Cases 413 Flashcards
(249 cards)
1
Q
Wall Layers of GIT
A
Mucosa, Submucosa, Muscularis externa, Serosa.
2
Q
Intrinsic Nervous Control
A
Enteric Nervous System (ENS).
3
Q
Extrinsic Nervous Control
A
Autonomic Nervous System (Parasympathetic enhances; Sympathetic inhibits).
4
Q
Peristalsis
A
Wave-like propulsion of content regulated by Motilin.
5
Q
Segmentation
A
Mixing contractions in short bowel sections regulated by ENS and Parasympathetic nervous system.
6
Q
Defecation Reflex
A
Mass movement → rectal stretch → reflex arc, with Gastrin relaxing ileocecal sphincter.
7
Q
Gastrin
A
Hormone from G cells in the stomach that increases HCl secretion, motility, and mucosal growth.
8
Q
Secretin
A
Hormone from the duodenum that increases bicarbonate, decreases gastrin, and decreases motility.
9
Q
CCK (Cholecystokinin)
A
Hormone from the duodenum that decreases gastric emptying and increases pancreatic enzymes and bile release.
10
Q
Ghrelin
A
Hormone from the stomach that stimulates appetite and motility.
11
Q
Motilin
A
Hormone from the duodenum that increases migrating motor complexes during fasting.
12
Q
GLP-1 (Glucagon-like peptide-1)
A
Hormone from the ileum that decreases gastric emptying and increases satiety.
13
Q
VIP (Vasoactive Intestinal Peptide)
A
Neurotransmitter from ENS that decreases gastric acid, relaxes smooth muscle, and increases secretion.
14
Q
Substance P
A
Neurotransmitter from ENS that increases motility and vasodilation.
15
Q
Bombesin
A
Neurotransmitter from ENS that increases gastrin release.
16
Q
Neuropeptide Y
A
Neurotransmitter from ENS that decreases motility.
17
Q
Hyoscine
A
Muscarinic antagonist used for smooth muscle relaxation in IBS and bowel colic.
18
Q
Mebeverine
A
Competitive mAChR antagonist that increases NA action for IBS treatment. Reduced excitability (tx: spasms, cramps)
19
Q
Loperamide
A
μ-opioid agonist in ENS that decreases ACh release and motility.
20
Q
Racecadotril
A
Enkephalinase inhibitor that preserves enkephalins and decreases secretion for acute diarrhea.
21
Q
Telotristat
A
Inhibits tryptophan hydroxylase to decrease 5-HT synthesis for carcinoid syndrome diarrhea.
22
Q
Bismuth Subsalicylate
A
COX inhibitor that decreases prostaglandins and has an antisecretory effect.
23
Q
Prucalopride
A
5-HT4 agonist that increases ACh in ENS and motility for IBS-C and chronic constipation.
24
Q
Linaclotide
A
Increases cGMP leading to CFTR activation and increased Cl⁻/H₂O secretion for IBS-C.
25
Lubiprostone
Activates ClC-2 channels to increase secretion for IBS-C and chronic constipation.
26
Methylnaltrexone
Peripheral opioid antagonist that relieves opiate-induced constipation.
27
Bisacodyl
Activates L-type Ca²⁺ channels and inhibits water reabsorption for constipation and bowel prep.
28
Simeticone
Surfactant that decreases gas bubble surface tension for flatulence and IBS.
29
PPIs (Proton Pump Inhibitors)
Irreversible H⁺/K⁺ ATPase pump inhibitors used for GORD, ulcers, and gastrinomas.
30
H2 Antagonists (Famotidine)
H2 receptor blockers that decrease acid secretion for GORD and ulcers.
31
Cephalic Phase
Triggered by sight/smell/thought leading to vagus nerve stimulation and increased HCl secretion.
32
Gastric Phase
Triggered by stomach distension leading to increased ACh and gastrin secretion.
33
Intestinal Phase
Initial increase in gastrin followed by decrease via secretin, CCK, and VIP (enterogastric reflex). Final stage of digestion, nutrient absorption. SI -> stomach
34
Mechanoreception
The process of sensing touch, pressure, and vibration.
35
Mechanoreceptors
Receptors that respond to mechanical pressure or distortion.
36
Thermoreception
The process of sensing temperature changes.
37
Thermoreceptors
Receptors that detect changes in temperature.
38
Nociception
The sensory process that provides signals that lead to the perception of pain.
39
Nociceptors
Receptors that respond to potentially damaging stimuli by sending signals to the spinal cord and brain.
40
Aβ-fibres
Myelinated fibers that transmit touch and pressure sensations. Activated in gate control theory (so myelinated transducts signals faster)
41
Aδ-fibres
Myelinated fibers that transmit sharp, well-localized pain sensations.
42
C-fibres
Unmyelinated fibers that transmit dull, burning pain sensations.
43
Myelin Sheath
A layer that surrounds the nerve fibers, affecting the speed of signal conduction.
