OSCE Flashcards

1
Q

what is the mechanism of action amiodarone

A

Target: non-selective for Na channel, Ca channel and α-adrenoceptors
Action: Non-selective inhibitor of the above channels and receptor Effect: prolongs the cardiac action potential seen as an increase in the QT interval on the ECG
Overall effect: Class III antiarrhythmic effect

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2
Q

what are the side effects of amiodarone

A

Common side effects: Corneal microdeposits
Important:
Thyoid disorders – hypothyroidism, hyperthyroidism
Pulmonary fibrosis
Phototoxicity
Peripheral neuropathy
Optic neuritis/neuropathy (can lead to blindness)
Hepatotoxicity
Slate-grey skin discolouration

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3
Q

what are the interactions of amiodarone

A

Other anti-arrhythmic (increased myocardial depression)
Digoxin (amiodarone increases plasma digoxin concentration – halve digoxin dose)
Warfarin (increased anticoagulant effect)
Beta blockers, calcium channel blockers (increased risk of bradycardia, AV block and myocardial depression)
Simvastatin (increased risk of myopathy)
Tricyclic antidepressants (increased risk of ventricular arrhythmias)
Phenytoin (increased plasma phenytoin concentration)
Lithium (increased risk of ventricular arrhythmias)

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4
Q

what is the therapeutic indication of amiodarone

A

Starting dose – 200mg 3 times daily for 1 week then twice daily for the following week Maintenance dose – 200mg once daily

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5
Q

what formulations does amiodarone come in

A

Tablet, injection, solution

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6
Q

how is amiodrone metabolised

A

This drug is metabolized to the main metabolite desethylamiodarone (DEA) by the CYP3A4 and CYP2C8 enzymes.
Metabolised in the liver

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7
Q

how is amiodarone excreted

A

Via the liver and bile

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8
Q

what are the contraindications of amiodarone

A

Caution in heart failure and the elderly
Avoid in sinus bradycardia, sino-atrial heart block, thyroid dysfunction and iodine sensitivity
Avoid intravenous amiodarone in severe respiratory failure, circulatory collapse and severe arterial hypotension
Discontinue if patient develops optic neuritis/neuropathy

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9
Q

what are brand names for amiodarone

A

Cordarone, Nexterone

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10
Q

what is the absorption of amiodarone

A

The bioavailability is between 35-65%

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11
Q

what is the MoA of Amitriptyline

A

Target: Noradrenaline and serotonin reuptake transporters on the pre-synaptic neuronal membrane
Action: Inhibitor
Effect: Prevent re-uptake and subsequent degradation of the monoamine neurotransmitters serotonin and noradrenaline from the synaptic cleft
Overall effect: Prolonged presence of serotonin and noradrenaline in the synaptic cleft leads to prolonged neuronal activity – in mood disorders such as depression there are low levels of these neurotransmitters in the brain. TCAs therefore restore the concentration to normal levels.

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12
Q

what is the absorption of Amitriptyline-

A

The bioavailability is between 30-60%

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13
Q

what is the distribution of amitriptyline

A

Widely distributed around the body. The protein binding is around 95%

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14
Q

how is amitriptyline metabolised

A

Metabolised in the liver and CYP2D6, CYP2C19, CYP3A4

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15
Q

how is amitriptyline excreted

A

Excreted as urine around 12-80%

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16
Q

what formulations does amitriptyline come in

A

Tablets, solutions, capsule

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17
Q

what is the therapeutic indication for amitriptyline

A

Starting dose – 75mg daily (30-75mg if elderly) (lower doses for indications other than depression)in divided doses or as a single dose nocte
Maintenance dose – varies depending on drug; for amitriptyline 150-200mg

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18
Q

what are the side effects for amitriptyline

A

Antimuscarinic effects – dry mouth, blurred vision, constipation, urinary retention
CNS side effects (particularly in elderly) e.g. anxiety, dizziness, agitation, confusion
Weight gain
Important:
**Cardiotoxic in overdose – caution in patients at risk of suicide
Neuroleptic malignant syndrome
Hyponatraemia (particularly in elderly)

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19
Q

what are the interactions for amitriptyline

A

**MAOIs (risk of hypertensive crisis and hyperthermia) – do not start a tricyclic until 2 weeks after stopping an MAOI and vice versa, do not co-prescribe
Antiepileptics (seizure threshold lowered)
Alcohol (increased sedative effect)
Anti-arrhythmics (increased risk of ventricular arrhythmias)

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20
Q

what are the contraindications for Amitriptyline

A

Caution in cardiovascular disease, hepatic impairment (avoid if severe), hyperthyroidism, epilepsy, diabetes, prostatic hypertrophy, chronic constipation, urinary retention, glaucoma, the elderly and those at high risk of falls and of suicide
Avoid following MI, in heart block and in the manic phase of bipolar disorder
Discontinue if patient enters a manic phase

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21
Q

what is the brand name for amitriptyline

A

Elavil

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22
Q

what is the MoA of Azathioprine

A

Azathioprine is metabolised to the 6- mercaptopurine, which is then converted intracellularly to purine analogues. These purine analogues are incorporated into DNA and inhibit clonal expansion of B lymphocytes during the induction phase of the immune response. This results in suppression of the antibody-mediated response.

