Drug profiles Flashcards

Question 1

Q

Propofol

Answer

A

2,6 diisopropylphenol
1%/2%; lipid emulsion (soy bean oil, egg phosphatide), pH 7.0; 20/50/100ml vials
Weak acid pKa 11
Physically incompatible with atracurium
Used for induction/maintenance; sedation; status, N+V
Dose 1.5-3mg/kg bolus; 4-12mg/kg/hour maintenance
Dose[P] 2-7mg/kg
MOA: Potentiates GABA-A + glycine; may reduce Na channel opening times; D2 antagonist
CVS: ↓SVR ↓SV ↓CO (20%) ↓BP (15-25%) ↓HR ↑DCCV energy
RS: Apnoea (bolus), ↓VT ↑RR ↓reflexes ↓chemoreceptor response, bronchodilatation
CNS: Hypnosis (1ABCT) ↓CMRO2 ↓ICP/CBF, myoclonus, reduces length of seizures ↓IOP
GI: Antiemetic (D2 antagonism)
Toxicity: Lipaemia -> Propofol infusion syndrome (rhabdo/hepatic failure/acidosis/bradycardia)
Issues: Pain on injection; green urine/hair
D: 98% PPB; VD 4L/kg; rapid tissue distribution
M: Liver to inactive glucuronide (ok in failure); likely extrahepatic also
E: Renal (ok in failure); T1/2 1-5h (CS)

Question 2

Q

Thiopentone

Answer

A

Thiobarbiturate
Yellow powder sodium salt + 6% sodium carbonate under N2; 500mg vial; reconstituted to 25mg/ml with water pH 10.8 - stable for days
Weak acid pKa 7.6; v. lipid soluble
Displays tautomerism - water soluble enol form favoured in high pH
Used for induction; status and brain protection in ↑ICP
Dose: 3-7mg/kg bolus IV; 1g/22kg weight PR
MOA: Potentiates GABA-A + glycine; membrane stabilising effect (Na + K channels)
CVS: ↓CO (20%) ↓BP ↓SVR, may ↑HR
RS: Apnoea ↓VT ↓chemoreceptor response, laryngospasm/bronchoconstriction
CNS: Hypnosis (1ABCT), ↓CMRO2 ↓ICP/CBF ↓IOP
Renal: ↑ADH (+↓CO) -> ↓UO
Toxicity: Anaphylaxis 1:20000
Issues: Porphyria; extravasation
A: Absorbed PO/PR
D: 80% PPB; VD 2L/kg; rapid distribution; displaced by NSAIDs; free drug ↑↑in critically ill
M: Liver. Oxidised by CYP450 -> pentobarb and inactive metabolites; INDUCER; Zero-order kinetics with infusion
E: Urine, T1/2 4-22h (CS)

Question 3

Q

Etomidate

Answer

A

Carboxylated imidazole derivative
2mg/ml, clear, colourless solution of enantiopure R(+)etomidate (10xeffect vs S(-)) with 35% propylene glycol, pH 8.1 or lipuro emulsion (faster onset)
Weak base, pKa 4.1
Used for induction; Rx of Cushing’s before surgery
Dose(A) 0.3mg/kg IV
MOA: Potentiation of GABA-A
CVS: Most cardiostable, mild ↓SVR but no effect on BP
RS: Apnoea with bolus, ↓RR + VT, cough, hiccup, laryngospasm reported
CNS: Hypnosis, involuntary movements, tremor, ↓CMRO2 ↓ICP/CBF ↓IOP
GI: PONV (40% if opiates also)
Endo: Inhibits 11β-hydroxylase and 17α-hydroxylase -> ↓cortisol ↓aldosterone for 24-48h
Haem: Antiplatelet effect -> ↑bleeding time
Toxicity: ↑mortality with infusions on ITU, anaesthetic doses ok unless risk of adrenal insufficiency
Issues: Pain on injection, thrombophlebitis, rare histamine release, porphyria
D: 75% PPB, VD 4L/kg, rapid distribution
M: Hepatic/plasma esterases to inactive metabolites
E: Renal (80%) + bile (20%); T1/2 1-4h (doubled in liver failure)

