The only medication that does not commonly cause tremors is carbamazepine.

The other drugs present with the following types of tremors as a side effect to their usage:
1. Sodium valproate – Postural tremor is most common, but a resting tremor can also occur. Approximately 25% of patients taking sodium valproate are found to develop a tremor within 12 months of starting therapy.
2. Lithium – fine hand tremor is very commonly seen and reported in as many as 50% of patients during the first week of therapy. The tremor tends to reduce with time and is only present in around 5% of patients taking the medication two years or longer.
3. Atypical antipsychotics, such as olanzapine and quetiapine – tremor and limb shakiness.

Phenytoin is in the anticonvulsants class of drugs and is used in the management and treatment of the following:
1. epilepsy
2. generalized tonic-clonic seizures
3. complex partial seizures
4. status epilepticus.

It works by inactivating the voltage-gated sodium channels responsible for increasing the action potential. It is non-specific and targets almost all voltage-gated sodium channel subtypes. More specifically, phenytoin prevents seizures by inhibiting the positive feedback loop that results in neuronal propagation of high-frequency action potentials.

Benzodiazepines are used as a first-line treatment in breaking seizures and in status epilepticus as they are rapid-acting.

Use of benzodiazepines in the late third-trimester or exposure during labour is associated with great risks to the foetus/neonate. Babies can exhibit either floppy infant syndrome, or marked neonatal withdrawal symptoms. Symptoms vary from mild sedation, hypotonia, and reluctance to suck, to apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. These symptoms have been reported to persist for periods from hours to months after birth.

They also cross into breast milk and should be used with caution in breastfeeding mothers

Prochlorperazine is a phenothiazine drug as it is categorized as a first-generation antipsychotic. It mainly blocks the D2 (dopamine 2) receptors in the brain. Along with dopamine, it also blocks histaminergic, cholinergic, and noradrenergic receptors.

It exerts its antiemetic effect via dopamine (D2) receptor antagonist. It is used to treat nausea and vomiting of various causes, including labyrinthine disorders.

Extrapyramidal side effects are most common with piperazine phenothiazines (fluphenazine, prochlorperazine, and trifluoperazine) and butyrophenones (fluphenazine, prochlorperazine, and trifluoperazine) (benperidol and haloperidol). The most common causative antipsychotic drug is haloperidol.

Tardive dyskinesia (rhythmic, involuntary movements of the tongue, face, and jaw) is most commonly associated with long-term or high-dose treatment. It is the most serious form of extrapyramidal symptoms because withdrawal of the causative drug may make it irreversible, and treatment is usually ineffective.

Dystonia (abnormal facial and body movements) is more common in children and young adults, and it usually shows up after only a few doses. Procyclidine 5 mg IV or benzatropine 2 mg IV as a bolus can be used to treat acute dystonia.

An unpleasant feeling of restlessness characterises akathisia. The inability to initiate movement is known as akinesia.

Renal impairment causes increased cerebral sensitivity, so lower doses should be used.

In elderly patients with dementia-related psychosis who are treated with haloperidol, there is an increased risk of death. This appears to be due to a higher risk of heart attacks and infections like pneumonia.

The following are some of the antipsychotic drugs’ contraindications:
Reduced level of consciousness/coma
Depression of the central nervous system
Phaeochromocytoma

Metoclopramide is used to treat nausea and vomiting. It works by blocking the central and peripheral D2 (dopamine 2) receptors in the medullary chemoreceptor trigger zone in the vomiting centre (area postrema). It decreases the sensitivity of the visceral sensory nerves that transmit from the GI system to the vomiting centre. Blockade of inhibitory dopamine receptors in the GI tract may allow stimulatory actions of ACh at muscarinic synapses to predominate.

At high doses, metoclopramide also blocks type-2 serotonin receptors though the effect is much weaker.

Aspirin inhibits cyclo-oxygenase irreversibly by covalently acetylating the cyclo-oxygenase active site in both COX-1 and COX-2. The production of prostaglandin and thromboxane is reduced as a result. As a result, platelet activation and aggregation are reduced. A single dose of aspirin has a half-life of 7-10 days, which is the time it takes for the bone marrow to produce new platelets.

Aspirin only inhibits COX-1, the enzyme that produces thromboxane A2, at low doses (75 mg per day), and thus has a primarily anti-thrombotic effect.

Aspirin inhibits both COX-1 and COX-2 at medium to high doses (500-5000 mg per day). COX-2 is involved in the production of prostaglandins, so it has an anti-inflammatory effect at these concentrations.

