadol
Weak opioid: codeine, dihydrocodeine, meptazinol
General information about opioids:
Dose adjustment:
1) Increment of morphine should not exceed 1/3 to ½ of the total daily dose every 24 hours
2) Breakthrough pain (given 30 minutes before activity that causes pain): 1/10-1/6 of the regular 24-hour dose (given q2-4h, up to hourly if severe/last days of life) morphine sulphate
10mg/5ml or oxycodone (immediate-release) can be used in breakthrough pain
CCI: acute resp depression, head injuries/ raised intracranial pressure (opioid analgesic can interfere with pupillary response vital for neurological assessment), comatose pt, risk of paralytic ileus
Caution: reduce dose in adrenocortical insufficiency/ elderly/ hypothyroidism, asthma (avoid during attack), convulsion, biliary tract disease, hypotension, IBD, MG, prostatic hypertrophy
S/E (long term use):
o dose-related hypogonadism and adrenal insufficiency amenorrhoea, reduced libido, infertility, depression, erectile dysfunction
o hyperalgesia (reduce dose of opioid/ switch therapy)
o resp depression (treated by artificial ventilation/ reversed by naloxone)
o overdose: cause symptoms e.g. coma, resp depression, pinpoint pupil, constipation, loss of appetite, reduced consciousness, n/v (antidote: naloxone)
P: CCI due to resp depression, withdrawal symptoms in neonates (when used during delivery); gastric stasis, aspiration pneumonia in mother (when used during labour)
Hepatic: avoid/ reduce dose (may precipitate coma)
Generic name Indications (other CCI (other CCIs in bold) CSE (other S/E) MOA/POI/ BP/ renal & hepatic impairment (other information in bold)
– drug class indications in bold)
Codeine mild to moderate pain obstructive airway disease n/v, [4] (1) tablet should not be crushed (2) overdose can cause hyperalgesia (3) avoid abrupt
phosphate short term treatment of acute respiratory depression drowsiness, withdrawal (4) don’t drive
– MOR acute moderate pain head injuries that increase dependence, dry B: avoid (may present in milk and cause opioid overdose in fetus)
agonist acute diarrhea intracranial pressure mouth, Renal: avoid/ reduce dose (increase cerebral sensitivity)
dry cough risk of paralytic ileus constipation Use of codeine in children: not indicated for < 12 (max dose for 12-18 = 240mg/d, use lowest
acute ulcerative/ antibiotics- effective dose, max 3/7 use)
associated colitis Prevalence of CYP2D6 metabolizer: North American/ Ethiopian/ Arabs > Caucasian > African
patients at all ages with known American > Hispanics/ Chinese/ ulphur
ultra-fast codeine metabolizer PK: metabolized in liver by 2D6 to morphine via O-demethylation; excerted via urine (main) &
(CYP2D6) faeces (metabolized mainly in liver by CYP – not suitable in liver failure – can use dihydrocodeine
<18 with tonsils/ adenoids 15mg as single dose and monitor effects)
removal for treatment of sleep
apnoea
Diamorphine acute pain delayed gastric emptying taste disturbance, Renal: avoid/ reduce dose
– MOR MI (acute treatment) phaeochromocytoma (medulla anorexia, mixing and compatibility:
agonist acute pulmonary oedema tumor that secrete high amount of increased o Diamorphine SC max 250mg/ml (max 40mg/ml + water for injection/ normal saline)
catecholamine) intracranial o cyclizine (>10mg/ml) or in the presence of normal saline may precipitate after 24 hrs
pressure o haloperidol (>2mg/ml) + diamorphine may precipitate after 24 hrs
Caution: CNS depression, severe diarrhea, severe cor pulmonale (pulmonary heart disease),
toxic psychosis
Morphine – acute/ severe pain impaired respiratory function n/v, constipation, [4] (1) tablet should not be crushed (2) may cause dependence (3) liable to addiction (4); monitor
MOR agonist chronic pain head injuries dependence, pain relief and S/E
acute pulmonary renal and hepatic impairment drowsiness Renal: avoid (reduce dose)
oedema delayed gastric emptying PK: metabolized in liver and gut via glucuronidation to produce morphine-3-glucoronide and
dyspnea in palliative phaeochromocytoma morphine-6-glucoronide; undergoes extensive first-pass metabolism; excreted mainly via urine/
care minor via faeces
PCA Oral solution: contain ethanol as excipient (may interact with metronidazole/ not suitable liver
cough in terminal failure, alcoholism) (discard 3/12 after opening)
illness
