Revise Pharma Notes PDF

**[Contents]** {#contents.TOCHeading} ========================== [Central Nervous System 5](#central-nervous-system) [Epilepsy 5](#epilepsy) [Bipolar Disorder 9](#bipolar-disorder) [Dementia 10](#dementia) [Parkinson Disease 11](#parkinson-disease) [Psychosis & Schizophrenia 13](#psychosis-sch...

**[Contents]** {#contents.TOCHeading} ========================== [Central Nervous System 5](#central-nervous-system) [Epilepsy 5](#epilepsy) [Bipolar Disorder 9](#bipolar-disorder) [Dementia 10](#dementia) [Parkinson Disease 11](#parkinson-disease) [Psychosis & Schizophrenia 13](#psychosis-schizophrenia) [Anxiety 16](#anxiety) [Depression 17](#depression) [Sleep Disorders 20](#sleep-disorders) [Attention Deficit Disorder 21](#attention-deficit-disorder) [Substance Dependence 22](#substance-dependence) [Migraines 24](#migraines) [Nausea & Vomiting 25](#nausea-vomiting) [Pain Management 26](#pain-management) [Multiple Sclerosis 28](#multiple-sclerosis) [Infectious Disease 29](#infectious-disease) [Antimicrobial Stewardship 29](#antimicrobial-stewardship) [Prescribing Pathways: 29](#prescribing-pathways) [Antibiotics 34](#antibiotics) [Tuberculosis: 45](#tuberculosis) [Malaria 45](#malaria) [Fungal Infections 48](#fungal-infections) [Viral Infections 49](#viral-infections) [Endocrine System 50](#endocrine-system) [Antidiuretic Hormone Disorders 50](#antidiuretic-hormone-disorders) [Corticosteroids 51](#corticosteroids) [Diabetes Mellitus 54](#diabetes-mellitus) [Osteoporosis 65](#osteoporosis) [Sex Hormone Responsive Conditions 67](#sex-hormone-responsive-conditions) [Thyroid Disorders 69](#thyroid-disorders) [Cardiovascular System 72](#cardiovascular-system) [Arrythmias 72](#arrythmias) [Bleeding disorders 79](#bleeding-disorders) [Heart failure 79](#heart-failure) [Hyperlipidaemia 80](#hyperlipidaemia) [Hypertension 82](#hypertension) [Myocardial Ischemia 86](#myocardial-ischemia) [Oedema 88](#oedema) [Stroke 90](#stroke) [Thromboembolism 91](#thromboembolism) [Gastrointestinal System 96](#gastrointestinal-system) [Anal Fissures and Haemorrhoids 96](#anal-fissures-and-haemorrhoids) [Chronic Bowel Disorders 96](#chronic-bowel-disorders) [Constipation 101](#constipation) [Diarrhoea 103](#diarrhoea) [Gastric Acid Disorders and Ulceration 104](#gastric-acid-disorders-and-ulceration) [Irritable Bowel Syndrome 107](#irritable-bowel-syndrome) [Liver Disorders 108](#liver-disorders) [Pancreatic Insufficiency 108](#pancreatic-insufficiency) [Short Bowel Syndrome 109](#short-bowel-syndrome) [Stoma Care 109](#stoma-care) [Genito-Urinary Tract System 111](#genito-urinary-tract-system) [Urinary Incontinence 111](#urinary-incontinence) [Urinary Retention 113](#urinary-retention) [Contraception 115](#contraception) [Erectile Dysfunction 121](#erectile-dysfunction) [Respiratory System 123](#respiratory-system) [Asthma 123](#asthma) [COPD 126](#copd) [Inhalation Therapies 128](#inhalation-therapies) [Croup 130](#croup) [Allergies & Anaphylaxis 130](#allergies-anaphylaxis) [Cystic Fibrosis 132](#cystic-fibrosis) [Immune System & Malignant Disease 133](#immune-system-malignant-disease) [Immunosuppression Therapy 133](#immunosuppression-therapy) [Cytotoxic Drugs 135](#cytotoxic-drugs) [Cytotoxin Side-Effects 135](#cytotoxin-side-effects) [Blood & Nutrition 140](#blood-nutrition) [Anaemias 140](#anaemias) [Neutropenia 143](#neutropenia) [Fluid and Electrolyte imbalance 143](#fluid-and-electrolyte-imbalance) [Metabolic Disorders 147](#metabolic-disorders) [Vitamins + Vitamin Deficiency 147](#vitamins-vitamin-deficiency) [Musculoskeletal System 150](#musculoskeletal-system) [Eyes 154](#eyes) [Ears, Nose & Oropharynx 155](#ears-nose-oropharynx) [Skin Conditions 156](#skin-conditions) [Vaccines 159](#vaccines) [Anaesthesia 161](#anaesthesia) Central Nervous System ====================== Epilepsy -------- [Focal Seizures:] Frist line Treatment: Lamotrigine or Levetiracetam Second line Treatment: Carbamazepine, Oxcarbazepine, Zonisamide [Generalised Seizures:] Tonic-Clonic: 1. Sodium Valproate 2. Lamotrigine/Levetiracetam Absence (ONLY): 1. [Ethosuximide] 2. [Sodium Valproate] Absence (Patients with absence seizures AND other seizure types too): 1. Sodium Valproate 2. Lamotrigine/Levetiracetam Myoclonic: 1. Sodium Valproate 2. Levetiracetam Atonic: 1. Sodium Valproate 2. Lamotrigine Tonic: 1. Sodium Valproate 2. Lamotrigine **Women to take second line option if at child bearing potential age -- currently, or in the future** October 2023 - MHRA Update: Full pack dispensing required for sodium valproate.\ November 2023 - MHRA Update: **Valproate must not be started in new patients (male or female) aged under 55 years, unless two specialists independently consider and document that there is no other effective or tolerated treatment.\ **June 2024 - MHRA Update: Topiramate is now contraindicated in pregnancy and women of childbearing potential unless the conditions of a Pregnancy prevention programme are fulfilled.\ September 2024 - MHRA Update: Male patients who may father children should use effective contraception during valproate treatment and for at least 3 months after stopping valproate. **Status Epilepticus:** Seizures lasting longer than 5 minutes Provide resuscitation and immediate emergency treatment: 1. Patient has an individualised emergency management plan that is immediately available 2. Patient doesn't have an individualised emergency management plan immediately available Treatment: - Seizures lasting longer than 5 minutes: - IV Lorazepam (if resuscitation facilities are available) - Buccal Midazolam or Rectal Diazepam (if in community) - Give a second dose if seizure doesn't stop within 5-10 minutes of first dose - If seizure fails to respond after 2 benzodiazepine doses: - Levetiracetam, Phenytoin, Sodium Valproate - If seizure fails to respond, try another second line. - If still not responding: - Phenobarbital or General Anesthesia [Anti-Epileptic Drugs:] **[Category 1]** Ensure patients are maintained on a specific brands. Carbamazepine, Phenobarbital, Phenytoin, Primidone **[Category 2]** Maintaining specific brand should be based on clinical judgement with patients' factors considered Clobazam, Clonazepam, Lamotrigine, Oxcarbazepine, Perampanel, Rufinamide, Topiramate, Valproate, Zonisamide **[Category 3]** Unnecessary to ensure patients are maintained on a specific brand Brivaracetam, Ethosuximide, Gabapentin, Lacosamide, Levetiracetam, Pregabalin, Tiagabine, Vigabatrin [Anti-Epileptic Interactions:] Carbamazepine, Phenytoin + Sodium Valproate: - Hepatoxicity: Amiodarone, Itraconazole, Macrolides, Alcohol - CYP Enzyme: Inducers (Phenytoin, Phenobarbital and Carbamazepine), Inhibitors (Sodium Valproate) - Drugs that lower seizure threshold: Tramadol, Theophylline, Quinolones Carbamazepine: Hyponatraemic drug (SSRI, Diuretics) Phenytoin: Anti-folates (Methotrexate, Trimethoprim) [Anti-Epileptic Drug Side-Effects:] Carbamazepine, Phenytoin + Sodium Valproate: - Depression - Hepatotoxicity - Hypersensitivity - Blood Dyscrasia - Vitamin D Deficiency - Exam question: Patient comes in complaining of bone pain, this is related to vitamin d deficiency. Check if they are on antiepileptic drugs Carbamazepine: Hyponatraemia + Oedema Phenytoin: Coarsening Appearance + Facial Hair Sodium Valproate: Pancreatitis + Teratogenic General side-effects: - Hypersensitivity: Carbamazepine, Phenobarbital, Phenytoin, Primidone, Lamotrigine (CP3L) - Skin rash: Lamotrigine Stevens-Johnson syndrome - Blood dyscrasia: Carbamazepine, Valproate, Ethosuximide, Topiramate, Phenytoin, Lamotrigine, Zonisamide (C.VET.PLZ) - Eye disorder: Vigabatrin (reduced visual field) Topiramate (second glaucoma) - Encephalopathy: Vigabatrin - Respiratory Depression: Gabapentin, Pregabalin [Carbamazepine --] Therapeutic Range: 4-12 mg/L Signs of Toxicity: - Hyponatraemia - Ataxia - Nystagmus - Drowsiness - Blurred vision - Arrhythmias - Gastrointestinal Disturbances [Phenytoin -- ] Therapeutic Range: 10-20 mg/L Signs of Toxicity: - Slurred Speech - Nystagmus - Ataxia - Confusion - Hyperglycaemia - Double Vision Epilepsy -- Driving - Driver must stop driving immediately and inform DVLA - First unprovoked/single isolated: stop driving for 6 months - Established epilepsy: stop driving for 1 year (or pattern of seizures established for 1 year with no impact on consciousness) - Medication change/withdrawal: - Should not drive for 6 months after last dose/dose change - Seizure occurs: license revoked for 1 year, reinstated for after 6 months if treatment resumed and no further seizures occur Epilepsy -- Pregnancy - Risk of harm to the mother and fetus from convulsive seizures outweighs the risk of continued therapy - Folic acid given, reduce the risk of neural tube defects in first trimester - Vitamin K injection administered at birth to minimise risk of neonatal hemorrhage - Most risk: Sodium Valproate (PPP) - Topiramate: Cleft Palate Epilepsy -- Breastfeeding - Encouraged to breast-feed if on single therapy - Seek specialist advice if combination therapy or risk factors (premature birth) - High presence in milk: Primidone, Ethosuximide, Lamotrigine, and Zonisamide (PELZ) - Risk of drowsiness: Primidone, Phenobarbital, and Benzodiazepines - Withdrawal effects (mother suddenly stops breast-feeding): Phenobarbital, Primidone, Benzodiazepines, and Lamotrigine Bipolar Disorder ---------------- **Extreme fluctuation between [manic] phases (overactive and excitability) and [depressive] phases (reclusive and lethargic)** [Treatment:] Acute: - Benzodiazepines - Antipsychotic drugs (normally Quetiapine, Olanzapine, or Risperidone) - Add in **Lithium** or sodium valproate Prophylaxis: - Carbamazepine, Sodium Valproate or Lithium Exam Question: A patient comes in to A&E, they have blurred vision, nausea, vomiting, confusion and tremor. Which drug is causing their toxicity? Is it Sodium Valproate, Quetiapine, Olanzapine, Lithium, Digoxin or Theophylline? -- Lithium [Lithium:] Therapeutic Range: **0.4 -- 1 mmol/L** (Acute episodes: **0.8 -- 1 mmol/L**) Measure levels 12 hours after a dose Weekly till stable, then 3 monthly for year 1, and then 6 monthly after that Toxicity - **R**enal impairment -- incontinence **E**xtrapyramidal Side-effects -- tremor **V**isual disturbances -- blurred vision **N**ervous system disorder -- confusion and restlessness **G**astrointestinal disorder -- diarrhoea and vomiting SICK + TREMOR The thing that distinguishes lithium, theophylline and digoxin toxicity is the tremor!! For Theophylline sis signs is sick and fast -- palpitations, tachycardia For Digoxin -- sick (diarrhoea, nausea, vomiting) and slow Side-Effects -- - Thyroid disorder - Nephrotoxicity - Rhabdomyolysis - QT Prolongation - Benign Intercranial Hypertension, i.e. headaches - 1^st^ Trimester = teratogenic Interactions -- - Hyponatraemia increases risk of toxicity -- diuretics - Salt imbalance -- whilst on lithium key to maintain good salt and fluid levels - Serotonin syndrome - Drugs that cause extrapyramidal side-effects -- haloperidol & metoclopramide, also antipsychotics - QT prolongation - Renally cleared drugs (increase risk of toxicity) - Reduced seizure threshold - Hypokalaemia Dementia -------- Treatment: increase the amount of acetylcholine Treatment of mild to moderate dementia: acetylcholinesterase inhibitors *Acetylcholinesterase Inhibitors: Inhibit the protein that breaks down acetylcholine* - Donepezil -- Neuroleptic Malignant Syndrome - Rivastigmine -- Gastrointestinal Side- effects (reduced in transdermal formulation) - Galantamine -- Stevens-Johnson Syndrome Treatment of moderate dementia: Memantine Aggravation in dementia is treated with antipsychotics Antipsychotics cannot be used in patients with Parkinsons disease [Side-Effects:] Increased Acetylcholine