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23
Q

what is the absorption of Azathioprine

A

The bioavailability is 60%

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24
Q

what is the distribution of Azathioprine

A

Protein binding is between 20-30%

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25
how is Azathioprine metabolised
Activated non-enzymatically, deactivated mainly by xanthine oxidase
26
how is Azathioprine excreted
Kidney; 98% as metabolites
27
what formulations does Azathioprine come in
tablets
28
what are the side effects of Azathioprine
Nausea Cancer risk – azathioprine increases the risk of lymphoma and skin malignancies Bone marrow suppression – anaemia, leucopenia, thrombocytopenia Hypersensitivity reactions including interstitial nephritis – discontinue immediately Pancreatitis
29
what are the interactions of Azathioprine
Allopurinol (risk of severe myelosuppression – do not co-prescribe) Warfarin (reduced anticoagulant effect) – may need to increase warfarin dose Aminosalicylates (bone marrow toxicity – may require increased monitoring Trimethoprim/co-trimoxazole (risk of blood disorders)
30
what are the contraindication of Azathioprine
Caution in hepatic and renal impairment Avoid in patients with known hypersensitivity to mercaptopurine, those with thiopurine methyltransferase (TPMT) deficiency and in breastfeeding women
31
name the brand names of Azathioprine
Azasan, Imuran
32
what is the MoA of buprenorphine
Target: G-protein coupled opioid ‘mu’ receptors in the CNS and peripheral nervous system Action: Full agonist (high affinity for receptors) Effect: Closure of N-type voltage-dependent calcium channels and opening of calcium-dependent inwardly rectifying potassium channels – this increases potassium conductance. Opioids also presynaptically inhibit the release of pain-signalling neurotransmitters such as substance P. Overall effect: Membrane hyperpolarisation and reduced neuronal excitability, reduction or inhibition of pain neurotransmission.
33
what is the absorption of buprenorphine
The bioavailability is Sublingual: 30% Intranasal: 48% Buccal: 65%
34
what is the distribution of buprenorphine
Protein binding is 96%
35
how is buprenorphine metabolised
liver
36
how is buprenorphine excreted
Via the bile duct and kidney
37
what are the formulation of buprenorphine
Plaster, film
38
what is the therapeutic indication for buprenorphine
For sublingual: Adults: 200–400 micrograms every 6–8 hours. For intravenous Adults: 300–600 micrograms every 6–8 hours.
39
what are the side effects of buprenorphine
``` Nausea/vomiting Constipation Important: Respiratory depression Hypotension Sedation and coma Tolerance Physical and psychological dependence Overdose – this is reversed with naloxone ```
40
what are the interactions of buprenorphine
CNS depressants (increased risk of respiratory depression) – alcohol, sedatives, hypnotics, general anaesthetics MAOIs (potentiate action of morphine) Alcohol (increased hypotensive and sedative effects)
41
what are the contraindications of buprenorphine
Caution in the elderly, hypotension, shock, prostatic hypertrophy, obstructive ir inflammatory bowel disorders, biliary disease, convulsive disorders, adrenocortical insufficiency, hepatic or renal impairment, pregnancy and patients with a history of drug dependence Avoid in acute respiratory depression, coma, head injury or raised ICP (opioids interfere with pupillary responses used in neurological assessment) and those at risk of paralytic ileus
42
name the brand names of buprenorphine
Belbuca, Bunavail, Buprenex, Buprenorphine, Butrans, Probuphine, Sublocade, Suboxone, Subutex, Zubsolv
43
MoA of Carbamazepine
44
absorption of Carbamazepine
The bioavailability is between 75-85%
45
distribution of Carbamazepine
The protein distribution is between 70-80%
46
how is Carbamazepine metabolised
Hepatic- by CYP3A4
47
how is Carbamazepine excreted
Urine (72%)
48
list the different formulations of Carbamazepine
Tablets, capsule, suspension
49
what is the therapeutic indication of Carbamazepine
Starting dose – 100-200mg 1-2 times daily (reduce if elderly); Maintenance dose 0.8-1.2g daily
50
what is the adverse effects of Carbamazepine
Drowsiness Nausea/vomiting Ataxia, dizziness Hyponatraemia (syndrome of inappropriate ADH secretion (SIADH)) Cardiac condution disturbances Leucopenia/bone marrow failure Stevens-Johnson syndrome (especially if Han Chinese or Thai origin due to HLA-B*1502 allele)
51
what are the interactions of Carbamazepine
Warfarin (reduced anticoagulant effect) Antipsychotics (impaired anticonvulsant effect) CYP450 inhibitors (plasma levels increased) – includes isoniazid, diltiazem, verapamil CYP450 inducers (plasma levels reduced) – includes phenytoin, phenobarbitone, theophylline
52
what are the contraindications of Carbamazepine
Caution in cardiac disease, hepatic or renal impairment, pregnancy, patients with history of haematological reaction to other drugs and those susceptible to angle-closure glaucoma Avoid in patients with AV conduction abnormalities (if not paced), history of bone marrow depression, acute porphyria and those with know hypersensitivity to tricyclic antidepressants Discontinue carbamazepine if patients develops acute liver disease or severe/progressive/symptomatic leucopenia
53
name the brand names of Carbamazepine
Tegretol, Temporol, Neurotol
54
MoA of Citalopram
Target: Serotonin re-uptake transporter on the pre-synaptic neuronal membrane Action: Inhibitor Effect: Prevents re-uptake and subsequent degradation of the monoamine neurotransmitter serotonin from the synaptic cleft Overall effect: Prolonged presence of serotonin in the synaptic cleft leads to prolonged neuronal activity – in mood disorders such as depression there are low levels of this neurotransmitter in the brain. SSRIs therefore restore the concentration of serotonin to normal levels.
55
absorption of Citalopram
The bioavailability is 80%
56
distribution of Citalopram
Protein binding is <80%
57
how is Citalopram metabolised
Via the liver via N-demethylation to its main metabolite, demethylcitalopram by CYP2C19 and CYP3A4
58
how is Citalopram excreted
12-23% of an oral dose of citalopram is found unchanged in the urine, while 10% of the dose is found in the faeces
59
what are the different formulations of Citalopram
Tablets, solution
60
what is the therapeutic indication of Citalopram
20 mg once daily, increased in steps of 20 mg daily if required, dose to be increased at intervals of 3–4 weeks; maximum 40 mg per day