44
Transduction
The process of converting a noxious stimulus into an action potential.
45
Transmission
The process where action potentials travel along peripheral afferents to the brain.
46
Modulation
The process of adjusting the pain signal through neurotransmitters at the dorsal horn.
47
Glutamate
The main excitatory neurotransmitter involved in pain transmission.
48
Substance P
A neuropeptide involved in the transmission of pain and inflammation.
49
CGRP
Calcitonin Gene-Related Peptide, involved in peripheral inflammation.
50
Ascending Pathway
The pathway that transmits pain signals from nociceptors to the cortex.
51
Descending Pathway
The pathway that modulates pain signals from the brain to the spinal cord.
52
Gate Control Theory
A theory that explains how non-painful input can close the 'gates' to painful input.
53
Wind-Up
A phenomenon where repeated stimulation increases the response to pain signals. Glutamate/NMDA
54
Decussation
The crossing of nerve fibers from one side of the spinal cord to the other.
55
Noradrenaline
Released from the thalamus; binds to α2 receptors on primary neurons, leading to reduced Ca²⁺ influx and increased K⁺ efflux, thus dampening excitability.
56
Serotonin (5-HT)
Acts on interneurons in the spinal cord; induces GABA release, which hyperpolarizes primary neurons by increasing Cl⁻ and K⁺ conductance.
57
Enkephalins
Bind to opioid receptors on primary neurons; inhibit AP generation by reducing Ca²⁺ channel activity.
58
Descending Circuitry
Originates in areas like the periaqueductal gray (PAG) of the midbrain; PAG receives input from the cortex, hippocampus, and amygdala, and projects to the rostroventral medulla (nucleus raphe magnus), then descends to the dorsal horn to regulate pain transmission.
59
Hyperalgesia
Sensitisation of nociceptors; central sensitisation leading to increased response to mild noxious stimulus due to tissue injury/inflammation.
60
Allodynia
Non-noxious stimulus causes pain due to altered central processing, often following short-term injury or high intensity.
61
Acute Inflammatory Pain
Mediated by Aδ-fibres and prostaglandins from arachidonic acid via COX; prolonged and mediated by C-fibres.
62
Chronic Inflammatory Pain
Caused by central sensitisation, increased afferent input, and kinase pathway modulation.
63
Neuropathic Pain (NP)
Results from nerve injury; VGSC subtype-specific changes include Nav1.7 ↑ (acute) and Nav1.8 ↓ (acute), leading to ↑ ectopic discharges, which are reversed in chronic cases.
64
Local NP Pathway
Involves phosphorylation of Nav1.7/1.8 leading to ectopic firing and subthreshold activation due to tissue damage and subsequent immune cell activity.
65
Peripheral Nerve Injury
Leads to ectopic action potential firing and changes in the density and function of voltage-gated sodium channels (VGSCs).
66
Sodium Channel Dynamics
Acute NP Pain is characterized by upregulation of NaV1.7 increasing ectopic firing and downregulation of NaV1.8; Chronic NP Pain involves upregulation of NaV1.8 sustaining ectopic discharges.
67
Gate Control Theory
Basic concept involves Aβ (large) fibres activating inhibitory interneurons that inhibit pain signals carried by C-fibres and Aδ-fibres.
68
Clinical Correlation of Gate Control Theory
Explains why rubbing a stubbed toe can temporarily reduce pain.
69
Glutamate
Primary excitatory NT in pain transmission; initiates and sustains AP in 2° neurons.
70
Substance P
Enhances and prolongs pain signal; promotes inflammation (vasodilation, mast cell activation).
71
CGRP
Inflammatory mediator; enhances transmission and vasodilation.
72
GABA
Main inhibitory NT in spinal cord; hyperpolarises 2° neuron (↑ Cl⁻ influx) → inhibition.
73
Enkephalins
Inhibits NT release (like glutamate, SP); ↑ K⁺ efflux = hyperpolarisation.
74
Serotonin (5-HT)
Descending modulation; can be inhibitory or excitatory depending on receptor subtype.
75
Noradrenaline (NA)
Inhibitory via descending control; hyperpolarises dorsal horn neurons (↑ K⁺ efflux).
76
Dopamine (minor)
Modulatory role; emerging evidence suggests it may influence descending inhibition.
77
Excitatory (pro-pain)
Glutamate, Substance P, CGRP promote transmission and sensitisation.
78
Inhibitory (anti-pain)
GABA, Enkephalins, Noradrenaline, Serotonin (some receptors) block or dampen signal.
79
Dual/Contextual
Serotonin, Dopamine effect depends on receptor subtype/location.
80
First Order Neurotransmitters
Glutamate, Substance P, CGRP, ATP.
81
Second Order Neurotransmitters
Glutamate (AMPA -fast & NMDA -wind up receptors), Substance P.
82
Third Order Neurotransmitters
Glutamate.
83
Descending Control Neurotransmitters
Noradrenaline, 5-HT, Enkephalins (Opioids), GABA.
