Pharmacology (drugs) Flashcards

Question

Fentanyl: MoA (inc onset/peak/duration) ## Footnote L1

Answer 1

Highly selective MOP agonist (GiPCR) (pre-synaptic) --> inhibition of AC --> reduced cAMP, closure of voltage-gated Ca channels Onset: <1-2min; Peak: 3-5min Duration: 30-60min

Answer 2

**Effects/Side effects** **CVS:** bradycardia (vagal); CO, MAP, SVR, PVR unaffected. Obtunds CV response to laryngoscopy and intubation **Resp:** potent respiratory depressant - decreases RR & tidal volume. Decreased ventilatory response to hypoxia and hypercapnia. Chest wall rigidity **CNS:** 50-80x more potent than morphine. Little hypnotic/sedative effect. Potent antitussive **GI:** decreases GI motility & gastric acid secretion. Spasm of sphincter of Oddi **Other** Secondary peak in plasma fentanyl concentration due to elution from muscle

Answer 3

Class/chemistry: Opioid analgesia. Synthetic phenylpiperidine derivative. pKa 7.1; 68% unionised at pH7.4 Admin/prep: White lyophilised powder to be reconstituted. 1/2/5mg vials. IV only

Answer 4

Titrated to response. 0.0125-1mic/kg/min infusion or 1mic/kg bolus dose over 30s - Analgesia in GA - Analgesia during labour - Analgesia/sedation during 'awake' fibreoptic

Answer 5

A: Given IV only D: 70% PB. VD (ss)= 0.3L/kg

Answer 6

M: Rapidly hydrolysed by non-specific plasma and tissue esterases --> remifentanil acid (4600x less potent) E: CSHT - fixed 4-5min. Elimination half life 10min

Answer 7

Pure MOP agonist (pre-synaptic Gi) Peak effect 1-3min Duration ~4min

Answer 8

**CVS:** decreases MAP + HR **Resp:** Potent respiratory depressant. May get chest wall rigidity similar to fentanyl **CNS:** analgesic potency similar to fentanyl. Centrally mediated vagal activity, miosis (EW nucleus) **GI:** decreased GI motility. Relatively low n+v

Answer 9

Chemistry: Hydrazine + non-hydrazine compounds Preparation: Mostly oral formulations Dose/Indication: (moclobemide 150mg starting dose) ○ Major depression (third line) ○ Some anxiety disorders/panic disorder

Answer 10

Inhibit MAO-A & MAO-B (located in the mitochondria and metabolise monoamines). MAO-A metabolises dopamine, NE, serotonin; MAO-B metabolises dopamine. Both enzymes exist in the brain + are distributed differently throughout the body

Answer 11

- CNS: increased NTs (5-HT, NE)--> improves postsynaptic NT binding. Supratherapeutically: seizures, mania, serotonin syndrome, restlessness, agitation, nausea, insomnia - CVS: MAO-A + B metabolise dietary tyramine --> inhibition of metabolism --> release of tyramine into general circulation --> triggers release of NE. May precipitate hypertensive crisis - Hepatic: can cause hepatotoxicity, hypoglycaemia Other specifics - Irreversible MAOIs will bind for the life of the MAOs (~2/52)

Answer 12

SSRI: initially block reuptake of 5-HT via SERT & result in increased length of time that serotonin is available in synapse, increasing postsynaptic receptor occupancy - They are 10x more selective for SERT than NET - Initial increase in synaptic serotonin eventually leads to increased production of neuroprotective proteins such as BDNF + Bc1-2 SNRI: inhibit SERT & NET

Answer 13

Class: Opioid analgesic Chemistry: Naturally occurring phenanthrene derivative. Weak base (pKa 8). 23% ionised at pH 7.4 Preparation/administration: - PO formulations various strengths - 5/30mg suppositories - IV 10/15/30mg/mL of morphine sulfate - Preservative free formulation needed for epidural/spinal injection . Routes: PO, IV, IM, S/c

Answer 14

Dose generally titrated to effect. Initial dose 0.1-0.2mg/kg s/c or 0.05-0.1mg/kg IV - Pre-mediation - Pain relief in terminal care - Treatment of ACS/LV failure

Answer 15

A: BA 30% (extensive FPM) D: 20-40% PB; VD ~ 4L/kg

Answer 16

M: Liver - Morphine-3glucuronide(60%-arousal), morphine-6-glucuronide (5-10% analgesic-13x more potent than parent), normorphine E: Urine, small percentage of metabolites in faeces. Half-life ~4hrs, accumulation of M6G in renal failure. Maximal CSHT 20min (regardless of duration of infusion)

Answer 17

Agonist at MOP & KOP. At pre-synaptic MOP: GiPCR --> inhibition of adenylate cyclase --> decreased cAMP --> decreased Ca2+ influx --> decreased Ca2+ mediated NT release - Post synaptic MOP: increases K+ conductance and hyperpolarisation of excitable cell membranes **Onset:** 5-10min, 30min PO; Peak: 20min **Duration:** 3-5hrs IV

Answer 18

**CVS:** may cause some histamine release - decreases SVR, may cause orthostatic hypotension **Resp:** respiratory depression, may cause bronchoconstriction in high doses **CNS:** potent analgesic. Euphoria **GI:** decreases GI motility, increases CBD pressure (spasm of sphincter of Oddi). N/v/constipation **Renal:** increases tone of ureters, bladder - retention **Endo:** morphine increases ADH Caution in hepatic/renal failure. Dependence is an issue pruritis may occur from eipdural/spinal admin

Answer 19

Class/chemistry: 2nd generation/atypical antipsychotic/ thienodiazepine PO, IM

Answer 20

Varies 5-10mg - Agitation/aggression (organic + psychiatric causes) - Delusional disorders - Schizophrenia - Huntington associated chorea

Answer 21

- Potent antagonism of 5HT2A +2C, D1-4, H1, alpha1-adrenergic receptors

Answer 22

CVS: orthostatic hypotension GI: constipation Metabolic: increased cholesterol

Answer 23

2nd generation/atypical antipsychotic/ dibenzothiazepine PO

Answer 24

Varies 25-100mg - Agitation/aggression (organic + psychiatric causes) - Delusional disorders - Schizophrenia - GAD

Answer 25

- 5HT2 + D2 antagonism with H1 + alpha effects - Nil cholinergic/benzo effects

Answer 26

CVS: increased BP, tachycardia Metabolic: cholesterol CNS: may cause EPS

Answer 27

Chemistry - 3-ring central structure plus side chain. Most have pKa ~8.5 § Tertiary amines have 2 methyl groups at the end of the side chain. They are generally more potent in blocking 5-HT over NE (amitriptyline, doxepin, imipramine) § Secondary amines have one methyl group at the end of the side chain. They are more potent in blocking NE (nortryptiline, desipramine) Preparation: most available in oral forms only Dose/Indication - Major depression. Dose is started at 25-75mg for all, with titration ever 2-3 days to 75-150mg - Clomipramine used in OCDs + cataplexy with narcolepsy - Imipramine can also be used for nocturnal enuresis

Answer 28

- Inhibit both NE + serotonin uptake - Also block cholinergic, histaminergic, alpha1-adrenergic and (inhibit fast Na channels in His-Purkinje system & myocardium --> similar to Class 1A antiarrhythmics)

Answer 29

- CVS - alpha1 blockade can cause orthostatic hypotension, QT prolongation, and other conduction delays - CNS - can lower seizure threshold - Anticholinergic - blurred vision, constipation, dry mouth, urinary retention - Antihistaminic - Increase appetite, cause sedation

Answer 30

-Delayed Absorption (dec. gut motility - anticholinergic); acidaemia- dec glycoprotein binding (incr free drug) Signs/symptoms - CNS - mental state changes (agitation, delirium), decreased GCS, seizures (? GABAA antag) - CVS - Hypotension (peripheral vasodilation - alpha1 blockage). Tachycardia (vagolysis) + reflex tachy. Can have arrhythmias. --> ECG: widened QRS (>100ms), QT prolongation - Anticholinergic (hyperthermia, flushing, dilated pupils) Management - Decontamination, Supportive care - Antidote: NaHCO3 - cardiac toxicity (QRS >100msec) --> Plasma alkalinsation (improves protein binding) --> Intracellular alkalosis (increases the unbinding rate of TCAs from Na+ channel receptor + favours the non-ionised state of the TCA) --> Sodium load

Answer 31

Class: Sedative Chemistry: Thiobarbituate. pKa 7.6, 61% unionised at pH 7.4 High lipid solubility Preparation/administration: (hygroscopic) yellow powder, stored under atmosphere of nitrogen. Reconstituted with water which is stable in solution for 24-48hrs

Answer 32

Induction of anaesthesia: 2-6mg/kg Management of status epilepticus Neuroprotection (raised ICP): 1.5-3.5mg/kg intermittent bolus dose

Answer 33

A: Is absorbed PO and PR D: PB 80%, Vd = 2L/kg

Answer 34

M: Liver - oxidation to pentobarbital & cleavage to urea + 3-C fragments. 15% dose metabolised/hr E: Elim half life - 3-22hrs. CSHT variable

Answer 35

- Prolong GABAA receptor opening duration, direct activation at higher doses - Primarily act at synapses by depressing post-synaptic sensitivity to NTs and impairs pre-synaptic NT release - Multisynaptic pathways depressed preferentially (eg. Reticular System) - Membrane stabilising effects - ↓s Na+ + K+ conductance