61
what are the side effects of Citalopram
GI upset (dose related) – nausea, vomiting, dyspepsia, abdominal pain, diarrhoea, constipation Anorexia with weight loss Increased risk of bleeding Hypersensitivity reactions – rash, urticaria, angioedema, anaphylaxis Convulsions Neuroleptic malignant syndrome
62
what are the interactions of Citalopram
Alcohol (increased sedative effect) NSAIDs (increased risk of bleeding) Antiepileptics (SSRIs lower the seizure threshold) Theophylline (half theophylline dose or avoid where possible) MAOIs – SSRIs should not be started until 2 weeks of stopping an MAOI, MAOIs should not be started until 7-14 days after stopping an SSRI
63
what are the contraindications of Citalopram
Caution in patients with epilepsy (discontinue if convulsions develop), cardiac disease, diabetes mellitus, susceptibility to angle closure glaucoma, history of mania or bleeding disorders, hepatic or renal impairment, those taking other drugs which increase risk of bleeding and those received concomitant electroconvulsive therapy Avoid in pregnancy Discontinue SSRIs if the patient enters a manic phase
64
name the brand names of Citalopram
Celexa, Cipramil
65
what is the MoA of Clozapine
Target: Muscarinic, histamine, dopamine, serotonin and adrenergic receptors Action: Mixed antagonists – main action is through antagonism of dopamine D2 receptors Effect: Reduced release of dopamine from dopaminergic nerve terminals, reduced electrical activity in dopaminergic neuronal pathways – action on mesolimbic/mesocortical pathways is responsible for the antipsychotic activity of these drugs, while action on the nigrostriatal pathways produces the unwanted side effects
66
what is the absorption of Clozapine
Bioavailability is between 60-70%
67
how is Clozapine excreted
80% in metabolized state: 30% biliary and 50% kidney.
68
how is Clozapine metabolised
liver
69
what are the different formulations of Clozapine
Tablets, suspension
70
what is the therapeutic indication of Clozapine
200-450mg daily in divided doses
71
what are the side effects of Clozapine
Drowsiness, sedation; Agitation Extrapyramidal symptoms; Postural hypotension – risk of falls in the elderly; Tardive dyskinesia (may be irreversible); Neuroleptic malignant syndrome; Agranulocytosis (clozapine only)
72
what are the interactions of Clozapine
Antihypertensive agents (increased hypotensive effect) Drugs that prolong QT interval (increased risk of arrhythmias including torsades de pointes) Antiepileptics (lower the seizure threshold) Opioids (increased CNS depression/sedation) • Alcohol (increased CNS depression)
73
what are the contraindications of Clozapine
Caution in cardiovascular disease, diabetes, Parkinson’s disease and hepatic impairment Avoid in CNS depression and coma
74
name the brand names of Clozapine
Clozaril, Leponex, Versacloz
75
MoA of Diazapam
Target: Benzodiazepine (BDZ) receptor on GABA-BDZ receptor complex Action: Agonist Effect: Increase affinity of the inhibitory neurotransmitter GABA for the GABAA receptor – this causes post-synaptic chloride ion channels to open Overall effect: Increased flow of negative chloride ions into the neurone leading to hyperpolarisation of the membrane – this prevents further excitation
76
absorption of Diazapam
76% (64–97%) by mouth, 81% (62–98%) recta
77
distribution of Diazapam
Despite high binding to plasma proteins (98-99%) - mainly albumin and to a lesser extent α1-acid glycoprotein - diazepam is widely distributed into tissues and crosses the blood-brain barrier and is highly lipid soluble, which causes the initial effects to decrease rapidly as it is redistributed into fat deposits and tissues
78
how is Diazapam metabolised
via the liver
79
how is Diazapam excreted
kidney
80
name the different formulations of Diazapam
Injection, tablet, solution, gel, emulsion
81
what is the therapeutic indication of Diazapam
Diazepam – 2mg tid increased if necessary to 15-30mg daily in divided doses (half dose in elderly)
82
what are the side effects of Diazapam
``` Drowsiness Dizziness Psychomotor impairment Important: Hypotension leading to increased risk of falls in the elderly Physical and psychological dependence Tolerance ‘Hangover effects’ ```
83
what are the interactions of Diazapam
Antihypertensives (enhanced hypotensive effect) • Clozapine (serious adverse effects reported with lorazepam)
84
what are the contraindications of Diazapam
Caution in the elderly, patients with respiratory disease, muscle weakness, myasthenia gravis (avoid if unstable) and those with a history of drug or alcohol abuse Avoid in patients with respiratory depression, marked neuromuscular weakness, acute pulmonary insufficiency, sleep apnoea syndrome, pregnancy and breastfeeding Should not be used for greater than 4 weeks
85
name the brand names of Diazapam
Valium, Vazepam, Valtoco
86
MoA of digoxin
Target: Na+ K + ATPase membrane pump Action: Inhibitor Effect: Increase in intracellular sodium. This leads to a subsequent rise in intracellular calcium through the Na+ Ca2+ exchanger on cardiac myocytes. Phases 4 and 0 of the cardiac action potential are prolonged leading to an increase in end diastolic volume. Overall effect: Positive inotropic effect (increased end diastolic volume leads to increased force of ventricular contraction according to Frank Starling curve), negative chronotropic effect – increases cardiac contractility, decreases heart rate
87
what is the absorption of digoxin
Bioavailability is between 60-80%
88
what is the distribution of digoxin
Protein binding is 25%
89
what is the metabolism of digoxin
liver
90
how is digoxin excreted
kidney
91
list the different formulations of digoxin
Tablet, injection
92
what is the therapeutic indication of digoxin
0.75–1.5mg in divided doses over 24 hours for rapid control of atrial fibrillation or flutter 125–250micrograms daily for maintenance of atrial fibrillation or flutter 62.5-125micrograms daily for heart failure (patient in sinus rhythm) Reduce dose in the elderly and those with renal impairment
93
what are the side effects of digoxin
DIGOXIN TOXICITY: Confusion; Loss of appetite; Nausea, vomiting, diarrhoea; Evidence of cardiotoxicity – palpitations, arrhythmias, conduction disturbances; Blurred or yellow vision If digoxin toxicity is known or strongly suspected and withdrawal of the drug/correction of electrolyte disturbances are ineffective, DIGOXIN-SPECIFIC ANTIBODY FRAGMENTS are indicated.
