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Y1 > Foundation - General Pharmacology > Flashcards

Foundation - General Pharmacology Flashcards

1
Q

Outline the steps in rational drug prescribing

A
  1. Make diagnosis
  2. Consider treatment options
  3. Prescription
  4. Patient counselling
  5. Monitoring
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2
Q

Define pharmacokinetics and pharmacodynamics

A

Pharmacokinetics: processing of drug by body

Pharmacodynamics: effect of drug on body

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3
Q

Measurement of pharmacokinetics

A
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4
Q

Name the classes of drugs under general pharmacology

A
  1. Corticosteroids
  2. Antihistamines
  3. Non-steroidal anti-inflammatory drugs
  4. Paracetamol
  5. Local analgesic
  6. General analgesic
  7. Opioids

ANTI-INFLAMMATORY
- Antihistamines
- Glucocorticoids
- NSAIDs

SEDATIVE
- Antihistamines (gen 1)
- General analgesic
- Opioids

ANALGESIC
- Paracetamol
- Local analgesic
- Opioids
- General analgesic (inhaled)

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5
Q

List the types of receptors and neurotransmitters, and where they can be found in the autonomic nervous system

A

PARASYMPATHETIC NS
Preganglionic neurone in brain stem/spinal cord → acetylcholine → nicotinic receptor on postganglionic neurone → acetylcholine → muscarinic receptor on effector organs

SYMPATHETIC NS
Preganglionic neuron in spinal cord → acetylcholine → nicotinic receptor on postganglionic neurone → norepinephrine → adrenergic receptor on effector organs

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6
Q

Name the types of adrenoreceptors and their locations in the body

A

Alpha 1: eyes, everywhere
Alpha 2: digestion
Alpha 1+2: vasoconstriction
Beta 1: heart, aqueous humour
Beta 2: lungs, uterus, others
Beta 3: urination, lipolysis, temperature

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7
Q

Describe the adrenergic agonistic effects giving rise to the fight or flight response at different organs

A

Eye:
- Alpha 1 agonism → contract iris dilator muscle → pupil dilation/mydriasis
- Alpha 1 agonism → relax ciliary muscle
- Beta 1 agonism → decrease aqueous humour production → decrease intraocular pressure
- Accommodate far vision

Salivary glands: alpha 1 agonism → inhibit saliva secretion

Lungs: beta 2 agonism → bronchodilation

Heart: beta 1 agonism → positive inotropic (force) and chronotropic (rate) effects

Peripheral blood vessels: alpha 1 and 2 agonism → vasoconstriction

Stomach/intestine:
- Alpha 1 and alpha 2 agonism → decrease motility and secretion

Liver and gallbladder:
- Alpha 1 and beta 2 agonism→ increase glycogenolysis
- Beta 3 agonism → increase lipolysis

Bladder:
- Alpha 1 agonism → contract bladder sphincter + lower urinary tract muscles
- Beta 3 agonism → relax detrusor → inhibit urination

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8
Q

Describe the MOA of the following non-specific direct adrenergic agonists
(i) Dopamine
(ii) Norepinephrine
(iii) Epinephrine

A

(i) Dopamine (a1 and b1)
- Used in cardiac resus esp for patients with renal failure due to insufficient renal perfusion

(ii) Norepinephrine (a > b)
- Used in severe hypotension

(iii) Epinephrine (b > a)
- Used in anaphylaxis
- More direct impact on heart and lungs (b1 and b2)

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9
Q

Describe the MOA of alpha-specific direct adrenergic agonists
(i) Oxymetazoline
(ii) Phenylephrine
(iii) Brimonidine

A

(i) Oxymetazoline (a1, a2)
- Used as nasal decongestant

(ii) Phenylephrine (a1)
- Used in hypotension

(iii) Brimonidine (a2)
- Used in open-angle glaucoma
- Topical to eye
- Preferred over non-selective alpha as it avoids unnecessary a1 action which affects pupil dilation and lens accomodation

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10
Q

Describe the MOA of beta-specific direct agonists
(i) Dobutamine
(ii) Isoprenaline
(iii) Salbutamol/terbutaline
(iv) Mirabegron

A

(i) Dobutamine (b1)
- Used in congestive heart failure

(ii) Isoprenaline (b1, b2)
- Used in cardiac resus, asthma

(iii) Salbutamol/terbutaline (b2)
- Tocolytic → prevent labour contractions by relaxing uterus during late pregnancy
- Used in asthma

(iv) Mirabegron (b3)
- Used for urinary incontinence

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11
Q

Describe the MOA of indirect adrenergic agonists
(i) Moclobemide
(ii) Tricyclic antidepressants
(iii) Ephedrine/pseudo-ephedrine

A

(i) Moclobemide → block monoamine oxidase → inhibit breakdown of norepinephrine so its adrenergic agonism effect can persist
- Used as an antidepressant

(ii) Block reuptake of norepinephrine into nerve → more NE at synapse for action
- NE signals are transmitted by presynaptic uptake 1

