Autonomic Nervous System, Pain Types, and Pharmacology of Analgesics and Seizures

Sympathetic Predominance

Characterized by exercise, anger, and the fight and flight response.

Parasympathetic Predominance

Characterized by rest, digest, and sleep.

Acetylcholine

A major neurotransmitter of the Autonomic Nervous System (ANS).

Noradrenalin (norepinephrine)

A major neurotransmitter of the Autonomic Nervous System (ANS).

Cholinergic Receptors

Two types: Muscarinic and Nicotinic, classified based on pharmacological action.

Muscarinic Receptors

Receptors that have stimulant effects at postganglionic nerve endings in cardiac muscle, smooth muscle, and glands.

Nicotinic Receptors

Receptors that have stimulant effects on the ganglia, adrenal medulla, and skeletal muscle.

DUMBBELS

An acronym for the excessive stimulation effects at muscarinic receptors: Diarrhoea, Urinination, Miosis, Bronchoconstriction, Bradycardia, Emesis, Lacrimation, Salivation.

Alpha Receptors

Stimulation mainly produces arterial vasoconstriction and smooth muscle contraction.

Alpha 1 Receptors

G protein that causes an increase in Phospholipase C and Ca.

Alpha 2 Receptors

G inhibitory protein that causes a decrease in cAMP.

Beta Receptors

Stimulation produces an increase in heart rate and contractility, vasodilation of arterioles supplying skeletal muscles, bronchial relaxation, and aqueous humour formation.

Beta 1 Receptors

G stimulatory protein that causes an increase in cAMP, found in the heart, kidney, and fat cells.

Beta 2 Receptors

G stimulatory protein that causes an increase in cAMP, found mainly in airway smooth muscle and mast cells.

Beta 3 Receptors

G stimulatory protein that causes an increase in cAMP, found mostly in intestinal smooth muscle and adipocytes.

Nociceptive Pain

Physiological pain arising from stimulation of nociceptors by noxious stimuli such as tissue injury or inflammation.

Neurogenic Pain

Pain that occurs because of central or peripheral nervous system dysfunction.

Psychogenic Pain

Pain caused or prolonged by mental, emotional, or behavioral factors, often with no physical cause.

Referred Pain

Pain felt in a part of the body remote from the tissue causing the pain.

Visceral Pain

Pain that arises from most viscera, which have only pain receptors.

Opioid Agonists

Morphine, a natural alkaloid present in opium, is the gold standard opioid analgesic.

Fentanyl

A strong opioid analgesic with a mechanism and actions similar to morphine.

Analgesia

The main clinical use of opioids.

Suppression of the cough reflex

An effect of opioids that reduces the urge to cough.

Respiratory depression

A serious adverse effect of opioids that can lead to death from overdose.

Sedation and sleep

An effect of opioids, hence the term 'narcotic analgesics'.

Euphoria

The feeling of contentedness and wellbeing associated with opioid use.

Dysphoria

Unpleasant feelings, hallucinations, and nightmares that can occur with opioid use.

Miosis

Pupillary constriction, often referred to as 'pinpoint pupils,' associated with opioid use.

Tolerance

A condition where increasing doses of opioids are required to achieve the same effect.

Dependence

A state where the body requires opioids to function normally, leading to withdrawal symptoms if not taken.

Buprenorphine

A partial agonist at µ receptors and antagonist at κ receptors, used for moderate-to-severe pain and treatment of opioid dependence.

Opioid Antagonist

Drugs like Naloxone and Naltrexone used to reverse the adverse effects of opioid agonists.

Naloxone

A short-acting antagonist used mainly for treatment of overdose or reversal of opioid depressant effects.

Naltrexone

A long-acting antagonist used mainly for treatment of alcohol or opioid dependence and for rapid opioid detoxification.

Non-opioid analgesics

The second main group of pain-relieving drugs that have significant anti-inflammatory actions.

NSAIDs

Non-steroidal anti-inflammatory drugs that are effective for mild-to-moderate pain and have opioid-sparing effects.

Aspirin

A non-opioid analgesic that inhibits platelet aggregation and decreases the risk of thrombosis.

Ibuprofen

A non-opioid analgesic that has anti-inflammatory and antipyretic properties.

Mechanism of action of NSAIDs

NSAIDs inhibit arachidonic acid production via cyclooxygenase (COX) isoenzymes, reducing production of pain mediators.

Respiratory failure

The common cause of death from acute toxicity after an overdose of an opioid such as heroin.

Adverse drug reactions with opioids

Serious effects including respiratory depression, excessive sedation, dysphoria, constipation, nausea, and vomiting.

COX inhibition

Accounts for most of the analgesic effects and also adverse effects.

Selective COX-2 inhibitors

Preferred for antiinflammatory effects and for reduced GIT adverse effects.

Analgesic action of non-opioids

Peripheral; do not cause tolerance or dependence, or modify psychological reactions to pain.

Antipyretic action

Due to inhibition of PG synthesis in the hypothalamus, the temperature-regulating centre of the body.

Common adverse drug reactions to NSAIDs

Include GIT disorders (dyspepsia, nausea and vomiting, diarrhoea/constipation and gastritis) due to reduced synthesis of mucoprotective PGs.

Contraindication for NSAIDs

NSAIDs are contraindicated in peptic ulcer disease.

Renal damage from NSAIDs

Due to inhibition of renal vasodilating PGs, particularly a problem in elderly patients on long-acting NSAIDs.

Other adverse effects of NSAIDs

Include allergic reactions such as asthma rashes and urticaria, sodium retention, heart failure, and hypertension.