84
NSAIDs Prostaglandins
Inhibit COX → ↓ prostaglandin synthesis → ↓ peripheral sensitization.
Prostaglandins are synthesized from arachidonic acid, a fatty acid that is a precursor for various lipid mediators. The COX enzymes catalyze the conversion of arachidonic acid into prostaglandins.
COX-1 vs. COX-2:
COX-1: Primarily involved in maintaining normal physiological functions, such as gastric mucosal integrity, platelet-initiated blood clotting, and renal function.
COX-2: Inducible enzyme primarily involved in mediating pain, inflammation, and fever.
85
5-HT
Weak COX inhibition + activates descending serotonergic pathways.
86
Opioids
μ, κ, δ receptor agonists → inhibit Ca²⁺, activate K⁺ → ↓ NT release.
87
Anticonvulsants
Bind α2δ subunit of Ca²⁺ channels → ↓ excitatory NT release.
88
TCAs / SNRIs
Block 5-HT & NA reuptake → ↑ descending inhibition.
89
Local Anesthetics
Block Na⁺ channels → prevent AP propagation.
90
NMDA Antagonists
Block NMDA receptors → prevent wind-up & central sensitization.
91
Triptans
5-HT1B/1D agonists → vasoconstriction + inhibit CGRP release.
92
CGRP Antagonists
Block CGRP or receptor → reduce migraine-associated vasodilation.
93
Capsaicin
TRPV1 agonist → Substance P depletion after repeated use.
94
Benzodiazepines
ENHANCE GABA-A → Cl⁻ influx → hyperpolarization.
95
General Anesthetics
Potentiate GABA-A, inhibit Na⁺/NMDA → CNS depression.
96
Peripheral Blockers
Target: Peripheral transduction, inflammation, Na⁺ channels
97
Prostaglandins
Inhibit COX → ↓ prostaglandins → ↓ sensitization
98
NSAIDs
Examples: Ibuprofen, Aspirin
99
5-HT
Paracetamol - Weak COX inhibition + boosts descending 5-HT - (Stops signal)
100
Local Anesthetics
Block Na⁺ channels → stop action potential
101
Substance P
Capsaicin - TRPV1 agonist → depletes Substance P over time
102
Mnemonic for Peripheral Blockers
NSAID-PaL Can Block Pain (NSAID, Paracetamol, Lidocaine, Capsaicin)
103
Central Dampeners
Target: Central modulation, spinal cord, descending pathways
104
Opioids
Examples: Morphine, Fentanyl; Activate μ, κ, δ receptors → ↓ Ca²⁺, ↑ K⁺ → ↓ NT release
105
Glutamate
NT Involved in Opioids
106
TCAs / SNRIs
Examples: Amitriptyline, Duloxetine; Block 5-HT & NA reuptake → ↑ descending inhibition
107
Benzodiazepines
Examples: Diazepam; Enhance GABA-A → ↑ Cl⁻ influx → hyperpolarize
108
General Anesthetics
Examples: Propofol, Sevoflurane; Potentiate GABA-A + inhibit Na⁺/NMDA
109
Mnemonic for Central Dampeners
Opiates Take Brains Down (Opioids, TCAs/SNRIs, Benzos, Downers like Propofol)
110
Channel/Glutamate Blockers
Target: Central excitation, ion channels, glutamate
111
Glutamate Anticonvulsants
Examples: Gabapentin, Pregabalin; Block Ca²⁺ α2δ subunit → ↓ glutamate release
112
NMDA Antagonists
Examples: Ketamine, Memantine; Block NMDA receptor → stop wind-up/central sensit.
113
Mnemonic for Channel/Glutamate Blockers
Anti-Ket Gluts No More (Anticonvulsants + Ketamine → no glutamate overdrive)
114
Migraine-Specific
Target: CGRP -either the NT itself or the receptors), vasodilation (goal: increase increase constriction), trigeminal nerve
115
CGRP, 5-HT Triptans
Example: Sumatriptan; 5-HT1B/1D agonist → vasoconstriction + ↓ CGRP
116
CGRP Antagonists
Examples: Erenumab, Rimegepant; Block CGRP or its receptor → ↓ migraine dilation
117
Botox A
Inhibits SNAP-25 → ↓ CGRP release, toxic to the vesicle itself
118
Mnemonic for Migraine-Specific
Trippy CGRP Busters
119
NSAIDs
Block COX enzymes to reduce prostaglandin synthesis, thus lowering peripheral nociceptor activation.
120
COX
Enzymes that convert arachidonic acid into prostanoids (prostaglandins, thromboxane A₂).
121
Paracetamol
Weak inhibitor of COX 1 and 2 with additional central action via activation of descending serotonergic pathways.
122
Opioids
Inhibit the release of neurotransmitters like Substance P and Glutamate.
123
TCAs/SNRIs
Inhibit the reuptake of neurotransmitters, increasing levels of 5-HT and NA.
