Foundation - General Pharmacology Flashcards
Outline the steps in rational drug prescribing
- Make diagnosis
- Consider treatment options
- Prescription
- Patient counselling
- Monitoring
Define pharmacokinetics and pharmacodynamics
Pharmacokinetics: processing of drug by body
Pharmacodynamics: effect of drug on body
Measurement of pharmacokinetics
Name the classes of drugs under general pharmacology
- Corticosteroids
- Antihistamines
- Non-steroidal anti-inflammatory drugs
- Paracetamol
- Local analgesic
- General analgesic
- Opioids
ANTI-INFLAMMATORY
- Antihistamines
- Glucocorticoids
- NSAIDs
SEDATIVE
- Antihistamines (gen 1)
- General analgesic
- Opioids
ANALGESIC
- Paracetamol
- Local analgesic
- Opioids
- General analgesic (inhaled)
List the types of receptors and neurotransmitters, and where they can be found in the autonomic nervous system
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
Name the types of adrenoreceptors and their locations in the body
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
Describe the adrenergic agonistic effects giving rise to the fight or flight response at different organs
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
Describe the MOA of the following non-specific direct adrenergic agonists
(i) Dopamine
(ii) Norepinephrine
(iii) Epinephrine
(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)
Describe the MOA of alpha-specific direct adrenergic agonists
(i) Oxymetazoline
(ii) Phenylephrine
(iii) Brimonidine
(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
Describe the MOA of beta-specific direct agonists
(i) Dobutamine
(ii) Isoprenaline
(iii) Salbutamol/terbutaline
(iv) Mirabegron
(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
Describe the MOA of indirect adrenergic agonists
(i) Moclobemide
(ii) Tricyclic antidepressants
(iii) Ephedrine/pseudo-ephedrine
(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
Describe the effects of adrenergic antagonism on the different target organs
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
Describe the MOA of alpha-specific direct adrenergic antagonists
(i) Phenoxybenzamine
(ii) ‘-zosin’s
(iii) Tamsulosin
(iv) Yohimbine
(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
Describe the MOA of beta-specific direct adrenergic antagonists
(i) Bisoprolol
(ii) Propanolol
(iii) Betaxolol
(iv) Timolol
(v) Sotalol
(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
What are the contraindications for propanolol?
- 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
Describe the MOA of indirect adrenergic antagonists
- Methyldopa
- Has some direct a2 antagonist effect → used to treat hypertension
- L-tyrosine inhibit tyrosine hydroxylase → decrease NE → decrease epinephrine + increase false transmitter methylnoradrenaline - 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
What are the contraindications for methyldopa?
- Haemolytic anaemia → must do blood test
- Hepatotoxicity → liver disease pts
Name the types of cholinergic receptors and their locations throughout the body
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
Describe the effects of cholinergic agonism involving rest and digest on the different target organs
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
Describe the MOA of the direct muscarinic receptor agonists
(i) Alkaloids
(ii) Quaternary choline esters
(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
What are the contraindications for alkaloids?
Patients with peptic ulcer disease and asthma
Describe the MOA of direct nicotinic receptor agonists: nicotine
- 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
Describe the MOA of partial nicotinic receptor agonist: varenicline
- Supports smoking cessation
- Can cause suicidal ideation
Describe the MOA of indirect, reversible cholinergic agonists aka acetylcholinesterase inhibitors
(i) Donepezil
(ii) Edrophonium
(iii) Neostigmine
(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