(iii) Ephedrine/pseudo-ephedrine
- Compete with NE for vesicular compartment and MAO → NE less broken down
- Ephedrine is more potent, no oral administration, pseudo-ephedrine is less potent, able to have oral administration

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12
Q

Describe the effects of adrenergic antagonism on the different target organs

A

Eye:
- Alpha 1 antagonism → relax iris dilator muscle → pupil constriction/miosis
- Alpha 1 antagonism → contract ciliary muscle
- Beta 1 antagonism → increased aqueous humour production → increased intraocular pressure
- Accommodate near vision

Salivary glands: alpha 1 antagonism → promote saliva secretion

Lungs: beta 2 antagonism → bronchoconstriction

Heart: beta 1 antagonism → negative inotropic (force) and chronotropic (rate) effects

Peripheral blood vessels: alpha 1 and 2 antagonism → vasodilation

Stomach/intestines: alpha 1 and 2 antagonism → promote motility and secretion

Liver and gallbladder:
- Alpha 1 and beta 2 antagonism → decrease glycogenolysis
- Beta 3 antagonism → decrease lipolysis

Bladder:
- Alpha 1 antagonism → relax bladder sphincter + lift up urinary tract muscles
- Beta 3 antagonism → contract detrusor muscle → promote urination

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13
Q

Describe the MOA of alpha-specific direct adrenergic antagonists
(i) Phenoxybenzamine
(ii) ‘-zosin’s
(iii) Tamsulosin
(iv) Yohimbine

A

(i) Phenoxybenzamine (a1, a2)
- Used for pheochromocytoma (adrenal gland tumour + hypertension)

(ii) Prazosin (a1)
- Used for chronic hypertension

(iii) Tamsulosin (a1)
- Used for benign prostate hyperplasia

(iv) Yohimbine (a2)
- Has indirect agonist effect → increases NE
- Act at presynaptic terminal
- Abused as weight loss and impotence substance

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14
Q

Describe the MOA of beta-specific direct adrenergic antagonists
(i) Bisoprolol
(ii) Propanolol
(iii) Betaxolol
(iv) Timolol
(v) Sotalol

A

(i) Bisoprolol (b1)
- Used for hypertension, angina, arrhythmias
- Additional anti-hypertensive effect due to block of renin secretion
- Low lipophilicity → little LA effect
- Use in caution in asthmatic patients due to cross sensitivity

(ii) Propanolol (b1, b2)
- High lipophilicity → LA effect
- Used for hypertension, angina, arrhythmias
- Additional anti-hypertensive effect due to block of renin secretion

(iii) Betaxolol (b1)
- Used in glaucoma
- Additional anti-hypertensive effect due to block of renin
- No LA effect, topical to eye

(iv) Timolol (b1, b2)
- Used in glaucoma
- Additional anti-hypertensive effect due to block of renin
No LA effect, topical to eye

(v) Sotalol (b1, b2)
- Class 2 and 3 anti-arrhythmic drug

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15
Q

What are the contraindications for propanolol?

A
  • Cannot give asthmatics as they block bronchodilation
  • Cannot give peripheral vascular disease patients as they further block vasodilation of blood vessels at skeletal muscles
  • Cannot give diabetics as they block insulin secretion
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16
Q

Describe the MOA of indirect adrenergic antagonists

A
  1. Methyldopa
    - Has some direct a2 antagonist effect → used to treat hypertension
    - L-tyrosine inhibit tyrosine hydroxylase → decrease NE → decrease epinephrine + increase false transmitter methylnoradrenaline
  2. Dexmedetomidine
    - Act at presynaptic a2 autoreceptors
    - Tap on feedback inhibition of NE release → decrease NE release for a receptors → visceral vasoconstriction + less signalling to brain
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17
Q

What are the contraindications for methyldopa?

A
  • Haemolytic anaemia → must do blood test
  • Hepatotoxicity → liver disease pts
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18
Q

Name the types of cholinergic receptors and their locations throughout the body

A

G-protein linked receptors
- M1: stomach, CNS
- M2: heart, CNS
- M3: lungs, CNS, glands, GIT
- M4: CNS
- M5: CNS

Ligand-gated Na channels
- Nm: skeletal muscle
- Nn: ganglion, CNS

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19
Q

Describe the effects of cholinergic agonism involving rest and digest on the different target organs

A

Eye:
- M3 agonism → contract iris sphincter muscle → pupil constriction/miosis
- M3 agonism → contract ciliary muscle, relax lens
- Accomodate near vision

Salivary glands: M3 agonism → increased salivation

Lungs: M3 agonism → bronchoconstriction, increased airway secretions

Heart: M2 agonism → bradycardia

Stomach/intestines:
- M3 agonism → increased GI motility and secretions
- M1 agonism → increased gastric acid secretions

Exocrine glands: M3 agonism → lacrimation/tearing

Gallbladder: M2 agonism → contraction

Bladder: M3 agonism → relax bladder internal sphincter + contract detrusor muscle → urination

Genitals: M2 and M3 agonism → erection, arterial dilation

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20
Q

Describe the MOA of the direct muscarinic receptor agonists
(i) Alkaloids
(ii) Quaternary choline esters

A

(i) Alkaloids (e.g. pilocarpine)
- Tertiary choline ester → can cross BBB
- Cannot be broken down by cholinesterases
- Used to treat xerostomia, glaucoma

(ii) Quaternary choline esters (e.g. bethanechol)
- Ionised in physiological state → cannot cross BBB
- Can be broken down by cholinesterases
- Used to treat GI atony and urinary retention

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21
Q

What are the contraindications for alkaloids?