Answer 36

**CNS:** anaesthesia, CBF, ICP, IOP ↓. Anticonvulsant **CVS:** negative ionotrope, ↓ CO, SVR **Resp:** Potent respiratory depressant, ↓ in ventilatory response to hypercapnoea. Laryngeal spasm occasionally seen, may get bronchoconstriction Other: contraindicated in porphyria

Answer 37

Class/chemistry: Typical antipsychotic/1st generation antipsychotic/ Butyrophenone Preparation/ Administration: PO tablets, capsules, syrup,, solution for injection, depot

Answer 38

IV 1-5mg; Po dose 1-15mg - Schizophrenia/psychoses - Nausea + vomiting - Acute confusional states + delirium - Premedication - Palliative care

Answer 39

- Central dopaminergic (D2) blockage --> increased threshold for vomiting at CTZ - Post synaptic GABA antagonism

Answer 40

CVS: some alpha2 antagonism - may have hypotension CNS: Neurolepsis, raises seizure threshold Metabolic: may cause hyperprolactinaemia Other: May produce extrapyramidal symptoms, including NMS

Answer 41

**Class: **Sedative **Chemistry: **Phencyclidine derivative. Racemic mixture (S-enantiomer more potent). Soluble in water **Preparation/ Administration: ** 50, 100mg/ml IV, IM, IN, Oral (lozenges)

Answer 42

**Induction: **1-2mg/kg **Procedural sedation: **0.2-0.5mg/kg every 5-10minutes **Analgesia:** 0.25-0.5mg/kg bolus, then 0.05-0.25mg/kg/hr

Answer 43

A: BA (oral 25%), nasal (50%), IM (93%) D: 20% PB, Vd = 3L/kg

Answer 44

M: CYP450 - Norketamine (25% activity of parent) E: Elim half life 2hr; 90% in urine

Answer 45

NMDAR non-competitive antagonist at NMDAR Inhibition of glutamate Onset: 1min; Duration 10-15min

Answer 46

**CVS: **Stimulates SNS, increases HR, CO, BP - however is a direct myocardial depressant. S-ketamine - less myocardial depressant effect **CNS: **Dissociative anaesthesia, analgesia. May increase CMRO2 **Resp: **Bronchodilation, respiratory rate. Airway reflexes intact **AS: **increases salivation **GI: **causes nausea + vomiting

Answer 47

Class: Sedative Chemistry: Imidazole derivative IV formulation. Nil additives

Answer 48

Dose 0.2-1mic/kg/hr - Procedural sedation - Sedative in ICU

Answer 49

- 94% PB; VD = 1.3L/kg

Answer 50

M: Hepatic via CYP & glucuronidation, inactive metabolites E: Urine; t1/2 - large variation in CSHT (~4min after 10min infusion - 2-3H post 8 hr infusion) T1/2 elimination = 2hrs

Answer 51

Selective alpha2 adrenoceptor agonist Sedative actions primarily post synaptic alpha2 adrenoceptors Inhibition of NAd release in locus ceruleus

Answer 52

CNS - sedation, easily roused. Decreases cerebral VO2, blood flow, ICP CVS - Higher doses cause peripheral alpha2 effects - decreased sympathetic output

Answer 53

Class: sedative/anxiolytic Chemistry: Benzodiazepine Preparation/administration: Tablets - 2mg, 5mg, oral liquid 1mg/mL IV solution 5mg/mL (2mL)

Answer 54

- Short term treatment of anxiety - 2-5mg - Alcohol withdrawal - individualised - Muscle spasm in tetanus or other spastic conditions

Answer 55

A: Rapidly absorbed. BA 86-100% D: 99% protein bound; Vd = 1L/kg

Answer 56

M: Liver. Major active metabolite = desmethyldiazepam (t1/2~100hrs). Other active metabolites - oxazepam + temazepam -formed by oxidation & further undergo glucuronidation. Low HER E: T1/2 20-40hrs

Answer 57

Targets (between α & γ subunits) GABA-A receptors in CNS -- enhances inhibitory effect of GABA (increased permeability to Cl-) **Onset: **IV 4-5min; **duration: **hours

Answer 58

**CVS:** Transient decrease in BP + CO **Resp:** respiratory depression in large doses **CNS:** anxiolysis, sedation, hypnosis, anticonvulsant properties, anterograde amnesia

Answer 59

**Class**: Anticonvulsant/Hydantoin. **Chemistry**: Little difference in activity between isomers Fosphenytoin is the water-soluble prodrug pKa 8 **Admin/prep: ** PO - 25/50/100/300mg capsules, syrup of 6mg/ml IV - clear, colourless solution 50mg/mL

Answer 60

1. Prophylaxis and treatment of GTC + partial epilepsies - Status: IV 15-20mg/kg with additional 5mg/kg post 12hrs if needed - 4-5mg/kg (usually 200-500mg) in 1 or 2 doses in epilepsy 2. Arrhythmias (especially from dig toxicity) - 3-5mg/kg 3. Trigeminal neuralgia Onset: 0.5-1hr IV; PO 2-24hrs

Answer 61

A: Absorption is slow via PO + IM routes. (Note IM may cause muscular damage) Bioavailability is 85-95% D: 90-93% protein bound in plasm - Vd = 0.5-0.7l/kg Crosses BBB + placenta

Answer 62

M: In liver. Large genetic variation in rate of metabolism. - Hydroxylated derivative --> conjugated to glucuronide - Exhibits zero order elimination just above therapeutic range E: 70-80% renally excreted by active tubular secretion as the major metabolite, 5% unchanged - t1/2 = 9-22hrs in the first-order kinetics range - plasma concentration increases disproportionately with increased dosage

Answer 63

- Blocks voltage and use dependent Na+ channels. Also delays outward K+ flux & Ca2+ flux - High affinity binding site for phenytoin in CNS, so likely endogenous binding site

Answer 64

CNS - stabilises the seizure threshold by preventing the speed of seizure activity, rather than abolish a primary discharging focus. Tonic phase can be abolished, but clonic seizure may be exaggerated/prolonged. Toxicity - nausea/vomiting, drowsiness, behavioural difference, tremor, ataxia, nystagmus, paradoxical seizures, peripheral neuropathy + cerebellar damage CVS - class IB antiarrhythmic properties + enhances AV nodal conduction. Hypotension may complicate rapid IV administration of the drug; complete heart block, VF & asystole Metabolic/other -Hyperglycaemia, hypocalcaemia + LFT derangement (suppresses ADH secretion) Haem - megaloblastic anaemia (folate deficiency with chronic use)

Answer 65

**Drug interactions** - Increase phenytoin toxicity: metronidazole + isoniazid - Reduces effect of benzodiazepines, pethidine + warfarin. May also decrease the MAC of volatiles - May enhance CNS toxicity of Las **Therapeutic drug monitoring** Limited correlation b/w therapeutic efficacy and plasma conc but may be useful to confirm toxicity or compliance

Answer 66

1. Single agent (or adjuvant) for seizures (myoclonic, partial, generalised epilepsy) - 250mg BD, then increase to 500mg in 2/52 (titrate to max 1.5g BD) - Loading dose in status 60mg/kg (to max 4.5g)

Answer 67

Not well understood - interact with SV2A (synaptic vesicle protein) to decrease release of neurotransmitters Peak effect ~ 5-30min IV

Answer 68

**CNS:** Sedation, anticonvulsant **Adverse effects:** - Ataxia, fatigue, dizziness, somnolence - Psychiatric disturbances - aggression, paranoid **Other:** - Does not interact with CytP450 - Dose reduce in renal failure

Answer 69

1. Primary generalised seizures - Initially 600mg daily in 2 doses. Maintenance 20-30mg/kg in 2 doses(max 2.5g daily) 2. Chronic pain of non-malignant origin - 200-400mg BD for migraine prevention 3. Bipolar disorder. Dosing similar to epilepsy

Answer 70

Inhibits GABA transaminase + succinate semialdehyde dehydrogenase (enzyme that metabolise GABA) Blocks voltage-gated ion (Na+, K+ & Ca2+) channels

Answer 71

**CNS:** anticonvulsant, minimal sedation **Metabolic:** infrequently, hyperammonaemia **Toxicity:** liver dysfunction, decreased GCS, thrombocytopaenia, coagulation dysfunction **Adverse effects:** weight gain, oedema, coagulation dysfunction, hepatic impairment, pancreatitis

Answer 72

Partial and generalised seizures - initial 25mg --> 100-200mg/day

Answer 73

Inhibits voltage gated Na+ channel & reduce release of glutamate

Answer 74

**CNS:** Anticonvulsant **Adverse:** Headache, nausea, diplopia & tremor, rarely aseptic meningitis, HLH, SJS

Answer 75

1. Epilepsy - PO 60-240mg daily nocte 2. Status epilepticus - 10-20mg/kg (max 1g) infused at <60mg/min. Repeat after 6hrs if needed

Answer 76

Enhance the binding of GABA to GABAA receptors. Extends the amount of time the chloride ion channel is open by interacting with GABAA receptor subunits.