Question 4

Q

Ketamine

Answer

A

Phencyclidine derivative
Colourless solution 10/50/100mg/ml racemic ketamine hydrochloride pH approx 4.5. Also available as S(+)ketamine in 5/25mg/ml solutions. Both contain benzethonium chloride.
Weak base, pKa 7.5
Used for induction (esp. hypotension/asthma); pre-hospital anaesthesia; maintenance; acute analgesia in hospital setting; chronic pain; sole agent for short, painful procedures and treatment of refractory asthma
Dose (induct): 0.5-2mg/kg IV (over 60secs); 4-10mg/kg IM
Dose (maint): 0.6-3mg/kg/h (GA); 0.3-1.2mg/kg/h (sed)
Dose (sed): 0.2-0.75mg/kg IV; 2-4mg/kg IM
Onset/Dur: 30s IV; 2-8min IM / 5-10min IV; 10-20min IM
May also be given PO, PR, nasally, IT, Epid
MOA: Non-competitive NMDA antagonist; inhibits presynaptic glutamate release; weak interaction with MOP, KOP and DOP; ACh antagonist; inhibits monoamine reuptake (NA, D, 5-HT); Na channel inhibition (LA activity at high dose)
CVS: ↑HR ↑BP ↑CVP ↑CO (↑sympathetic drive), masks direct myocardial depressant effect (↓with S(+))
RS: ↑RR, reflexes preserved, bronchodilatation (R(-) > S(+))
CNS: Analgesia, dissociative anaesthesia, ↑ICP/CBF ↑CMRO2 ↑IOP, mydriasis/nystagmus/hypertonus, altered EEG (+BIS); emergence phenomena/hallucinations (↓with S(+) or BDZ)
GI: Hypersalivation, PONV
GU: Uterotonic, detrusor dysfunction in chronic abuse
Immune: Reduced WBC function in sepsis; suppresses inflammatory response
Issues: Pain on injection, drug of abuse
A: BA 20-25% (PO) 25-50% (nasal) 93% (IM)
D: 35% PPB, VD 3L/kg
M: Liver CYP450, norketamine (30% potent) -> glucuronidated
E: Renal. T1/2 2.5h

Question 5

Q

Nitrous Oxide

Answer

A

N2O
Produced by heating ammonium nitrate to 250degC; NH4NO3 -> N2O + H2O then purified
Stored in French Blue cylinders as liquid below critical temperature; 44bar at 15degC; filling ratio 0.75 temperate, 0.67 tropical.
Or as Entonox as 50:50 mix with O2 (O2 bubbled through N2O) which is a gas above pseudocritical temperature of -7degC (Poynting effect). Stored in French Blue with Blue/white shoulders at 137bar. Lamination below -7degC -> risk of hypoxic mix delivery
BP -88degC; CT 36.5degC; CP 72bar; B:G 0.47; O:G 1.4; MAC 105%
Used as adjuvant to GA; analgesia; refrigerant for cryosurgery
Dose: Typically 70% N2O in O2 for adjuvant to GA
Exhibits concentration and second gas effect due to 30x solubility vs N2
MOA: non-competitive NMDA antagonism; K2P enhancement -> hyperpolarisation; supraspinal opioid+GABA effect in PAG
CVS: ↓SV ↑SVR, BP stable but SV drops further in combination with opioid, or volatile/IV agents
RS: ↓VT ↑RR ↓MV, diffusion hypoxia (Fink effect)
CNS: Analgesia + anaesthesia (LOC >80%), MAC-sparing (additive), ↑ICP, neuromuscular problems with chronic use (confusion, paraesthesia, ataxia, weakness, spasticity), SCDC
GI: N&V/PONV
Haem: Oxidation of B12 -> megaloblastic anaemia + pancytopaenia with prolonged use
Safety: Max environmental exposure 100ppm (UK); Possible teratogen; Store Entonox on side; CI in PTX/ENT Sx/Prolonged ETT Sx
A: Freely diffuses across alv-cap membrane
M: Negligible metabolism
E: Lungs and skin

Question 6

Q

Isoflurane

Answer

A

Halogenated methyl ethyl ether
[draw]
MW 184; BP 48; SVP(20) 33kPa; B:G 1.4; O:G 98; MAC 1.15
Structural isomer of enflurane
MOA: Potentiation at GABAA + glycine; K2P enhancement; NMDA inhibition
CVS: ↓SVR ↓BP, HR unaffected ↓SV (dose related). Historic concern re ‘coronary steal’
RS: ↓VT ↓MV, reduced chemoreceptor response, ↓HPV, bronchodilatation, irritant
CNS: Hypnosis, ↓CMRO2 ↑CBF/ICP (dose related)
GI: PONV
GU: Uterine relaxant (esp >1.4 MAC)
Issues: MH trigger
A: Slow to equilibrate
M: 0.2% by liver -> TFAA and fluoride ions
E: Lung. Metabolites in urine