Parasympathetic Side-Effects Parasympathetic system is rest, digest and secrete. Rest = relaxation of muscles, lower heart rate Digest = diarrhoea Secret = urinary incontinence, salvation **D**iarrhoea **U**rinary Incontinence **M**uscle Weakness **B**radycardia **B**ronchospasms **E**mesis **L**acrimation **S**alivation Parkinson Disease ----------------- Treatment is increasing the amount of dopamine in the body Two types of patients: 1. Patients whose motor symptoms [decrease their quality of life]: a. Levodopa + Carbidopa / Benserazide 2. Patients whose motor symptoms [don't affect their quality of life]: b. Levodopa c. Non-ergot-derived dopamine-receptor d. Monoamine-oxidase-B inhibitors [Levodopa:] - Carbidopa/benserazide is added in order to prevent the breakdown of levodopa before it crosses into the brain - Only 10% of levodopa crosses the blood brain barrier -- and 10% of that, i.e. 1% of drug actually reaches the correct part of the brain Side-Effects: - Impulse disorder - Pathological Gambling - Binge eating - Hypersexuality - Sudden onset of sleep (treat with modafinil) - Red urine [Non-Ergot-Derived Dopamine-Receptor:] E.g. Pramipexole, Ropinirole and Rotigotine Side-Effects: - Impulse disorders - Sudden onset of sleep - Hypotension Non-ergot drugs are the most likely to create the most impulse disorders [Monoamine-Oxidase-B Inhibitors:] E.g. Rasagiline or Selegiline - Causes hypertensive crisis if given with phenylephrine (Sudafed) Patients who develop dyskinesia or motor fluctuations despite optimal levodopa therapy should add an adjuvant to the levodopa: - Non-ergotic dopamine-receptor agonists, monoamine oxidase B inhibitors - COMT Inhibitors [COMT Inhibitors:] E.g. Entacapone or Tolcapone Entacapone: Red-brown urine Tolcapone: Hepatotoxic Increase sympathetic side-effects -- Increase in CVD events Exam question: Work of the strength of the patch that is recommended for the patient? If symptoms are not adequately controlled with a non-ergot-derived dopamine-recpetor agonist as an adjunct to levodopa: - Ergot-derived dopamine-receptor agonist [Ergot-derived dopamine-receptor agonists:] E.g. Bromocriptine and Cabergoline Pulmonary Reactions: Report SOB, Chest Pain and cough Pericardial Reactions: Chest pain *Bromocriptine also used in Neuroleptic malignant syndrome* - Do not withdrawal medication abruptly - If person has "off periods" due to end of dose deterioration -- use MR preparations - Treat nocturnal akinesia with levodopa or oral dopamine-receptor agonist as first-line options and rotigotine as second-line 20/01/2024 - Monoamine oxidase-B (MAO-B) inhibitors (selegiline, rasagiline, and safinamide) do not cause an interaction after consumption of tyramine-rich foods. Interactions still occur with MAO-A inhibitors. Psychosis & Schizophrenia ------------------------- Positive symptoms: Delusions, hallucinations, disorganisations Negative symptoms: Social withdrawal, neglect, poor hygiene Two classes of antipsychotics: First-generation and Second-generation. In practice second-generation is used, most commonly aripiprazole due to much smaller side-effect profile **[First-Generation: ]** **[Phenothiazines]** Group 1 Chlor[promazine], levome[promazine] and [promazine] Mose sedation, moderate antimuscarinic and EPSEs Groups 2 Pericyazine Moderate sedation, least EPSEs Group 3 Fluphenazine, prochlorperazine and trifluoperazine Moderate sedation, high EPSEs In Parkinsons there is a decreased amount of dopamine in the body. Antipsychotics further decrease the levels of dopamine, therefore antipsychotics are contraindicated in Parkinson. Especially Group 3 drugs due to the EPSE side effects **[Butyropenones ]** Ben[peridol] and halo[peridol] Moderate sedation, high EPSEs (similar to group 3 phenothiazines) **[Thioxanthenes ]** Flupentixol and zuclopenthixol Moderate sedation, antimuscarinic effects and EPSEs **[Others]** Pimozide and sulpiride Reduced sedation, antimuscarinic effects and EPSEs **[Second-Generation, i.e atypical antipsychotics ]** - Amisulpride - Aripiprazole - Clozapine - Olanzapine - Quetiapine - Risperidone Exam question: A patient comes into the pharmacy complaining that since they have started their antipsychotics they have gained a lot of weight, which of the following drugs is the cause? - Amisulpride, Aripiprazole, Clozapine, Olanzapine, Quetiapine, Risperidone Answer: Clozapine and Olanzapine [Side-effects:] - Extrapyramidal Side-Effects: Most in Group 3 Phenothiazine and Butyrophenones - Hyperprolactinaemia: Least in Aripiprazole - Sexual dysfunction: All Antipsychotics - Cardiovascular Side-Effects: QT Prolongation most common with Pimozide and Haloperidol - Hypotension: Clozapine & Olanzapine - Hyperglycaemia: Clozapine, Risperidone, Olanzapine and Quetiapine - Weight gain: Clozapine and Olanzapine - All psychotic drugs have a risk of Neuroleptic Malignant Syndrome - Stop treatment Treat with Bromocriptine Should resolve in 5-7 days [Monitoring:] - **Weight**: Start, weekly for the first 6 weeks, at 12 weeks, at 1 year, then yearly - **Fasting blood glucose, HbA1c and blood lipid concentrations**: Start, at 12 weeks, at 1 year, and then yearly - **ECG**: Before initiation - **Blood pressure**: Start, at 12 weeks, at 1 year, then yearly - **FBC, U&E's and LFTs**: Start, then yearly **[Clozapine:]** - Used in resistant schizophrenia: - Only used when 2+ antipsychotics including one 2^nd^ Generation has been used for 6-8 weeks each - If missed more than 48 hours of doses - specialist reinitiation        - Monitor leucocyte and differential blood counts: - Weekly for 18 weeks - Fortnightly till one year - Monthly for the rest of treatment and 1 month after Side-Effects: - Myocarditis and Cardiomyopathy: - *Most common side effect* - Report and stop on tachycardia - Agranulocytes and Neutropenia: - Monitor leucocyte and differential blood counts as previously