Answer 77

CVS: can cause bradycardia,hypotension, syncope CNS: CNS depression, confusion, dizziness, drowsiness GI: constipation, nausea, vomiting Resp: can get apnoea (especially with rapid IV use), hypoventilation, respiratory depression **Other:** Concentration monitoring 10-40mg/L or 24-180micrmol/L Previously used as anaesthetic - but now rare use due to haemodynamics

Answer 78

Class: Sedative/hypnotic Chemistry: Alkylphenol derivative. 2,6-diisopropylphenol

Answer 79

Not well understood. Potentiates inhibitory neurotransmitters (GABA + glycine) - presumably GABA-A agonism

Answer 80

Opaque, white liquid. 1% liquid emulsion (1mg/mL). Excipients include: - soy bean oil, Egg lethicin - NaOH (to adjust pH) - EDTA (disodium edetate), which retards bacterial growth - glycerol Administered IV

Answer 81

1. Induction + maintenance of general anaesthesia 1.5-3mg/kg bolus, followed by 4-12mg/kg/hr - 50% dose increase for children, and dose reduce for elderly 2. Sedation in ventilated ICU patients - 1-3mg/kg/hr (max 4mg/kg/hr) 3. Intractable nausea + vomiting in chemotherapy patients 4. Termination of status epilepticus

Answer 82

A: 98% protein bound in plasma with VD = 4L/kg. Highly lipophilic. pKa ~11 D: Short distribution half life. Has initial effect (alpha phase) before distribution to tissues.

Answer 83

M: There are 2 metabolic pathways - glucuronide metabolite (inactive) by liver - hydroxylated metabolite (quinol) which is sulfated and glucuronidated by cyt P450 Extrahepatic metabolism (40%) Inter-individual variability effects which pathway it is metabolised. E: Metabolites are renally excreted. Quinol metabolite can cause green discolouration of urine + hair. Maximal CSHT ~20min

Answer 84

**CVS:** Bradycardia, decreases cardiac output by 20% (decreases systemic vascular resistance due to production and release of NO & blunts baroreceptor reflex) **CNS:** Causes hypnosis/sedation. Some people may have initial jerking movements (? Imbalance in subcortical inhibitory/excitatory centres), anticonvulsant, decreases CBF, ICP, CMRO2, antiemetic **Resp:** Causes decrease in tidal volume, apnoea, decreased response to hypercarbia + hypoxia, decreases laryngeal reflexes **Other:** Toxicity - propofol infusion syndrome - rhabdo, renal failure, multi-organ failure

Answer 85

Naturally occurring nucleoside Clear, colourless solution 3mg/mL

Answer 86

- Diagnosis and treatment of paroxysmal SVT. Initially 3-6mg IV, followed by 12mg at 1-2min intervals until effect observed

Answer 87

Metabolism - absorbed from plasma into RBCs --> phosphorylated to AMP or deaminated to inosine. T1/2 <10sec

Answer 88

Direct agonist at A1 and A2 receptors. Adenosine activates acetylcholine sensitive K+ current in the atrium and sinus & AV nodes - shortens APD, hyperpolarisation + slowing of normal automaticity **Onset** 10 seconds **Duration** 10-20 seconds

Answer 89

CVS: depression of SA & AV nodal activity; coronary vasodilation - endothelial A2 receptors Resp: increase in depth + rate of respiration. May induce bronchospasm CNS: infusion results in increased CBF **Adverse effects:** Facial flushing, dyspnoea, chest discomfort

Answer 90

Mg2+ 2nd most abundant intra-cellular cation Mg2+ oxide, chloride, sulphate PO & IV IV MgSO4 (50% Mg & inorganic sulphate, 40mmol/100ml), ampoule 10mmol/5ml

Answer 91

Dose: depends on Mg2+ level, 10-20mmol over 20/60 Eclampsia & pre-eclampsia Premature labour Low Mg2+ Ventricular dysrhythmias incl TDP Asthma

Answer 92

**Absorption:** BA: 25-65% **Distribution:** ECF: 1% (0.7-1mmol/L) Bone: 60% ICF: 39% (15-20mmol/L) 30% bound to albumin

Answer 93

**Metabolism** Dissociates into active Mg2+ No metabolism Bound to bone or filtered into kidneys **Elimination:** Renal 90% reabsorbed in TAL LOH

Answer 94

Same role of endogenous Mg2+ Multiple mechanisms * Reduces membrane excitability e.g. muscle & nerve * Reduces NT release cholinergic & adrenergic synapses Ca2+ antagonist -> relax smooth muscle Onset: immediate after IV

Answer 95

- CVS: Direct vasodilator - ¯ SVR, ¯ BP, ¯ cardiac conduction & force of contraction, ¯ HR, ¯ catecholamine release - Resp: Bronchodilator - CNS: ¯ catecholamine from adrenal medulla & adrenergic nerve terminals, CNS depressant, Anti-convulsant, Cerebral vasodilator - GIT: Osmotic laxative -> diarrhoea - GU: Renal vasodilator, Diuretic - O&G: ¯ uterine tone & contractility

Answer 96

N&V, facial flushing, CNS depression, areflexia, respiratory depression. Reverse with Ca2+ Plasma level (mmol/L) Effect <0.7 Arrhythmia 4-6 Nausea, ¯ reflexes, speech impaired 6-10 Muscle weakness, resp depression, ¯ HR >10 Cardiac arrest

Answer 97

**Class**: Anticholinergic **Chemistry**: Racemic mixture of D- and l-hyoscyamine (l- form is active) **Prep/admin**: Clear, colourless solution for injection in 0.5/0.6mg/mL and 3mg in 10mL

Answer 98

- Bradycardia with haemodynamic compromise - 0.5-1mg - repeat 3-5minutely - Counter the muscarinic effects of anticholinergic agents - During CPR - treatment of organophosphate poisoning, tetanus

Answer 99

A: Well absorbed IM D: 50% PB; Vd = 2-4L/kg. Crosses BBB & placenta

Answer 100

M: Hydrolysed in liver and tissues to tropine + tropic acid E: T1/2 = 2.5hrs, excreted in 24hrs in urine

Answer 101

Competitive antagonism of acetylcholine at muscarinic receptors (GPCR) Onset: immediate

Answer 102

CVS: tachycardia, increased CO. Decreases AV nodal conduction time Resp: Bronchodilation, secretions reduced, RR increases CNS: CNS excitation or depression can occur GI: antiemetic, decreases gastric motility Metabolic: reduces sweating, BMR increases, suppresses ADH secretion

Answer 103

Class: sedative/anxiolytic Chemistry: Imidazobenzodiazepine Preparation: Vials 5mg/5ml Administration: IV + IM

Answer 104

- Induction of anaesthesia - 0.15-0.2mg/kg - Sedation in ICU- 0.03-0.2mg/kg/hr - Termination of seizures

Answer 105

A: Poor bioavailability 44% D: 96% protein bound (albumin) with Vd = 0.8-1.5L/kg

Answer 106

M: Extensively hepatic (CYP3A4). Hydroxylated and forms many active metabolites E: Renally excreted as hydroxylated metabolites T1/2 = 2hrs; CSHT 70-80min post 8hr infusion

Answer 107

Targets (between α & γ subunits) GABA-A receptors in CNS -- enhances inhibitory effect of GABA (increased permeability to Cl-) Different receptor subtypes are responsible for the nuances in effects of the different benzos Onset: IV 1-5min; Duration: ~1hr for sedation

Answer 108

- CNS: sedation, hypnosis, anterograde amnesia. CMRO2 & CBF decrease - CVS: decrease in SVR, decrease in BP with compensatory increase in HR - Resp: Can cause apnoea, impairs ventilatory response to hypercapnoea

Answer 109

- Iodinated benzofuran derivative (Class 3 antiarrhythmic) - PO tablets 100mg or 200mg; IV 30 or 50mg/ml amiodarone hydrochloride

Answer 110

- tachydysrhythmias resistant to other treatment + related to WPW syndrome Initial loading dose 5mg/kg in 250mL 5% dextrose. Maintenance 15mg/kg/day. PO dose initially 200mg TDS, which is reduced to 100-200mg daily after 1/52 - cardiac arrest: shockable rhythm. 300mg IV every 3 cycles

Answer 111

- Absorption: bioavailability of 22-86% (Smith) or 35-65% (Katzung) - Distribution: 96-98% protein-bound in plasma; VD is 1.3-65.8L/kg, according to dose

Answer 112

- Metabolism: largely in liver, to desethyl-amiodarone (has anti-arrhythmic properties and is cumulative) - Excretion: 1-5% in urine, mostly in bile + faeces T1/2 variable - up to 60days

Answer 113

prolongs cardiac action potential & delays refractory period. - partial antagonism of alpha- and beta- agonists by reducing number of receptors or by inhibiting the coupling of receptors to the regulatory subunit of the adenylate cyclase system - Delays K+ efflux, depresses Na+ influx & depresses Ca2+ influx - Onset: within 1hr IV, PO 2-3days-weeks - Duration after discontinuation can be weeks to months. Half-life (elimination half-life has slow (3-10days) and rapid (weeks) components)

Answer 114

CVS - marked prolongation of the action potential duration (and QT interval on the ECG) by blockade of intracellular K. ○ Sinus rhythm is slowed secondary to reduction in the slow diastolic depolarisation in nodal cells. Automaticity is depressed and AV nodal conduction is slowed by 25% - Other: Contraindicated in porphyria