Question 7

Q

Sevoflurane

Answer

A

Polyfluorinated isopropyl methyl ether
[draw]
MW 200; BP 58; SVP(20) 23kPa; B:G 0.65; O:G 50; MAC 2.0
MOA: Potentiation at GABAA + glycine; K2P enhancement; NMDA inhibition
CVS: (dose related) ↓SVR ↓BP, can↓HR ↓SV, may prolong QT
RS: ↓VT ↑RR ↓MV, reduced chemoreceptor response, ↓HPV, non-irritant
CNS: Hypnosis, ↓CMRO2 ↑CBF/ICP (dose related)
GI: PONV
GU: Uterine relaxant (esp >1.4 MAC)
Issues: MH trigger; rapid emergence in children -> agitation; Down’s Syndrome -> bradycardia; Compounds A-E from reaction with soda lime (A = nephrotoxic but probably not at clinical concentrations)
A: Intermediate equilibration time (vs. iso + des)
M: 2-5% by liver CYP2E1 (induced by chronic EtOH) -> fluorides
E: Lung. Metabolites in urine

Question 8

Q

Desflurane

Answer

A

Fluorinated methyl ethyl ether
[draw]
MW 168; BP 23; SVP(20) 89kPa; B:G 0.4; O:G 26; MAC 6.0
MOA: Potentiation at GABAA + glycine; K2P enhancement; NMDA inhibition
CVS: (dose related) ↓SVR ↓BP, can↑HR ↓SV
RS: ↓VT ↑RR ↓MV, reduced chemoreceptor response, v irritant, not bronchodilator
CNS: Hypnosis, ↓CMRO2 ↑CBF/ICP (dose related), potentiation of NMB
GI: PONV
GU: Uterine relaxant (esp >1.4 MAC)
Issues: MH trigger; ++airway irritation in children; specific vaporiser
A: Fastest equilibration time (vs. iso + sevo)
M: 0.02% by liver -> TFAA
E: Lung. Trace metabolites in urine

Question 9

Q

Halothane

Answer

A

Halogenated alkane
[draw]
MW 197; B:G 2.3; O:G 224; MAC 0.75
MOA: Potentiation at GABAA + glycine; K2P enhancement; NMDA inhibition
CVS: (dose related) ↓SVR ↓BP, ↓HR ↓SV, myocardial sensitisation -> arrhythmia
RS: ↓VT ↓RR ↓MV, reduced chemoreceptor response, bronchodilatation, non-irritant
CNS: Hypnosis, ↓CMRO2 ↑↑CBF/ICP
GI: PONV, ↓motility, Halothane Hepatitis (hypoxic injury and autoimmune stimulation)
GU: ↓GFR, Uterine relaxant (esp >1.4 MAC)
Issues: MH trigger; Shivering post-op
A: Slowest equilibration time of volatiles
M: 20% by liver -> TFAA + halides
E: Lung. Metabolites in urine

Question 10

Q

Enflurane

Answer

A

Halogenated methyl ethyl ether
[draw]
MW 184; B:G 1.8; O:G 98; MAC 1.68
MOA: Potentiation at GABAA + glycine; K2P enhancement; NMDA inhibition
CVS: (dose related) ↓SVR ↓BP, ↓HR ↓SV, myocardial sensitisation -> arrhythmia
RS: ↓VT ↑RR ↓MV, reduced chemoreceptor response, bronchodilatation, irritant
CNS: Hypnosis, ↓CMRO2 ↑↑CBF/ICP, EPILEPTIFORM ACTIVITY, MUSCLE RELAXATION
GI: PONV
GU: Uterine relaxant (esp >1.4 MAC)
Issues: MH trigger; Shivering post-op
A: Slower onset than Iso
M: 2% by liver -> Fluorides
E: Lung, skin, sweat. Metabolites in urine

Question 11

Q

Suxamethonium

Answer

A

Succinylcholine (dicholine ester of succinic acid)
Two acetylcholine molecules joined at acetyl end
Depolarising neuromuscular blocker
Clear, colourless solution containing sux chloride; pH 4; 50mg/ml; 2ml ampoules; store at 4degC
Used for fast onset muscle relaxation eg. for RSI
Dose: 1-2mg/kg IV; up to 2.5mg/kg IM [TBW]
Onset/duration: 30s/3-5 mins
MOA: Competitive agonist at α-subunit of nAChR. Not degraded by AChE -> Prolonged depolarisation of skeletal muscle fibres preventing further action potentials. Also has an effect on prejunctional AChRs (incompletely characterised). Also weak agonist at mAChRs (hence SEs)
CVS: ↓HR and ↑BP, ventricular arrhythmias (esp. with repeated doses)
RS: Apnoea due to paralysis
NS: Fasciculations then Phase I (depolarising) NMB [prejunctional ↑ ACh release] (Sustained tetany, absence of post-tetanic facilitation, TOFR >0.7, potentiation by anticholinesterases [plasma cholinesterase also inhibited]), Phase II block with repeated administration [upregulation of Na/kATPase] (Poorly sustained tetany, post-tetanic facilitation, TOFR <0.3, reversal by anticholinesterases, tachyphylaxis), ↑IOP ↑ICP/CBF
GI: ↑Intragastric pressure with concomitant ↑LOS pressure
Issues: MH trigger; Anaphylaxis risk (11 per 100k); Sux apnoea; Myalgia (esp young, fit ambulant); Hyperkalaemia (esp burns in last 2y and neuromuscular disorders [extrajunctional AChRs release K+ into circulation])
D: Rapid redistribution and metabolism in plasma (20% reaches NMJ)
M: Plasma cholinesterase -> succinylmonocholine (weakly active) + choline; then to succinic acid and choline (inactive)
E: Urine, 5% unchanged. T1/2 3 mins