124
Gabapentinoids
Bind to the α₂δ subunit of voltage-gated Ca²⁺ channels in glutamatergic neurons, reducing glutamate (wind up) release.
125
Ketamine
Blocks NMDA receptors, leading to a decrease in Glutamate.
126
Triptans
Act on CGRP pathways to reduce CGRP levels indirectly. Triptans, like sumatriptan, act as selective 5-HT1 receptor agonists, mainly targeting 5-HT1B and 5-HT1D receptors. This mechanism primarily involves vasoconstriction of dilated cranial blood vessels and inhibition of the release of vasoactive peptides from trigeminal nerve endings.
127
Capsaicin
Depletes Substance P, leading to reduced pain signaling.
128
Benzos
Enhance GABAergic inhibition, leading to increased GABA levels.
129
Inflammatory Pain
Pain resulting from tissue damage that activates the COX pathway.
130
COX-1
Ubiquitous enzyme expressed in various tissues, including gastric parietal cells.
131
COX-2
Inducible enzyme expressed during inflammation, particularly in dilated arteries.
132
Aspirin
An NSAID that irreversibly inhibits COX enzymes.
133
Selective COX-2 inhibitors (Coxibs)
Lower gastrointestinal risk but may increase cardiovascular complications, because predominantly on vascular receptors.
134
Analgesic Ladder
A stepwise approach to pain management, starting from low-risk analgesics to strong opioids.
135
Weak Opioids
Used for mild to moderate pain, often combined with NSAIDs or paracetamol for synergy.
136
Strong Opioids
Used for severe pain, including cancer pain and severe acute or chronic non-malignant pain.
137
Acute Pain
Often inflammatory pain with a strong peripheral component, such as post-injury.
138
Chronic Pain
May involve central sensitization and often requires adjuvants for management.
139
Local Anesthetics
Block voltage-gated Na⁺ channels, administered topically or regionally.
140
Gabapentinoids (Gabapentin, Pregabalin)
Provide analgesia, euphoria, and calmness by reducing neurotransmitter release.
141
Benzodiazepines & Z-Drugs
Used for anxiety, insomnia, and sometimes neuropathic pain by enhancing GABAergic inhibition.
142
Mu (μ)
Main receptor for analgesia but with risk for respiratory depression, tolerance, and addiction.
143
Kappa (κ)
Mediate spinal analgesia; may cause hallucinations.
144
Delta (δ)
Provide peripheral analgesia; potential for proconvulsant effects.
145
NOP (ORL)
May produce spinal analgesia but can counteract supraspinal opioid effects.
146
Mechanism of Opioids
GPCR-mediated inhibition of adenylate cyclase.
147
Calcium and Potassium Channels
Inhibit Ca²⁺ channels and open K⁺ channels to reduce neurotransmitter (e.g., glutamate) release.
148
Ketamine
Blocks NMDA receptors; used for dissociative anesthesia and acute pain management.
149
Dextromethorphan/Memantine
NMDA blockers with less potent analgesic effects.
150
Tension Headache
Prevalence: 80-90%; Characteristics: Bilateral, non-pulsating, mild to moderate intensity.
151
Migraine
Prevalence: ~10%; Criteria (must fulfill at least 5 attacks): Unilateral location, Pulsating quality, Moderate/severe intensity, Aggravation by routine physical activity, Nausea and/or vomiting, Photophobia, phonophobia, or osmophobia.
152
Migraine Aura
Positive Neurological Symptoms: Visual flashes, zigzag lines, or tingling sensations that resolve within 1 hour; Negative Neurological Symptoms: Brief visual blind spots, numbness, or speech difficulties that resolve within 1 hour.
153
Cluster Headache
Characteristics: Excruciating, continuous unilateral pain, typically occurring in clusters (episodes lasting 4-12 weeks, often seasonal).
154
Typical Patient for Cluster Headache
Middle-aged male smoker.
155
Tricyclic Antidepressants (TCAs)
Inhibit reuptake of serotonin and noradrenaline, boosting descending inhibition.
156
SNRIs
Similar to TCAs with fewer side effects; used for neuropathic pain and conditions like trigeminal neuralgia.
157
Triptans
Agonists at 5-HT₁B/1D receptors induce vasoconstriction and inhibit CGRP release (e.g., Sumatriptan).
158
CGRP Antagonists
Monoclonal antibodies (Eptinezumab, Galcanezumab, Fremanezumab; receptor blocker Erenumab) and small molecules (Rimegepant) target migraine pathways.
159
Beta-Blockers
(e.g., Propranolol) help prevent migraine by reducing vasodilation.
160
Botulinum Toxin A
Inhibits SNAP-25, reducing CGRP release; used in chronic migraine prophylaxis.
161
Capsaicin
Agonist at TRPV1 receptors; repeated application leads to desensitization, substance P depletion, and reduced pain signaling.