Answer 115

○ Hypotension - Vasodilation w ↓ SVR (due to polysorbate 80) ○ ↓ CO - Decreased cardiac contractility ○ May get bradycardia/complete HB resistant to atropine, Ad & NAd

Answer 116

○ Pulmonary fibrosis § Tends to occur during chronic therapy § May be rapidly progressive and fatal § Risk factors: underlying lung disease, high doses, recent pulmonary insults (e.g. pneumonia) § Rx: Withdrawal of drug; high dose glucocorticoids [MIMS]

Answer 117

○ Peripheral: - Peripheral neuropathy [MIMS] □ Typically exposure-dependent (long term; high dosage) □ Sensory > motor neuropathy (glove and stocking paraesthesia; disequilibrium) □ Incomplete resolution on drug withdrawal ○ Central effects: § Tremor § Dizziness § Vertigo **Ocular:** ○ Corneal microdeposits (almost ubiquitous, but usually asymptomatic) [Katzung, Goodman and Gilman’s] § Occasional visual changes (e.g. halos in peripheral visual fields) [Katzung, Goodman and Gilman’s] ○ Optic neuritis w blindness [Katzung, Goodman and Gilman’s]

Answer 118

* Musculoskeletal system: ○ Proximal myopathy [MIMS] * Cutaneous: ○ Photodermatitis (photosensitivity) [Katzung] ○ Grey-blue discolouration in sun-exposed areas [Katzung] * Thrombophlebitis

Answer 119

* Endocrine effects: ○ Blocks peripheral de-iodination of T4 to T3 [Katzung] ○ Hyperthyroidism ○ Hypothyroidism (Wolf-Chaikoff effect) ○ Amiodarone-induced thyroiditis (types 1 and 2)

Answer 120

* Pharmacokinetic interactions: § Enzyme inhibition: □ CYP3A4 □ CYP2C9 § Efflux pump inhibition (PGP): * Pharmacodynamic interactions: § Negative chronotropes/dromotropes: risk of bradyarrhythmias § Synergistic QTc prolongation with other agents

Answer 121

○ Nausea and vomiting ○ Hepatic: ○ Drug-induced liver injury § Δ AST, ALT, ALP § Rarely, acute liver failure ○ Hypersensitivity hepatitis [Katzung]

Answer 122

HTN, angina 2.5-5mg daily (max 10mg daily)

Answer 123

Class IV antiarrhythmic Non-dihydropyridine/phenylalkylamine

Answer 124

240-480mg BD-TDS; - Hypertension - Angina - pSVT, AF, flutter - 2.5-10mg IV

Answer 125

Competitive blockade of slow Ca2+ channels, leading to decrease Ca2+ influx into vascular smooth muscle and myocardium Onset: PO 10-20min; IV 3-5min Duration: PO 6-8hrs; IV 0.5-6hrs

Answer 126

CVS: decreases automaticity and conduction velocity, increases refractory period. Decreases SVR, potent coronary artery vasodilator CNS: cerebral vasodilation **Adverse effects** Dizziness, flushing, nausea, first or second degree heart block **Other** Avoid co-administration with dantrolene

Answer 127

Ca2+ channel blocker - dihydropyridine

Answer 128

IV infusion and tablets (30mg) **D/I** - Prevention of cerebral vasospasm secondary to subarachnoid haemorrhage - Dose: 60mg Q4H; IV 1mg/hr for first 2hrs -->2mg/hr 5-14 days - Migraine - Drug-resistant epilepsy

Answer 129

CNS: headache, cerebral vasodilation, increased CBF CVS: hypotension, bradycardia GI: nausea

Answer 130

**Absorption** Rapidly and well absorbed, significant FPM - BA low (30%) **Distribution** Highly protein bound, large Vd (1-2L/kg)

Answer 131

**Metabolism** Liver **Excretion** Urine t1/2 up to 6hrs

Answer 132

Modulates opening of Ca2+ channels on vascular smooth muscle (?preferential action on cerebral vasculature) --> prevents Ca2+ influx --> vasodilation

Answer 133

B-blocker/antiarrhythmic

Answer 134

Usually ~80mg BD initially - AF, maintenance of sinus rhythm - SVT Ventricular arrhythmias

Answer 135

Non-selective B-blocker - prolongation of atrial action potentials. K+ channel blocker - prolongs phase 3 of ventricular AP Onset: 1-2hrs PO

Answer 136

CVS: slows heart rate, decreases AV nodal conduction, increased AV nodal refractoriness, prolongation of atrial and ventricular action potentials **Adverse effects** Bradycardia, chest pain, palpitations, dizziness, fatigue, headache, dyspnoea

Answer 137

Cardiac glycoside. Contains steroid nucleus

Answer 138

Doses - loading dose 250-500microg every 4-6hours to effect (max daily dose 1.5mg). Then maintenance at 125-250microg daily Indication - use in AF + Flutter, heart failure, prevention of supraventricular dysrhythmias post thoracotomy

Answer 139

- Direct action - binds to & inhibits Na+/K+ ATPase in sarcolemma cell membrane--> ↑ intracellular Na+ & ↓ intracellular K+. ↑Na/Ca exchange via INCX - ↑ intracellular Ca-->ionotropy. Decreased K+ leads to slowed AV conduction & ↓ pacemaker cell action - Indirectly modifies autonomic activity & ↑ efferent vagal activity **Onset:** PO 1-2hrs; IV 5-60min **Duration of action:** 3-4 days; Half life: 36-48hrs

Answer 140

- CVS - ↑ ionotropy. ↓ HR (depression of SA node discharge, AV node conduction), ↑ AV nodal refractory period & indirect vagal effect. Rapid IV administration may cause vasoconstriction, leading to HTN & ↓ CBF. ECG changes - prolonged PR, ST depression, T wave flattening & shortened QT ○ (toxicity) - any dysrhythmia - esp junctional brady, ventricular bigemini, 2nd/3rd degree HB. Reverse tick on ECG - Renal - mild intrinsic diuretic effect - GI - (toxicity): anorexia, nausea, vomiting, diarrhoea, abdo pain Neuro - (toxicity): headache, drowsiness, confusion, visual disturbances, muscular weakness, coma

Answer 141

Toxicity - Therapeutic range is 0.6-1.0nmol/L (=0.25 ng/mL) digoxin-specific antibody fragments can treat toxicity. They form complexes with dig molecules then are excreted in urine. ○ Indications for treatment: life-threatening arrhythmia, cardiac arrest, K>5.0 ○ Consider treatment when: end organ dysfunction, mod-severe GI symptoms, serum dig >12ng/mL (25nmol/L), significant features of dig toxicity with serum dig > 4nmol/L ○ Formulation - 40mg reconstituted in 4mL. Response in ~20min (0-60) **Other specifics** ○ Increased risk of dysrhythmias with concurrent sux/pancuronium or B-agonists ○ Increased likelihood of toxicity with: low K, Hyper Na, Hyper Ca, Low Mg, acid-base disturbance, hypoxaemia and renal failure ○ Increased plasma dig levels with coadmin of verapamil, nifedipine, amiodarone, diazepam ○ Cannot be removed by dialysis

Answer 142

B-blocker/ antihypertensive Racemic mixture of 4 stereoisomers

Answer 143

Dose: 100-800mg PO BD; 5-20mg bolus IV or titratable infusion 20-160mg/hr - Hypertensive emergencies - All grades of hypertension

Answer 144

A: Rapidly absorbed but extensive FPM. BA 10-90% D: 50% PB; Vd up to 15L/kg

Answer 145

M: Metabolized by the liver via CYP3A4 and CYP2D6 – inactive compounds E: Elimination half-life of 5-8 hours. Excreted in the urine and feces.

Answer 146

Non selective B-blocker with α1 blockade. Has some intrinsic sympathomimetic activity. Alpha:beta 1:3 PO or 1:7 IV Onset: IV – 5-30min Duration: IV – 50min

Answer 147

CVS: beta-1 & beta-2 blockade in cardiac tissue à decreased HR & contractility Alpha-1 block à vasodilation à 20% decrease BP Decreases HR + CO by ~10% Renal: decreased renal VC à increased RBF à GFR unchanged

Answer 148

- Hypertension - PO initial 12.5mg daily --> 25mg (max 50mg) Chronic heart failure with reduced ejection fraction - initial 3.125mg BD to max 25mg BD

Answer 149

Non selective B-blocker with α1 blockade, No ISA. Onset: 30-60min Duration: Long (t1/2 = 7-10hrs)

Answer 150

CVS: ↓CO, ↓HR, ↓ reflex orthostatic tachycardia, vasodilation, ↓PVR, ↑ANP Renal: ↓renal VC, ↓ plasma renin

Answer 151

**Class/chemistry** Sodium channel blocker Tertiary amine pKa 7.9, ionisation 25% **Administration/preparation** - Multiple routes - IV, S/c, IT, epidural, topical - 1-2% IV solution for injection, topical gel - Combined formulations with adrenaline

Answer 152

- Local anaesthetic (3mg/kg to max 200mg) - Class Ib antiarrhythmic - Rx for ventricular tachydysrhythmias - IV bolus 1mg/kg over 2 min, Inf 20-50mic/kg/min

Answer 153

**Absorption** Absorption of LAs related to site of injection, dose, VCs (delay absorption) **Distribution** ~ 70% PB (alpha-1 glycoprotein); VD = ~1L/kg