mentioned - Gastrointestinal Disturbances: - Report and stop on constipation intestinal block Anxiety ------- Treatment: [Acute:] - Benzodiazepines [Chronic:] - SSRI -- Sertraline, Citalopram, Escitalopram, Fluoxetine - Propranolol -- alleviates physical symptoms only **[Benzodiazepines ]** - Use very carefully, especially in elderly - Can induce hepatic coma, especially long-acting benzodiazepines - Treat with lowest dose for shortest period - Long-acting benzodiazepines: Diazepam, alprazolam, chlordiazepoxide hydrochloride, and clobazam - Short-acting benzodiazepines: Lorazepam, oxazepam and midazolam - Short-acting preferred in patients with hepatic impairment and elderly - Short-acting carry a great risk of withdrawal symptoms (use for 2-4 weeks) - Can cause paradoxical effects: - Aggression, hostility, talkative, anxious, excited etc - Sedation increased with use of alcohol, CNS depressants or CYP Enzyme Inhibitors -- avoided concomitant use - Avoid driving if feeling drowsy - Benzos that have a legal driving limit: Clonazepam, Oxazepam, Lorazepam, Diazepam, Flunitrazepam and Temazepam (COLD FT) - Overdose treated by flumazenil [Withdrawal:] Dependence: anxiety, sweating, weight loss, tremors, loss of appetite Three steps: 1. Convert all medication to a once nightly dose of diazepam, e.g. table in BNF that converts dose of lorazepam to diazepam 2. Reduce by 1-2mg (1/10^th^ on larger doses) every 2-4 weeks a. Only further withdrawal if the patient has overcome any withdrawal symptoms 3. Reduce further (0.5mg near the end) Depression ---------- A reduction of serotonin, dopamine, norephedrine at the synaptic cleft - Mild: Cognitive Behavioural Therapy - Moderate-Severe: Antidepressants - Patient may feel worse in the first 1-2 weeks - Should be taken for 4 weeks (6 weeks in elderly) before deemed ineffective - Take for 6 months after remission, 1 year in elderly, 2 years in recurrent [Treatment:] First line treatment with SSRI: - If that doesn't work: - Increase dosage - Change SSRI - Mirtazapine - MAO-I (specialist) - TCA or Venlafaxine (severe) - If that doesn't work, add in another class, lithium or antipsychotics - Use electroconvulsive therapy in sever refractory depression Exam question: A 15 year old girl visits GP, she has depression and wants to be prescribed an SSRI. The GP is unaware of which one to prescribe. The options are: Sertraline, Fluoxetine, Mirtazapine or Citalopram. Answer: Fluoxetine. As 17 years or less, first line Fluoxetine Exam Question: If patient has risk of bleeding, which one would be used? Sertraline, Fluoxetine, Mirtazapine or Citalopram. Answer: Mirtazapine [SSRIs] - Better tolerated and are safer in overdose - Considered first-line for treating depression - Sertraline safest in patients with cardiac events - In children aged 17 and under -- use fluoxetine Side-Effects: - GI disturbances (Diarrhoea and Vomiting) - Appetite/Weight gain - Sexual dysfunction - Risk of bleed - Insomnia (Take medication in morning) - QT prolongation (Escitalopram + Citalopram) Interactions: - CYP Enzyme Inhibitors (avoid grapefruit, increase plasma concentration) - CYP Enzyme Inducers (reduce effectiveness) - Drugs that cause QT prolongation (Amioderone, Sotolol, Quinolones) - Drugs increasing risk of bleed - Hyponatraemia (Carbamazepine and diuretics) - Serotonin syndrome Serotonin syndrome - Cognitive effects: Headache, agitation, hypomania, coma, confusion - Autonomic effects: Sweating, hyperthermia, nausea, diarrhoea - Neuromuscular excitation: Myoclonus, tremor, teeth grinding - Caused by: - SSRIs, TCA, MAO-I - Triptans - Tramadol - Lithium - Antibiotic: Linezolid [Tricyclic Antidepressants] - Sedating -- better for agitated and anxious patients - Amitriptyline, clomipramine, dosulepin and trazadone - Less sedating -- better for withdrawn and apathetic patients - Imipramine, Lofepramine and nortriptyline **Amitriptyline + Dosulepin: dangerous in overdosage -- not recommended for the treatment of depression** Side-Effects: - Cardiac events - Anti-muscarinic - Seizures - Hypotension more associated with overdose in TCAs - Hallucinations - Dangerous in OVERDOSE Interactions: - CYP Enzyme inhibitors (avoid grapefruit, increases plasma concentration) - CYP Enzyme Inducers (reduce effectiveness) - Drugs that cause QT prolongation (Amioderone, Sotolol, Quinolones) - Anti-muscarinic drugs - Antihypertensive drugs - Serotonin syndrome [MAO-Inhibitors ] - Specialist use only - Cause hepatoxicity (phenelzine + isocarboxazid) - Hypertensive crisis -- do not give OTC pseudoephedrine - Avoid Tyramine rich foods - Tranylcypromine + Clomipramine = FATAL Exam question: If a patient was swapping from Tranylcypromine to Clomipramine, how long should they wait? 3 weeks MAO-I washout periods: - Antidepressants should not be started for weeks after treatment with MAOIs (3 weeks for clomipramine or imipramine) - Don't start MAOI until: - 2 weeks after a previous MAOI has been stopped (0 weeks for moclobemide) - 1-2 weeks after tricyclic or related antidepressant has been stopped (3 weeks for clomipramine or imipramine) - 1 week after an SSRI or related antidepressant has been stopped (5 weeks for fluoxetine) Sleep Disorders --------------- Three types of Sleep Disorders: 1. Transient Insomnia a. External factors such as noise, shift work, and jet lag b. Rapidly eliminate hypnotic should be chosen, and only one or two doses should be given c. First line treatment: OTC, such as Nytol 2. Short-Term Insomnia d. Emotional problem or serious medical illness e. Hypnotic can be useful but should not be given for more than 3 weeks (preferably only 1 week) -- as likelihood patient will become dependant f. Examples: Zopiclone 3. Chronic Insomnia g. Normally secondary to other underlying conditions such anxiety, depression, and alcohol/drug abuse h. The underlying psychiatric complaint should be treated [Benzodiazepines:] Long-Acting