Aspirin, when used as an antipyretic for a viral illness in children, can cause Reye’s syndrome. Reye’s syndrome is a potentially fatal liver disease that causes encephalopathy and liver failure.

The inability of aspirin to reduce platelet production of thromboxane A2, and thus platelet activation and aggregation, is known as aspirin resistance. Although the exact frequency and mechanism of aspirin resistance are unknown, it is thought to affect about 1% of users. Women are more likely than men to experience this phenomenon.

According to new research, taking aspirin on a regular basis lowers the risk of colorectal cancer. It may also protect against cancers of the breast, bladder, prostate, and lungs.

Advanced paediatric life support (APLS) recommends phenytoin as the first choice for second-line anticonvulsant in a patient that continues to seize ten minutes after the second dose of the first-line anticonvulsant (benzodiazepine). (step 3 of the APLS algorithm)

The recommended dose of phenytoin infusion is up at 20 mg/kg over 20 minutes. If the patient has already taken phenytoin as maintenance therapy or is allergic to phenytoin, then a phenobarbitone infusion should be set up at 20 mg/kg over 30-60 minutes.

Lithium toxicity manifests itself in the following ways:
Ataxia
Clonus
Coma
Confusion
Convulsions
Diarrhoea
Increased muscle tone
Nausea and vomiting
Nephrogenic diabetes insipidus
Renal failure
Tremor

Diazepam boosts GABA’s effects, giving it sedative, hypnotic, anxiolytic, anticonvulsant, and muscle-relaxing properties. It can be administered orally, rectally, or intravenously.

With a half-life of 20-100 hours, it is a long-acting benzodiazepine. Midazolam, oxazepam, and alprazolam are examples of short-acting benzodiazepines with a half-life of less than 12 hours (Xanax).

If used in the presence of hepatic impairment, benzodiazepines can cause coma. If treatment is necessary, benzodiazepines with shorter half-lives should be used in lower doses. Diazepam is a sedative that crosses into breast milk and should be avoided by breastfeeding mothers.

Acute dyskinesias and dystonic reactions, tardive dyskinesia (rhythmic, involuntary movements of the tongue, face, and jaw), Parkinsonism (tremor, bradykinesia, and rigidity), akinesia, akathisia, and neuroleptic malignant syndrome are all examples of extrapyramidal side effects. They are caused by dopamine depletion or blockade in the basal ganglia; this lack of dopamine frequently mimics idiopathic extrapyramidal pathologies.

The first-generation antipsychotics, which are strong dopamine D2 receptor antagonists, are the drugs most commonly associated with extrapyramidal side effects. Haloperidol and fluphenazine are the two drugs in this class that are most commonly associated with extrapyramidal side effects. Extrapyramidal adverse effects are less common in second-generation antipsychotics (e.g., olanzapine) than in first-generation antipsychotics.

Other drugs are linked to extrapyramidal symptoms as well, but at a lower rate. Some antidepressants, lithium, various anticonvulsants, antiemetics, and, in rare cases, oral contraceptive agents are among them.

If a convulsing child reaches step 3 of the APLS algorithm, then a phenytoin infusion should be set up at 20 mg/kg over 20 minutes. If they are already taken phenytoin as maintenance therapy, then a phenobarbitone infusion should be set up at 20 mg/kg over 30-60 minutes.

According to a 2018 audit conducted by the Royal College of Emergency Medicine (RCEM), the standard of care for children presenting to EDs with fractured limbs has deteriorated, with most patients waiting longer than ever before for pain relief. More than one-tenth of the children who came in with significant pain from a limb fracture received no pain relief at all.

For all patients, including children, the Agency for Health Care Policy and Research (AHCPR) in the United States recommends using the ABCs of pain management:
A – Ask about pain regularly. Assess pain systematically.
B – Believe the patient and family in their reports of pain and what relieves it.
C – Choose pain control options appropriate for the patient, family, and setting.
D – Deliver interventions in a timely, logical, coordinated fashion.
E – Empower patients and their families. Enable patients to control their course to the greatest extent possible.

The RCEM guidelines recommend assessing a child’s pain within 15 minutes of arrival. This is a fundamental requirement. For the assessment of pain in children, a variety of rating scales are available; which one is used depends on the child’s age and ability to use the scale. These are some of them:
Faces of Wong-Baker Scale for assessing pain
Scale of numerical evaluation
The behavioural scale is a scale that measures how people behave.

