Lecture notes - dexamphetamine, diazepam, dicloxacillin and flucloxacillin, donepezil, famciclovir PDF

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- - - - merged files: Dexamphetamine.docx - diazepam.docx - Dicloxacillin and flucloxacillin.docx - Donepezil.docx - Famciclovir.docx...

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Dexamphetamine (5mg tabs breakable) MoA: ↑dopaminergic and noradrenergic neurotransmission activity - Immediate improvement in impulsive behaviours but less effective in aggressive behaviours - This helps compensatory brain neural networks which promote more appropriate cognition, behaviour and emotions in children with ADHD) Indications:  ADHD  Narcolepsy o Brain's inability to regulate sleep-wake cycles normally o People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia Dose  ADHD (I f total daily dose >5 mg, give in 2 or 3 doses (morning, lunch and afternoon)  usual range of 0.5– 1 mg/kg (max40 mg) daily o 6-12 years - initially 2.5 mg in the morning for 1 week; increase daily dose by 2.5–5 mg each week, according to response and tolerability, to usual range. o >12 years - initially 5 mg in the morning for 1 week; increase daily dose by 5 mg each week as clinically indicated to usual range  Narcolepsy o initially 10 mg each morning; gradually increase as clinically indicated to a max of 60 mg daily in divided doses common: insomnia, ↓appetite, tachycardia, palpitation, ↑BP  As its stimulant so sympa s/e o infreq: o rare: psychosis), o

Adverse Effects (Most adverse effects of dexamphetamine are dose-dependent)  Common - its stimulant so sympa s/e o insomnia (from too much NA) o sympa sx: tachycardia, palpitation, ↑BP o loss of appetite o headache (vasodilate), nausea, 

Infrequent: o movt disorders, tics (sudden movt) o from loss of appetite weight loss, growth retardation

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Rare: psychosis(as ↑neuronal activity), liver dysfunction

Precautions  Substance abuse  C/I  Acute psychotic disorder  C/I as can worsen  Drug diversion by parents/carers/sibling C/I   

Treatment with, or within 14 days of stopping, a MAOI  C/I Tic disorders, Tourette's syndromemay be exacerbated by dexamphetamine; monitor closely or consider alternative treatment, eg atomoxetine, clonidine. Diseases (you don’t want ↑symp tone) will worsen from it: Tx use with care and seek specialist advice o Cardiac: Angina, arrhythmia hypertension o o

hyperthyroidism, glaucoma, CNS; anxiety, agitation, phaeochromocytoma (tumour on medulla gland)

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Structural cardiac abnormalitiesuse with caution as sudden death has been reported with psychostimulants. Pregnancy (CAT B3) o Previously commenced therapy should be tapered off as soon as pregnancy is suspected (APF) o Minimum effective dose should be used for narcolepsy (APF) Breastfeeding - Significant amounts may enter breast milk avoid

Monitor:  Weight , height: growth suppression, weight loss  BP, HR  sleep Interactions  MAOIs (phenelzine, tranylcypromine, linezolid) o Given with nonselective MAOI result in hypertensive crisis and possibly cause intracranial haemorrhage or acute heart failure; avoid combination o Need to wait 14 days after discontinuing MAOI before starting dexamphetamine  Moclobemide (reversible inhibitor of MAO-A) o may result in hypertensive crisis, although this is less likely to occur than with a nonselective MAOI; avoid combination Counselling  Indication: This medication has a few uses… o ADHD  This medication will help you concentrate better o Narcolepsy  This medication will help you combat any day time sleepiness  Dose o Take as directed by the doctor - This medication may cause loss of appetite so take after breakfast o Avoid taking doses later than 2pm as this medication can cause you to have trouble sleeping at night ( this may make you feel drowsy next day)  Adverse effects o Some other side effects include headache and nausea, o It can also cause your heart to beat faster and may increase your blood pressure so if you have high BP  be sure to monitor your blood pressure closely  Referral o If you feel and chest pain, SOB or tightness in the chest you need to go to the emergency department immediately o if you feel like your condition is not well controlled you should go back to the doctor  Lifestyle o Because of the restrictions placed on this medication we need to keep your prescription here and if you require any further repeats you will need to come back to this same pharmacy o Avoid any Strenuous exercise or activity and drinking alcohol while taking DEXAMPHETAMINE. If you drink alcohol, it could make some of the unwanted side effects of DEXAMPHETAMINE worse o Worsen the dizziness, headache o Monitor: weight o ADHD: o Keep instructions brief and clear o May Need more prompting, encouraging o Use a school-home communication diary to keep informed with the teacher Practice points  Do not continue dexamphetamine if there is no benefit after optimal treatment 