Benzodiazepines: - Nitrazepam, diazepam and flurazepam - Higher hangover effect on the following day - Used for sleep maintenance -- keep patients sedated throughout the night Short-Acting Benzodiazepines: - Loprazolam, lormetazepam and temazepam - Little or no hangover effect - Used for sleep onset -- to help patients fall asleep initially - Higher chance of withdrawal symptoms [Z-Hypnotics] - Zolpidem and Zopiclone - Increase GABA CNS Depression - Not recommended to give more than 14 days - Dependency occurs within 3-14 days of use - Should be taken intermittently - Should be used for 4 weeks max Side-effect: - Paradoxical side effects - Drowsiness - Dependence - Benzos + Z-drugs: avoid in the elderly due to risk of falls and injury - Antihypertensives, diuretics -- given in combination with Z-drugs increases risk of falls Attention Deficit Disorder -------------------------- [Child aged 5 years and over:] 1. Methylphenidate as first-line treatment 2. If a 6-week trial of Methylphenidate at the maximum tolerated dose does not reduce symptoms -- switch to Lisdexamfetamine a. Lisdexamfetamine causes long duration of side effects -- if an issue for patient use Dexamfetamine Children who are intolerant of both Methylphenidate and Lisdexamfetamine: 3. Atomoxetine or Guanfacine [Adult Treatment:] 1. Use Methylphenidate or Lisdexamfetamine (Dexamfetamine if patients can't tolerate long duration of action) 2. Atomoxetine (Causes QT prolongation, hepatoxicity and suicidal ideation) Modified-release preparations are preferred because of their pharmacokinetic profile, convenience and improved adherence Modified-release preparations should be prescribed as brand only **[Methylphenidate:]** - CNS Stimulant - High BP, tachycardia, and arrhythmias - Behaviour/mood change, drowsiness and sleep disorders - Decreased appetite, growth retardation and weight loss - Monitor pulse, blood pressure, psychiatric symptoms, appetite, weight and height at initiation, following dose adjustment, then 6 monthly **[Lisdexamfetamine & Dexamfetamine:]** Similar side-effects to methylphenidate Overdose -- - Causes: wakefulness, excessive activity, paranoia, hallucinations and hypertension - Followed by: exhaustion, convulsions, hyperthermia and coma Similar monitoring to methylphenidate Substance Dependence -------------------- [Alcohol Dependence:] Mild: Usually do not need assisted alcohol withdrawal Moderate: Treated in a community setting unless they are at high risk of developing alcohol withdrawal seizures or delirium Severe: Undergo withdrawal in an inpatient setting Treat dependence with Cognitive Behavioural Therapy or with Acamprosate or Naltrexone (*Alternative: disulfram* -- causes bad side effects to the patients which puts them of drinking) [Withdrawal symptoms]: long-acting benzodiazepines such as Chlordiazepoxide or Diazepam (Alternative: Carbamazepine or Clomethiazole) [Delirium:] Lorazepam [Wernicke's Encephalopathy]: Thiamine (Vitamin B1) [Nicotine Dependence:] - Varenicline - Avoid in epilepsy, cardiovascular disease and psychiatric illness - Nicotine receptor blocker -- after a certain amount of medication it blocks the nicotine receptors so will not have any effect from smoking, physiologically there will not be a need to smoke - Bupropion - Avoid in psychiatric illness, seizures and eating disorders - Can cause serotonin syndrome - Nicotine Replacement Therapy (NRT) - Use a patch (16-hour patch if pregnant or experience nightmares) **AND** - Use a short-term reliever: lozenges, gum, sublingual tablets, inhalator, nasal spray and oral spray [Opioid Dependence:] Treatment for opioid dependence should be initiated under the supervision of an appropriately qualified prescriber -- not just any GP Prescribed on an FP10MDA (blue scripts) -- Maximum supply of 14 days Three or more missed doses: refer patient back to specialist Treatment should be continued throughout pregnancy Naloxone can be prescribed as well if the patient is at a high risk of overdose Buprenorphine: - Less sedating than methadone - Milder withdrawal symptoms - Lower risk of overdose - Suboxone (buprenorphine with naloxone) when there is a risk of injecting Methadone: - Causes QT prolongation - Carefully titrated according to patients needs - Sugared methadone causes more local irritation if it is injected NOT a legal requirement that the pharmacist needs to supervise -- just recommended Migraines --------- **Unilateral, pulsating**, and may be severe enough to impact daily activities. Frequently accompanied by nausea, vomiting, photophobia and phonophobia Migraine can come with aura which usual precede the onset of headache: - Visual symptoms (zigzag or flickering lights, spots, lines) - Sensory symptoms (pins and needles, or numbness), - Dysphasia Lifestyle Advice: - Maintain hydration, sleep and exercise - Avoid chocolate and wine - Relax after stress - A headache diary may be useful to identify potential triggers [Acute Treatment:] Treat with Aspirin, Ibuprofen, or a 5HT1-receptor agonist (Sumatriptan favourable) Triptan is contraindicated in patients with uncontrolled hypertension, as works by constricting blood vessels Take as soon as the patient knows that they are developing a migraine With Aura: Triptan taken at the start of the headache and not at the start of the aura Triptan ca be repeated after 2 hours (4 hours in Naratriptan) **ONLY** if there has been a response to first dose but not fully adequate Use soluble paracetamol if unable to take first line options -- due to faster onset of action, as already dissolved therefore will get into system quicker Antiemetics may be needed: Metoclopramide or Prochlorperazine [Migraine Prophylaxis:] - First Line: Propranolol - If contraindicated: use Metoprolol or Nadalol - Amitriptyline is effective - Use less sedating TCA if Amitriptyline is not tolerated - Topiramate can also be used in