Answer 154

**Metabolism** Liver with multiple metabolites. Some lower seizure threshold, some with antiarrhythmic properties **Elimination** Half life ~100min <10% in urine

Answer 155

Diffuse into cells in unionised form, combine with H+ --> enters internal opening of Na+ channel and combines with receptor --> decreases Na+ conductance --> prevents depolarisation of cell membrane Acts on Nav1.5 subunit of fast voltage gated Na channels Onset: 1-5min local infiltration; rapid IV Duration: ~1-2hrs local (increased with adrenaline); 10-20min IV

Answer 156

CVS: decreases rate of rise of phase 0 of ventricular AP, slows AP propagation + reduces automaticity. In toxicity, it decreases PVR & contractility --> hypotension + CV collapse Resp: Bronchodilation. Resp depression in toxicity CNS: biphasic effect - excitation then depression **Other** Not removed by dialysis

Answer 157

**Class/chemistry** Antiarrhythmic Class 1c **Dose/indication:** PO 50-100mg BD (max 400mg daily) IV 2mg/kg (max 150mg) - SVT - Suppression of irritable foci eg. ventricular tachycardia + ectopics - In treatment of re-entry dysrhythmias eg WPW - In treatment of pAF

Answer 158

Sodium channel blocker. Reduces maximum rate of depolarisation --> slows conduction. Has greatest effect on His-Purkinje system + ventricular myocardium

Answer 159

CVS: markedly slows phase 0 of action potential, but decreases ERP - may be proarrhythmogenic. Increases QRS duration, PR prolongation CNS: may have visual disturbances **Adverse effects** May exacerbate heart failure, ventricular dysrrhythmias, increases non-fatal cardiac arrest

Answer 160

Class: Organic nitrate Chemistry: Ester of nitric acid

Answer 161

- Stable, unstable, variant angina Dose: 0.3mg s/l; 0.4-0.8mg s/l buccal spray; 5-10mg/24 transdermal; - LV failure secondary to MI - Perioperative control of BP Start 5-10mic/min. Increase up to 200microg/min IV infusion (sometimes up to 400mic/min)

Answer 162

**Absorption:** Rapid + efficient s/l (40%). POBA 3% **Distribution:** PB 60% Vd ~2L/kg

Answer 163

**Metabolism:** by liver + RBCs to mono- & di-nitrates + nitrites - all have lower activity than parent **Excretion:** 80% urine. T1/2 1-3min

Answer 164

Metabolised to NO --> stimulates guanylate cyclase in vascular smooth muscle --> increased cGMP--> phosphorylation cascade--> relaxation **Onset:** 1-3min s/l or ~100s IV **Duration:**15-30min s/l or 3-5min IV

Answer 165

**CVS:** at low doses, venodilation --> veno + arterial at higher doses. Decreases afterload, decreases myocardial O2 demand, increases myocardial oxygen supply. Reflex tachycardia in normal individuals **CNS:** ICP may increase due to cerebral vasodilation **Other:** 40-80% of IV GTN adsorbed onto plastic giving-sets (needs non-PVC)

Answer 166

Class: Inorganic nitrate Chemistry: Central Fe atom with 5 cyanide groups + 1x NO

Answer 167

Absorption: - Distribution: Vd up to 0.2L/kg (EC space)

Answer 168

IV infusion 0.5-6microg/kg/min - Hypertensive crisis - Aortic dissection prior to surgery - LV failure

Answer 169

**Metabolism:** * Rapid non-enzymatic hydrolysis in RBCs --> 5x cyanide ions per molecule of SNP * --> 1x cyanide reacts with methaemoglobin --> cyanomethaemoglobin * --> 4x cyanides enter plasma --> 80% react with thiosulfate --> thiocyanate (catalysed by hepatic rhodanese). Remainder of cyanide reacts with hydroxycobalamin to form cyanocobalamin **Excretion:** Metabolites excreted unchanged in urine. T1/2 2 min (thiocyanate 2 days)

Answer 170

Interacts with sulfhydryl groups on smooth muscle membrane --> releases NO --> vasodilation **Onset:** 1-2min **Duration:** 3-7min IV

Answer 171

**CVS:** decreases SBP, CO well maintained. Decrease Myocardial O2 consumption. Causes both veno - and arterio dilation **Resp:** attenuates HPV in lungs **CNS:** cerebral vasodilation, increased ICP. Shifts autoregulation to left **Other** Can be removed by haemodialysis Needs to be protected from light Can get cyanide toxicity

Answer 172

Antihypertensive Pthalazine derivative

Answer 173

- acute severe hypertension - Pre-eclampsia IV 5-10mg, administered slowly. May repeat 20-30min later. IVI initially 200-300microg/min, maintenance 50-150microg/min - chronic moderate to severe hypertension - PO 50-200mg daily in divided doses

Answer 174

Activates ATP sensitive K+ channels --> inhibits opening of voltage gated Ca channels by hyperpolarising membrane --> electromechanical decoupling + inhibition of contraction **Onset:** 5-20min when given IV **Duration:** 2-6hrs

Answer 175

**CVS:** predominately arteriolar vasodilation --> decreases SVR. Compensatory tachycardia **CNS:** CBF increases **Metabolic:** increases plasma renin **Other:** Additive hypotensive effects with volatiles

Answer 176

Antihypertensive Aniline derivative

Answer 177

0.05-0.6mg PO (max 900microg/day), IV 0.15-0.3mg - Hypertension - Migraine - Chronic pain, opiate and alcohol withdrawal - premedication in anaesthesia

Answer 178

Stimulates alpha 2 (200:1 ratio alpha 2:alpha1 affinity) receptors (pre-synaptic) --> decreases NAd release --> decreased sympathetic tone. GiPCR--> decrease cAMP --> dec Ca2+ influx & Ca-mediated NAd release Analgesic effect - activation of alpha 2 R in dorsal horn of spinal cord (inhibits neurotransmission) **Onset:** Within 5min IV **Duration:** 3-7hrs when given IV

Answer 179

CVS: transient increase in BP (stimulation of alpha1), then sustained decrease. SVR decreased with long term treatment CNS: Decreases cerebral blood flow + IOP. Depressant effect on spontaneous sympathetic outflow & afferent A delta- & C-fibre mediated somatosympathetic reflexes Sedation Analgesia

Answer 180

0.5mg -1mg BD or TDS initially. Maintenance 3-20mg in divided doses - Hypertension - CCF - Raynauds (1-2mg BD) - BPH

Answer 181

Inhibits post synaptic alpha1 receptors --> GqPCR --> inhibits PLC --> decreased IP3 + DAG --> decreased intracellular {Ca2+] **Onset:** 30-90minutes **Duration:** 10-24hrs

Answer 182

CVS: decrease in SVR without reflex tachycardia Genitourinary: Improvement in urinary flow Adverse: orthostatic hypotension, rarely tachycardia

Answer 183

Synthetic sympathomimetic amine

Answer 184

hypotension, nasal decongestant, mydriatic agent. 50-100microg bolus doses

Answer 185

Direct acting selective alpha-1-adrenoceptor agonist (nil B-effects) Duration of action 15-20min IV; onset immediate

Answer 186

- CVS - rapid increase in SBP + DBP, SVR. Reflex brady - may reduce CO - CNS - mydriasis - Renal - RBF decreased

Answer 187

(Argipressin is synthetic compound which is identical to endogenous human vasopressin) **Class/chemistry:** - Naturally occurring nonapeptide prohormone produced in posterior hypothalamus **Preparation/Administration:** Available in 3 synthetic analogues: (all clear, colourless liquids) - Argipressin in 20IU/mL (SC/IV or IM) - draw up into 20U/20mL - terlipressin - desmopressin in oral, IV, IN | (Note - analogues L2)

Answer 188

- Management of catecholamine-refractory shock: Argipression is 0.6-2.4IU/hr - Cranial diabetes insipidus & Management of polyuria/polydipsia post hypophysectomy: 100mic TDS desmopressin, adjusted to response - Bleeding oesophageal varices: terli: 0.5mg/hr for 48/24 - Perioperative/trauma management of people with haemophilia and VW disease

Answer 189

Absorption: desmopressin - 0.08-0.16% of dose is absorbed via PO route; 10% via IN route Distribution: Argi: Vd = 0.14L/kg, not protein bound. Largest is terlipressin: 0.5l/kg

Answer 190

Metabolism: Endogenous vasopressin metabolised by vasopressinases (endothelial peptidases). Argi = 35% metabolised, desmo - minimal, terli - completely metabolised Excretion: Endogenous vaso has a half life of 10-35 minutes; argi is shorter (10-20), terli is longer (50-70), desmo is 2-3hrs. 65% of argi and desmo is unchanged in urine

Answer 191

Act on GPCR vasopressin receptor - V1 = GqPCR - act via PLC --> IP3 + DAG --> increase IC Ca - V2 = GsPCR - activated AC --> cAMP --> increase IC Ca Onset 1-2min Duration up to 20min

Answer 192

- CVS: V1 receptors in smooth muscle - activation causes vasoconstriction (via increased intracellular calcium) - increases MAP + SVR. At very low doses, causes vasodilation of pulmonary artery - GU: reduction in urine output and resolution of polydipsia in DI (V2 in DCT + CDs), activation leads to aquaporin-2 trafficking from intracellular vesicle membranes within renal epithelial cells into apical cell membrane --> water resorption - Endo: release of ACTH from pituitary