94
what are the interactions of digoxin
Amiodarone (increased plasma digoxin concentration – halve dose of digoxin) Calcium channel blockers (increased plasma digoxin concentration) Drugs which cause hypokalaemia e.g. diuretics increase the risk of cardiotoxicity (secondary to the hypokalaemia
95
what are the contraindications of digoxin
Caution in sick sinus syndrome, hypokalaemia, thyroid disease, severe respiratory disease and in patients who have had a recent MI Avoid in heart block, Wolff-Parkinson-White syndrome, ventricular tachycardia or fibrillation, myocarditis and constrictive pericarditis Reduce dose in renal impairment
96
name the brand name of digoxin
Lanoxin
97
what is the MoA of Diltiazem
Target: L-type calcium channels - Diltiazem and Verapamil favour the hyperpolarised Ca++ channels more commonly found in cardiac muscle cells Action: Antagonist Effect: Inhibit influx of calcium ions into cardiomyocytes through L-type calcium channels Overall effect: Negative inotropic effect – decreases cardiac contractility
98
what is the absorption of Diltiazem
The bioavailability is 40%
99
what is the distribution of Diltiazem
Protein binding is about 70-80%
100
how is Diltiazem metabolised
the liver
101
how is Diltiazem excreted
Via the kidney and biliary
102
name the different formulations for Diltiazem
Capsule, tablet
103
what is the therapeutic indication of Diltiazem
60mg three times daily, increase if necessary to 360mg daily
104
what are the side effects of Diltiazem
Headache • Flushing • Tachycardia • Peripheral oedema • Constipation, particularly in elderly patients • Sino-atrial and AV block with diltiazem, particularly in those taking digoxin and/or beta blockers
105
what are the interactions of Diltiazem
Antihypertensives (increased hypotensive effect) • Beta blockers (asystole, severe hypotension, heart failure) • Anti-arrhythmics (increased risk of bradycardia, AV block and myocardial depression)
106
what are the contraindication of Diltiazem
Caution in heart failure, first degree AV block and bradycardia (avoid if severe) • Avoid in second or third degree AV block, SA block, sick sinus syndrome, Wolff-ParkisonWhite syndrome, hypotension and cardiogenic shock
107
name the brand names of Diltiazem
Cardizem, Dilacorxr,
108
what is the MoA of Enoxaparin
Target: Antithrombin III (a serine protease inhibitor) Action: Activate/stimulate Effect: Inhibit factor Xa in the common pathway of the clotting cascade Overall effect: Factor Xa is needed to convert prothrombin to thrombin, therefore LMWHs inhibit coagulation
109
what is the absorption of Enoxaparin
The absolute bioavailability is 100%
110
what is the distribution of Enoxaparin
Enoxaparin binds to antithrombin III. The percentage of plasma protein binding for enoxaparin is not readily available
111
how is Enoxaparin metabolised
liver
112
how is Enoxaparin excreted
kidney
113
list the different formulation of Enoxaparin
injection
114
what is the therapeutic indication of Enoxaparin
Prophylaxis of DVT in surgical patients – 20mg 2 hours before surgery then 20mg every 24 hours (40mg if high risk e.g. orthopaedic surgery) Prophylaxis of DVT in medical patients – 40mg once daily Treatment of DVT/PE – 1.5mg/kg once daily Treatment of acute MI – inital dose 30mg, then 1mg/kg every 12 hours for up to 8 days
115
list the side effects of Enoxaparin
Haemorrhage Heparin-induced thrombocytopenia (HIT) Hyperkalaemia
116
what is the interactions of Enoxaparin
NSAIDs (incerased risk of haemorrhage) ACE inhibitors, ARBs (increased risk of hyperkalaemia) Antiplatelet agents (increased risk of haemorrhage)
117
what is the contraindication of Enoxaparin
Caution in the elderly, renal impairment,hepatic impairment (avoid if severe) and those with low body weight Avoid in haemophilia and other haemorrhagic disorders, thrombocytopenia, recent cerebral haemorrhage, severe hypertension, peptic ulcer disease, acute bacterial endocarditis, following major trauma and in patients with known hypersensitivity to heparins Discontinue if patient develops HIT
118
name the brand names of Enoxaparin
Lovenox, Clexane, Xaparin
119
MoA of Haloperidol
Target: Muscarinic, histamine, dopamine, serotonin and adrenergic receptors Action: Mixed antagonists – main action is through antagonism of dopamine D2 receptors Effect: Reduced release of dopamine from dopaminergic nerve terminals, reduced electrical activity in dopaminergic neuronal pathways – action on mesolimbic/mesocortical pathways is responsible for the antipsychotic activity of these drugs, while action on the nigrostriatal pathways produces the unwanted side effects
120
absorption of Haloperidol
The bioavailability is between 60-70% when taken orally
121
what is the distribution of Haloperidol
Protein binding is approximately 90%
122
how is Haloperidol metabolised
Liver-mediated
123
how is Haloperidol excreted
Biliary and in urine
124
list the different formulations of Haloperidol
Tablet, solution, injection
125
what is the therapeutic indication of Haloperidol
starting dose 0.5starting dose 0.5-3mg 2-3 times daily; maintenance dose 5-30mg daily
126
list the side effects of Haloperidol
Drowsiness, sedation; Agitation Extrapyramidal symptoms; Postural hypotension – risk of falls in the elderly; Tardive dyskinesia (may be irreversible); Neuroleptic malignant syndrome; Agranulocytosis (clozapine only)
127
what are the interactions of Haloperidol
Antihypertensive agents (increased hypotensive effect) Drugs that prolong QT interval (increased risk of arrhythmias including torsades de pointes) Antiepileptics (lower the seizure threshold) Opioids (increased CNS depression/sedation) Alcohol (increased CNS depression)
128
what are the contraindications of Haloperidol
Caution in cardiovascular disease, diabetes, Parkinson’s disease and hepatic impairment Avoid in CNS depression and coma
129
name the brand names of Haloperidol
Haldol
130
what sit he MoA of lithium
Patients with bipolar affective disorder have diminished GABA neurotransmission. Thus, low GABA levels can result in excitatory toxicity. Lithium increases the levels of GABA which in turn reduces glutamate and down regulates the NMDA receptor. Lithium also directly activates the GABA receptor.
131
what is the absorption of lithium
132
what is the distribution of lithium
No protein binding
133
how is lithium metabolised
Kidney
134
how is lithium excreted
>95% kidney
135
what are the different formulations for lithium