studies show that atomoxetine and psychostimulants used to treat ADHD are not associated with increased risk of CV events, eg stroke, MI

BZD: Diazepam - MOA: they bind to an accessory site on the GABAa recep that promotes the binding of GABA to GABAa recep cause Cl channel to open  Cl- ions go in  causes hyperpolarisation so harder to excite the cell ↓firing of neuron ↓excitation - Tx: Epilepsy: - Acute Tx of seizures, including status epilepticus (Prolonged & uncontrolled seizure) o Prevention of recurrent febrile seizures, in children at high risk of severe or complicated seizures (seek specialist advice) - Muscle spasm Anxiety:  Short-term management of anxiety, agitation  Acute alcohol Benzodiazepine withdrawal

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Acute behavioural disturbance Parasomnias (night terrors, sleepwalking)

Dosage form: Ranzepam, Antenex , Valium , Valpam Tab 2mg, 5mg oral liquid , inj Dose: - Anxiety, agitation, parasomnias o Oral, 1–10 mg up to 3 times a day. - Premedication o IV, 0.1–0.2 mg/kg. - Acute severe anxiety, agitation, behaviour disturbance o IV, 5–10 mg, repeated if necessary every 5–10 minutes to a maximum of 30 mg. Benzodiazepine withdrawal - This is suitable only for people using more than the usual dose for sedation at night. - Oral, give a dose equivalent to estimated total daily BZD intake in 3 or 4 divided doses each day at fixed times; gradually taper dosage (eg by 10–20%) each week over several weeks. Supervision is required, eg regular review when withdrawal is undertaken as an outpatient. Elderly and/or debilitated - Halve the usual adult dose. Seizures - IV, 10 mg, repeat once after 10–15 minutes if necessary. - Rectal solution, 10–20 mg, repeat once after 10–15 minutes if necessary. Muscle spasm - IV, 10 mg, repeat if necessary after 4 hours. - Oral, 2–15 mg daily in divided doses up to a maximum of 60 mg daily. Administration advice - Give IV no faster than 5 mg/minute. - Avoid extravasation, intra-arterial or IM injection. - Avoid dilution and infusion of injection, as diazepam has low solubility and adsorbs to PVC giving sets. Precaution - Respiratory: C/I in respiratory depression. o Compromised respiratory drive in respiratory disease or sleep apnoea may result in hypoventilation and hypoxaemia. Musculoskeletal: C/I in myasthenia gravis

- Muscle weakness may worsen. Renal - Increased sensitivity to CNS effects in renal impairment; use a lower initial dose in severe impairment. Hepatic - C/I in severe hepatic impairment, particularly when hepatic encephalopathy is present. - In mild-to-moderate impairment, use low doses of a short-acting benzodiazepine to reduce risk of precipitating coma. Elderly - Use low doses of a short- or medium-acting agent; increased risk of oversedation, ataxia, confusion, falls, respiratory depression and short-term memory impairment. Children - Avoid, except short term in specific conditions (eg night terrors, sleepwalking); greater sensitivity to CNS effects. Pregnancy Cat C - Avoid if possible, particularly large doses and regular use (risk of growth restriction and neonatal withdrawal syndrome). Administration of high doses near term or during labour may cause respiratory depression, hypothermia and floppy infant syndrome (hypotonia, lethargy and poor suckling). If used during pregnancy short-acting drugs are preferable to long-acting; plan to stop gradually before delivery; Breastfeeding: Avoid repeated doses; may cause lethargy and poor feeding in infant. Adverse effects Common: drowsiness, oversedation, light-headedness, memory loss, hypersalivation, ataxia, slurred speech Infrequent: confusion, respiratory depression hypotension euphoria, - IV injection: pain and thrombophlebitis, severe hypotension, arrhythmias, respiratory arrest Rare - allergic rxn, blood disorders- leucopenia, , jaundice, transient elevated liver function tests