Methadone– severe pain impaired respiratory function n/v, constipation, [3] (1) don’t drive (2) enhanced effect with alcohol (3) avoid in renal and hepatic impairment
MOR agonist cough in terminal illness head injuries drowsiness, B: OK during maintenance therapy (monitor S/E in infants)
adjunct in the treatment comatose state headache, Caution: QT prolongation/ taking other medications that can cause QT prolongation
of opioid dependence phaeochromocytoma hallucination
,Buprenorphin moderate to severe pain impaired respiratory function DDGSBTHH [4] (1) caution in: dependence, hypotension, when starting/ ending patches before/ after other
e adjunct in the treatment head injuries dry mouth, opiates (2) enhanced effect with alcohol (3) long duration of action compared to morphine
– Partial of opioid dependence paralytic ileus drowsiness, GID, (4) effect only partially reversed by naloxone
agonist of sweating, B: Low level present in breast milk
MOR & KOR bradycardia, Renal + hepatic: avoid
tachycardia, Specific caution: (transdermal patch) other opiates should not be given within 24 hrs of patch
hypotension, removal in adult due to long DOA; (when used in adjunct in opioid dependence); hepatitis B, C
headache infection, pre-existing enzyme abnormality; (interactions) concomitant use with hepatotoxic drugs;
(fever) may increase absorption
Partial agonist may precipitate withdrawal symptoms
PK: hepatic metabolism via oxidation by CYP3A4 isoenzyme to the pharmacologically active
metabolite N-dealkylbuprenorphine (norbuprenorphine); excreted via faeces mainly
Fentanyl – severe pain risk of paralytic ileus dry mouth, [6] (1) patch changed every 72 hrs (2) caution in: renal and hepatic impairment, hypotension,
MOR agonist post op analgesic dizziness, dependence, impaired resp function (3) monitor increased S/E (4) care when starting/ ending
breakthrough pain headache, GID, patches (5) increased risk of resp depression in opioid naïve patient (6) don’t drive
urinary retention, B: OK (monitor S/E in infants)
Dose conversion of 24 hrly PO morphine dose to 72hrly
insomnia, HT, Renal: avoid/ reduce dose (alfentanil preferred in renal disease due to very short elimination
fentanyl patch:
tremor, vaso- half-life and it is hepatically metabolized)
dilation, Specific caution: mucositis (increased PO absorption)
Morphine salt daily (mg) Fentanyl patch (mcg/hr) anorexia, PK: metabolized in liver via N-dealkylation and hydroxylation by 3A4 isoenzyme; excreted via urine
30 12 myoclonic (main)/ faeces (minor)
60 25 movement (IV) Instructions of using the patch:
90 37.5 1. clean the skin with cold water (don’t use soap, oil & do not stick the patch on straight after a
120 50 hot bath or shower)
180 75 2. it is waterproof (don’t scrub the patch) can bath, shower, swim
240 100 3. do not expose patch in direct heat (e.g. hot water, sunbath) may increase the amount of
medicine entering the systemic circulations
4. apply on the upper body/ arms (no joints) in adult and upper back in children
5. stick a new patch straight away if the old one falls off (then record the time change after 3
days)
Oxycodone – Severe pain Acute abdomen Renal: avoid eGFR<10 (max 2.5mg Q6H with mild to moderate renal impairment)
MOR agonist PCA Chronic constipation
Moderate/ severe pain Delayed gastric emptying
in palliative care
Tramadol – moderate to severe acute intoxication with EtOH/ Fatigue, postural [1] caution: excessive bronchial secretion, Hx of epilepsy, not for substitute of opioid-dependent
MOR agonist (acute pain) analgesics/ hypnotics/ opioids hypotension P: manufacturer advise avoid; B: amount too small to be harmful (manufacturer advise avoid)
+ inhibit 5HT & post-op pain uncontrolled epilepsy MR formulations: 12-hourly (Tramulief SR, Zydol SR, Tramquel SR); 24-hourly (Zydol XL)
NA reuptake
Meptazinol – Moderate and severe MI Arrythmias, [2] caution: effect only partially reversed by naloxone; n/v more common on initiation
partial agonist pain (including post-op, Pheochromocytoma dizziness, Renal: dose may be reduced in moderate to severe RF
of mu opioid renal colic) drowsiness, dry
receptor mouth, n/v
Non-opioid analgesics/ NSAIDs/ migraine
Non-opioid analgesic: paracetamol, NSAIDs, nefopam (no resp S/E, but sympathomimetics & antimuscarinic effect), ziconotide (intrathecal infusion, only used by hospital specialist as adjunct to opioid analgesic)