Question 12

Q

Atracurium

Answer

A

Benzylisoquinolinium non-depolarising muscle relaxant
Clear, colourless solution; 10mg/ml of atracurium besilate; 2.5/5/25ml ampoules; Stored at 4degC to avoid Hofmann degradation; pH 3.5
4 chiral centres -> 10 stereoisomers! Available in mixed stereoisomer form (above) or as enantiopure cisatracurium 2mg/ml (dose 0.15mg/ml) - less histamine release; 80% Hofmann
Used as muscle relaxant for intubation/surgery
Dose: 0.5mg/kg (IBW)
Onset/duration: 1.5-2mins intubating conditions, maximal 3-5 mins / 15-35 mins
MOA: Competitive non-depolarising antagonism at α-subunit of nAChR; prejunctional block -> fade on TOF
CVS: Minimal ↓HR/SVR/BP (histamine related)
RS: Apnoea, Histamine -> bronchospasm (0.2%)
NS: Non-depolarising NMB (Tetanic fade, TOFR <0.3, Post-tetanic potentiation), no effect on IOP/ICP, Critical illness neuropathy with prolonged infusions
GI: Unaffected
Issues: Anaphylaxis (4 per 100k)
D: VD 0.15 L/kg
M: 2 pathways - Ester hydrolysis by non-specific esterases (60%) and Hofmann degradation (40%) both to laudanosine and other inactive metabolites (high laudanosine concs. cause seiures but not at clinical levels)
E: T1/2 20mins; independent of liver/renal Fn

Question 13

Q

Mivacurium

Answer

A

-Benzylisoquinolinium non-depolarising muscle relaxant
-Clear, colourless solution; 2mg/ml mivacurium hydrochloride; 5/10ml amps; Stored at RT; pH 4.5
-Mixture of three stereoisomers (trans-trans[58%]/cis-trans[36%]/cis-cis[6% - only 10% potent])
-Used as muscle relaxant for intubation/surgery, short duration
-Dose: 0.2mg/kg (IBW), give over 30s
-Onset/duration: 2-3mins intubating conditions / 20 mins
-MOA: Competitive non-depolarising antagonism at α-subunit of nAChR; prejunctional block -> fade on TOF
-CVS: Minimal ↑HR ↓SVR/BP (histamine related)
-RS: Apnoea, Histamine -> bronchospasm
-Skin: Histamine -> Rash/erythema
-Issues: Anaphylaxis (3 per 100k)
D: VD 0.25L/kg
M: Hydrolysis by plasma cholinesterases to inactive metabolites (except cis-cis) - effects prolonged by abnormal plasma cholinesterase (sux apnoea)
E: Urine and bile. Effects prolonged by hepatic/renal failure; T1/2 2 mins

Question 14

Q

Rocuronium

Answer

A

Aminosteroid non-depolarising muscle relaxant
Monoquaternary amine drug
Clear, colourless liquid; 10mg/ml Rocuronium Bromide; 5ml amps; stored at 4degC
Used for intubation/RSI/Surgical relaxation
Dose: 0.6mg/kg; 1mg/kg RSI [IBW]
Onset/duration: 2 mins (1min RSI) / 20-60mins
MOA: Competitive non-depolarising antagonism at α-subunit of nAChR; prejunctional block -> fade on TOF
CVS: ↑HR with high dose
RS: Apnoea
NS: Skeletal muscle relaxation
Issues: Pain on injection; Anaphylaxis (6 per 100k); Reversal with sugammadex
D: VD 0.2L/kg
M: Mainly unchanged, some hepatic deacetylation
E: Bile 60%, Urine 40%, effect prolonged in renal/hepatic dysfunction