Interactions: o CNS depression drugs as BZD causes CNS depression Sx – drowsiness, RD, oversedation  –OH, antihistamines, antidepress, antipsy, opioid analgesic - When using BZD as an antiepileptic, use cautiously, if at all, with drugs that lower the seizure threshold

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Clozapine: BZD increase risk of respiratory arrest with clozapine; use with caution and appropriate monitoring, especially at start of treatment.

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Olanzapine: parenteral benzodiazepine given simultaneously with short-acting IM olanzapine is contraindicated  cardiorespiratory depression, oversedation o Tx: it at least 1 hour after IM olanzapine before giving a parenteral benzodiazepine

diazepam + phenytoin - Diazepam may possibly increase or decrease phenytoin concentration; monitor phenytoin concentration, for loss of efficacy and for phenytoin toxicity; adjust phenytoin dose as necessary. Monitor: crcl, LFT - a/e: Resp Rate, - No. of seizures Counsel D - If you take this medicine regularly for more than 2wks your body may become used to it and you may need a higher dose for it to continue to work. If you stop the medicine suddenly, you may have unpleasant effects (eg feeling anxious, difficulty sleeping). Discuss how to stop the medicine with your doctor first. A - You may feel drowsy while taking this medication; drowsiness may persist the following day; avoid driving or operating heavy equipment until you know how you react. - Avoid alcohol and other medications that may cause drowsiness while taking this drug.

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Practice points - use of diazepam for conscious sedation now less common; other agents, including midazolam, are often used in preference - reserve for short-term use only (eg 2–4 weeks); they should be part of a broader treatment plan, not a first or sole treatment

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Tolerance & dependence o BDZ best for short term use (2- 4 weeks) as Long-term use  physical dependence  ↑ dose & duration of BZD↑dependence o Tolerance also occurs during long-term use of BDZs o Sx= craving, disturbed work, drug-seeking behaviour etc If med is abruptly stoppedwithdrawal syndrome Withdrawal syndrome is worst for short t1/2 drugs o Sx (opp what they do)= anxiety, insomnia, seizures, hypertension, tachycardia, psychosis, hallucination o Hence need taper dose. o Tx: calculate the BZD total daily dose taken and change to equivalent Diazepam o Give diazepam in 3 divided doses and gradulally decrease dose by 10-20% q week. (usu take 1-2 months)

Epilepsy - Do not stop taking this medicine suddenly unless your doctor tells you to - Avoid meds that lower seizure threshold e.g SJW Practice points - rectal diazepam is often given instead of IV diazepam when IV access cannot be obtained; delayed respiratory depression may occur after rectal administration Practice points from Benzodiazepines - BZD are not generally suitable for long-term treatment of epilepsy because of their sedative effect and the development of tolerance in a high proportion of people - stop treatment if clear and lasting therapeutic benefit cannot be demonstrated - withdraw treatment slowly by gradually reducing the dose over several months (may need 6 months or longer)