migraine prophylaxis - Sodium valproate, Pizotifen or Botox used normally under specialist use **Cluster Headaches:** - Intense unilateral pain in or around one eye - Acute: SC Sumatriptan (Nasal Sumatriptan/Zolmitriptan given if unavailable) - Prophylaxis: Verapamil, Lithium, Prednisolone or Ergotamine tartate (rarely used) **Trigeminal Neuralgia:** - Severe facial pain like having an **[electric shock]** in the jaw, teeth, or gums - Treat with Carbamazepine **Tension Headache:** - [Bilateral] throbbing pain like a [tight band] around your head - Paracetamol or Ibuprofen Exam Question: Someone comes into the pharmacy complaining of a severe headache at the back of the head, where the neck is. It was a sudden pain similar to being kicked in the back of the head all of a sudden. What is the course of action? Give paracetamol/ibuprofen, codeine, refer to GP or refer to A&E? Answer: Refer to A&E -- indicates subarachnoid hemorrhage -- a bleed in the brain, life threating Nausea & Vomiting ----------------- Antihistamines (Cyclizine and Promethazine) or phenothiazines (Prochlorperazine) are useful in the prophylaxis and treatment of nausea and vomiting Indications: 1. Pregnancy: avoid drug therapy, use promethazine if needed March 2024 - In addition to promethazine, the following can now be used too: chlorpromazine, cyclizine, doxylamine with pyridoxine, metoclopramide, prochlorperazine, and ondansetron. 2. Postoperative: 5HT3-receptor antagonist (Ondansetron) or Dexamethasone 3. Preoperative anticipatory: Lorazepam 4. Motion sickness: Hyoscine **[HYDRO]**bromide a. July 2023 - MHRA Update: Risk of severe anticholinergic side-effects with hyoscine hydrobromide patches. b. Hyoscine [Butyl]bromide (Buscopan) is used in IBS 5. Terminal illness: Antipsychotic (Haloperidol and Levomepromazine) 6. Patients with Parkinson's: Domperidone [Domperidone] - Does not cross the blood brain barrier -- therefore suitable to be used in Parkinson's Disease - Dose: 10mg TDS - Minimum age: 12 years old - Maximum use: 7 days - Patient should be 35kg + - Causes QT prolongation [Metoclopramide] - Causes Extrapyramidal Side-Effects -- Do not use in Parkinson's Disease - Does cross the blood brain barrier - Dose: 10mg TDS - Minimum age: 18 years old - Maximum use: 5 days Exam question: Patient due to have surgery is vomiting due to anxiety, what would treatment be? -- Lorazepam as PREoperative Pain Management --------------- [Mild-Pain:] - Non-Opiates: Paracetamol, NSAIDs, Aspirin [Mild-Moderate Pain:] - Weak Opiates: Codeine, Dihydrocodeine - Moderate: Tramadol (Lower seizure threshold, serotonin syndrome, increased risk of bleed, psychiatric disorder) [Moderate-Sever Pain:] - Strong opiates: Morphine, Oxycodone, Methadone, Buprenorphine, Fentanyl Exam Question: What is the maximum dose of morphine? -- Varies patient to patient -- weight, tolerance... **Codeine** - Use in patients over the age of 12 years - Do not use in children under 18 who had tonsils removed due to sleep apnoea - Avoid in patients who are ultra-rapid metaboliser (Afro-Caribbean) due to toxicity - Avoid in breastfeeding patients [Side-Effects:] - Act on the mu-pathway causing: - Dry mouth - Constipation - CNS depression - Nausea and vomiting - Hypotension - Miosis (pupil constriction) [Strong Opiates] - Prolonged use: Hypogonadism, Adrenal Insufficiency, Hyperalgesia - **Hyperalgesia** -- the body becomes dependent, smaller sensations will cause bigger pained reactions -- therefore causing increased dose of opioids needed - Overdose: Use Naloxone - Avoid in paralytic ileus, respiratory disease and head injury - Breakthrough pain **1/6^th^ to 1/10^th^** of the total daily dose every 2-4 hours PRN. Max use of breakthrough pain is 6 times a day - Increase doses of opiate by ½ to 1/3 each day - Reduce dose by ½ to 1/3 when switching between opiates to prevent overdose: - E.g. Morphine 30mg Oxycodone 15mg - Oxycodone more potent than Morphine -- more appropriate in patients who can't consume large quantities due to nausea - Patches: avoid exposure to heat, apply to a dry hairless area, rotate site - Fentanyl: remove patch immediately if there are signs of toxicity Exam Question: Calculate breakthrough pain dose!!! [Neuropathic Pain:] - Tricyclic Antidepressant: Amitriptyline or Nortriptyline - Antiepileptics: Gabapentin or Pregabalin - Pregabalin may slightly increase the risk of major congenital malformations if used in pregnancy. Patients should continue to use effective contraception during treatment and avoid use in pregnancy unless clearly necessary. - Opiates: Tramadol, Morphine or Oxycodone - Topical localised: Lidocaine or Capsaicin Exam Question: The patient would like to stop taking their gabapentin, how should they stop? Is it by reducing by half everyday to stop within 3 days, stop immediately or reduce over minimum of 1 week? Answer: Gradually withdraw over 1 week -- the same with pregabalin Multiple Sclerosis ------------------ **Chronic autoimmune disease demyelinating the central nervous system** Three types: 1. Relapsing 2. Progressive 3. Or Both Active = 2 relapses in the past 2 years despite treatment with **interferon beta** No cure, aim is to manage symptoms: - Spasticity: baclofen, diazepam, tizanidine and dantrolene - Relapse: methylprednisolone - Oscillopsia (objects appear to vibrate): gabapentin - Mood alteration: amitriptyline - Fatigue: Amantadine or Fampridine With baclofen: dose is increased slowly. This is to avoid 2 major side-effects: sedation and hypotonia (muscle weakness). Infectious Disease ================== Antimicrobial Stewardship ------------------------- **Importance of Stewardship:** PREVENTS ANTIBIOTIC RESISTANCE - Less unnecessary treatment, more caution - Higher risk of resistance with broad spectrum antibiotics - Try to give narrow spectrum instead -- less chance of resistance **[NICE Guidance:]** **Do not start antibiotics without clinical evidence of bacterial infection.