Question 15

Q

Vecuronium

Answer

A

Aminosteroid non-depolarising muscle relaxant
Monoquaternary amine drug
White lyophilised powder in 10mg vial; reconstituted with 5ml water to 2mg/ml vecuronium bromide + sodium salts + mannitol; pH 4
Used for intubation/surgical conditions
Dose: 0.1mg/kg [IBW]
Onset/duration: 1.5-2mins / 45 mins
MOA: Competitive non-depolarising antagonism at α-subunit of nAChR; prejunctional block -> fade on TOF
CVS: Cardiostable
RS: Apnoea
NS: Skeletal muscle relaxation. Critical illness myopathy with prolonged administration
Issues: Possible ↑PT/APTT
D: VD 0.2L/kg
M: Hepatic deacetylation to active metabolites 3-, 17- and 3,17-dihydroxyvecuronium, only relevant in prolonged dosing
E: Bile 70%, Urine 30% (unchanged), T1/2 60 mins

Question 16

Q

Pancuronium

Answer

A

Aminosteroid non-depolarising muscle relaxant
Clear, colourless solution 2mg/ml pancuronium bromide; 2ml amps; stored at 4degC
Bis-quaternary amine drug
Used for intubation/surgical conditions; lethal injection in US; long-acting
Dose: 0.1mg/kg [IBW]
Onset/duration: 1.5-2mins / 90mins
MOA: Competitive non-depolarising antagonism at α-subunit of nAChR; prejunctional block -> fade on TOF
CVS: Vagolytic + blocks NA reuptake -> ↑HR ↑CO ↑BP
RS: Apnoea
NS: Prolonged muscle relaxation
Issues: Sweating/flushing
D: up to 40% PPB; VD 0.25L/kg
M: Hepatic -> 3-, 17- and 3,17-hydroxypancuronium (3- has 50% potency)
E: Bile 50%, Urine 50% (unchanged), T1/2 120mins, prolonged in hepatic and renal failure

Question 17

Q

Neostigmine

Answer

A

Quaternary amine anticholinesterase
Medium duration of action (1-2h)
15mg tablets or SFI 2.5mg/ml and combination with glyco (0.5mg/ml)
Used for reversal of non-depolarising NMB; Rx of myasthenia gravis and paralytic ileus
Dose: 0.05mg/kg for reversal (1ml dose for 50kg adult); 15-30mg 4 hourly in MG
Onset/duration(IV): Peak at 8-10mins / 1-2h
MOA: Reversible binding to esteratic site of AChE, carbamylates the enzyme, slowing hydrolysis -> reduces ACh breakdown -> ↑synaptic conc. -> competes with NMBs. Also inhibits plasma cholinesterase.
CVS: ↓HR ↓BP (muscarinic)
RS: Bronchoconstriction, ↑secretions
NS: Miosis, blurred vision, muscle spasm (low dose), neuromuscular blockade (high dose -> receptor flooding)
GI: ↑secretions + motility, N+V
Skin: Sweating
GU: Involuntary urination
Issues: Usually given with antimuscarinic
A: 1-2% BA PO
D: 10% PPB; VD <1L/kg
M: Plasma esterases to inactive alcohol, minor hepatic metabolism
E: Urine 60%, bile 40%, T1/2 60 mins

Question 18

Q

Edrophonium

Answer

A

Quaternary amine anticholinesterase
Clear, colourless SFI, 10mg/ml
Used for reversal of NMB; diagnosis of myasthenia gravis (Tensilon test); differentiation of myasthenic and cholinergic crises
Dose: 0.6mg/kg (reversal) ; 2mg then 8mg for MG Dx; 2mg for test in crisis (atropine available)
Onset/duration: 1 min / 10 mins
MOA: Binds to both anionic and esteratic AChE sites, competitively inhibiting the enzyme’s activity on ACh -> ↑synaptic conc. -> competes with NMBs
CVS: ↓HR ↓BP (muscarinic)
RS: Bronchoconstriction, ↑secretions
NS: Miosis, blurred vision, muscle spasm (low dose), neuromuscular blockade (high dose -> receptor flooding)
GI: ↑secretions + motility, N+V
Skin: Sweating
GU: Involuntary urination
Issues: Usually given with antimuscarinic
D: VD 1L/kg
M: Some hepatic glucuronidation
E: Urine 60%, bile 40%, T1/2 110 mins

Question 19

Q

Organophosphates

Answer

A

Class of compounds with varied characteristics
eg. malathion/parathion/TEPP (pesticides), Sarin (nerve agent), echothiophate (Glaucoma Rx)
Irreversible binding to AChE at esteratic site -> inactivation; also inhibit plasma cholinesterase
Highly lipid-soluble -> absorbed through skin
Cause muscle contraction/spasm -> apnoea, muscarinic SEs (autonomic instability, D+V, bronchoconstriction + secretions) and central excitation -> depression -> coma
Treatment is supportive, ↑↑dose atropine and AChE reactivator PRALIDOXIME/OBIDOXIME [hydrolyse phosphorylated enzyme]