Tablets, solution
136
what is the therapeutic indication of lithium
Initially 1–1.5 g daily, dose adjusted according to serum-lithium concentration, doses are initially divided throughout the day, but once daily administration is preferred when serum-lithium concentration stabilised.
137
list the side effects of lithium
GI upset; Fine tremor; Weight gain Hypothyroidism Hyperparathyroidism, hypercalcaemia Lithium toxicity – blurred vision, muscle weakness, drowsiness, coarse tremor, slurred speech, ataxia, confusion, convulsions, nausea, vomiting and ECG changes If toxicity is suspected: o Stop lithium immediately o Check lithium levels, serum creatinine, U&E o Refer to A&E if clinically necessary o Seek advice from psychiatry for re-initiation of lithium
138
what are the interactions of lithium
The following drugs increase lithium levels: antibiotics metronidazole, tetracyclines and cotrimoxazole; NSAIDs, ACE inhibitors, ARBs and diuretics The following drugs decrease lithium levels: xanthines theophyllines, aminophylline and caffeine; sodium salts and acetazolamide Amiodarone (increased risk of ventricular arrhythmias
139
what are the contraindications of lithium
Caution in the elderly and those with psoriasis and myasthenia gravis Avoid in serious cardiac disease (heart failure, sick sinus syndrome), Addison’s disease, renal impairment (if possible), pregnancy and breastfeeding Reduce dose or discontinue lithium in diarrhoea, vomiting and intercurrent infection (especially if patient is sweating profusely) Discontinue lithium 24 hours before surgery and restart as soon as renal function and fluid balance are back to normal
140
what is the brand name of lithium
141
what is the MoA of methadone
Target: G-protein coupled opioid ‘mu’ receptors in the CNS and peripheral nervous system Action: Full agonist (high affinity for receptors) Effect: Closure of N-type voltage-dependent calcium channels and opening of calcium-dependent inwardly rectifying potassium channels – this increases potassium conductance. Opioids also presynaptically inhibit the release of pain-signalling neurotransmitters such as substance P. Overall effect: Membrane hyperpolarisation and reduced neuronal excitability, reduction or inhibition of pain neurotransmission.
142
what is the absorption of methadone
The bioavailability is 15-20% when taken subcutaneously 100% when taken intravenously, 41-99% when taken orally
143
what is the distribution of methadone
The protein binding is between 85-90%
144
how is methadone metabolised
via the liver
145
how is methadone excreted
urine and faeces
146
what is the therapeutic indication of methadone
–10 mg every 6–8 hours, adjusted according to response, on prolonged use not to be given more frequently than every 12 hours.
147
what are the side effects of methadone
``` Nausea/vomiting Constipation Respiratory depression Hypotension Sedation and coma Tolerance Physical and psychological dependence ```
148
what are the interactions of methadone
CNS depressants (increased risk of respiratory depression) – alcohol, sedatives, hypnotics, general anaesthetics MAOIs (potentiate action of morphine) Alcohol (increased hypotensive and sedative effects)
149
what are the contraindications of methadone
Caution in the elderly, hypotension, shock, prostatic hypertrophy, obstructive ir inflammatory bowel disorders, biliary disease, convulsive disorders, adrenocortical insufficiency, hepatic or renal impairment, pregnancy and patients with a history of drug dependence Avoid in acute respiratory depression, coma, head injury or raised ICP (opioids interfere with pupillary responses used in neurological assessment) and those at risk of paralytic ileus
150
name the brand names of methadone
Diskets, Dolophine, Metadol, Metadol-D, Methadose
151
what is the MoA of methotrexate
Target: Dihydrofolate reductase enzyme Action: Competitive inhibitor Effect: Inhibits reduction of dihydrofolate to its active form tetrahydrofolate Overall effect: Immunosuppressant activity
152
what is the absorption of methotrexate
The bioavailability is between 64-90%
153
what is the distribution of methotrexate
Protein binding is between 46.5-54%
154
how is methotrexate metabolised
Methotrexate is metabolized by folylpolyglutamate synthase to methotrexate polyglutamate in the liver as well as in tissues. Gamma-glutamyl hydrolase hydrolyzes the glutamyl chains of methotrexate polyglutamates converting them back to methotrexate. A small amount of methotrexate is also converted to 7-hydroxymethotrexate
155
how is methotrexate excreted
Methotrexate is >80% excreted as the unchanged drug and approximately 3% as the 7-hydroxylated metabolite.1 Methotrexate is primarily excreted in the urine with 8.7-26% of an intravenous dose appearing in the bile
156
name the different formulations of methotrexate
Injection, tablet, solution
157
what is the therapeutic indication of methotrexate
dose range 5-25mg once weekly
158
what are the side effects of methotrexate
Nausea, diarrhoea Alopecia Stomatitis, mucositis Myelosuppression including leucopenia and neutropenia Hepatotoxicity Pulmonary fibrosis, interstitial pneumonitis Pericarditis, pericardial tamponade
159
what are the interactions of methotrexate
``` Trimethoprim/co-trimoxazole (risk of pancytopenia, do not co-prescribe) NSAIDs (may reduce methotrexate excretion but unlikely to cause clinically significant adverse effects, concomitant use common in rheumatic disease) Clozapine (increased risk of agranulocytosis – avoid concomitant use) Acitretin (increased plasma methotrexate concentration, increased risk of hepatotoxicity – avoid concomitant use) Live vaccines (high risk of infection due to immunosuppressive effect of methotrexate) ```
160
what are the contraindication of methotrexate
Caution in ulcerative colitis, peptic ulcer disease and ulcerative stomatitis Avoid in pregnancy and breastfeeding, severe hepatic or renal impairment, blood disorders (severe anaemia, leucopenia or thrombocytopenia), untreated folate deficiency and history of alcohol abuse/cirrhosis Hold methotrexate temporarily if patient is systemically unwell with significant infection requiring anti-infective intervention
161
name the brand names of methotrexate
Metoject, Nordimet, Otrexup, Rasuvo, Reditrex, Trexall, Xatmep
162
what is the MoA of phenytoin