162
Stages of Anesthesia
Stage 1 (Induction): Sedation but consciousness maintained; Stage 2 (Excitement): Delirium, disinhibition, potential airway reflex sensitivity; Stage 3 (Surgical Anesthesia): Deep anesthesia with loss of reflexes; Stage 4 (Overdose): Excess depression of vital centers leading to respiratory failure.
163
Mechanisms of General Anesthetics
Many potentiate GABA at GABA-A receptors; some activate two-pore domain K⁺ channels or inhibit Na⁺ and NMDA receptors.
164
Examples of General Anesthetics
Propofol (IV induction/maintenance), Isoflurane/Sevoflurane (inhalational), Nitrous Oxide.
165
TENS (Transcutaneous Electrical Nerve Stimulation)
Activates Aδ fibres to induce central long-term depression of nociceptive signals.
166
Cognitive Behavioral Therapy (CBT)
Techniques aimed at altering pain perception and coping strategies.
167
Acne features
Comedones (blackheads and whiteheads)
Inflamed spots
Seborrhoea (excessive production of sebum; oily skin
168
Acne formation
Excessive sebum production secondary to stimulation by androgens
Abnormal follicular keratinization and desquamation resulting in formation of a follicular plug.
Proliferation of the anaerobe c
Inflammation.
169
Bactteria responsible for acne
Gram positive bacteria Cutibacterium acnes
170
ACNE treatment:
NICE recommends a 12-week course of one of the following treatment options, depending on severity of acne, patient preference, advantages and disadvantages of each treatment etc. Wait for 12 weeks prior to changing plan -AMR growing.
171
Topical combination of adapalene with benzoyl peroxide for any acne severity
Can cause skin irritation, photosensitivity, and bleaching of hair and fabrics.
Adapalene is contraindicated in pregnancy or planning pregnancy.
Does not contain antibiotics
172
Topical combination of tretinoin with clindamycin for any acne severity
Can cause skin irritation, photosensitivity, and bleaching of hair and fabrics.
Tretinoin is contraindicated in pregnancy or planning pregnancy.
Contains antibiotic
173
Topical combination of benzoyl peroxide and clindamycin for mild to moderate acne
Can cause skin irritation, photosensitivity, and bleaching of hair and fabrics.
Can be used with caution during pregnancy and breastfeeding.
Contains antibiotics
173
174
Topical combination of adapalene with benzoyl peroxide together with either oral lymecycline or doxycycline for moderate to severe acne
Helpful for difficult to reach affected areas
Topical combination can cause skin irritation, photosensitivity, and bleaching of hair and fabrics.
Adapalene is contraindicated in pregnancy or planning pregnancy.
Contains oral antibiotic- risk of systemic side effect and resistance
Oral tetracyclines such as doxycycline and lymecycline can cause photosensitivity and should not be used in pregnancy as can cause discoloration of the child’s teeth and affect skeletal development.
175
Topical azelaic acid with either oral lymecycline or oral doxycycline for moderate to severe acne.
Helpful for difficult to reach affected areas
Contains oral antibiotic- risk of systemic side effect and resistance
Oral tetracyclines such as doxycycline and lymecycline can cause photosensitivity and should not be used in pregnancy as can cause discoloration of the child’s teeth and affect skeletal development.
176
Benzoyl Peroxide MOA
Antiseptic, anti-inflammatory, reduces keratinisation
High lipophilic = penetrates pilosebaceous duct
to release free oxygen radicals, which have potent bactericidal activity in the sebaceous follicles and anti-inflammatory action. It also has effects on noninflammatory lesions by reducing follicular hyperkeratosis.
177
Retinoids (Adapalene, Tretinoin) MOA
Anti-inflammatory, normalise keratinocyte growth
Derived from vit A
a rapid anti-inflammatory action. Vitamin A and other retinoids reduce abnormal growth and development of keratinocytes within the pilosebaceous unit. Helps to 'unplug' the follicle.
inhibits development of the microcomedones and noninflammatory lesions.
178
Azelaic Acid MOA
Anti-inflammatory, normalises follicular keratinisation
comedogenesis by partially normalizing the disturbed terminal differentiation of keratinocytes in the follicular infundibulum.
A direct anti-inflammatory effect has been demonstrated.
179
Tetracyclines/Clindamycin MOA:
Inhibit protein synthesis
180
In general the MOA of acne meds is:
all anti inflammatory reduce keratinization of skin if I short circuit in exam
181
General skin self care
Avoid over-cleaning the skin as can cause dryness and irritation
Use a non-alkaline (skin pH neutral or slightly acidic) synthetic detergent cleansing product twice daily on acne-prone skin.
Avoid oil-based comedogenic skin care products, make-up and sunscreens.
If make-up is used, remove at the end of the day.
Persistent picking or scratching of lesions can increase risk of scarring.
There is not enough evidence to support specific diets for treating acne but maintain a healthy diet.