A

Patients with peptic ulcer disease and asthma

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22
Q

Describe the MOA of direct nicotinic receptor agonists: nicotine

A
  • Main clinical use is for smoking cessation
  • Low dose to prevent addiction
  • Depolarisation and excitation at Nm receptor → skeletal contraction, fasciculations, spasms
  • Stimulate release of ACh from presynaptic ganglion by depolarisation → promote adrenaline release + activate Nn receptors on postsynaptic ganglion → increase sympathetic and parasympathetic activity → increase HR, BP etc
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23
Q

Describe the MOA of partial nicotinic receptor agonist: varenicline

A
  • Supports smoking cessation
  • Can cause suicidal ideation
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24
Q

Describe the MOA of indirect, reversible cholinergic agonists aka acetylcholinesterase inhibitors
(i) Donepezil
(ii) Edrophonium
(iii) Neostigmine

A

(i) Donepezil
- Tertiary choline ester → can cross BBB
- Reversible AChE inhibitor → increase ACh at NMJ
- Used for dementia/Alzheimer’s (lack cholinergic)

(ii) Edrophonium
- Short-acting/short half-life
- Used for diagnosis of myasthenia gravis: provide ACh and see if any short-term relief

(iii) Neostigmine
- Ionised in physiological state → cannot cross BBB
- Increase ACh at synapse → overcome “competitive inhibition” aka reverse paralysis by non-depolarising neuromuscular blocking agents (NMBA) like pancuronium
- Used for myasthenia gravis

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25
Q

Define organophosphates and describe the MOA of the indirect, irreversible cholinergic agonists aka acetylcholinesterase

A

Organophosphates are “suicide inhibitors” of acetylcholinesterase → donate their phosphate group and become destroyed

E.g. insecticides (malathion, parathion), chemical weapons (sarin, soman)

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26
Q

What are the treatments for organophosphate poisoning?

A

Pralidoxime: higher affinity to phosphate than AChE → take away phosphate and regenerate AChE before drug permanently changes structure

Atropine: competitively bind to muscarinic receptor → prevent ACh binding → no cholinergic effect

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27
Q

List the common side effects of cholinergic agonists

A

Diarrhoea
Urination
Miosis/muscle weakness
Bronchoconstriction
Bradycardia
Emesis/vomiting
Lacrimation
Salivation/sweating

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28
Q

Describe the effects of cholinergic antagonism on the different target organs

A

Eye:
- M3 antagonism → relax iris sphincter muscle → pupil dilation/mydriasis
- M3 antagonism → relax ciliary muscle, contract lens
- Accomodate far vision

Salivary glands: M3 antagonism → decreased salivation

Lungs: M3 antagonism → bronchodilation, decreased airway secretions

Heart: M2 antagonism → tachycardia

Stomach/intestines:
- M3 antagonism → decreased GI motility and secretions
- M1 antagonism → decreased gastric acid secretions

Exocrine glands: M3 antagonism → dry eyes

Gallbladder: M2 antagonism → relaxation

Bladder: M3 antagonism → contract bladder internal sphincter + relax detrusor muscle → urinary incontinence

Genitals: M2 and M3 antagonism → arterial constriction, reduced blood flow

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29
Q

Describe the MOA of the direct muscarinic receptor antagonists
(i) Atropine
(ii) Benzatropine
(iii) Scopolamine
(iv) Oxybutanin
(v) Ipratropium bromide

A

(i) Atropine
- Tertiary amine → cross BBB
- Treat bradycardia (at high dose)
- Used in organophosphate overdose and ophthalmic examinations (pupil dilation)

(ii) Benzatropine
- Tertiary amine → cross BBB
- Used in Parkinson’s disease (lack dopamine)

(iii) Scopolamine
- Tertiary amine → cross BBB
- Used for motion sickness

(iv) Oxybutinin
- Tertiary amine → cross BBB
- Used for urinary incontinence (although mirabegron is still preferred)

(v) Ipratropium bromide
- Quaternary amine → does not cross BBB → limit systemic absorption
- 1st line for COPD, 2nd line for asthma
- Sedative effect due to CNS effects of bromide

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30
Q

What are the contraindications for direct muscarinic receptor antagonists?

A

Cannot use in narrow angle glaucoma as it relax constrictor muscle → obstruct IOP clearance

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31
Q

Describe the MOA of succinylcholine/suxamethonium

A
  1. Opens Na channels associated with nAChRs → depolarisation → muscle contraction/fasciculation/twitching
  2. Persistent depolarisation → Na channel closes/is blocked
  3. Desensitisation → prevent muscle from responding to subsequent nerve impulses
  4. Gradual repolarisation → flaccid paralysis
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32
Q

Describe the MOA of botulinum toxin

A
  1. Toxin from bacteria cleaves SNARE proteins
  2. Inhibits capture/docking of synaptic vesicles at presynaptic membrane
  3. Prevent exocytosis of ACh containing synaptic vesicles
  4. Paralysis of muscle
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33
Q

What are the possible side effects of botulinum toxin?