,Generic name Indications (other CCI (other CCIs in bold) CSE (other S/E) MOA/POI/ BP/ renal & hepatic impairment (other information in bold)
– drug class indications in bold)
Paracetamol mild to moderate pain Dose (oral suspension): MOA: inhibit PG production and inhibit hypothalamic heat-regulating center to allow peripheral
pyrexia 120mg/5ml 6-year plus (250mg/5ml) vasodilation
2m-3m 2.5ml BD 6-8 5ml QDS [3] (1) adult max dose 4g/d (2) lower dose for lower weight patients (adult weight 10-50kg
3m-6m 2.5ml QDS 8-10 7.5ml QDS dose:15mg/kg q4-6h, max 60mg/kg) (3) caution in alcohol dependence, chronic malnutrition,
6m-24m 5ml QDS 10-12 10 ml QDS dehydration
2-4 7.5ml QDS 12-16 10-15 ml QDS B/P: OK
4-6 10ml QDS ≥16 10-20ml QDS Renal: Increase infusion dose interval to q6h when eGFR<30
Overdose:
1) can cause n/v, encephalopathy, hemorrhage, cerebral oedema, lead to hepatocellular
necrosis, renal tubular necrosis
2) antidote: acetylcysteine (most effective when given within 8hrs of ingestion given in 3
N-acetylcysteine adverse reactions infusions 150mg/kg over 1 hr, then 50mg/kg over 4 hrs, then 100mg/kg over 16hrs)
1) Anaphylactoid reactions (common in 1st loading dose): n/v, flushing, skin rash, precursor of GSH (glutathionine) that can protect the liver by increasing the non-toxic ulphur
pruritus (severe: angioedema, bronchospasms, resp distress, hypotension) conjugation
abolish by temporarily suspending the infusion then recommence at the lowest 3) assess serum paracetamol level, AST, ALT, arterial pH, lactate level, U&E, RF
infusion rate (asthmatic patients may have increased risk of anaphylactoid reactions) 4) 2 types of overdose:
2) Coagulation: increase/ decrease prothrombin time A) Acute overdose (>150mg/kg in less than 1 hr) offer activated charcoal (if overdose
3) Fluid & electrolyte: may cause fluid overload leading to hyponatraemia and seizures; occur in the previous hr); offer acetylcysteine if pt at risk of hepatic impairment if plasma
may also cause hypokalaemia paracetamol concentration is at or above the treatment curve of paracetamol overdose
nomogram (from 4 hrs to 24 hrs after ingestion)
RF of paracetamol toxicity: B) ‘staggered’ overdose (with uncertain time of overdose) – involve ingestion of overdosed
1) Taking P450 inducing drugs e.g. C, P, phenobarbitone paracetamol over 1 hr offer acetylcysteine (unless patient is asymptomatic + normal
2) Hx of self-harm, frequent use of paracetamol LFT, RF, INR + undetectable paracetamol concentration)
3) Glutathione deficiency – acute/ chronic starvation, malnutrition, CF
Ibuprofen – Mild to moderate pain Active/Hx GI bleed/perforation [4] (1) tablet should not be crushed (2) take with food (3) may cause renal impairment (4) caution for PO use: present/
non-selective (migraine, dental, RA, related to NSAIDs use (CCI if Hx Hx of cardiac failure, oedema, asthma, IBD (may be exacerbated), peripheral arterial disease, IHD, uncontrolled HT
COX-I dysmenorrhea, ≥ 2 distinct episodes) P: avoid; B: caution (too low to be harmful)
postoperative NSAIDs HS Hepatic: avoid in severe (increased risk of GI bleed + fluid retention); Renal: avoid in severe (inc topical form)
analgesia) Severe HF Specific caution (topical use): avoid close contact with eyes, broken skin, mucous membrane; avoid excessive
, Pyrexia exposure under sunlight after application due to photosensitivity; large application quantity may result in systemic effect
Inflammation Max dose for adult: 2.4g/d
Dose (oral suspension):
Ibuprofen oral suspension (100mg/5ml)
3m-6m 2.5ml TDS
6m-12m 2.5ml TDS-QDS
1-3 5ml TDS
4-6 7.5ml TDS
7-12 10ml TDS
>12 10-20ml TDS
Conception: long term use may reduce fertility (reversed by stopping treatment)
Overdose: can cause n/v, epigastric pain, tinnitus; antidote: activated charcoal
Aspirin – Mild to moderate pain NSAIDs HS causing angioedema, Increased [2] (1) avoid use in gout (aspirin can compete with uric acid for kidney excretion) (2) take with
non-selective Pyrexia bronchospasm, rhinitis, uritcaria bleeding time, skin food/ use gastro-resistant formulation too reduce GID;
COX-I & Immediate (Cross HS with NSAIDs: Difflam, HS, GID P: avoid analgesic dose in the last few weeks of pregnancy (high dose can cause growth
antiplatelet management & 2nd cocillanna compound, restriction, teratogenic effect & caution in antiplatelet dose during 3rd trimester; B: avoid (Reye’s