182
Tinea Corporis (Body)
scaly, itchy skin and
Single or multiple red or pink, flat or slightly raised annular (ring-shaped) asymmetrical patches of variable sizes (typically 1–5 cm), which widen outwards and usually have a clear central area and an active red, scaly expanding edge (e.g., Tinea corporis or ringworm).
Usually caused by a variety of species from Trichophyton and Microsporum genera of dermatophytes.
183
Pathogen in Tinea Corporis
variety of species from Trichophyton and Microsporum genera of dermatophytes.
184
Tinea Pedis (Foot)
nterdigital (4th-5th toe spaces)
Moccasin (dry soles)
Vesiculobullous (blisters on arches)
Usually associated with itchy, scaly, or painful skin of the feet and caused by Trichophyton rubrum, Trichophyton interdigitale or Epidermophyton floccosum.
Different subtypes of fungal foot infections:
Interdigital type or toe web infections (most prevalent) — Usually, marks the lateral interdigital space between the fourth and fifth toes and then spreads medially. It is presented with white or red, fissured, dry, peeling and scaling skin or macerated areas between the toes.
185
Tinea cruris:
Usually characterised by red or red-brown, flat or slightly raised plaques with definite borders with or without pustules or vesicles on skin of inguinal folds, proximal medial thighs, perianal area, buttocks, and above the waistline. Usually caused by Trichophyton rubrum and Epidermophyton floccosum
186
Fungal infection treatment non severe + MOA
Terbinafine, Imidazoles, Itraconazole: Inhibit ergosterol synthesis (fungal membrane) available OTC for specific age groups) .
187
Fungal infection treatment severe + MOA
:
take skin sample and send for mycological examination and consider prescribing an oral antifungal medication if:
A positive result for fungal infection.
A strong clinical suspicion of fungal infection before mycology results are back (depending on clinical judgement)
A negative mycology result, but clinical features are very indicative of fungal infection. In this case, repeat the mycological examination
If oral antifungal medication is indicated, can prescribe terbinafine as first-line treatment and itraconazole or griseofulvin if terbinafine is not tolerated or is contraindicated. But need to follow local antimicrobial guidelines as first-line resource.
Consider referring to a specialist if necessary
188
Microemulsion
Micro-emulsion is a “swollen micelle” micelle = 2-5 nm, micro-emulsion = 10-200 nm (50 nm). A portion of oil stays in core. Need adjunct surfactant, surface tension ~zero, needs 25-30% w/v surfactant. Thermodynamically stable, transparent, forms spontaneously. Smaller than a normal emulsion and stable. A true colloid rather than dispersion.
189
Oswald Ripening
Occurs in emulsions containing polydisperse (presence of very large and very small) droplets. The component of small droplets are forced to be reconstituted in the body of larger droplets. This is related to a pressure difference between small (high) and large (low) droplet pressures.
190
Coalescence
two or more droplets collide and form one larger droplet, and it is irreversible. Caused by various factors, including pH change, salt concentration, emulsifier concentration, phase-volume ratio, temperature, etc
191
Osmotic/solvation forces
On droplet “close approach” the polymer chains start to overlap – effectively get a concentrated polymer solution. Creating an osmotic gradient in solution – concentrated polymer solution in the overlap region and dilute solution in the bulk solution. Water enters the concentrated region
192
Entropic/steric effects
on droplet “close approach” the polymer chains start to overlap. With a subsequent loss into the freedom of motion of the polymer chains, a loss of entropy. This situation is thermodynamically unfavourable and forces the droplets apart
193
HLB < 10
lipophilic surfactants → W/O
194
HLB > 10
hydrophilic surfactants → O/W
195
Bancroft's rule
Mixtures often used to match oil’s required HLB
Type of emulsion depends more on the emulsifier’s solubility, not phase ratio
Type of emulsion produced will actually depend on the emulsifier used (shape, HLB) not how much oil or how much water, just shape/HLB
196
Above waste microflora
Gram-positive (e.g., Cutibacterium, Corynebacterium, Staphylococcus)
197
Below waste microflora
Mixed Gram-positive and Gram-negative (e.g., Enterobacteriaceae), excreting feces
198
Importance of Filaggrin in skin barrier function
protein w. key role in forming the stratum corneum, the outermost layer of skin. It helps maintain skin hydration, prevents moisture loss, and acts as a barrier against irritants and allergens. Filaggrin deficiency, often linked to genetic mutations, can lead to dry, sensitive skin, and increased susceptibility to conditions like eczema and atopic dermatitis.
199
Barrier to infection -dry
Inhibits Gram-negatives
Normally 20% hydration; occlusion results in >100% hydration.
After occlusion, the nature of microflora changes. (Nappy rash)
200
pH (Acid Mantle) barrier to infection
4.0–6.0;
Do not try to strive for neutral w/ skin care, acidity is beneficial bc:
supports normal flora, deters pathogens
areas of higher moisture tend to have slightly higher pH).
Acidity mainly due to fatty acid secretions.