A
  • Paralysis of wrong muscle groups
  • Allergies
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34
Q

List the side effects of NMBAs at high doses

A
  • Flushing (due to histmine release)
  • Oedema
  • Hypotension
  • Increased HR (muscarinic receptor antagonism)
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35
Q

Classify the types of NSAIDs and their relative risks of bleeding

A
  1. Reversible, non-selective COX inhibitors
  2. Irreversible, non-selective COX inhibitors: aspirin
  3. COX-2 selective inhibitors: “-coxib”
  4. CNS-selective inhibitors: paracetamol

Aspirin (highest risk, COX1>2)
Ketoprofen
Piroxicam
Indomethacin
Naproxen
Ibuprofen
Diclofenac
Mefenamic acid
Celecoxib
Parecoxib
Eterocoxib (lowest risk, COX2>1)

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36
Q

Outline the depolarising blockade

A
  1. Depolarising blockers bind to nicotinic receptors → depolarisation → muscle contraction/fasciculation/twitching
  2. Unlike ACh, depolarising blockers are not rapidly hydrolysed by acetylcholinesterase → persistent depolarisation
  3. Desensitisation → prevent muscle from responding to subsequent nerve impulses
  4. Muscle paralysis
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37
Q

List the common side effects of cholinergic antagonists

A
  1. Dry mouth
  2. Urinary retention
  3. Amnesia
  4. Constipation
  5. Drowsiness
    *Extent of CNS effects depends on whether drug crosses BBB
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38
Q

Outline the synthesis of cycloxygenase and its downstream enzymes from cell membrane phospholipids, linking it to the inhibition by NSAIDs

A

Normally,
phospholipids → phospholipase A2 → arachidonic acid → COX → prostanoids

COX-1 → prostacyclin, prostaglandins, thromboxane
COX-2 → prostacyclin, prostaglandins

NSAIDs inhibit COX → inhibit production of prostanoids

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39
Q

Describe the clinical uses of botulinum toxin

A
  • Upper limb spasticity
  • Cosmetic
  • Migraine and headache
  • Cervical dysplasia (neck muscles contact involuntarily)
  • Blepharospasm (excessive blinking), strabismus (squints)
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40
Q

Distinguish between COX-1 and COX-2 inhibition

A

Generally COX-1 = constitutive and COX-2 = inducible except in:
1. Female repro tract
2. CNS
3. Kidneys
4. Synovial joints

COX-1 → prostacyclin, prostaglandins, thromboxane (predominantly expressed in platelets)
COX-2 → prostacyclin, prostaglandins (predominantly expressed in inflammatory cells at sites of acute inflammation)

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41
Q

Describe the MOA of non-depolarising NMDAs aka direct nucleotide receptor antagonists

A
  • Block Nm acetylcholine receptors (nAChRs) → block neurotransmission of NMJ → somatic muscle cannot be regenerated → paralysis of skeletal muscle
  • Used for surgical paralysis/intubation to relax skeletal muscles

Short-acting (e.g. rocuronium)
- ~0.5-3 minutes
Intermediate-acting (e.g. pancuronium)
- ~2-5 minutes
Long-acting (e.g. tubocuronine)
- ~2-13 minutes

ONSET: fingers/eyes → limbs/trunks → diaphragm
RECOVERY: diaphragm → limbs/trunk → fingers/eyes

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42
Q

Describe the MOA of NSAIDs (4)

A
  1. Anti-inflammatory
    - PGI2 decrease → vasodilation decrease
    - PGE2 decrease → vascular permeability decrease → less extravasation of fluids
    - Less swelling, redness, warmth
  2. Analgesic
    - PGE2 decrease → less sensitisation/amplification of pain signal from bradykinins at nociceptive fibres → less pain perception
  3. Anti-pyretic
    - PGE2 decrease → less temp alleviation
    - Does not reduce normal body temp
  4. Anti-platelet (especially aspirin)
    - PGI2 regenerate after few hours with new COX enzyme whereas TXA2 takes 1-2 weeks with new platelet formation
    - PGI2 effect&raquo_space; TXA2
    - Antiplatelet&raquo_space; prothrombosis
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43
Q

Describe the phenomenon of analgesic ceiling

A

Still have normal stimulation from bradykinin → basal nerve impulses sent to brain → some pain perception persists

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44
Q

What are the contraindications of NSAIDs?