The RCEM has provided the following visual guide:
The RCEM has established the following guidelines for when patients in severe pain should receive appropriate analgesia:
100% within 60 minutes of arrival or triage, whichever is earliest
75% within 30 minutes of arrival or triage, whichever is earliest
50% within 20 minutes of arrival or triage, whichever is earliest

A single dose of IV benzodiazepine will terminate the seizure in 60 to 80 percent of patients who present with seizures.

Because benzodiazepines are lipid-soluble, they cross the blood-brain barrier quickly. This explains their quick onset of action.

As a first-line treatment, IV lorazepam should be given. If IV lorazepam is not available, IV diazepam can be used instead, and buccal midazolam can be used if intravenous access cannot be established quickly. Lorazepam can be administered via the rectal route, but it is less reliable and has a lower absorption rate and bioavailability.

Cyclizine is a piperazine derivative that functions as an antihistamine (H1-receptor antagonist). To prevent nausea and vomiting, it is thought to act on the chemoreceptor trigger zone (CTZ) and the labyrinthine apparatus. It has a lower antimuscarinic effect as well.

Paracetamol is predominantly metabolized in the liver by three main metabolic pathways:
1. Glucuronidation (45-55%)
2. Sulphate conjugation (30-35%)
3. N-hydroxylation via the hepatic cytochrome P450 enzyme system (10-15%)

Cytochrome P450 enzymes catalyse the oxidation of acetaminophen to the reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI primarily contributes to the toxic effects of acetaminophen. NAPQI is an intermediate metabolite that is further metabolized by fast conjugation with glutathione. The conjugated metabolite is then excreted in the urine as mercapturic acid. High doses of acetaminophen (overdoses) can lead to hepatic necrosis due to depleting glutathione and high binding levels of reactive metabolite (NAPQI) to important parts of liver cells.

Flumazenil is a benzodiazepine antagonist that can be helpful in some overdose situations. It works quickly (in less than a minute), but the effects are fleeting, lasting less than an hour. The dose is 200 micrograms every 1-2 minutes with a maximum dose of 3 milligrams per hour.

Flumazenil should be avoided by patients who are addicted to benzodiazepines or who take tricyclic antidepressants because it can cause withdrawal symptoms. It can cause seizures or cardiac arrest in these situations.

Naloxone is a short-acting, specific antagonist of mu(μ)-opioid receptors. It is used to reverse the effects of opioid toxicity.

It can be given by a continuous infusion if repeated doses are required and the infusion rate is adjusted according to the vital signs. Initially, the infusion rate can be set at 60% of the initial resuscitative IV dose per hour.

Naloxone has a shorter duration of action (6-24 hours) than most opioids and so close monitoring according to the respiratory rate and depth of coma and repeated injections are necessary. When repeated doses are needed in opioid addicts, naloxone administration may precipitate a withdrawal syndrome with abdominal cramps, nausea and diarrhoea, but these usually settle within 2 hours.

An initial dose of 0.4 to 2 mg can be given intravenously and can be repeated at 2 to 3-minute intervals to a maximum of 10mg.

If the intravenous route is inaccessible, naloxone can be administered via an IO line, subcutaneously (SQ), IM, or via the intranasal (IN) route.

The metabolism of ethinyl oestradiol and progestogens has been shown to be increased by enzyme-inducing antiepileptics. The oral contraceptive pill (OCP) is less effective in preventing pregnancy as a result of this increased breakdown.

Antiepileptic drugs that induce enzymes include:
Carbamazepine
Phenytoin
Phenobarbital
Topiramate

Antiepileptics that do not induce enzymes are unlikely to affect contraception. Non-enzyme-inducing anticonvulsants include the following:
Clonazepam
Gabapentin
Levetiracetam
Piracetam
Sodium valproate is a type of valproate that is used to

Lamotrigine is an antiepileptic drug that does not cause the production of enzymes. It does, however, require special consideration, unlike other non-enzyme-inducing antiepileptics. The OCP does not appear to affect epilepsy directly, but it does appear to lower lamotrigine levels in the blood. This could result in a loss of seizure control and the occurrence of seizures.

Phenytoin is a commonly used antiepileptic drug. A well-recognized side-effect of phenytoin is gingival enlargement and occurs in about 50% of patients receiving phenytoin. It is believed that reduced folate levels may cause this, and evidence suggests that folic acid supplementation may help prevent this in patients starting phenytoin.

As evidence suggests, drug-induced gingival enlargement may also improve by substituting with other anticonvulsant drugs and reinforcing a good oral hygiene regimen. Surgical excision of hyperplastic gingiva is often necessary to correct the aesthetic and functional impairment associated with this condition to manage it successfully.