Inhibitory to number of environmental bacteria (e.g. Proteus spp.).
201
Salt in sweat - barrier to infection
High salt inhibits many pathogens
High salt concentration in sweat.
Particularly when drying.
Resident microflora are resistant to high salt.
202
Flucoxacclin
Acid stable, can be given by month
Penicillinase-resistant
203
1st choice for S. Aureus (unless MRSA)
Flucloxacillin
204
Why can't saphil. Cocci be treated with classic penacillins?
Issue with saphil. Cocci produce penicilase and are resistant to classic penacilins
205
How is Flucloxacillin penilicase resistant and therefore first line?
Utilizes steric hindrance to avoid hydrolyzing and maintaining drug activity (removes isozaloe group)
Structural
Can also add beta lactamase inhibitors -IE cab malonic acid
Protects the drug
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Impetigo
Highly contagious; S. aureus, S. pyogenes -gram positive (tend to be chained)
Types: Non-bullous (most common -70%), bullous
Non-bullous
Staph. aureus, Strept. pyogenes or both.
Bullous (often on trunk, arms & legs)
Staph. aureus
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Impetigo treatment
Hydrogen peroxide, fusidic acid, mupirocin (not systemic)
Hydrogen peroxide: Oxidation reactions
Fusidic acid – a steroid antibiotic:inhib protein synth.
Mupirocin – pseudomonic acid A:
Active predominantly vs. Gram-positives
Derived from pseudomonas
Inhibits isoleucyl-transfer RNA, thereby obstructing bacterial protein synthesis.
Bacteriostatic at low concs. Bactericidal over long exposures. For systemic: Flucloxacillin, clarithromycin or erythromycin
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Cellulitis
Deep dermis/subcutaneous; S. aureus, GAS. Features: Red, hot, swollen; not sharply demarcated
Pronounced redness and oedema, sometimes blistering, ulceration and/or abscess formation.
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Erysipelas
Superficial; often face/legs; GAS (Typically Streptococcal infection (often GAS).
Exotoxin production.
Erysipelas is a more superficial form of cellulitis (esp. Face + legs).
Typically infection of the dermis -upper layer of skin.
Features: Red, shiny, well-demarcated; fever
Fever and light red, shiny swollen cheeks near the nostrils.
Clearly defined areas.
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Treatment (Cellulitis & Erysipelas)
Treatment
Antibiotics (use local recommendations):
Flucloxacilli
Clarithromycin
Co-amoxiclav if near eyes or nose
Plus others if MRSA or anaerobes suspected
Also: Analgesics, antipyretics
Ensure: Exclude other causes e.g. Inflammatory reactions and other non-infectious causes e.g. chronic venous insufficiency
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Necrotising Fasciitis
Tissue necrosis from bacterial enzymes/toxins
Release of bacterial toxins & enzymes results in thrombosis.
Destruction of the soft tissues and fascia (connective tissue)
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Necrotising Fasciitis pathogen
I: Polymicrobial
Hardest to target
II: GAS, S. aureus
III: Clostridial/gas gangrene
Rare IIII: marine organisms and fungal infections,
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Scalded Skin Syndrome
Ritter’s disease: A serious staphylococcal skin infection (babies/children <5y.o.).
Caused by strains of Staph. aureus producing ‘exfoliatin’ (epidermolytic toxin)
Toxin causes destruction of the intercellular connections and separation of the top layer of epidermis.
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Allergic rhinitis
Seasonal: triggered by seasonal pollen shifts Perennial: year round from dust mites, pet dander, mold spores
Occupational: allergens by occupations (flour, dust, latex, chemicals)
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Pathophysiology -allergic rhinitis
Sensitization, Early phase reaction (w/in minutes), Late phase (hours)
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Sensitization
First exposure to an allergen → Dendritic cells present antigen to T-helper cells → B-cell activation → IgE production → IgE binds to mast cells.
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Early Phase (minutes)
Re-exposure leads to mast cell degranulation → Histamine, prostaglandins, leukotrienes released → Mucosal swelling, sneezing, itching.
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Late phase (hrs)
Recruitment of eosinophils, basophils → Persistent inflammation → Chronic symptoms.
