MedLearn LOs Flashcards
“Autonomic Pharmacology: Identify the principal target organs of (a) the sympathetic nervous system and (b) the parasympathetic nervous system and describe how each responds to autonomic stimulation.”
1 - Intro to ANS
Most have both, some only one(1), some have one for both(2), trachea and bronchioles have adrenaline for sympathetic, skin sweating is sympathetic (cholinergic)
Eye - pupil, pupil + ciliary muscle
* Trachea and Bronchioles - dilate, constrict
2 Liver - glycogenolysis, gluconeogenesis
1 Adipose - lipolysis
1 Kidney - increased renin secretion
Ureters and Bladder - detrusor, trigone + sphincter
Salivary Glands - thick viscous or watery secretion
Skin * 2 - piloerection, sweating
Heart - rate/contractility
GI - motility and tone - sphincter contract, secretion
Blood Vessels 1 - skeletal muscles (dilatation), skin/mucous membrane/splanchnic area (constrict)
“Autonomic Pharmacology: Identify the transmitters released from pre- and postganglionic fibres in the sympathetic and parasympathetic nervous systems.”
1 - Intro to ANS
Parasympathetic - (Only 1 type) Long pre-ganglionic, short post-/discrete, localised 1:1
Acetylcholine (ACh)
Sympathetic - (1 type w/ exceptions) Short pre-ganglionic, long post-/coordinated, divergent 1:20 (formation of trunk)
ACh then NorA (90%)
- Same but no post ganglionic, adrenal medulla secretes A/NorA (80:20)
- Same but ACh for both (e.g. sweat gland)
“Autonomic Pharmacology: Classify the cholinoceptors/adrenoceptors located in the ANS and state (a) where each type is found and (b) the signalling systems they each employ.
”
1 - Intro to ANS
Cholinoceptors
Nicotinic - in nervous system [between pre and post ganglion], type 1 ionotropic
Muscarinic - in effector tissue where ACh is neurotransmitter, type 2 g protein coupled
M1 Neural, M2 Cardiac, M3 Exocrine (+M4 and M5)
Adrenoceptors
a1, a2, b1, b2
Only in sympathetic nervous system effector organs, type 2 g protein coupled
“Autonomic Pharmacology: Summarise the processes involved in the biosynthesis, release and metabolism of acetylcholine, noradrenaline and adrenaline and identify potential targets for pharmacological manipulation of cholinergic/adrenergic transmission.”
1 - Intro to ANS
See textbook for adrenaline
Summarise general 7 step process
- Precursor
- Synthesis of neurotransmitter
- Packaging in vesicle
- Exocytosis
- Receptor binding
- Formation of degradation products via metabolism
- Reuptake
Specific pathway for ACh
Acetyl CoA + Choline
ACh + CoA (Choline acetyltransferase)
Acetate + Choline (Acetylcholinesterase)
Specific pathway for NorA Tyrosine DOPA (Tyrosine hydroxylase) Dopamine (DOPA decarboxylase) NorA (Dopamine hydroxylase) [Uptake 1 and 2] (MOA-A, COMT)
See diagram
“Pharmacodynamics: Explain the following terms: drug, drug target site, receptor, agonist, antagonist, affinity, efficacy (‘intrinsic activity’) and potency.”
2 - Drug Receptor Interactions
Drug - A chemical substance that interacts with a biological system to produce a physiological effect.
Drug Target Site - What a drug acts on, 4 types
Receptor - They are activated by neurotransmitters or hormones
Agonist - Something that stimulates or activates a receptor e.g. ACh, nicotine
Antagonist - Something that blocks the receptor e.g. atropine (musc), hexamethonium (nico)
Efficacy or ‘intrinsic activity’ - Efficacy ‘intrinsic activity’ - its action e.g. conformational change of receptor
Potency - combination of affinity and efficacy
“Pharmacodynamics: Explain the concept of drug selectivity (cf. specificity) and how this relates to ‘structure activity relationships’.”
2 - Drug Receptor Interactions
The receptor population which the drug interacts with. Will overlap more as drug dosage is increased causing unwanted side effects.
Not the same as specificity as as drugs will overlap to some degree.
The activity of a drug is strongly dependent on its structure and this confers selectivity. ‘Lock and key’ is a good analogy for affinity and efficacy.
Small changes in structure can produce big changes in activity. This can also have a large change in the pharmacokinetics e.g. metabolism and duration of action. It is common to create new antagonists from agonists.