Target: Voltage-gated neuronal sodium ion channels Action: Block Effect: Inhibits influx of sodium ion into neuronal cells/slows rate of recovery of sodium channels from inactivation Overall effect: Stabilises the neuronal membrane and prevents hyperexcitability, thus limiting the spread of seizure activity and reducing seizure propagation
163
what Is the absorption of phenytoin
The bioavailability is 70-100%
164
what is the distribution of phenytoin
Protein binding is approximately 90% bound
165
how is phenytoin metabolised
liver
166
how is phenytoin excreted
Urinary 23-70%, bile
167
name the different formulations of phenytoin
Capsule, tablet, injection, suspension.
168
what is the therapeutic indication of phenytoin
Starting dose – 3-4mg/kg or 150-300mg daily, increased gradually as necessary while monitoring plasma phenytoin concentration Maintenance dose – 200-500mg daily (reduce in hepatic impairment to avoid toxicity)
169
what is the side effects of phenytoin
``` P= P450 interactions H = Hirsutism E = Enlarged gums N = Nystagmus Y = Yellow-browning of the skin T = Teratogenic O = Osteomalacia I = Interferes with folate metabolism, leads to anaemia N = Neuropathies: vertigo, ataxia, headaches ```
170
what are the interactions of phenytoin
Phenytoin is a cytochrome P450 Inducer OCP (reduced contraceptive effect) Theophylline (reduced plasma concentration of both drugs) Cimetidine (reduced plasma phenytoin concentration) Amiodarone (increased plasma phenytoin concentration)
171
what are the contraindications of phenytoin
Caution in patients undergoing enteral feeding Avoid in patients of Han Chinese or Thai origin (HLA-B*1502 allele increases risk of StevensJohnson syndrome) Discontinue phenytoin if severe leucopenia develops
172
name the brand names of phenytoin
Dilantin, Phenytek
173
what is the MoA of Prednisolone
Target: Intracellular steroid receptors Action: Agonist – prednisolone and other corticosteroids mimic the action of the endogenous mediator cortisol at steroid receptors Effect: Binding of a corticosteroid to the cytoplasmic steroid receptor exposes a DNA binding domain on the receptor. This allows the steroid-receptor complex to associate with glucocorticoid response elements present in the promoter regions of target genes. Overall effect: Upregulation of gene transcription
174
what is the absorption of Prednisolone
The bioavailability is 70% when taken orally
175
what is the distribution of Prednisolone
Protein binding is between 65-91%
176
how is Prednisolone metabolised
liver
177
how is Prednisolone excreted
Excreted 98% in the urine
178
name the different formulations of Prednisolone
Tablet, ointment cream, suppository, injection, suspension.
179
what is the therapeutic indication of Prednisolone
Starting dose – 10-20mg mane after breakfast Maintenance dose – 2.5-15mg daily
180
what is the side effects of Prednisolone
Moon face with plethoric cheeks • Steroid induced cataracts • Steroid induced psychosis • Buffalo hump fat distribution • Central fat distribution with striae • Thin limbs with paper money skin and easy bruising • Hypertension • Steroid induced diabetes mellitus
181
what are the interactions of Prednisolone
Antihypertensives (reduced hypotensive effect) NSAIDs (increased risk of peptic ulceration and bleeding) Antidiabetics (reduce hypoglycaemic effect) Wafarin (may enhance or reduce anticoagulant effect) Live vaccines – avoid concomitant use due to increased risk of infection
182
what are the contraindications of Prednisolone
Caution in pregnancy (risk of intrauterine growth restriction)
183
name the brand names of Prednisolone
Millipred Dp 6 Day, Pediapred
184
what is the MoA of Quetiapine
Target: Muscarinic, histamine, dopamine, serotonin and adrenergic receptors Action: Mixed antagonists – main action is through antagonism of dopamine D2 receptors Effect: Reduced release of dopamine from dopaminergic nerve terminals, reduced electrical activity in dopaminergic neuronal pathways – action on mesolimbic/mesocortical pathways is responsible for the antipsychotic activity of these drugs, while action on the nigrostriatal pathways produces the unwanted side effects
185
what is the absorption of Quetiapine
The bioavailability is 100%
186
what is the distribution of Quetiapine
The protein binding 83%
187
how is Quetiapine metabolised
Liver via CYP3A4-catalysed sulfoxidation to its active metabolite norquetiapine
188
how is Quetiapine excreted
Kidney 73% faeces- 20%
189
what is the formulation of Quetiapine
Tablets, capsule
190
what are the side effects of Quetiapine
Drowsiness, sedation; Agitation
191
what is the therapeutic indication of Quetiapine
25 mg twice daily for day 1, then 50 mg twice daily for day 2, then 100 mg twice daily for day 3, then 150 mg twice daily for day 4, then, adjusted according to response, usual dose 300–450 mg daily in 2 divided doses, the rate of dose titration may need to be slower and the daily dose lower in elderly patients; maximum 750 mg per day.
192
what are the interactions of Quetiapine
Antihypertensive agents (increased hypotensive effect) Drugs that prolong QT interval (increased risk of arrhythmias including torsades de pointes) Antiepileptics (lower the seizure threshold) Opioids (increased CNS depression/sedation) Alcohol (increased CNS depression)
193
what are the contraindications of Quetiapine
Caution in cardiovascular disease, diabetes, Parkinson’s disease and hepatic impairment Avoid in CNS depression and coma
194
name the brand name of Quetiapine
Seroquel
195
what is the MoA of Rivaroxaban
Target: Factor Xa Action: Competitive inhibition Effect: Inhibits activated factor Xa, which is required for the conversion of prothrombin to thrombin in the common pathway of the coagulation cascade Overall effect: Lack of thrombin prevents conversion of fibrinogen to fibrin and therefore inhibits thrombus formation
196
what is the absorption of Rivaroxaban
The bioavailability is between 80-100%
197
what is the distribution of Rivaroxaban
Protein binding is between 92-95%
198
how is Rivaroxaban metabolised
CYP3A4, CYP2J2 and CYP-independent mechanisms
199
how is Rivaroxaban excreted
Liver
200
what is the different formulations of Rivaroxaban
Tablets, capsule, suspension
201
what is the therapeutic indication of Rivaroxaban
10mg once daily for 2 weeks to be started 6-10 hours after surgery
202
what are the side effects of Rivaroxaban
``` Nausea Renal impairment (rivaroxaban) ```
203
what are the interactions of Rivaroxaban
``` NSAIDs (increased risk of bleeding) Amiodarone (increased plasma dabigatran concentration – reduce dose of dabigatran) Verapamil (increased plasma dabigatran concentration – reduce dose of dabigatran) Triazole antifungals (avoid combination with rivaroxaban) ```