Question 20

Q

Sugammadex

Answer

A

Gamma cyclodextrin
Clear, colourless solution 100mg/ml; 2/5ml amps
Used to reverse Rocuronium and Vecuronium
Dose: 16mg/kg (intubating dose); 4mg/kg (deep block - post-tetanic count 1-2); 2mg/kg (moderate block - >1 twtich on TOF). Works in seconds
MOA: Ring structure is hydrophilic on outside and lipophilic on inside, encapsulates Roc/Vec within lipophilic centre, preventing drug effect and facilitating urinary excretion. Creates gradient drawing drug out of NMJ.
Issues: Significant anaphylaxis unlikely; reduces effectiveness of OCP (1 missed day) and parenteral hormonal contraceptives (alt. contraception for 1/52); Very rarely bradycardia
VD 12L; linear kinetics; not metabolised; renal excretion, T1/2 2.5h

Question 21

Q

Atropine

Answer

A

Tertiary amine antimuscarinic
Named after Atropos - Greek fate
Naturally occurs eg. in Atropa belladonna (deadly nightshade)
Commercially synthetic - racemic mixture of D/L-hyoscyamine (only L active)
Clear, colourless solution 0.6mg/ml atropine sulfate; also 600mcg tablets for premed
Used for premed (secretions); Rx of bradycardia, muscarinic SEs, organophosphate poisoning and tetanus
Dose(A): 0.2-0.6mg IV
Dose(P): 20mcg/kg
MOA: Competitive antagonism at mAChR; some nAChR effect at high dose; crosses BBB
CVS: ↑HR, precipitates arrhythmias
RS: ↑RR, bronchodilatation, ↓ secretions
NS: Antiemetic, antiparkinsonian, central anticholinergic Sx (confusion, somnolence, hallucinations, agitation, amnesia, ataxia)
GI: ↓salivation ↓motility, antispasmodic ↓LOS tone
GU: Urinary retention
Issues: Pain on IM injection; ↓sweating + hyperpyrexia in children
A: Well absorbed, 20% BA PO
D: 50% PPB, VD 3L/kg; crosses placenta
M: Hepatic -> inactive metabolites
E: Urine, some unchanged, T1/2 2.5h

Question 22

Q

Glycopyrronium

Answer

A

Synthetic quaternary amine antimuscarinic
Clear, colourless solution 0.2mg/ml; 3ml amps; also in combination with neostigmine (0.5mg glyco + 2.5mg neo/ml)
Used for premed (secretions); mitigation of anticholinesterase SEs; Rx of bradycardia, hyperhidrosis and symptom control at end of life
Dose(A): 0.2-0.4mg IV/IM
Dose(P): 4-10mcg/kg
Peak effect at 3 mins, 2-3h duration
MOA: Competitive antagonism at peripheral mAChR; does not cross BBB
CVS: ↑HR, less arrhythmogenic than atropine
RR: Significant bronchodilatation -> ↑deadspace
NS: Headache, drowsiness, weak LA activity
GI: ↓↓salivation (++vs atropine) ↓motility, antispasmodic ↓LOS tone
GU: Urinary retention
Issues: ↓sweating but no effect on temperature
A: 5% BA PO
D: VD 0.5L/kg, rapid redistribution
M: Minimal
E: Urine 85% + bile 15%, T1/2 1h

Question 23

Q

Hyoscine

Answer

A

Tertiary amine antimuscarinic
Naturally occurring alkaloid
Clear, colourless solution as hydrobromide (0.4mg/ml) or butylbromide (20mg/ml); butylbromide available as tablet and hydrobromide as a patch (1mg/72h)
Racemic mixture, only L-hyoscine active
Used for premed (secretions); Rx of N+V/motion sickness; antispasmodic; palliative care
Dose: 5-10mcg/kg IV; 10-15mcg/kg IM; 20mg 6 hrly PO
MOA: Competitive antagonism at peripheral mAChR; butylbromide does not cross BBB; hydrobromide does cross BBB
CVS: Mild ↑HR IV
RS: ↑RR ↓↓secretions, bronchodilatation
NS: Mydriasis +++, Sedation, amnesia, antanalgesia, central anticholinergic syndrome (confusion, somnolence, hallucinations, agitation, amnesia, ataxia) [reduced with butylbromide]
GI: Antiemesis, ↓↓salivation, antispasmodic
GU: Urinary retention
Issues: ↓sweating
A: 10% BA PO
D: VD 2L/kg
M: Liver esterases -> inactive metabolites
E: Urine, T1/2 1h