“Pharmacodynamics: List the four main categories of drug target sites.”
2 - Drug Receptor Interactions
- Receptors - 4 types, categorised by structure (transduction system), ACh (agonist), Atropine (antagonist of muscarinic)
- Ion channels - 2 types, voltage sensitive (VSCC) and receptor linked (nAChR), local anaesthetics and antihypertensives
- Transport systems - TCAs and cardiac glycosides
- Enzymes - enzyme inhibition (anticholinesterases [glaucoma]), false substrate to false neurotransmitter (methylDOPA to methylNorA [lowers BP]), prodrugs (chloral hydrate to trichloroethanol [hypnotic drug])
“Pharmacodynamics: Differentiate between a full and partial agonist.”
2 - Drug Receptor Interactions
Full agonists can generate the maximal agonist response of tissue.
Partial agonists have antagonist activity when administered in the presence of a full agonist e.g. beta blockers.
“Pharmacodynamics: Differentiate between the four principal types of drug antagonism.”
3 - Mechanism of Drug Action
- Receptor Blockade - receptor antagonist, competitive or irreversible*
- Physiological Antagonism - different receptors which cause opposite effects in the same tissue e.g. NorA and histamine for BP
- Chemical Antagonism - Interaction of drugs in solution e.g. dimercaprol as a chelating agent
- Pharmacokinetic Antagonism - one antagonist may reduce concentration of the active drug at the site of action by decreasing absorption, increasing metabolism, increasing excretion**
*use dependency for ion channels - the more active a tissue is, the more effective an ion channel will be as the drug can only work when the channel is open. Therefore local anaesthetics bind selectively to actively firing fibres to a certain degree.
**e.g. barbiturates are enzyme inducers over the long term and speed up the metabolism of some other drugs
“Pharmacodynamics: Interpret log dose response curves to a specific agonist in the absence and presence of i) a competitive antagonist and ii) an irreversible antagonist and explain the principal differences between competitive and irreversible antagonists.”
3 - Mechanisms of Drug Action
Competitive - Same site, surmountable, D-R curve to right e.g. atropine, propranolol
Irreversible - Tightly or at a different site, insurmountable e.g. hexamethonium
“Pharmacodynamics: List the four main families of receptors. Explain how they are distinguishable.”
3 - Mechanisms of Drug Action
Type 1 [ionotropic, ligand gated] - ion channel linked, ms, nAChR; GABA a, depolarisation, 4 or 5 subunits w/ 4 TM segments; subunits join to form receptor
Type 2 [metabotropic] - G-protein coupled, secs, b1 adrenoceptor, secondary messengers, 7 TM segments
Type 3 - kinase-linked, mins, insulin; growth factor, protein phosphorylation, catalytic domain e.g. protein phosphorylation
Type 4 [nuclear] - intracellular steroid, hrs, steroids; thyroid hormones, regulate DNA transcription, DNA binding domain (“zinc fingers”)
“Pharmacodynamics: Define ‘drug tolerance’. Explain the five different cellular mechanisms that may account for, or contribute to, this phenomenon.”
3 - Mechanisms of Drug Action
Tolerance is the gradual decrease in responsiveness to a drug with repeated administration (days/weeks) e.g. benzodiazepines (Valium)
- Pharmacokinetic factors - increased rate of metabolism, enzyme inducers e.g. barbiturates, alcohol
- Loss of receptors - cells don’t like repeated stimulation, receptor “down-regulation” via membrane endocytosis e.g. b adrenoceptors*
- Change in receptors - receptor desensitization via conformational change e.g. nAChR at NMJ
- Exhaustion of mediator stores e.g. amphetamine, acts by entering cell via uptake, binding to vesicles and causing exocytosis of NorA (loss of endogenous NorA stores)
- Physiological adaptation - Homeostatic responses e.g. BP, antihypertensives. However, helpful in developing tolerance to side effects; disappear after continuous use
*N.B. receptor “up-regulation”
(denervation supersensitivity)
“Autonomic Pharmacology: Explain how drugs targeting the autonomic nervous system can used in the treatment of glaucoma.”
? 1 - Intro to ANS
“Pharmacokinetics: Identify the routes and biochemistry of Phase 1 & Phase 2 metabolism.”
5 - Drug Metabolism
“Pharmacokinetics: List the major routes by which drugs may be administered and their advantages and disadvantages”
[2] - Bioavailability tutorial
4 - Pharmacokinetics