204
what are the contraindications of Rivaroxaban
Caution in the elderly, patients weighing <50kg, active or recent GI ulceration and those with bleeding disorders Avoid in active bleeding and in severe renal or hepatic impairment, pregnancy and breast feeding. Discontinue if severe bleeding occurs
205
name the brand name of Rivaroxaban
Xarelto
206
what is the MoA of Sildenafil
Sildenafil is an oral therapy for erectile dysfunction. The physiological mechanism responsible for the erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.
207
what is the absorption of Sildenafil
The bioavailability is 41%
208
what is the distribution of Sildenafil
Protein binding is approximately 96%
209
how is Sildenafil metabolised
liver
210
how is Sildenafil excreted
Faeces and urine
211
list the different formulations of Sildenafil
Tablet, injection, suspension
212
what is the therapeutic indication of Sildenafil
For pulmonary arterial hypertension: Oral: 20mg 3x a day Injection: 10mg 3x a day For erectile dysfunction: initially 50mg approx. 1 hour before sexual activity, adjusted accordingly to response 25-100mg as required. To be taken as a single dose maximum one dose a day.
213
what are the side effects of Sildenafil
Alopecia; anaemia; anxiety; cough; diarrhoea; dizziness; fluid retention; gastrointestinal discomfort; gastrointestinal disorders; headaches; increased risk of infection; insomnia; nasal complaints; nausea; night sweats; pain; skin reactions; tremor; vasodilation; vision disorders
214
what are the interactions of Sildenafil
215
what are the contraindications of Sildenafil
Hereditary degenerative retinal disorders; history of non-arteritic anterior ischaemic optic neuropathy; recent history of myocardial infarction; recent history of stroke When used for Erectile dysfunction avoid if systolic blood pressure below 90 mmHg (no information available); patients in whom vasodilation or sexual activity are inadvisable; recent unstable angina When used for Pulmonary arterial hypertension: sickle-cell anaemia
216
name the brand name of Sildenafil
Revatio, Viagra, Vizarsin
217
what is the MoA for Sodium Valproate
Target: Voltage-gated sodium channels Action: Inhibitor Effect:Inhibit inactivation of inhibitory neurotransmitter GABA and block its reuptake into neurones Overall effect: Inhibition of action potential transmission both pre- and post-synaptically, leading to increased levels of GABA in the brain and interruption of seizure activity
218
what is the absorption for Sodium Valproate
Rapid absorption
219
what is the distribution for Sodium Valproate
Protein binding is between 80-90%
220
how is Sodium Valproate metabolised
via the liver
221
how is Sodium Valproate excreted
via the urine
222
list the different formulations of Sodium Valproate
Injection, tablet, syrup, capsule
223
what is the the therapeutic indication for Sodium Valproate
Starting dose – 600mg daily in 1-2 divided doses, increase by 200mg every 3 days Maintenance dose – 1-2g daily (reduce in renal impairment)
224
what is the side effects for Sodium Valproate
GI disturbance (nausea, gastric irritation, diarrhoea) • Weight gain • Drowsiness Thrombocytopenia Pancreatitis Hyperammonaemia Reduced bone mineral density Hepatic dysfunction (including fatal hepatic failure)
225
what are the interactions for Sodium Valproate
Antidepressants (reduced anticonvulsant effect) – SSRIs, TCAs, MAOIs Antimalarials (reduced anticonvulsant effect) – mefloquine, chloroquine
226
what are the contraindications for Sodium Valproate
Caution in renal impairment and systemic lupus erythematosus Avoid in active liver disease, hepatic impairment, pregnancy and in patients with family history of severe hepatic dysfunction Discontinue if patient develops abnormally prolonged prothrombin time, pancreatitis, blood disorder or hepatic dysfunction
227
name the brand names for Sodium Valproate
Depakene, Depakote, Epival
228
what is the MoA for Spironolactone
Target: Intracellular aldosterone receptors (mineralocortocoid receptors (MR)) in the renal tubules Action: Competitive antagonist, blocks adosterone-MR translocation into the nucleus reducing the production of aldosterone induced proteins (AIPs) Effect: Inhibits Na+ /K+ exchange in the distal tubule and collecting ducts, promoting potassium retention and sodium and water loss Overall effect: Weak diuresis, potassium retention and hypotensive effect
229
what is the absorption for Spironolactone
The bioavailability is between 60-80%
230
what is the distribution for Spironolactone
Protein binding is 88% to albumin
231
how is Spironolactone metabolised
liver
232
how is Spironolactone excreted
Urine and in bile
233
list the different formulations for Spironolactone
Tablet, capsule
234
what is the therapeutic indication for Spironolactone
Ascites: 50mg twice daily (increase to 200mg twice daily if required) Heart failure 25mg once daily
235
what are the side effects for Spironolactone
GI upset Hyperkalaemia Gynaecomastia/hypogonadism, impotence in males, menstrual irregularities in females (due to cross-reaction with intracellular androgen receptors) Acute renal failure
236
what are the interactions for Spironolactone
Drug affecting RAAS (increased risk of hyperkalaemia) – ACE inhibitors, ARBs, direct renin inhibitors Other potassium sparing diuretics e.g. amiloride, triamterene (increased risk of hyperkalaemia) Potassium supplements Antihypertensives (increased hypotensive effect) NSAIDs (increased risk of nephrotoxicity) Lithium – excretion is inhibited by spironolactone
237
what are the contraindications for Spironolactone
Caution in the elderly and those with renal impairment (avoid if severe) Avoid in hyperkalaemia, hyponatraemia, anuria and Addison’s disease
238
name the brand names for Spironolactone
Aldactazide, Aldactone, Carospir
239
what is the MoA of Tamoxifen
Tamoxifen competitively inhibits oestrogen binding to its receptor, which is critical for it's activity in breast cancer cells.1 Tamoxifen leads to a decrease in tumour growth factor α and insulin-like growth factor 1, and an increase in sex hormone binding globulin. The increase in sex hormone binding globulin limits the amount of freely available estradiol.1 These changes reduce levels of factors that stimulate tumour growth.
240
what is the absorption of Tamoxifen
The bioavailability is approximately 100%