A
  1. Salicylate poisoning in children with viral infection → increased risk of Reye’s syndrome
  2. Bleeding risk → bruising in elderly
  3. Precipitating asthma attack in patients with NSAID-exacerbated respiratory disease (NERD)
  4. Premature closure of ductus arteriosus in late pregnancy → cannot give in 3rd trimester
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45
Q

Describe the side effects of NSAIDs

A
  1. Link to PGE2 function in GIT
    - Decreased secretion of mucus/HCO3-
    - Decreased mucosal blood flow
    - Increased gastric acid secretions
    - → Ulcer formation, dyspepsia, nausea and vomiting
  2. Link to PGI2 function in renal system
    - Decreased renin & aldosterone secretion → hypertension
    - Decreased Na+ reabsorption → water retention, oedema, acute renal failure
    - Decreased K+ excretion → hyperkalaemia
  3. Unwanted COX-2 inhibition effects
    - Shunting of COX to COX-2 pathway → TXA&raquo_space; PGI2 → thrombosis → impaired wound and ulcer healing
    - Delayed follicular rupture
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46
Q

Alternative name for paracetamol

A

Acetaminophen

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47
Q

Explain the pathogenesis of paracetamol overdose and how it is treated

A

Paracetamol overdose → induce minor pathway enzymes → deplete glutathione + produce toxic metabolites

N-acetyl cysteine → replenish glutathione → detoxification of toxic metabolites → prevent hepatotoxicity

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48
Q

Describe the specific use of indometacin

A

Given to premature babies to close the ductus

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49
Q

Discuss the efficacy of indometacin compared to other NSAIDs

A

Stronger anti-inflammatory as it inhibits production of phospholipase A2 → decrease arachidonic acid → decrease 15-lipoxygenase + COX + 5-lipoxygenase → decrease ALL eicosanoids (leukotrienes, prostanoids, lipoxins)

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50
Q

Describe the specific use of diclofenac and discuss its efficacy

A

Joint pain

Accumulates in synovial fluid → prolonged anti-inflammatory and analgesic effect

Relatively short plasma half-life → decrease GIT adverse effects

51
Q

Describe how NSAID-induced pseudoallergies arise

A

COX inhibition → shunting of COX to 5-lipoxygenase pathway → increased leukotrienes → increased activation of cysteinyl leukotriene receptors → promot mast cell degranulation and allergic response

52
Q

Discuss the principles of corticosteroid therapy

A
  1. Not curative, only symptomatic
  2. Do not stop abruptly
  3. Start with lowest dose
  4. Check for opportunistic infections
  5. Host response is the cause of symptoms
53
Q

Describe the MOA of corticosteroids

A

Inhibit phospholipase A2 → decrease production of arachidonic acid → decrease 15-lipoxygenase + COX + 5-lipoxygenase → decrease ALL eicosanoids (leukotrienes, prostanoids, lipoxins)

54
Q

Name the pro-inflammatory gene targets of corticosteroids

A

Decrease expression of:
1. Pro-inflammatory cytokines (e.g. TNF-alpha, IL-2, IFN-gamma)
2. Chemokines (e.g. RANTES)
3. Inflammatory enzymes (e.g. 5-LOX, COX-2)
4. Adhesion molecules (e.g. ICAM-1, VCAM-1)
5. Receptors (e.g. IL-2R, TCR)

55
Q

Name the anti-inflammatory gene targets of corticosteroids

A

Increase expression of:
1. Annexin-A1 (PLA2 inhibitor)
2. Beta-2 adrenoreceptor
3. IL-1 receptor antagonist
4. IL-IR2 (decoy receptor)
5. Neutral endopeptidase
6. Endonucleases
7. IKB-alpha (inhibitor of NF-kB)
8. MAPK phosphatase-1 (MKP-1)

56
Q

List the effects of corticosteroids on smooth airway muscles

A
  1. Increase expression of beta2 adrenoreceptors
  2. Decrease expression of cytokines
57
Q

List the effects of corticosteroids on the immune cells

A
  1. Decrease circulating immune cells except neutrophils
  2. Decrease size and lymphoid content of lymph nodes
  3. More effect on cellular than humoral immunity
  4. Increase macrophage phagocytosis
58
Q

Describe the main clinical uses for corticosteroids

A

First line immunosuppressant in solid organ and haematopoietic stem cell transplantation to prevent rejection

59
Q

Distinguish the different types of corticosteroids based on their duration of action and dosage

A

Hydrocortisone/cortisol: 8-12 hour action, 20mg dose

Prednisolone: 12-36 hour action, 5mg dose

Methylprednisolone: 12-36 hour, 4mg dose

Triametholone: 12-36 hour, 4mg dose

Betamethasone: 24-72 hour, 0.6mg dose

Dexamethasone: 24-72 hour, 0.75mg dose

60
Q

Distinguish the different types of corticosteroids based on their glucocorticoid: mineralocorticoid ratios

A

Hydrocortisone/cortisol: 1:1
Prednisolone: 5:0.3
Methylprednisolone: 5:0
Triametholone: 5:0
Betamethasone: 25-40:0
Dexamethasone: 30:0

61
Q

List the adverse effects of corticosteroids

A

Cushing’s syndrome (moon face, buffalo humps, truncal obesity)
Osteoporosis
Retardation of growth
Thin skin, bruising
Immunosuppression
Cataracts, glaucoma
Obesity
Suppression of HPA axis
Tired muscles → weakness, atrophy, myopathy
Emotional disturbances
Rise in BP and lipids → chronic heart failure
Oedema
Increased hair growth
Diabetes mellitus, hyperglycaemia
Stomach upset and ulcers