Question 24

Q

Morphine

Answer

A

Naturally occurring phenanthrene derivative
Strong opiate
Wide range of preparations and routes; tabs (SR/MR), syrup, suppos., SFI -clear, colourless 10/15/30mg/ml sulphate; pres-free
Weak base; pKa 8.0
Used for mod/sev pain; PCA; Premed; Palliative care and Rx of diarrhoea
Dose(A): 5-20mg 4hrly po; 25-30mg 4hrly pr; 0.05-0.1mg/kg IV; 0.1-0.2mg/kg sc/im; 0.2-1mg IT; 1-5mg Epi
Onset/duration: 10/30mins IV/IM / 3-4h duration
MOA: MOP + KOP agonism -> ↑K+ efflux -> hyperpol; ↓AC -> ↓cAMP; ↓VGCC activity; affects cortex, BG, PAG and SC (presynaptic primary afferents)
CVS: Histamine -> ↓SVR; OH; ↓HR (high dose)
RS: ↓RR ↓chemoreceptor response, antitussive, bronchoconstriction (high dose)
NS: Analgesia, sedation, euphoria, hallucinations, meiosis, rigidity + seizures (high dose), ↓MAC/BIS
GI: ↓motility -> constipation, ↓secretions, N+V, SoO spasm
GUS: ↑ureteric/bladder sphincter tone -> retention
Endo: ↑ADH -> ↓Na, ↓adrenal steroids
Skin: Itching, sweating
Issues: Controlled drug; Caution in liver / renal failure, hypopituitarism and chronic T2RF; Delayed ↓RR with IT/Epi; caution in children/neonates
A: BA 20-50% PO (FPM)
D: 40% PPB; VD 4L/kg (reduced in elderly -> ↑peakCp); xplacenta
M: Hepatic -> M-3- (70%, possible weak agonist), M-6-glucuronide (13x potency) and normorphine (inactive)
E: Urine 90%, Bile 10%; T1/2 2-4h

Question 25

Q

Diamorphine

Answer

A

Synthetic morphine derivative - Diacetylmorphine
Strong opioid prodrug
Wide range of routes; 10mg tabs; white lyophilised powder diamorph hydrochloride for reconstitution with water/saline, range of strengths
Weak base pKa 7.6
Used for mod/sev pain; Premed; Palliative care; Dyspnoea associated with acute LVF
Dose(A): 5-10mg IV/IM; 0.1-1mg IT; 1-3mg Epi
Onset/duration: <10min / 90min
MOA: Prodrug -> 6-MAM and morphine are first active metabolites; MOP + (↓)KOP agonism -> ↑K+ efflux -> hyperpol; ↓AC -> ↓cAMP; ↓VGCC activity; affects cortex, BG, PAG and SC (presynaptic primary afferents)
CVS: Only with high dose. Histamine -> ↓SVR, OH, ↓HR
RS: ↓RR ↓chemoreceptor response, antitussive, bronchoconstriction (high dose)
NS: Analgesia, sedation, euphoria++, hallucinations, meiosis, rigidity + seizures (high dose), ↓MAC/BIS
GI: Less than morphine. ↓motility -> constipation, ↓secretions, N+V
GUS: ↑ureteric/bladder sphincter tone -> retention
Endo: ↓stress response to Sx
Skin: Itching, sweating
Issues: Controlled drug; Caution in chronic T2RF; No delayed ↓RR with IT/Epi
A: Low BA (FPM)
D: 40% PPB; VD 5L/kg; xplacenta
M: Plasma, RBC and tissue esterases -> 6-MAM + morphine. Then hepatic -> M-3- (70%, possible weak agonist), M-6-glucuronide (high potency) and normorphine (inactive)
E: Urine, 60% as morphine metabolites. Diamorph T1/2 3 mins

Question 26

Q

Alfentanil

Answer

A

Synthetic phenylpiperidine derivative
Strong opioid
Clear, colourless solution alf hydrochloride; 0.5/5mg/ml
Weak base; pKa 6.5
Used for short acting analgesia; obtunding airway reflexes and sedation on ITU
Dose(A): 5-50mcg/kg bolus; 30-60mcg/kg/h IVI
Onset/duration: 90 sec / 5-10 mins; exhibits CSHT
MOA: Highly selective MOP agonist -> ↑K+ efflux -> hyperpol; ↓AC -> ↓cAMP; ↓VGCC activity; affects cortex, BG, PAG and SC (presynaptic primary afferents)
CVS: sympatholytic ↓HR -> ↓response to laryngoscopy, BP stable
RS: ↓RR, ↓chemoreceptor response, antitussive
NS: Analgesia, meiosis, minimal sedation, ↓IOP, ↓MAC/BIS
GI: ↓motility -> constipation, ↓secretions, N+V, SoO spasm
GUS: ↑ureteric/bladder sphincter tone -> retention
Endo: ↓stress response to Sx
Issues: Controlled drug; caution in liver/renal failure
D: 90% PPB; VD 0.6L/kg
M: Hepatic CYP3A4 -> noralfentanil (inactive), competition for 3A4 by midazolam -> ↓metabolism
E: Urine, T1/2 90 mins