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Antihistamines generation differences
First generations can cross BBB = sedating/increased dementia risk (IE Diphenhydramine)
Second generations can't cross = non sedating (IE cetirizine)
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Decongestants
Oral: Pseudoephedrine (short-term use only, risk of rebound congestion)
Topical: Oxymetazoline, Xylometazoline (max 3–5 days use)
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Intranasal corticosteroids
Fluticasone, Budesonide, Mometasone (most effective for persistent symptoms)
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Non pharmacological allergies
avoid allergens, saline irrigation, HEPA filters
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Advantages of Nasal Drug Delivery
Rapid absorption (high vascularization), avoids first pass metabolism, direct action on certain target tissue (IE rhinitis), non invasive, pt friendly
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Nasal absorption ideal factors
pH = 5.5 - 6.5
lipophilic (membrane)
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Psuudoephedrine MOA
Acts as adrenaline mimic on a, this leads to increased IP3 and DAG and Ca2+ = contraction, this leads to vasoconstriction and less blood flow/inflammation to increase mucous release
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Antihistamines MOA
Allergen-activated IgE binds to mast cells to release histamine (degranulation)
Histamine initiates allergic reaction, mucous secretion and allergic reaction
Antihistamines bind to H1 receptors and hence treating and preventing allergic reactions and mucous secretion. Must be taken prophylactically
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Glucosteroids MOA
Corticosteroids bind to their nuclear receptors to induce the expression of inhibitory proteins to inhibit the release of arachidonic acid and prevent the formation of leukotriene and prostaglandins. Corticosteroids suppress the expression/ activity of inflammatory immune cells and inhibit the release of inflammatory cytokines
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Mucolytic agents
Make mucous less vicous and easier to secrete for coughs caused by intense mucous production in illness
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internal structure of the turbinate bones (or conchae) on each side help to achieve nasal passage function through:
narrow orifice
large surface area
mucus & cilia
turbulent airflow
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Degranulation and histamine release process
ulation triggering:
The IgE receptor (FcεRI) is a tetramer (α, β, 2 γ), associated with a kinase (Lyn)
Once antigen is bound to multiple receptors, the kinase crosslinks the receptors and phosphorylates specific motifs (shown in red)
This recruits another kinase (Syk) which can amplify the signal by phosphorylating multiple targets, such as the LAT linker
PhospholipaseC binds to LAT and can be phosphorylated, activating it to allow conversion of PIP2 in the membrane to IP3
IP3 binds to its receptor on the ER, releasing signalling calcium to initiate degranulation
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Mass cell degranulation in allergic rhinitis
When mast cells degranulate they deposit histamine, heparin, cytokines, and growth factors in the local area
The allergic response is mediated by the H1 receptor, a GPCR expressed throughout the body:
in smooth muscles
on vascular endothelial cells
in the heart
in the central nervous system
adrenal medulla
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What does activation of the H1 receptor trigger?
H1 receptor activates phospholipase C and the phosphatidylinositol (PIP2) signalling pathway
Nerve stimulation: Itching & sneezing
Vasodilation:
Erythema
Leaking fluid from blood vessels:
Rhinorrhoea
Nasal congestion & eyelid swelling
“Allergic shiners”
Hives/urtica:
Histamine-mediated blotches or raised bumps on the skin:
red (vasodilation)
swelling (leaky vessels)
itchy (nerve stimulation)
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Variants of Interest (VOIs) (escalates to….)
May affect transmissibility, severity, immune evasion, or diagnostics.
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Variants of Concern (VOCs)
Increased transmissibility, more severe disease, reduced neutralization by antibodies.
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Nirmatrelvir + Ritonavir (Paxlovid):
Protease inhibitor combo.
Ritonavir boosts plasma levels by inhibiting CYP enzymes.
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Sotrovimab:
Monoclonal antibody → binds spike protein → blocks ACE2 binding.
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Remdesivir:
Nucleoside analogue → premature chain termination.
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Molnupiravir:
Causes lethal mutagenesis by mimicking cytidine/uridine.
Concerns: may increase viral mutation or pose host DNA risk.
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Influenza antivirals
1. Oseltamivir (Tamiflu) – Orally active (capsules or suspension). 2. Zanamivir (Relenza) – Administered via inhalation; requires a cumbersome and expensive device; also available in IV form. Both are neuraminidase inhibitors.
3. Baloxavir marboxil (Xofluza)
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Influenza
Haemagglutinin (HA) (18 subtypes in A viruses).
Neuraminidase (N) (11 subtypes in A viruses).
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Varicella (chickenpox)
Stay away from school/work until ALL the spots have formed a scab. A very itchy (pruritic) blister-like rash. Progresses quickly from macular to papular to vesicular lesions before crusting
First appears on chest, back, face, then spreads over body, appearing over 3-5 d. Symptoms usually last 4 – 7 d but may vary person to person
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Ruvella/measles
A non-itchy (usually) rash, erythematous (abnormal redness) maculopapular (a rash with both flat and raised parts) exanthema (eruptive disease) appearing a few days after the initial symptoms
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Expectorant
Promote mucus production (IE Guaifenesin)
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Where is the cough control center?
Medulla Oblongata
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Mucolytic drugs
Clear mucous by reducing viscosity Carbocisteine/Bromhexine
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Antitussive
Cough Suppressant (Codeine/dextromethforman)
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Guaifenesin MOA
Bromhexine depolymerises muco-polysaccharides in mucus making it less viscous. Activates nervous system to cough more increasing mucous excretion.
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CYP2D6 + codeine toxicity risk
The prevalence of CYP2D6 ultrarapid metabolizers varies significantly across populations, with estimates ranging from 1-10% in Caucasians to potentially 20-29% in East African populations