62
Q

Describe the specific use of fludrocortisone

A

Mineralocorticoid synthetic analogue
Treat conditions where the body does not produce enough steroids (e.g. Addison’s disease, salt-losing adrenogenital syndrome)

63
Q

Discuss the efficacy of betamethasone

A

Highly effective for topical application

64
Q

Describe the different histamine receptors and their respective functions

A

H1: triple vascular response of Lewis → FLUSH (capillary dilation), WHEAL (oedema), FLARE (arteriolar dilation)

H2: regulate gastric acid secretion

H3: heteroreceptors for neuronal function/cognition; autoreceptors to regulate neuronal histamine turnover

H4: immune cell chemotaxis, immune response, inflammation

65
Q

Which histamine receptors are found on mast cells?

A

H1 and H4
But only H1 targeted by drugs so far

66
Q

Describe the MOA of antihistamines

A

Inverse agonists of histamine receptors (increase activity in the opp direction), specifically for H1 receptors

67
Q

Classify the types of antihistamines, listing examples of each

A

1st gen (“Dont Cook The Pretty Kitten”)
1. Diphenhydramine
2. Chlorphenmiramine
3. Triprolidine
4. Promethazine
5. Ketotifen

2nd gen (“ine)
1. Cetirizine
2. Loratadine
3. Fexofenadine

3rd gen
- L-isomer of citiridine → levocetirizine
- Active metabolite of loratadine → desloratadine

68
Q

Distinguish between the 1st and 2nd generations of antihistamines

A
  1. High lipophilicity vs low lipophilicity
  2. Low affinity with p-glycoprotein efflux pumps vs high affinity
  3. Can cross BBB/high CNS penetration vs cannot cross BBB/low CNS penetration
  4. Low H1 receptor selectivity so various “crossover” antagonism vs higher H1 receptor selectivity
  5. Lower molecular weight, lasts shorter (4-6 hours) vs higher molecular weight, lasts longer (12-24 hours)
  6. Sedating vs non-sedating (except cetirizine)
69
Q

Why are antihistamines usually not given topically

A

Can cause contact dermatitis/systemic allergies

70
Q

List the side effects of 1st gen antihistamines

A

Due to cholinergic antagonism
1. Xerostomia → sip water/suck hard candy to reduce
2. Urinary retention
3. Sinus tachycardia

Due to adrenergic antagonism
4.Postural hypotension
5. Dizziness
6. Reflex tachycardia

Due to cholinergic and muscarinic antagonism
7. Close/narrow angle glaucoma

Due to histamine H1
8. Impaired cognition and psychomotor function
9. Increased appetite, weight gain
10. Sedation

Due to 5-HT receptor antagonism
11. Increased appetite, weight gain

71
Q

1st gen antihistamines is contraindicated in

A
  1. Women in third trimester of pregnancy or breastfeeding
  2. Avoid taking alcohol, opioid analgesics, antidepressants or any other CNS depressant drugs concurrently
72
Q

Describe the general uses of 1st and 2nd gen antihistamines

A

1st gen is to reduce inflammation and also provide antiemetic effect (due to additional muscarinic and dopamine antagonism being shunted)

2nd gen is for allergic reactions (e.g. rhinitis, urticaria/hives since histamine is the primary mediator)

73
Q

Describe the use of these four examples in showcasing the MOA of antihistamines

A

Diphenhydramine: motion sickness/antiemetic

Chlorphenmiramine + triprolidine: rhinorrhoea, nasal congestion

Promethazine: rhinorrhoea, nasal congestion, stronger antiemetic

Ketotifen: prevent asthma attack

74
Q

What is the contraindication for promethazine?

A

Children below 2 years old cannot use due to fatal respiratory depression

75
Q

Describe the precautions that must be taken with fexofenadine

A

Don’t drink fruit juice from 4 hours before to 1-2 hour after closing → inhibit organic anion transporting polypeptides and interferes with absorption

76
Q

Describe the different opioid receptors and their general functions

A
  1. miu: strong respiratory depression and sedation + dependence
  2. lambda: some respiratory depression + euphoric feeling, no sedation/dependence
  3. kappa: no respiratory depression + no dependence

Overall, they aim to
- Inhibit propagation of pain signals
- Alter the emotional perception of ppain
- Elevate pain threshold

77
Q

Discuss the general guidelines for opioid dosing

A
  1. Always start with lowest dose and carefully increase until adequate
  2. Lower doses required for pain maintenance to not raise tolerance → if no analgesia with increased dose, could indicate tolerance
  3. Neuropathic pain require more opioids than nociceptive pain
  4. Patients with chronic pain will have higher threshold for analgesic effects
  5. Elderly usually require lower doses to achieve pain relief
78
Q

List some examples of endogenous opioid peptides

A

Produced endogenously by the body
1. Enkephalins
2. Dymorphins
3. Beta-endorphins

79
Q

Discuss the general MOA of exogenous opiates/opioid agonists

A

Act as neurotransmitters that mimic exogenous opioid peptides and interact with specific opioid receptors