Phenytoin is also the only anticonvulsant therapy associated with the development of Dupuytren’s contracture.
Other side effects are:
1. Ataxia
2. Drug-induced lupus
3. Hirsutism
4. Pruritic rash
5. Megaloblastic anaemia
6. Nystagmus

Carbamazepine is primarily used to treat epilepsy, and it is effective for both focal and generalised seizures. It is not, however, effective in the treatment of absence or myoclonic seizures. It’s also commonly used to treat neuropathic pain, as well as a second-line treatment for bipolar disorder and as a supplement for acute alcohol withdrawal.

Carbamazepine works as a sodium channel blocker that preferentially binds to voltage-gated sodium channels in their inactive state. This prevents an action potential from firing repeatedly and continuously.

Lithium is the drug of choice for bipolar disorders but is commonly associated with side effects and toxicity.

Fine hand tremor is very commonly seen and reported in as many as 50% of patients during the first week of therapy with Lithium. The tremor tends to reduce with time and is only present in around 5% of patients taking the medication two years or longer. Lithium tremors are more common with older age, presumably due to the additive effects of age-related essential tremors.

Option The normal therapeutic range is 2.0-2.5 mmol/l: Lithium should be carefully monitored as it has a very low therapeutic index. The normal therapeutic range is 0.4-0.8 mmol/l. Levels should be checked one week after starting therapy and one week after every change in dosage. (Option Levels should be checked one month after starting therapy)

Option It can induce hyperthyroidism: Lithium has a known effect on thyroid function. Lithium decreases the production of T4 and T3 and commonly causes hypothyroidism. More rarely, lithium causes hyperthyroidism due to thyroiditis.

Option It can induce diabetes mellitus: Lithium can induce nephrogenic diabetes insipidus but not diabetes mellitus.

Cinnarizine is a piperazine derivative with an antihistamine effect that makes it anti-emetic. Motion sickness and vestibular disorders, such as Méniéres disease, are the most common conditions for which it is prescribed.

In pregnancy and postpartum, lithium is an effective treatment for relapse prevention in bipolar disorder. However, lithium has also been associated with risks during pregnancy for both the mother and the unborn child. Recent large studies have confirmed the association between first-trimester lithium exposure and an increased risk of congenital malformations.

Lithium levels need to be monitored more frequently throughout pregnancy and the postnatal period.

If given in the 1st-trimester, lithium is associated with a risk of fetal cardiac malformations, such as Ebstein’s anomaly.

If given in the 2nd and 3rd-trimesters, there is a risk of the following:
1. hypotonia
2. lethargy
3. feeding problems
4. hypothyroidism
5. goitre
6. nephrogenic diabetes insipidus in the neonate

Heroin is injected into the veins and is the most commonly abused drug. Acute intoxication with opioid overuse is the most common cause of death by drug overdose.

The clinical features of opioid overdose are:
1. Decreased respiratory rate
2. Reduced conscious level or coma
3. Decreased bowel sounds
4. Miotic (constricted) pupils
5. Cyanosis
6. Hypotension
7. Seizures
8. Non-cardiogenic pulmonary oedema (with IV heroin usage)

The main cause of death secondary to opioid overdose is respiratory depression, which usually occurs within 1 hour of the overdose. Vomiting is also common, and aspiration can occur.

Naloxone is a short-acting, specific antagonist of mu(μ)-opioid receptors. It is used to reverse the effects of opioid toxicity.

It can be given by a continuous infusion if repeated doses are required and the infusion rate is adjusted according to the vital signs. Initially, the infusion rate can be set at 60% of the initial resuscitative IV dose per hour.

Naloxone has a shorter duration of action (6-24 hours) than most opioids, and so close monitoring according to the respiratory rate and depth of coma with repeated injections is necessary. When repeated doses are needed in opioid addicts, naloxone administration may precipitate a withdrawal syndrome with abdominal cramps, nausea and diarrhoea, but these usually settle within 2 hours.

An initial dose of 0.4 to 2 mg can be given intravenously and can be repeated at 2 to 3-minute intervals to a maximum of 10mg.

If the intravenous route is inaccessible, naloxone can be administered via an IO line, subcutaneously (SQ), IM, or via the intranasal (IN) route.

Codeine phosphate is a mild opiate that can be used to treat mild to moderate pain when other pain relievers like paracetamol or ibuprofen have failed. It can also be used to treat diarrhoea and coughs that are dry or painful.