** - If there is evidence or suspicion of bacterial infection, use local guidelines to start prompt, effective antibiotic treatment. - Obtain cultures - knowing the susceptibility of an infecting organism can lead to narrowing of broad-spectrum therapy, changing therapy to effectively treat resistant pathogens, and stopping antibiotics when cultures suggest an infection is unlikely. - Avoid broad-spectrum antibiotics (for example, co-amoxiclav, quinolones and cephalosporins) if narrow-spectrum antibiotics remain effective, because the former increase the risk of Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA) and antibiotic-resistant urinary tract infections. - Avoid widespread use of topical antibiotics (especially those that are also available as systemic preparations, such as fusidic acid). Prescribing Pathways: --------------------- **[Bites:]** **Human and animal bites -** - First Line: Co-Amoxiclav -- broad spectrum antibiotic - Second Line: Doxycycline **AND** Metronidazole -- given if patient has penicillin allergy - Prophylaxis: 3 Days - Treatment: 5 days -- if symptoms are present **Tick bites (Lyme disease) -** - First Line: Doxycycline (100mg BD) - Second Line: Amoxicillin (1000mg TDS) - TREATMENT FOR 21 DAYS -- usually prescribed prophylactically **[Diabetic Foot Infection:]** **Mild (less than 2cm) -** - Flucloxacillin - Penicillin Allergy: Clarithromycin / Erythromycin / Doxycycline **Moderate /Severe (abscess, osteomyelitis) -** - Flucloxacillin or Co-amoxiclav +/ - Gentamicin - Penicillin Allergy: Co-trimoxazole +/ - Gentamicin **[Cellulitis:]** - First Choice: Flucloxacillin - Penicillin allergy or if flucloxacillin unsuitable: - Clarithromycin or Erythromycin (in pregnancy) - Doxycycline - Co-Amoxiclav If infection near eyes or nose - - Co-Amoxiclav - Penicillin Allergy: Clarithromycin AND Metronidazole **[Community Acquired Pneumonia:]** **Low Severity -** - First Line: Amoxicillin - Second Line: Doxycycline or Clarithromycin (Erythromycin in pregnancy) **Moderate Severity -** - First Line: Amoxicillin - Second Line: Doxycycline or Clarithromycin - Amoxicillin + Clarithromycin / Erythromycin if atypical pathogens are suspected **High Severity -** - First Line: Co-Amoxiclav AND Clarithromycin (Erythromycin in pregnancy) - Second Line: Levofloxacin **[Diarrhoea:]** **Clostridium Difficile (10 days treatment) -** - First Line: Vancomycin - Second Line: Fidaxomicin - Life-threatening: Vancomycin and IV metronidazole **Traveller\'s Diarrhoea -** - Prophylaxis/treatment: Bismuth Subsalicylate - Ciprofloxacin can be used as prophylaxis, but not routinely recommended. **[Ear Infections:]** **Otitis Media (Inner ear) -** - First Line: Amoxicillin -- require systemic treatment - Second Line (worsening symptoms despite 2-3 days treatment): change to Co-Amoxiclav - Penicillin Allergy: Clarithromycin (Erythromycin in pregnancy) **Otitis Externa (outer) -** - First Line: Topical Acetic Acid 2% - Second Line: Topical Neomycin Sulphate with Corticosteroid - **If systemic treatment needed: Flucloxacillin** **[Helicobacter pylori:]** **Triple Therapy -** - PPI - omeprazole, esomeprazole etc - Two of the following three antibiotics: - Amoxicillin (1000mg BD) [OR] Metronidazole (400mg BD) [OR] Clarithromycin (500mg BD) - Amoxicillin always included in triple therapy unless patient has penicillin allergy - Esomeprazole -- interacts with clopidogrel - First Line PPI: Lansoprazole **Diagnosed by Urea (13C) Breath Test -** - Shouldn\'t be performed within 2 weeks of taking PPls - Shouldn\'t be performed withing 4 weeks of taking antibiotics **[Hospital Acquired Pneumonia:]** **Non-Severe -** - First Line: Co-Amoxiclav - Second Line (adults): Doxycycline, or Cefalexin, or Co-trimoxazole, or Levofloxacin - Second Line (children): Clarithromycin **[Impetigo:]** **Localised non-bullous -** - First Line: Hydrogen Peroxide 1% - Second Line: Fusidic Acid (mupirocin 2% if fusidic acid resistance suspected) **Widespread non-bullous -** - First Line: Fusidic Acid (Mupirocin 2% if fusidic acid resistance suspected) **Bullous or patients who are systemically unwell -** - First Line: Flucloxacillin - Second Line: Clarithromycin (Erythromycin in pregnancy) **[Lower Urinary Tract Infection:]** **Treatment in Men -** - First Line: Nitrofurantoin or Trimethoprim **Treatment in Non-Pregnant Women first choice -** - First Line: Nitrofurantoin or Trimethoprim - Second Line: Pivmecillinam or Fosfomycin **Treatment in Pregnant Women -** - First Line: Nitrofurantoin -- can't give trimethoprim as it is teratogenic - Second Line: Cefalexin or Amoxicillin **Nitrofurantoin should only be used if eGFR ≥45 ml/minute** **Treatment Duration -** Men: 7 days treatment Pregnancy: 7 days treatment Uncomplicated UTI in women: 3 days treatment Catheter Associated: 7 days treatment **[Strep Throat and Scarlett Fever:]** - Streptococcus bacteria family - First Line: Phenoxymethylpenicillin - Second Line: Clarithromycin or erythromycin (in pregnancy) **[Scarlett Fever:]** - Streptococcus bacteria family - Flu like symptoms, high temperature, swollen neck glands - A red rash with small raised bumps, rough feeling like sandpaper - White coating on tongue **[Other Infections:]** - Acne Vulgaris: Adapalene, Clindamycin, Benzoyl Peroxide, Lymecycline - Bacterial Vaginosis and Trichomoniasis: Metronidazole - Chlamydia: Doxycycline - Conjunctivitis and Blepharitis: Chloramphenicol -- avoid under 2 or pregnant - Dental Abscess: Amoxicillin/ Phenoxymethylpenicillin or Metronidazole - Gonorrhoea: Ceftriaxone or Ciprofloxacin - Meningitis: Benzylpenicillin - Scabies: Permethrin -- apply to whole body - Sinusitis: Phenoxymethylpenicillin (Penicillin Allergy: Doxycycline) - Threadworm: Mebendazole - avoid under 2 or pregnant **[Most Common Pathogens:]** - Community Acquired Pneumonia: Streptococcus Pneumoniae - Urinary Tract Infection: Escherichia Coli - Thrush: Candida Albicans - Cellulitis: Staphylococcus Aures - Meningitis: Streptococcus Pneumonia Exam Question: Mr Hue Berculosis has been admitted to the hospital after being diagnosed with mild community acquired pneumonia. The doctors would like to initate the patient on some antibiotics, although the patient has a known penicillin allergy. What is the most appropriate antibiotic to prescribe? a. Phenoxymethylpenicillin b. Vancomycin c. Co-amoxiclav d. Doxycycline e. Azithromycin Answer: Doxycycline. First line treatment for mild community acquired pneumonia is Amoxicillin. Due to the penicillin allergy, we could use either Doxycycline, Clarithromycin or Erythromycin Antibiotics ----------- **[Aminoglycosides:]** Amikacin, Gentamicin, Neomycin, Streptomycin and Tobramycin **Serum-aminoglycoside concentrations -** - Measured in all patients receiving parenteral aminoglycosides - Must be determined in obesity, high doses, cystic fibrosis, elderly Measure serum-gentamicin concentration after 3 or 4 doses, then every 3 days and after a dose change (more frequently in renal impairment) Measure 1 hour after dose (peak) and just before next dose (trough) **For multiple daily dose regimen -** - Peak serum concentration: 5-10 mg/L - Endocarditis peak serum concentration: 3-5 mg/L -- lower as abx is co-prescribed with other abx - Trough serum concentration: \< 2 mg/L - Endocarditis trough serum concentration: \< 1 mg/L **Dose Adjustments -** - Trough too high: increase dose interval - Peak too high: decrease dose **Renal Impairment -** - Renal Impairment: increase dose interval - Severe Renal Impairment: reduce dose as well **Avoid concomitant use of nephrotoxic drugs** **MHRA Warning:** The use of aminoglycosides is associated with ototoxicity Interactions with ototoxicity: - Cisplatin - Loop Diuretics (Furosemide, Bumetanide, Torasemide) - Vancomycin - Vinca Alkaloids (Vinblastine, Vincristine, Vindesine, Vinflunine) Further interactions: drugs that cause renal impairment e.g. NSAID, ACE, ARB, Metformin **Contraindication --** Myasthenia Gravis **Pregnancy --** - Avoided: risk of auditory or vestibular nerve damage - Monitor serum concentrations **Obese Patients -** - Use ideal body weight based on height to calculate parenteral dose - Done to avoid overdose **[Cephalosporins:]** **First Generation**: Cefadroxil, Cefalexin and Cefradine - Fad Fal Frad **Second Generation:** Cefuroxime, Cefoxitin and Cefaclor - Furry Fox Face Third and Fifth Generation are all parenteral apart from oral Cefixime Patients with hypersensitivity to penicillin and other beta-lactams should not receive a cephalosporin due to cross-sensitivity **[Chloramphenicol -]** - Most commonly used in eye infections - Avoid in pregnancy - Risk of neonatal \'grey-baby syndrome\' if used in third trimester - OTC Guidance: - Children aged 2 years + **[Clindamycin -]** - Associated with antibiotic-associated colitis - can be FATAL - More common in elderly patients - Discontinue and contact a doctor immediately if severe, prolonged or bloody diarrhoea develops - In Clostridium difficile suspected -- DISCONTINUE - Seek specialist advice when antibiotic cannot be stopped, and the patient is experiencing severe diarrhoea **[Glycopeptides:]** *Dalbavancin, Teicoplanin, Telavancin and Vancomycin* - Vancomycin should only be given parenterally for systemic infections due to reduced absorption with oral intake - Should be avoided in pregnancy unless benefit outweighs risk - Initial doses based on body-weight, then dose adjustments based on serum-vancomycin concentrations - Trough concentration should be **15-20 mg/litre** -- measured an hour before next dose - Can cause ototoxicity and nephrotoxicity - Same interactions as aminoglycosides **[Side-effects -]** - Red man syndrome - hypersensitivity - Severe cutaneous adverse reactions -- Stephen Johnson syndrome - Blood Dyscrasias: Agranulocytosis, eosinophilia, and neutropenia - Cardiogenic shock on rapid intravenous injection - Risk of anaphylactoid reactions at infusion sites - avoid rapid infusion and rotate site **[Linezolid:]** Important safety information: - Risk of severe optic neuropathy - Report visual impairment (blurry / altered vision) - **Monitored regularly if treatment more than 28 days** - Risk of blood disorders - Monitor full blood counts weekly - **Monitored regularly after if treatment more than 10-14 days** - Interacts with tyramine-rich foods: - Mature cheese - Marmite - Yeast extract - Fermented soya bean extract - Some beers and wines - Serotonin Syndrome: Build up of serotonin - SSRis, Dopaminergic, 5-HT1 agonists, TCAs, Lithium, other MAOls **[Macrolides:]** *Azithromycin (Once Daily) can be given 3 x a week for prophylaxis in COPD patients* *Clarithromycin 4x a day* *Erythromycin once daily* **Cautions -** - Patients with myasthenia gravis - Erythromycin preferred in pregnancy over clarithromycin - Avoid clarithromycin in first trimester of pregnancy **Side-effects -** - Can cause hepatotoxicity - Can cause ototoxicity - Can cause hearing loss in large doses - High level of gastrointestinal disturbances - Nausea, Vomiting, Diarrhoea etc - Can cause QT Prolongation **Interactions -** Macrolides are **CYP Enzyme Inhibitors** - Statins - increased risk of myopathy - Warfarin - increased risk of bleeding Macrolides can cause **hypokalaemia** - Loop/Thiazide Diuretics, Steroids, Salbutamol, Theophylline Macrolides increase risk of **QT Prolongation** - Amiodarone, Domperidone, Fluconazole, Lithium, Methadone,\ Ondansetron, Quinine, Quinolones, Sotalol, SSRIs, etc Exam Question: Mr Trim Ethoprim has been diagnosed with endocarditis, where he is expected to be initiated on gentamicin. Due to his elderly age, the doctors would like to monitor his serum levels closer. What trough serum levels should be expected? a. 4-12mg/L b. 5-10mg/L c. \