Chemical class: phenanthrenes

80
Q

Discuss the approach to pain management using opioids

A

According to the WHO analgesic ladder,

  1. Non-opioids (e.g. paracetamol/NSAIDs) +/- adjuvants
  2. Weak opioids (e.g. codeine, dihydrocodeine, tramadol) +/- adjuvants
  3. Strong opioids (e.g. morphine, oxycodone, methadone, buprenorphine, fentanyl) and non-opioids +/- adjuvants
81
Q

Distinguish between strong and weak opioids

A
  1. Strong miu agonist vs weak miu/lambda agonist
  2. High maximum analgesic efficacy vs low
  3. High liability for addiction/dependence vs low liability
82
Q

Describe the side effects of morphine and the contraindications

A

Trigger histamine release from mast cell degranulation → bronchoconstriction, urticaria, itching, hypotension

Contradicted in asthmatics

83
Q

Describe the special use of methadone

A

Long acting (plasma t1/2 >24 hrs) → take drug once a day → reduce physiological dependence on drug → assist with social aspect of addiction

84
Q

Describe the special uses of fentanyl

A

Antitussive
Short-acting anaesthetic adjuvant → provides quick relief before anaesthesia

85
Q

Describe the special uses of pethidine/meperidine

A

Shorter duration of action than morphine → especially in neonates → used in labour

Restlessness rather than sedation

86
Q

Describe the side effects of opioid agonists

A
  1. Miosis/pinpoint pupils @ occulomotor nucleus (but could become dilation if hypoxia occurs)
  2. Nausea and vomiting @ chemoreceptor trigger zone
  3. Postural hypotension and bradycardia @ cardioregulatory nucleus in medulla
  4. Decreased GI motility → constipation
  5. Increased bladder sphincter tone → urinary retention
  6. Immunosuppression with long term use
87
Q

Describe the clinical use of opioid antagonists

A

Counter opioid overdose

88
Q

Explain what precautions must be taken when using opioid antagonists

A

Use with caution in opioid dependent patients → withdrawal may be fatal

89
Q

List the common withdrawal symptoms

A
  1. Anxiety, irritability
  2. Chills, hot flushes
  3. Joint pain
  4. Nausea, vomiting, diarrhoea
  5. Lacrimation, rhinorrhoea
90
Q

Name some examples of opioid antagonists, along with their route of administration and duration of action

A

Naloxone
- Short-acting
- Usually IV

Naltrexone
- Long-acting
- Oral

Nalmefene
- Long-acting
- IV

91
Q

Describe the MOA of local anaesthesias

A

“-caine”s
1. Work on inactivated and activated Na channels that are open
2. Close channel, preventing Na+ entry
3. Inhibit propagation of action potential
4. Use dependency: depth of LA increases with action potential frequency (parts that hurt more)

92
Q

Describe the precautions that must be taken when using local anaesthesia

A
  1. Restrict area of application to prevent systemic toxicity
  2. Combine with epinephrine (peripheral vasoconstriction)
  3. Bupivacaine is cardiotoxic
  4. Cocaine blocks NE reuptake, increasing NA and causing vasoconstriction and hypertension
93
Q

Describe the factors affecting LAs

A
  1. Lipophilicity: more lipophilic, longer lasting action
  2. Size of nerve + myelination: small myelinated > small non-myelinated > large myelinated
  3. LAs are weak bases → unionised in alkaline pH → increase absorption → increase action
94
Q

List some examples of each type of local anaesthesia

A

ESTER TYPE
1. Benzocaine
2. Cocaine
3. Procaine
4. Tetracaine

AMIDE TYPE
1. Lidocaine
2. Mepivacaine
3. Bupivacaine
4. Etidocaine
5. Prilocaine
6. Ropivacaine

95
Q

Distinguish between the diff types of local anaesthesia

A

ESTER VS AMIDE TYPE
1. Ester bond vs amide bond
2. Less prone to hydrolysis, longer duration of action vs more prone to hydrolysis, shorter duration of action
3. PABA derivatives (e.g. benzocaine, procaine) can give allergic reactions vs minimal allergic reactions for amide type
4. Avoid use in kidney failure vs avoid in liver failure

96
Q

What are the factors of a good general anaesthesia

A
  1. Amnesia/ unconsciousness
  2. Hypnosis/ inhibition of reflex
  3. Analgesia/ pain relief
97
Q

Classify the general anaesthesias into inhalants and IV

A

Inhalants: sevoflurane, halothane, isoflurane, nitrous oxide

IV: propofol, thiopentone, ketamine

98
Q

Describe the properties of inhalant general anaesthesia

A

Higher solubility → stay in blood longer → low Vd

Fast onset, fast recovery

99
Q

Describe the MOA of inhalant general anaesthesia

A
  1. Allosterically increasing GABA receptor sensitivity to activation by GABA itself → enhance neurotransmission at inhibitory synapse

2.Allosterically decreasing NMDA receptor sensitivity to activation by glutamate → block glutamate neurotransmitter at excitatory synpase