prevention of thrombotic mesalazine, salicylic acid, syndrome)
events (MI, stroke) sulphasalazine, thymol gargle Hepatic: avoid in severe (increased risk of GI bleed); Renal: avoid in severe (increase fluid
Pre-eclampsia (i.e. HT compound) retention)
and proteinuria in Previous/ current peptic Caution: anaemia, asthma, G6PD deficiency, thyrotoxicosis
pregnancy, especially ulceration Overdose: can cause hyperventilation, tinnitus, deafness, vasodilation, sweating & coma (severe);
at from 20 weeks Children under 16 (Reye’s antidote: activated charcoal (within 1 hr after ingestion) + replace fluid loss + IV NaHCO3 (after
onwards) syndrome) unless for Kawasaki correction of K+ as hypokalaemia can cause urine alkalinisation) to increase urinary salicylate
disease (widespread secretion (pH 7.5-8.5); haemodialysis in severe case
inflammation in blood vessels) RF of pre-eclampsia: DM, HT, CKD, having other conditions e.g. lupus, anti-phospholipid
Haemophilia and other blood syndrome, FH, > 40, BMI≥35, twins, first/ multiple pregnancy, pregnancy interval of more than 10
disorders years
Indomethacin – licensed for the treatment of patent ductus arteriosus (heart disease) in neonates
Naproxen – Pain and inflammation Same as ibuprofen Skin HS, fluid [4] (1) tablet should not be crushed (2) may cause renal impairment (3) associated with the lowest
non-selective Dysmenorrhea retention, GID thrombotic risk compared to other NSAIDs (4) caution: present/ Hx of cardiac failure/ oedema
COX-I Acute gout P: avoid; B: caution (too low to be harmful)
Hepatic: Avoid in severe (increased risk of GI bleed); Renal: avoid when eGFR<30
Conception: same as ibuprofen
Sumatriptan Acute migraine Previous cerebrovascular disease Drowsiness, [6] (1) caution in sulphonamide HS, elderly, CVD (2) avoid alcohol (3) tablet should not be
–5HT (1B/1D) Cluster headache Peripheral vascular disease dizziness, crushed (4) many DIS (5) take 2nd dose after 2 hrs if 1st dose is partially responded (6) don’t take
agonist Moderate to severe HT dyspnea, transient 2nd dose if 1st dose is not responding
Ischemic heart disease increase in BP, P: avoid; B: withhold breastfeeding 12 hrs after treatment
>65 (unlicensed) flushing, sudden Hepatic: reduce dose to 25-50mg (avoid in severe hepatic impairment); Renal: caution
heat sensation at Classifications of triptan (fast onset): sumatriptan, almotriptan, rizatriptan, zolmitriptan,
any part of the eletriptan; (slow onset): frovatriptan, naratriptan
body Prevention of migraine: considered when (1) pt suffer ≥ 2 attack a month that produce
disability lasing for 3 days or more (2) increasing frequency of headaches (3) having significant
disability despite suitable treatment (4) cannot take suitable treatment
o Med for migraine prophylaxis (unlicensed use): beta blockers (e.g. propranolol, atenolol,
metoprolol, nadolol, timolol), TCA, topiramate, valproates, gabapentin, pizotifen (histamine and
5HT blocker; can cause weight gain), botulinum toxin A
Standard treatment of cluster headache: sumatriptan SC (alternative: sumatriptan/ zolmitriptan
nasal spray – both unlicensed); Prophylaxis: verapamil, Li, prednisolone (unlicensed)
Neuropathic pain
Generic name Indications (other CCI (other CCIs in bold) CSE (other S/E) MOA/POI/ BP/ renal & hepatic impairment (other information in bold)
– drug class indications in bold)
Amitriptyline Depression Immediate recovery period post MI Arrhythmias, [1] (1) caution in elderly (more prone to S/E)
– TCA (inhibit Neuropathic pain Arrhythmias (heart block) antimuscarinic P: use if +ve>-ve; B: too small to be harmful
NA and 5HT (unlicensed) Mania effect sedation, Hepatic: avoid in severe (increase sedation)
reuptake) Migraine prophylaxis confusion, Treatment cessation: should gradually withdraw over 4 weeks (6m for long term treatment);
(unlicensed) mydriasis (dilation withdrawal symptoms occur within 5 days of treatment cessation
of pupils) Overdose: can cause dry mouth, coma, hypotension (due to alpha blockage), hypothermia,
convulsion, resp failure, tachycardia (due to increase level of NA), QRS prolongation (due to
inhibition of Na+/K+ ATPase pump slow depolarization and propagation of cardiac action
potential); antidote: activate charcoal (within 1 hr) + IV lorazepam/ diazepam for convulsion