Answer 193

* Class: Ionotrope * Chemistry: Bypyridine molecule * Preparation/Administration: Clear, colourless solution for injection in 10-20mL glass ampoules (1mg/mL)

Answer 194

* Severe treatment-resistance congestive cardiac failure * Low cardiac output states following cardiac surgery (loading dose 50mic/kg over 10min; infusion between 0.375-0.75mic/kg/min titrated to response)

Answer 195

* Absorption: - * Distribution: Vd = 0.3-0.4L/kg; 70-80% protein bound

Answer 196

* Metabolism: 12% glucuronidated in liver; Mostly cleared renally - unchanged * Excretion: Mostly cleared renally - unchanged; half life 2.3hrs in patients with heart failure, longer in renal dysfunction

Answer 197

* Mechanism of action: Selective inhibition of type III cAMP PDE in cardiac + vascular muscle (PDE responsible for cAMP catabolism) --> increased intracellular Ca --> increased contractility in cardiac; decreased vascular contraction

Answer 198

* CVS: positive ionotropic effect --> CI increases by 25-30%, decreased SVR + MAP. May increase AV nodal conductance (may lead to increase in ventricular response in pts with atrial flutter or AF) * Renal: u/o + GFR may increase due to increased CO **Other** - Decrease infusion rate in renal failure

Answer 199

- Indications: Hypertension, HFrEF, Post MI, diabetic nephropathy - Examples: - Captopril (dose range 6.25mg-max 150mg/24hrs. Usually 12.5mg BD for HTN), - perindopril (2.5mg arginine = 2mg erbumine. Usually 4-5mg (max 8-10mg daily)), - ramipril dosing same as perindopril arginine

Answer 200

ACEIs: Blocks ACE which catalyses conversion of angiotensin I--> angiotensin II ARBs: Block AT1 receptor (10000-fold more selective for AT1 than AT2). Inhibits biological effects of AngII, similar to ACEIs

Answer 201

Organ effects: - CVS: ↓vasoconstriction & ↓hypertrophic remodelling (less ATII) & ↑ bradykinin levels (decrease breakdown) --> stimulates PGs --> vasodilation - Renal: ↑ natriuresis Adverse effects: - Hypotension, - cough (accumulation of lung bradykinin), - hyperkalaemia (in pts taking K+ sparing diuretics) - Note: ARBs: ARF, less cough Contraindicated in pregnancy (teratogenesis, fetal hypotension, anuria, renal failure)

Answer 202

Hypertension, some ACEs approved for diabetic nephropathy, valsartan for HF Dose: - Irbesartan (150mg daily - max 300mg) - candesartan (4mg daily to max 32mg) - telmisartan (40mg - max80mg)

Answer 203

- Class/chemistry: Propanedinitrile derivative - Preparation/administration: Clear, yellow or orange solution for injection – 2.5mg/mL in 5 & 1-mL ampoules

Answer 204

Severe decompensated heart failure unresponsive to other therapies. Cardiogenic shock post cardiac surgery in pts with EF <40% Infusion at 0.05-0.2microg/kg/min. Used for ~24/24

Answer 205

- MoA: Increases calcium sensitivity by binding to myocardial troponin C, leading to stabilisation and increased duration of calcium binding. This results in increased myocardial contractility without impairment of myocardial relaxation or increased oxygen demand. Also stimulates ATP-sensitive K+ channels leading to vasodilation

Answer 206

--- CVS – Increases myocardial contractility via increased calcium sensitivity without increased myocardial oxygen demand. Also causes coronary and peripheral vasodilation. Hypotension

Answer 207

- Class/chemistry: Synthetic isoprenaline derivative - Preparation/administration: 12.5mg or 50mg/mL of dobutamine (diluted prior to infusion)

Answer 208

For low cardiac output states eg: acute heart failure & cardiogenic shock. Dose: 2.5-20mic/kg/min (~100-3000mic/min)

Answer 209

Predominately selective β-1 agonist, weak β2 agonist. Acts directly on catecholamine receptors to activate adenylate cyclase, which catalyses the conversion of of ATP to cAMP

Answer 210

--- CVS – activate cardiac β-1-adrenoceptors. SA automaticity increased and AV nodal conduction velocity also increased. Also has activity at α- and β2-adrenoceptors. It decreases LVEDP and SVR --- CNS – stimulation occurs at high dose ranges. Fatigue/nervousness/headache **Other** Should not be used in people with cardiac outflow obstruction. Tachyphylaxis can occur during prolonged infusion

Answer 211

Synthetic sympathomimetic amine

Answer 212

Adjunct in treatment of hypotension. 0.5-2mg bolus dose. Infusion 0.5-10mg/hr

Answer 213

Absorption: - Distribution: Does not cross BBB. Vd = 4L/kg; 45% PB. Distributes into catecholamine storage vesicle - persists for days

Answer 214

Metabolism: Not metabolised Excretion: Eliminated slowly over hrs/days - distribution t1/2 rapid. Half life - minutes

Answer 215

Direct and indirect acting sympathomimetic. Agonist effect at alpha-1 adrenoceptor, but also some beta-adrenoceptor activity. Causes noradrenaline release from intracytoplasmic stores, in addition to causing adrenaline release Duration of action - 20-60min; onset 1-2min

Answer 216

- CVS - Sustained increase in systolic and diastolic blood pressures due to increase in systemic vascular resistance. Reflex bradycardia. Indirect increase in coronary artery flow - CNS - cerebral blood flow decreased - Renal - renal blood flow decreased **Other:** - Excessive hypertension may occur when administered in patients with hyperthyroidism or those receiving MAOIs

Answer 217

Synthetic catecholamine

Answer 218

Complete heart block, bradycardia with haemodynamic compromise 0.5-10mic/min1

Answer 219

Non-selective Beta-adrenergic agonist. Its actions are mediated by membrane-bound adenylate cyclase and subsequent formation of cAMP Onset: immediate DoA: 10-15min

Answer 220

- CVS - Positive ionotrope + chronotrope --> increased CO; decreased, PVR (B2 effect) & DBP * Side effects = tachycardia, hypotension, arrhythmias, angina - Resp - Potent bronchodilator - CNS - CNS stimulant **Other** - Tachyphylaxis may occur with prolonged use

Answer 221

Naturally occurring catecholamine

Answer 222

Low cardiac output states, especially post cardiac surgery. Initial 2-10mic/kg/min; maintenance up to 50mic/kg/min

Answer 223

Stimulates adrenergic and dopaminergic receptors. Lower doses mainly dopaminergic stimulating (renal + mesenteric vasodilation), higher doses both dopaminergic & β1 stimulating, large doses stimulate α-adrenergic receptors Onset: 5 min Duration: <10min

Answer 224

- CVS - Dose dependent - increased ionotropy, CO, coronary BF (beta effects); increased vasoconstriction, SBP (alpha effects) - Resp - may decrease ventilatory response to hypoxia - CNS - Nausea (direct stimulation of CTZ). Does not cross BBB - Renal - in low doses, marked reduction in renal vascular resistance --> increases flow. Diuresis via D1 receptors at luminal and basal membranes of PCT **Other** - Reduce dose in people who have taken recent MAOIs

Answer 225

* Class/chemistry: Catecholamine/Endogenous sympathomimetic * Preparation/administration: Clear, colourless solution in 0.1mg/ml or 1mg/ml - can be administered IV/subcut; 1% ophthalmic solution; aerosol (280mic/MD)

Answer 226

* Indication/Dose: -- Anaphylaxis - 0.1-0.5mg subcut -- Cardiac arrest - 1mg IV; -- Low CO states: 0.01-0.1mic/kg/min as infusion in shock -- Glaucoma -- Local vasoconstrictor (added to LA solutions to prolong duration)

Answer 227

* Absorption - inactivated with oral administration; slower subcut vs IM. Well absorbed from tracheal mucosa.pKa 9.7 * Distribution - Vd = 0.1-0.2L/kg; 12 % protein bound

Answer 228

* Metabolism - Metabolised rapidly by COMT (liver)--> metadrenaline + noradrenaline; MAO (neurons); final common products (normetadrenaline + VMA) are inactive. * Excretion - urine; half life ¬2min

Answer 229

* Mechanism of action - directly acting sympathomimetic amine. Agonist of α + β adrenoceptors, with ¬equal activity at both. At α1 - results in release of IP3 --> vasoconstriction. β1 + 2 -->cAMP Onset: immediate Duration: 1-5min

Answer 230

* Effects +/- side effects -- CVS - Positive ionotrope + chronotrope. Increases cardiac output, myocardial O2 consumption, coronary blood flow. May result in tachycardia, dysrhythmias, ischaemia -- Resp - mild resp stimulant (increases both tidal volume and respiratory rate). Potent bronchodilator but tends to increase the viscosity of bronchial secretion -- CNS - Increases cutaneous pain threshold and enhances neuromusclar transmission. Little overall effect on CBF. Cerebral haemorrhage may result -- Renal - decreases renal blood flow by up to 40%, but filtration rate remains mostly the same. Inhibits contraction of pregnant uterus -- Metabolic/other - elevated BSL (increases glucagon secretion, stimulates gluconeogenesis, decreases insulin secretion. Plasma renin increased (B1 effect), plasma conc of FFAs increase (activates triglyceride lipase). Increases BMR by 20-30% * Special points: -- Dose decrease with volatile anaesthetics (risk of ventricular dysrhythmias - mainly halothane, enflurane + isoflurane)