Typical adult dosage of Paracetamol

Two tablets to start, then one tablet (500 mg) every 3-6 hours, with maximum daily intake 4 g (8 standard tablets).

Use of Paracetamol in children

Safe for mild fevers, colds, and flu symptoms; not associated with Reye's syndrome.

Safety of Paracetamol

Safe to use during pregnancy and lactation.

Overdose of Paracetamol

Can cause acute liver damage if not promptly treated.

Pregabalin

An analogue of the neurotransmitter GABA that reduces the release of various transmitters.

Gabapentin

An anticonvulsant drug effective in the relief of neuropathic pain and blocks Ca2+ channels.

Capsaicin

An alkaloid found in chilli peppers, used in topical creams for treatment of neuralgias and arthritic pain.

Mechanism of Capsaicin

Activates capsaicin receptors; causes initial release and then depletion of substance P from nerve fibres.

Local anaesthetics

For example, lidocaine, used for their analgesic effects.

Adjuvant medications

Used in combination with opioid or NSAID analgesics to enhance pain relief or treat symptoms that exacerbate pain.

Tricyclic antidepressants

Useful in neuropathic pain; mechanism involves inhibition of 5-HT reuptake and blockade of sodium channels.

Corticosteroids

Such as dexamethasone, help relieve pain associated with inflammation and swelling.

Psychoactive drugs

Including phenothiazines and benzodiazepines, may be useful for their sedating, antianxiety, and muscle-relaxing properties.

Bisphosphonates

Reduce bone turnover and are useful for metastatic or osteoporotic bone pain.

Clonidine

A centrally acting α2-adrenergic agonist used for various types of pain including diabetic neuropathy and cancer pain.

General anaesthetics

Depress all excitable tissues of the body at concentrations that produce anaesthesia; the pattern of depression is reversible.

Higher cortical functions

Conscious thought, memory, motor control, perception of sensations that are depressed first, while medullary centres are depressed last.

Gama Aminobutyric acid (GABA)

An inhibitory neurotransmitter whose depressant actions are potentiated by anaesthetic binding via opening of chloride channels.

Two-pore-domain potassium channels

Channels whose opening mediates the effects of some volatile general anaesthetics.

N-Methyl-D-aspartic acid (NMDA) receptors

Receptors whose inhibition dampens neural activity.

Inhalation anaesthetics

Anaesthetics administered through inhalation, e.g., nitrous oxide, methoxyflurane.

Intravenous anaesthetics

Anaesthetics administered intravenously, e.g., propofol, ketamine, midazolam.

Lidocaine

A local anaesthetic that binds to voltage-dependent sodium channels, blocking their opening and preventing sodium influx.

Epilepsy

A group of chronic neurological disorders characterized by sporadic, recurrent episodes of convulsive seizures due to excessive disorderly discharges in neuronal pathways.

Unprovoked seizures

Seizures occurring without an identifiable cause, used in diagnosing epilepsy.

Recurrent epilepsy

A diagnosis given to about 1% of people who experience recurrent unprovoked seizures.

Clinical presentation of seizures

Includes loss of consciousness, muscle stiffness, muscle jerking, sensory disturbances, and abnormal behaviour.

Primary epilepsy

Epilepsy with no identifiable cause, accounting for nearly 70% of seizures.

Secondary epilepsy

Epilepsy with an identifiable underlying cause, accounting for around 30% of cases.

Seizure triggers

Factors that may provoke seizures in idiopathic epilepsy, including hyperventilation, trauma, lack of sleep, poor nutrition, and stress.

Drugs that may cause seizures

Drugs that reduce the seizure threshold in the CNS, including anticholinesterases, antipsychotics, and narcotic analgesics.

Classification of seizures

Requires accurate diagnosis through medical history, laboratory tests, neurological examination, and EEG.

Electroencephalogram (EEG)

A test necessary for the classification of seizure types.

Convulsive seizures

Seizures characterized by excessive disorderly discharges in neuronal pathways leading to convulsions.

Traumatic head injury

An underlying cause of secondary epilepsy.

Cerebrovascular infarct or haemorrhage

An underlying cause of secondary epilepsy.

Brain tumour

An underlying cause of secondary epilepsy.

Metabolic imbalance

An underlying cause of secondary epilepsy.

Computed tomography (CT) scans

Imaging technique used to detect anatomical defects or locate small focal brain lesions.

Magnetic resonance imaging (MRI)

Imaging technique used to detect anatomical defects or locate small focal brain lesions.

Focal seizures

Seizures that originate within CNS networks limited to one hemisphere and are associated with irritation of a specific part of the brain.

Dyscognitive seizures

Seizures characterized by brief alterations in consciousness, unusual stereotyped movements, changes in temperament, confusion, and feelings of unreality.

Generalised seizures

Seizures that arise within the CNS and rapidly involve bilaterally distributed networks in the brain.

Generalised absence seizures

Seizures most often seen in childhood, consisting of temporary lapses in consciousness lasting a few seconds, with children appearing inattentive and possibly exhibiting rhythmic eye movements.

Myoclonic seizures

Seizures characterized by sudden shock-like muscle jerks, often with loss of consciousness, which may be atonic, tonic, or tonic-clonic.

Tonic-clonic generalised epilepsy

The most commonly seen type of epilepsy, characterized by a warning aura, sudden loss of consciousness, motor control, and a series of clonic muscular contractions.

Status epilepticus

A clinical emergency defined as continuous seizure activity or repeated seizures without an intervening period of consciousness, with a 10-20% mortality rate due to anoxia.

Neonatal seizures

Seizures occurring in infants younger than 1 month old, commonly caused by congenital defects, CNS infections, hypoxia, and other metabolic disturbances.