The use of all opioids is contraindicated for the following reasons:
Respiratory depression (acute)
Patients who are comatose
Head injury (opioid analgesics impair pupillary responses, which are crucial for neurological evaluation)
Intracranial pressure has risen (opioid analgesics interfere with pupillary responses vital for neurological assessment)
There’s a chance you’ll get paralytic ileus.

The use of codeine phosphate is contraindicated in the following situations:
Because of the significant risk of respiratory side effects in children under the age of 12, it is not recommended for children under the age of 12.

Patients of any age who have been identified as ultra-rapid codeine metabolizers (CYP2D6 ultra-rapid metabolizers)

Because codeine can pass through breast milk to the baby and because mothers’ ability to metabolise codeine varies greatly, it is especially dangerous in breastfeeding mothers.

If other painkillers, such as paracetamol or ibuprofen, fail to relieve acute moderate pain in children over the age of 12, codeine should be used. In children with obstructive sleep apnoea who received codeine after tonsillectomy or adenoidectomy, a significant risk of serious and life-threatening adverse reactions has been identified.

Amitriptyline is a tricyclic antidepressant (TCA) that is most commonly used to treat depression, but it can also be used to treat anxiety disorders, chronic pain, and attention deficit hyperactivity disorder (ADHD). It inhibits reuptake, raising serotonin and noradrenaline levels while also inhibiting acetylcholine action.

TCAs have a number of drawbacks, including:
Acute Porphyria
Arrhythmias
During bipolar disorder’s manic phase
Heart block
After a myocardial infarction, there is an immediate recovery period.

TCA levels in breast milk are too low to be harmful, and use can be continued while breastfeeding.

Acetaminophen is an acetanilide derivative and is a widely used non-prescription analgesic and antipyretic medication for mild-to-moderate pain and fever.

The route of elimination: Metabolites are mainly excreted in the urine. <5% is excreted as free (unconjugated) acetaminophen, and >90% of the dose administered is excreted within 24 hours.

It is thought to work by selectively inhibiting COX-1 receptors in the brain and spinal cord: It is categorized by the FDA as an NSAID as it is believed to selectively inhibit cyclo-oxygenase 3 (COX-3) receptors in the brain and spinal cord.

COX-3 is a unique variant of the more known COX-1 and COX-2. It is responsible for the production of prostaglandins in central areas, which sensitizes free nerve endings to the chemical mediators of pain. Therefore, by selectively inhibiting COX-3, paracetamol effectively reduces pain sensation by increasing the pain threshold.

Toxicity is primarily due to glutathione production: Acetaminophen metabolism by the CYP2E1 pathway releases a toxic metabolite known as N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI primarily contributes to the toxic effects of acetaminophen. NAPQI is an intermediate metabolite that is further metabolized by fast conjugation with glutathione. The conjugated metabolite is then excreted in the urine as mercapturic acid. High doses of acetaminophen (overdoses) can lead to hepatic necrosis due to depleting glutathione and high binding levels of reactive metabolite (NAPQI) to important parts of liver cells.

It has a half-life of 6-8 hours: Acetaminophen can be administered orally, rectally, or intravenously. It is predominantly metabolized in the liver, and the elimination half-life is 1-3 hours after a therapeutic dose. But maybe greater than 12 hours after an overdose.

It is primarily metabolized via the cytochrome p450 enzyme system: It is predominantly metabolized in the liver by three main metabolic pathways:
1. Glucuronidation (45-55%)
2. Sulphate conjugation (30-35%)
3. N-hydroxylation via the hepatic cytochrome p450 enzyme system (10-15%)

A postural tumour is observed when a person maintains a position against gravity, such as holding the arms outstretched. (The patient holding her tray against gravity)

Sodium valproate is the most commonly prescribed medication for epilepsy. It is commonly associated with tremors as valproate-induced tremors occur in around 6-45% of patients. The tremors are commonly postural, but a resting tremor may also occur.

Approximately 25% of patients taking sodium valproate are found to develop a tremor within 3-12 months of initiating therapy.

Lithium is the drug of choice for recurrent bipolar illness but should be carefully monitored as it has a very low therapeutic index. The normal therapeutic range is 0.4-0.8 mmol/l.

The lower end of the range is usually the target for the elderly and as maintenance therapy. Toxicity is usually seen at levels >1.5 mmol/l. Samples should be taken 12 hours after the dose, and levels should be checked one week after starting therapy and one week after every change in dosage.