Dicloxacillin/Flucloxacillin NARROW SPECTRUM Pc with anti-staph activity Spectrum:  + B-lactamse producing staph aureus (not against MRSA)  - has no G-ve activity e.g Neisseria, Pasterulla MOA: Pc Tx: Dicloxacillin/Flucloxacillin  staph skin infect: Boils (pus fill lesion), stab wounds, infected scabies, Folliculitis (inflam hair follicles), Bullous impetigo  Pneumonia  Osteomyelitis, septic arthritis  Septicaemia  Empirical tx for endocarditis  Surgical prophylaxis Dosage form: Dicloxacillin  For srs staph infections: cap, 250 mg, 500mg Distaph, Diclocil  inj, 500 mg, 1g Flucloxacillin - cap 250,500mg Flopen, Staphylex - oral liq 25 mg/mL, 50 mg/mL Flucil - inj 500mg, 1g

Dosage: Dicloxacillin/Flucloxacillin Adult: - Oral, 250–500 mg every 6 hours. Max 4 g daily. - IV, 1–2 g every 6 hours. Maximum 12 g daily, eg endocarditis, staphylococcal pneumonia. Renal impairment - CrCl 2 weeks; pre-existing hepatic impairment is not a risk factor. Precautions from Penicillins = see Amoxycillin

Adverse effects Common: can ↑liver enzymes & bilirubin so need monitor Rare: - cholestatic hepatitis o (May occur less frequently with dicloxacillin than flucloxacillin; risk is higher in people >55 years and with courses >2 weeks.

A/e from Penicillins – see Amoxycillin Interactions Pc- see Amoxycillin Warfarin: Dicloxacillin may decrease warfarin's anticoagulant effect; monitor INR and increase warfarin dose if necessary. Monitor: - LFT: liver enzymes(AST" and "ALT) and bilirubin o As high lvls of AST, ALT in blood means something wrong with liver as releasing them o monitor LFT if tx continues for >2 wks, esp if there are other risk factors - Crcl - a/e: allergy

Counsel : See- Amoxycillin D: This medicine is absorbed best if taken on an empty stomach at least ½ an hour before food or 2 hours after food.

Practice points Flucloxacillin May be used as an alternative to dicloxacillin and vice versa Practice points from Penicillins – see Amoxicillin

Anticholinesterases: Donepezil ( tab 5,10mg: Aricept, Aridon), - Galantamine, Rivastigmine MoA: ↓breakdown of Ach by inhibit cholinesterase. Reducing the deficiency of cholinergic neurotransmitter activity in Alzheimer's disease. Indication: Alzheimer’s Disease Dose: Initially 5 mg OD for a min of 4 weeks. Increase to 10 mg OD according to clinical response Adverse Effects  Common o GI s/e: NVD, abdominal pain, dyspepsia weight loss, anorexia o as parasym NS more acid release o Parasymp sx: urinary incontinence(involuntary peeing), sweating, o Brain s/e: dizzy, drowsy, headache o Sleep: vivid dreams, insomnia, o hypertension, syncope (faint) , fatigue o tremor, muscle cramps,  Infrequent o Parasymp sx: bradycardia, heart block o seizure, GI haemorrhage o (too much Ach) hallucination, confusion  Rare o neuroleptic malignant syndrome (NMS) - a life-threatening neurological disorder most often caused by an adverse rxn to neuroleptic/ antipsychotic drugs - Sx (due too much Ach/low DA): muscle rigidity, fever, tachycardia, autonomic instability and cognitive changes such as delirium, and is associated with elevated plasma creatine phosphokinase - Treatment 1. The first step is to stop neuroleptic drugs 2. Treat the hyperthermia aggressively, such as with cooling blankets or ice packs to the axillae (armpit) and groin. 3. Supportive care in ICU capable of circulatory and ventilatory support is crucial Precaution   