100
Q

Define minimum alveolar concentration (MAC)

A

Minimum [ ] of drug in alveolar air that produce immobility in 50% of the patients exposed to pain stimulus

Low MAC = high inhalation anaesthetic potency

101
Q

Rank the inhalants by ascending order of MAC/descending order of potency

A

Halothane (0.75%)
Isoflurane (1.4%)
Sevoflurane (2%)
Nitrous oxide (105%)

102
Q

Describe the usage and adverse effects of halothane

A

Little to no analgesia before unconsciousness, must combine with other analgesics

Dose-dependent respiratory/cardiac depression

Halothane-associated hepatitis

103
Q

Describe the use and adverse effects of isoflurane

A

Lowers systemic vascular resistance/BP

Dose-dependent respiratory/cardiac depression (but less than halothane)

104
Q

Describe the use and adverse effects of sevoflurane

A

Metabolised in the liver to release inorganic fluoride

Nephrotoxic

105
Q

Describe the use and adverse effects of nitrous oxide

A

Used alone as analgesic agent in simple dentistry procedures/delivery

Gives analgesia and amnesia but not complete unconsciousness → cannot use in surgery alone

106
Q

Describe the properties of IV general anaesthesia

A
  • Help induce unconsciousness
  • Mostly short-acting
  • Depress respiration → require manual ventilation
  • Supplement and potentiate effects of inhalants
107
Q

Describe the use and adverse effects of thiopentone

A

Enters brain rapidly and easily (10-20s) but short-acting → require multiple doses/infusion

Potentiate action of GABA on GABA receptor-gated Cl ion channels → increased entry of Cl → hyperpolarisation → CNS depression

Liver failure due to active metabolite

108
Q

Describe the use and adverse effects of propofol

A

Extensively used in day surgery

Similar induction rate as thiopentone (~60s) but more rapid recovery

Possible significant CVS events during induction, hypotension

109
Q

Describe the use and adverse effects of ketamine

A

Suitable for continuous infusion without lengthening duration of action

Causes dissociative anaesthetic state → hallucinations, disturbing dreams, delirium

The only IV anaesthetic with analgesic properties → used in third world countries

110
Q

How to decrease psychological adverse effects associated with ketamine?

A

Use diazepam or midazolam

111
Q

Discuss the advantages of combination therapy

A
  1. Permit lower dosage of inhalants used
  2. Produce effects that cannot be achieved with inhalant alone
112
Q

Define complementary medicine

A

Medicine that is used together with conventional medicine

113
Q

Define alternative medicine

A

Not mainstream practice, used in place of conventional medicine

114
Q

Outline the main problems associated with supplements

A

Contamination
Adulteration: change to toxic form when mixed with Western drugs
Misidentification

115
Q

Describe the benefits of garlic

A
  • Inhibit HMG-CoA reductase → block cholesterol synthesis
  • Inhibit TXA2 synthesis + Ca-dependent platelet aggregation → inhibit clot formation
  • Dilate blood vessels, increase arterial elasticity → lower BP
116
Q

Describe the side effects of garlic

A
  • Antiplatelet → do not give patients on blood thinners/ aspirin
  • GIT related: nausea and vomiting, diarrhoea, flatulence → avoid in pts with IBD
  • Burning sensation in mouth
  • Precipitate asthma
117
Q

Describe the benefits of St John Wort

A

Yellow flowers containing active ingredient hypericin
- Inhibit monoamine oxidase (MAO) and reuptake of serotonin, NE and dopamine → increase neurotransmitter levels at synapse
- Enhance serotonin levels
- Inhibit amine digestion

118
Q

Describe the side effects of St John Wort

A
  • CYP450 inducer → decrease effectiveness of drugs broken down by CYP450
  • Allergic dermatitis, photodermatitis
  • GIT discomfort
  • Dry mouth
  • CNS effects: anxiety, agitation, dizziness, insomnia, irritability
119
Q

Describe the benefits of Gingko Biloba

A
  • Decrease blood viscocity + dilate blood vessels
  • Suppress platelet-aggregating factor → inhibit platelet aggregation
  • Erectile dysfunction
  • Improve thinking and cognition in younger patients
  • Peripheral vascular disease
120
Q

Describe the side effects of Gingko Biloba

A
  • Antiplatelet → do not give patients on blood thinners/ aspirin
  • Avoid during pregnancy and breastfeeding
  • Avoid drugs with lower seizure threshold
121
Q

Describe the benefits of Ginseng

A
  • Enhance memory
  • Improve cardiac function and blood vessels
  • Lower blood sugar (esp not the post-prandial after lunch/dinner)
  • Blood thinner/antiplatelet
  • Immunomedullatory (prevent URTI, cancer)
122
Q

Describe the side effects of Ginseng

A
  • Osteogenic properties → abnormal menstruation/breast swelling
  • Excessive brain activity → insomnia, nervousness
  • Hypertension
123
Q

What precautions should be taken when consuming ginseng?

A
  • Do not give diabetics/ immunocompromised
  • Do not give patients on CNS acting/blood thinners → increased bleeding with warfarin

Y1 (14 decks)

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