Answer 231

Naturally occurring sympathomimetic amine

Answer 232

* Indication/Dose: -- Hypotension occurring in general, spinal or epidural anaesthesia - 3-7.5mg (max 9mg), repeated every 3-4 min to a max of 30mg, titrated to response -- Nasal decongestant -- Other: Nocturnal enuresis, narocolepsy, diabetic autonomic neuropathy, hiccups

Answer 233

* Absorption - rapidly and completely absorbed via all routes * Distribution - rapidly and extensively absorbed. Vd = ~4L/kg. Crosses placenta & excreted to breast milk

Answer 234

* Metabolism - resistant to MAO + COMT metabolism. Small amount metabolised to norephedrine (may produce central stimulant effect) in liver * Excretion - 55-99% excreted unchanged in urine. Half life 6hrs

Answer 235

* Mechanism of action - acts both indirectly (causes release of NA from sympathetic nerve terminals) and directly by stimulating α & β-adrenoceptors Onset: rapid Duration: 1hr

Answer 236

* Effects +/- side effects -- CVS - Similar to adrenaline but more prolonged - positive ionotrope + chronotrope--> increases cardiac output, myocardial work and myocardial oxygen consumption -- Resp - resp stimulant + marked bronchodilation -- CNS - stimulatory effect similar to amphetamine. Increases CBF -- Renal - constricts renal blood vessels - decreases renal blood flow & GFR -- Metabolic - stimulates glycogenolysis, may increase BMR, thermogenesis **Special points:** -- Tachyphylaxis occurs with prolonged use. Dysrhythmias with halothane -- Clonidine premedication enhances pressor effects of ephedrine

Answer 237

Class/chemistry: Catecholamine/endogenous sympathomimetic Preparation/Administration: Clear, colourless liquid containing 2mg/ml. Administered via CVC in 40mic/ml conc infusion

Answer 238

Dose: titrated to effect. Usually 0.1-0.4ug/kg/min Indication: refractory hypotension

Answer 239

Absorption: Undergoes significant first pass metabolism and is inactive when administered orally Distribution: VD 0.1-0.4L/kg; 25% protein bound

Answer 240

Metabolism: Endogenous NA is metabolised via 2 pathways: - oxidative deamination to aldehyde by mitochondrial MAO (in liver, brain, kidney) and - methylation by cytoplasmic catechol-O-methyl transferase(COMT) to normetanephrine. Predominant metabolite is VMA Excretion: half-life is ~2minutes, 5% of dose excreted unchanged

Answer 241

Mechanism of action: non-selective sympathomimetic - acts on α & β adrenoceptors. Effect of action depends on distribution of these receptors throughout the body. It is generally a poor β2 agonist. Adrenoceptors are G-protein coupled receptors (GPCR) and binding causes a chain of downstream effects - Onset: immediate - Duration of action: 5-10minutes; tachyphylaxis with prolonged administration

Answer 242

Adverse effects: (inc toxicity) Link above to organ systems: - CNS - not much change to cerebral blood flow (mildly reduced) + reduction in O2 consumption. ○ Toxicity/Adverse effects: Anxiety, headache, photophobia - CVS - positive ionotrope - works on the β1 receptor in heart to increase contractility, however does not increase HR like adrenaline (reflex vagal stimulation leads to compensatory bradycardia). CO remains the same or decreases slightly ○ Vasopressor effect - α agonist causing vasoconstriction and raised peripheral vascular resistance, causing rise in SBP + DBP ○ Coronary vasodilation (unclear how/why - possibly β2 stimulation mediated, although NA usually poor β2 agonist) ○ Adverse: chest pain - Resp - increased minute volume, very slight bronchodilation - GU - increases contractility of uterus (may induce fetal bradycardia + asphyxia), increases tone of bladder neck, reduces renal blood flow (GFR well maintained) - Skin: significant cutaneous vasoconstriction. Adverse: pallor; Toxicity: Gangrene. Extravasation - sloughing + tissue necrosis *And others:* - Serious cardiac dysrhythmias during halothane anaesthetics - Co-administration with MAOIs or tricyclic antidepressants can precipitate serious hypertensive episodes

Answer 243

* Class/chemistry: Opioid analgesic. Semi-synthetic phenanthrene. pKa 8.5 * Preparation: Clear colourless solution containing 300mic/mL, 200/400microg tablets and various strengths of transdermal patches

Answer 244

Mod-severe pain - 0.3-0.6mg Q6-8hrly IV or 0.2-0.4mg s/l

Answer 245

Extensive FPM --> given s/l (44-94%). 40-90% IM High PB & Vd (96% PB. VD = 3L/kg) Met to Norbuprenorphine in liver (active) Excretion: Predominantly via faeces unchanged Elimination t1/2 - 5hrs

Answer 246

* MoA: Partial agonist at MOP. Affinity for KOP (but low intrinsic activity here). Dissociates slowly from receptor - reason for prolonged analgesic effect. * Onset: <15min S/l, <30min t/d; Peak 60-90min, hrs t/d; Duration: up to 72hrs s/l or 96hrs t/d

Answer 247

* CVS: HR, SBP decrease * Resp: respiratory depressant + antitussive * CNS: 25x more potent than morphine. Decreases cerebral glucose metabolism by 30% **Other:** Naloxone does not completely reverse respiratory depression, but doxapram will. Partial agonism precipitates abstinence syndromes in opioid-dependent subjects

Answer 248

Class/chemistry: Anticonvulsant, analgesic. Acetic acid derivative that is structurally related to GABA Preparation: PO formulations

Answer 249

Can be titrated on initiation * post-herpetic neuralgia * painful diabetic neuropathy * partial seizures with or without secondary generalisation * neuropathic pain - dose up to 1800mg/day

Answer 250

Well absorbed, BA 60%, Medium VD (0.8L/kg), Not metabolised, Excreted unchanged in urine. Half life 5-7hrs

Answer 251

* Binds α2δ subunit of voltage gated Ca+ channels --> Disrupts regulatory functions of α2δ - dec Ca2+ channel delivery to cell membrane & dec activation of channels * This decreases NT release. * May also reduce NMDA response to glutamate, reduce MAO release, stimulate enzyme conversion of glutamate to GABA & increase synaptic release of GABA

Answer 252

* CNS: analgesic + anticonvulsant properties. May have dizziness, nausea, nystagmus, tremor, somnolence

Answer 253

* Class/chemistry: Anticonvulsant, analgesic, anxiolytic. GABA analogue * Preparation: PO formulations

Answer 254

Initial 150mg/day * peripheral and central neuropathic pain * partial seizures * GAD

Answer 255

Rapidly absorbed, BA >90%, medium VD (0.5L/kg), minimal metabolism, 98% of dose excreted unchanged. Half life 6hrs

Answer 256

* Binds α2δ subunit of voltage gated Ca+ channels --> Disrupts regulatory functions of α2δ - dec Ca2+ channel delivery to cell membrane & dec activation of channels * This decreases NT release. * May also reduce NMDA response to glutamate, reduce MAO release, stimulate enzyme conversion of glutamate to GABA & increase synaptic release of GABA

Answer 257

* CNS: analgesic, anticonvulsant, anxiolysis. Dizziness + somnloence may occur

Answer 258

* Class/chemistry: Synthetic opioid of the aminocyclohexanol group. Racemic mixture of two enantiomers * Preparation: PO 50/100/150/200/300/400mg tablets; IV 50mg/mL

Answer 259

Analgesia - moderate to severe pain 50-100mg Q4-6H (max 400mg)

Answer 260

High BA, low protein bound, high Vd (4l/kg), 80% crosses placenta, mostly metabolised in liver to one active metabolite (O-desmethyltramadol). 90% renally excreted; 10% in faeces. t1/2=4hrs

Answer 261

Non-selective agonist at mu- kappa- and delta- opioid receptors (relatively higher affinity for mu). Also inhibits neuronal reuptake of NE + enhances 5-HT release

Answer 262

* CNS: analgesic potency equivalent to pethidine. Only 30% reversed by naloxone. SEs include nausea, dizziness, sedation, diaphoresis * Other: Should be avoided in ESKD

Answer 263

* Class/chemistry: Analgesic * Preparation: PO formulation only

Answer 264

Short term management of severe pain 50-100mg IR Q4-6H (max 600mg)

Answer 265

Rapidly absorbed, but high FPM (low BA), High Vd (~7L/kg), low PB(20%). Extensively metabolised in liver (inactive metabolites). 99% renal excretion. T1/2 ~4hrs

Answer 266

Opioid and non-opioid activity: - Binds to u-opioid receptor --> decreased NT release - SNRI activity (mostly), some SSRI

Answer 267

CNS: analgesia, dizziness, drowsiness, headache GI: constipation, nausea, vomiting Rare: SIADH

Answer 268

Selective pulmonary vasodilator. Inorganic gas Indication/Dose: Pulmonary hypertension: 5-20ppm dosing - injected into patient limb of inspiratory circuit or via continuous flow