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GI or ureteric obstruction—C/I Active peptic ulcer—C/I as cause dyspepsia, GI haemorrhage People with these diseases - risk of aggravation. o Hx of peptic ulcer disease – see active peptic ulcer o Seizures – lowers seizure threshold o heart block, bradyarrhythmias (including sick sinus syndrome), - as causes bradycardia o (DRP) Parkinson's disease* - as in PD’s there is low DA and high Ach o asthma, obstructive pulmonary disease— as causes bronchoconstriction (parasym effect) Tx with drugs with anticholinergic effects antagonises therapeutic effect; avoid combination. Tx with drugs that can cause bradycardia—increases risk of bradycardia and hypotension; use with caution. Pregnancy: Cat B3 o Avoid use (galantamine CAT B1; rivastigmine CAT B2) Breastfeeding: No data available; avoid breastfeeding

Interactions  Drugs with anticholinergic activity= antagonise the effects of anticholinesterases; o Tx: avoid these combinations.  Drugs that can cause bradycardia= Anticholinesterases cause bradycardia  Additive bradycardia + hypotension o Tx: Monitor heart rate and BP 

Suxamethonium (Indication: Skeletal muscle relaxation in anaesthesia) o Anticholinesterases, eg neostigmine, donepezil may increase acetylcholine concentration and prolong activity of suxamethonium o use cautiously and monitor neuromuscular blockade closely

Counselling  I: This medication is to manage your Alzheimer’s disease (which involves brain tissue degeneration). o Moa: There is an imbalance of chemicals in your brain, the drug helps correct this  Dose o take in the evening just before bedtime, but if your feel that you are having trouble sleeping (insomnia or vivid dreams) you can take it in the morning o Try to take it at around the same time each day so that your remember to take them o You need to take this medication everyday even if you are feeling well o It may take several weeks for donepezil to take effect, so do not be discouraged if you do not see an improvement straight away.  Adverse Effects o Common a/e: NV, headache and loss of appetite o #12 This medication may also make you dizzy or drowsy so do not drive or operate machinery until you know how this medication affects you o #16 You may feel dizzy when standing so get up slowly from a sitting or lying position  Referral o You need to see your doctor immediately if you have a sudden increase in temp, BP and severe muscle rigidity o You also need to see a doctor if you Trembling and shaking of the hands and fingers, shuffling walk and stiffness of the arms and legs  Lifestyle o If you forget to take it for more than one week, call your doctor before taking any more o If you have trouble remembering to take your medication just let me know and I may be able to help you – e.g webster pack

Practice points  dose of 10 mg daily appears to provide marginally more benefit than 5 mg daily but increases risk of a/e  omit 1 or more doses if a/e occur; reduce to previous well-tolerated dose if a/e persist  if treatment is interrupted for several days, restart at initial dosage to min the risk of severe vomiting  anticholinesterases do not reduce the risk of developing Alzheimer's disease or dementia in patients with mild cognitive impairment

Antiviral: Guanosine analogue Aciclovir (ACV), Valaciclovir (prodrug of ACV), Ganciclovir Valganciclovir (prodrug of ganciclovir) Famciclovir 125mg, 250mg, 500mg Famvir MOA: acts as nucleoside analogue and slots into vDNA, inhibtting DNA syn Tx: - Tx/ Px of herpes simplex infections (aciclovir, famciclovir, valaciclovir) - Shingles (i.e varicella zoster virus reactivation) (aciclovir, famciclovir, valaciclovir) Dose -

for renal impairment: Give dose immediately after haemodialysis o Need a lower dose as drug is cleared slower Immune-compromised need a higher dose

Genital herpes simplex Immunocompetent adult: normal renal function -

Initial infection, 250 mg TDS for 5–7 days.

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Recurrent infection, 125 mg BD for 5 days

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or 500 mg for the first dose, then 250 mg every 12 hours for 3 doses

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or 1 g BD for 1 day.

Prevention, 250 mg BD

Immunocompetent adult: renal impairment -

Recurrent infection (5-day course) or prevention, CrCl 10–29 mL/minute, 125 mg BD

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Recurrent infection (1-day course): o

CrCl 40–59 mL/minute, 500 mg BD

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CrCl 20–39 mL/minute, 500 mg as a single dose.

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CrCl...