241
what is the distribution of Tamoxifen
The protein binding of tamoxifen in plasma is over 98% and mostly to serum albumin
242
how is Tamoxifen metabolised
Hepatic
243
how is Tamoxifen excreted
Faeces and urine
244
name the different formulations of Tamoxifen
tablet
245
what is the therapeutic indication for Tamoxifen
For adult, initaly 20mg on days 2,3,4,5 of cycle. If necessary the daily dose may be increased to 40mg then 80mg for subsequent courses. If cycle is irregular, start initial course on any day, with subsequent course starting 45 days later or on day 2 of cycle if period occurs
246
what are the adverse effects of Tamoxifen
Alopecia; anaemia; cataract; cerebral ischaemia; constipation; diarrhoea; dizziness; embolism and thrombosis; fatigue; fluid retention; headache; hepatic disorders; hot flush; hypersensitivity; hypertriglyceridaemia; muscle complaints; nausea; neoplasms; retinopathy; sensation abnormal; skin reactions; taste altered; uterine disorders; vaginal haemorrhage; vomiting; vulvovaginal disorders
247
what are the interactions for Tamoxifen
Acenocoumarol and warfarin ( increases anticoagulant effect), buproin and cinacalcet and fluoxetine ( decrease the efficacy) fosphenytoin- high dose might increase the cocncentration of fosphenytoin
248
what are the contraindications for Tamoxifen
Void if you have a history of getting DVT
249
name the brand names for Tamoxifen
Nolvadex-D, Soltamox
250
what is the MoA for Temazepam
Target: Benzodiazepine (BDZ) receptor on GABA-BDZ receptor complex Action: Agonist Effect: Increase affinity of the inhibitory neurotransmitter GABA for the GABAA receptor – this causes post-synaptic chloride ion channels to open Overall effect: Increased flow of negative chloride ions into the neurone leading to hyperpolarisation of the membrane – this prevents further excitation
251
what is the absorption of Temazepam
The bioavailability is approximately 96%
252
what is the distribution for Temazepam
96% of unchanged temazepam is bound to plasma proteins
253
how is Temazepam metabolised
via the liver
254
how is Temazepam excreted
via the kidney
255
name the different formulations for Temazepam
Capsule, solution, suppositry
256
what is the therapeutic indication for Temazepam
10–20 mg once daily, alternatively 30–40 mg once daily, higher dose range only to be administered in exceptional circumstances, dose to be taken at bedtime, for debilitated patients, use elderly dose. For elderly dose: 10 mg once daily, alternatively 20 mg once daily, higher dose only to be administered in exceptional circumstances, dose to be taken at bedtime.
257
what are the side effects for Temazepam
``` Drowsiness Dizziness Psychomotor impairment Hypotension leading to increased risk of falls in the elderly Physical and psychological dependence Tolerance ‘Hangover effects’ ```
258
what are the interactions for Temazepam
Antihypertensives (enhanced hypotensive effect) | Clozapine (serious adverse effects reported with lorazepam)
259
what are the contraindication for Temazepam
Caution in the elderly, patients with respiratory disease, muscle weakness, myasthenia gravis (avoid if unstable) and those with a history of drug or alcohol abuse Avoid in patients with respiratory depression, marked neuromuscular weakness, acute pulmonary insufficiency, sleep apnoea syndrome, pregnancy and breastfeeding Should not be used for greater than 4 weeks
260
name the brand name of Temazepam
Restoril
261
what is the MoA for warfarin
Target: Vitamin K epoxide reductase Action: Competitive inhibitor Effect: Prevents post-translational gamma-carboxylation clotting factors II, VII, IX and X Overall effect: Depletion of active clotting factors II, VII, IX and X; this produces a potent anticoagulant effect
262
what is the absorption for warfarin
Bioavailability is between 79-100%
263
what is the distribution for warfarin
Protein binding is 99%
264
how is warfarin metabolised
liver
265
how is warfarin excreted
Kidney
266
what are the formulation of warfarin
Injection, tablet, solution
267
what is the therapeutic indication of warfarin
Loading dose 5-10mg Daily maintenance dose 3-9mg at the same time each day Dose depends on patient’s prothrombin time (INR), wide interindividual variation in dose
268
what are the side effects of warfarin
Haemorrhage Skin necrosis Hypersensitivity
269
what are the interactions of warfarin
``` enhances anticoagulant effects: NAIDs including aspirin anti-arrhythmias eg amiodarone antibacterials- chloramphenicol anti fungals lipid lowering drugs ulcer healing drugs ``` ``` reduces anti coagulant effects: antieplieptics antifungals oral contraceptives vitamin k retinoids antidepressants ```
270
what are the contraindications of warfarin
Caution in patients who have undergone recent surgery, those taking other druigs which increase the risk of bleeding and those with renal impairment (avoid if severe) Avoid in pregnancy, peptic ulcer disease, severe hypertension and those with hepatic impairment (especially if prothrombin time already prolonged)
271
name the brand names of warfarin
Coumadin, Jantoven
272
what is the MoA for Zopiclone
these drugs bind with high selectivity to the α1 subunit of the GABAA receptor/chloride ion channel complex. As such they have strong hypnotic activity but negligible anxiolytic, myorelaxant and anticonvulsant properties. They are for short term use only (up to 4 weeks).
273
what is the absorption of Zopiclone
The bioavailability is between 75-80%
274
what is the distribution of Zopiclone
Protein binding is between 52-59%
275
how is Zopiclone metabolised
hepatic
276
how is Zopiclone excreted
urine
277
name the different formulations of Zopiclone
tablet
278
what is the therapeutic indication of Zopiclone
For adults 7.5 mg once daily for up to 4 weeks, dose to be taken at bedtime. For elderly Initially 3.75 mg once daily for up to 4 weeks, dose to be taken at bedtime, increased if necessary to 7.5 mg daily.
279
what are the side effects of Zopiclone
Dry mouth, `anxiety, dizziness. Confusion
280
what are the interactions of Zopiclone
Antihypertensives (enhanced hypotensive effect) | Clozapine
281
what are the contraindications of Zopiclone
Marked neuromuscular respiratory weakness; myasthenia gravis; respiratory failure; severe sleep apnoea syndrome Don’t take while pregnant and breastfeeding Don’t drive while taking this medication or using heavy machinery as can make you feel drowsy
282
name the brand names of Zopiclone
Imovane