Question 27

Q

Fentanyl

Answer

A

Synthetic phenylpiperidine derivative
Strong opioid
Lozenges, patches (range of strengths); Clear, colourless solution fentanyl citrate; 50mcg/ml
Weak base; pKa 8.4
Used for mod/sev pain; PCA; chronic pain; palliative care; obtunding airway reflexes and sedation on ITU
Dose(A): 1-100mcg co-induction IV; 50-100mcg premed IV; 1mcg/kg bolus for pain; 10-30mcg IT; 25-100mcg Epi; 2-4mcg/kg/h IVI
Onset/duration: 2-5 min / 30mins - 6h (CSHT)
MOA: Highly selective MOP agonist -> ↑K+ efflux -> hyperpol; ↓AC -> ↓cAMP; ↓VGCC activity; affects cortex, BG, PAG and SC (presynaptic primary afferents)
CVS: sympatholytic ↓HR -> ↓response to laryngoscopy, BP stable
RS: ↓RR, ↓chemoreceptor response, antitussive, ‘wooden chest’ with high doses
NS: Analgesia, meiosis, minimal sedation, ↓MAC/BIS
GI: ↓motility -> constipation, ↓secretions, N+V
GUS: ↑ureteric/bladder sphincter tone -> retention
Endo: ↓stress response to Sx
Issues: Controlled drug; No delayed resp depression with IT
A: 33% BA PO
D: 90% PPB; VD 4L/kg
M: Hepatic CYP3A4 -> norfentanyl and further metabolites (inactive),
E: Urine 90%, Bile 10%; T1/2 3h+ (CSHT)

Question 28

Q

Remifentanil

Answer

A

Synthetic phenylpiperidine derivative
Strong opioid
White lyophilised powder, containing glycine buffer, in 1/2/5mg vials for reconstitution with saline, typically to 50mcg/ml for infusion
Used for analgesia and induction of hypotension during GA; sedation on ITU and during awake airway procedures
Dose: 1mcg/kg slow bolus; 2-60mcg/kg/h IVI
Onset/duration: 2 mins / 5-10 mins, context-insensitive
MOA: Pure MOP agonist -> ↑K+ efflux -> hyperpol; ↓AC -> ↓cAMP; ↓VGCC activity; affects cortex, BG, PAG and SC (presynaptic primary afferents)
CVS: sympatholytic ↓HR/SV/BP (20%), ↓response to airway manipulation
RS: ↓RR, ↓chemoreceptor response, antitussive, ‘wooden chest’ with high doses
NS: Analgesia, meiosis, minimal sedation, ↓MAC/BIS
GI/GU: Reduced compared to morphine/fent
Endo: ↓stress response to Sx
Issues: Controlled drug; Profound ↓HR with rapid boluses
D: 70% PPB; VD 0.1L/kg
M: Plasma/tissue esterases -> inactive carboxylic acid derivatives
E: Urine; T1/2 90mins

Question 29

Q

Pethidine

Answer

A

Synthetic phenylpiperidine derivative
Originally designed as an anticholinergic
Strong opioid
Tabs (50mg); clear, colourless solution for injection (10/50mg/ml)
Weak base, pKa 8.7
Used for labour analgesia; antispasmodic in colic; Rx of post-operative shivering
Dose: 50-150mg 4hrly PO; 25-100mg 4hrly IV/IM
MOA: MOP + KOP agonism -> ↑K+ efflux -> hyperpol; ↓AC -> ↓cAMP; ↓VGCC activity; affects cortex, BG, PAG and SC (presynaptic primary afferents); Anticholinergic effect; SSRI effect
CVS: ↑HR (anticholinergic), OH (opioid)
RS: ↓RR ↓VT ↓chemoreceptor response
NS: Analgesia, mydriasis (anticholinergic), euphoria+
GI: N+V, constipation (supposedly less than morphine)
GU: Urinary retention, uterotonic
Endo: ↑ADH -> ↓Na, ↓adrenal steroids
Issues: Crosses placenta -> fetal norpethidine accumulation (active metabolite + proconvulsant); Interaction with MAOIs -> hypertension, seizures, hyperpyrexia; caution in renal failure
A: 50% BA PO
D: 60% PPB; VD 4.5L/kg; xPlacenta
M: Hepatic demethylation -> norpethidine (50% potency, proconvulsant) -> pethidinic acid
E: Renal, T1/2 3h+