Answer 269

Diffuses into vascular smooth muscle --> stimulates guanylate cyclase (GC) --> ↑cGMP --> vasodilation via following mechanisms - cGMP: - Inhibits Ca2+ entry into cell - Activates K+ channels --> hyperpolarisation + relaxation - Stimulates cGMP dependent protein kinase --> activates MLCP --> smooth muscle relaxation

Answer 270

Resp: - Tachyphylaxis - Rebound pulmonary vasospasm (decreased intrinsic NO production) - NO2 formation --> pneumonitis & pulmonary oedema Other: - Haem: methaemaglobinaemia - CVS: systemic vasodilation/hypotension

Answer 271

Inhaled pulmonary vasodilator. Epoprostenol is the synthetic analogue of naturally occurring prostacyclin (PGI2) Indications: ---- pulmonary hypertension -->IV 2-40ng/kg/min; neb 10-50ng/kg/min. Iloprost: 2.5-5microg/dose 6-9x per day ---- pre-eclampsia ---- Haemolytic-uraemic syndrome ---- anticoagulant during RRT & cardiopulmonary bypass --> 5ng/kg/min

Answer 272

Stimulates adenylate cyclase--> increase in cAMP --> activates PKA --> phophorylates + inhibits MLCK --> smooth muscle relaxation + vasodilation. * Increased cAMP in platelets leads to inhibition of platelet phospholipase and COX, and ultimately of platelet aggregation PD effects: Resp: decrease in PVR and interferes with hypoxic pulmonary vasoconstriction

Answer 273

- Resp: cough, bronchospasm - Haem: powerful platelet inhibitor - bleeding; thrombocytopaenia - CVS: Systemic vasodilation - flushing, hypotension - CNS: Cerebral vasodilation - increased cerebral blood flow - Other: Jaw pain, peripheral oedema

Answer 274

Class: B-agonist/inhaled bronchodilator Chemistry: similar in structure to NE + adrenaline. Terminal amine group is modified to confer β2-selectivity

Answer 275

Preparation: Inhaled via MDI, or nebulised. Salbutamol available in IV + PO (liquid)

Answer 276

Dose titrated - begins with 1-2 puffs Q4H (100microg/dose) - Relief of bronchospasm in asthma or COPD (severe asthma - IV infusion 5-20mic/min) - Exercise induced asthma or other situations known to induce bronchospasm - IV salbutamol used in threatened/preterm labour - relaxes uterine smooth muscle via uterine β2 receptors (~10-50mic/min) - Hyperkalaemia

Answer 277

Absorption: BA 10% inhal via neb Distribution: PB 10%; Vd 1.3L/kg Metabolism: hepatic to inactive sulphate Excretion: mostly excreted in urine; t1/2 ~4hrs

Answer 278

Activation of Gs protein coupled receptor pathway (adenylate cyclase --> cAMP --> PKA --> phosphorylative events) - leading to bronchial smooth muscle relaxation - Lowers intracellular Ca2+ concentration - Acute inhibition of PLC-IP3 pathway and its mobilisation of cellular Ca2+ Acts as functional antagonists (reverse bronchoconstriction irrespective of the contractile agent

Answer 279

- Resp: bronchodilation - CVS: sometimes induces tachycardia in high doses - Endo: Hypokalaemia (effect on Na/K ATPase)

Answer 280

Oxygen is a diatomic gas with density and viscosity slightly higher than that of air Preparation: Clear colourless gas. Produced via fractional distillation of atmospheric air or an oxygen concentrator ○ 'wall' O2 delivered at ~ 4 atm of pressure & close to 0degC ○ Compressed gas cylinder (137bar)- variable sizes (B=170L --> G= 8000L) Administration: Delivered as inhaled gas through a range of delivery devices; delivered IV (via oxygenated blood, eg ECMO); or given externally (hyperbaric oxygen)

Answer 281

- supplementation (eg. In hypoxia), - prophylaxis (pre-anaesthetic induction), - antidote (CO toxicity), - therapeutics (antibiotic in deep anaerobic infections - via hyperbaric; decrease volume of air-filled body cavities by de-nitrogenation - ie Ptx/pneumocephalus; management of decompression sickness)

Answer 282

- **Absorption:** most pulmonary absorption (250ml/min with 21% FiO2 at rest), some cutaneous absorption <1mL/min ○ Begins at 159mmHg at mouth --> 1-10mmHg at mitochondria (oxygen cascade) - **Distribution:** bound to Hb & dissolved in plasma - distributes to all body tissues. Carriage (CaO2)= 16-22mLO2/dL ○ Body storage: ~1.55L O2 storage - 850mL in blood, 450mL in FRC, 200mL bound to myoglobin, 50mL in tissues

Answer 283

- **Metabolism:** metabolised in all tissues. Mainly by cytochrome c mitochondrial enzymes. Zero-order kinetics, roughly 200mL/min. Main metabolites are CO2 and H2O - **Excretion:** exhaled as CO2, or combined with H2O to produce HCO3- and eliminated in urine

Answer 284

Involved in oxidative phosphorylation in mitochondria, where O2 acts as final electron acceptor ○ Generation of reactive O2 species by macrophages + neutrophils for antimicrobial purposes Onset/Offset: minutes

Answer 285

Resp: de-nitrogenation of gas filled spaces, absorption atelectasis, inhibition of hypoxic pulmonary vasoconstriction **Toxicity** (increased with dose + time exposure - eg. Increased with hyperbaric O2) - Airway - oxygen-associated airway irritation (drying out membranes, - Respiratory - Risk of hypercapnia in some COPD patients --> Free radical formation--> pneumonitis/worsening ARDS (lipid peroxidation of the alveolar capillary membrane) - CVS - Hyperoxia: ↓CO, PVR, PAP & coronary vasoconstriction with prolonged administration - CNS - risk of delirium/seizures Other - note fire risk (esp in ALS with defib)

Answer 286

Class: Inhaled bronchodilator/muscarinic antagonist Chemistry: Quaternary ammonium compound. Derived from atropine Prepatation/administration: Solution or powder for inhalation

Answer 287

COPD, asthma 250-500mic Q6H (nebulised), or 42microg (2 puffs) Q6-8H

Answer 288

Absorption - 10-30% of dose deposited in lungs. Mostly swallowed and passes into GIT (low GIT absorption) Distribution - <20% protein bound, Vd = 4.6L/kg. Does not cross BBB Metabolism - partially metabolised to inactive ester hydrolysis products Excretion - urine + faeces; 2 hrs half life

Answer 289

Competitive, non-selective antagonist of Ach binding to muscarinic cholinergic receptors - block the effects of endogenous ACh at muscarinic receptors. Binds M1 & M3 receptors - GqPCRs --> decreased IP3 + DAG --> decreased Ca2+ influx --> bronchodilation

Answer 290

- Resp - Bronchodilation, dyspnoea, cough - CNS - drowsiness, dizziness, confusion - CVS - tachycardia - GI - constipation, nausea, dyspepsia

Answer 291

**Class:** methylxanthine **Chemistry:** A complex of theophylline and ethylenediamine. Aminophylline is a pro-drug --> dissociates into theophylline (active compound) Chemically similar to caffeine **Preparation:** PO/PR/IV formulations

Answer 292

High bioavailability (88-96%), 50-60% protein bound (albumin), Vd = ~0.5L/kg, liver metabolism (CYP1A2)- active metabolites. May have zero-order + first order kinetics. Under first-order, t1/2= 8hrs

Answer 293

- Inhibition of PDE - non-selective PDE inhibitor --> increased cAMP --> bronchodilation - Adenosine receptor antagonism - may reduce inflammation by blocking A2B Receptor on mast cells (activated by adenosine in asthmatics). This mechanism accounts for serious side effects (blockage of cardiac + central A1 receptors) □ May promote apoptosis of eosinophils + neutrophils (by A2A antagonism) + T lymphocytes (PDE inhibition) - Histone deacetylase (HDAC2) activation enhances anti-inflammatory effects of corticosteroids. This happens at the low concs used in asthma Onset 1-2hrs PO; 30mins if IV

Answer 294

- CNS: headache, nausea, vomiting (due to inhibition of PDE4); at high concs, may have seizures from central A1 receptor antagonism - CVS: in high concentrations, cardiac arrhythmias may occur due to PDE3 inhibition & antagonism of cardiac A1 receptors - GI: Increased acid secretion (PDE inhibition), abdo discomfort - Renal: diuresis (Adenosine A1 inhibition) Other - Large variations in clearance - dosage needs to be individualised by measurement of plasma concentrations - Plasma monitoring important. Target theophylline conc 5-10mg/L - May have a role in prevention of progression of COPD due to anti-inflammatory effects

Answer 295

Preparations: Inhaled, PO & IV MoA: Binds cytosolic receptor (glucocorticoid receptor, GR) --> forms dimer --> transported to nucleus --> interrupts with gene transcription. Increased transcription and expression of anti-inflammatory proteins & repression of inflammatory genes

Answer 296

Inhaled: dysphonia (hoarse voice), oropharyngeal candidiasis, increased risk of respiratory tract bacterial colonisation Systemic: - Short term - hyperglycaemia, gastritis/ulcer formation, sleep disturbance - Long term § Metabolic/endocrine: adrenal suppression, cushingoid features, weight gain, skin thinning, osteoporosis, myopathy § Cardiovascular: fluid retention, hypertension § Other: cataracts, immune suppression

Pharmacology (drugs) Flashcards

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