Pharmacology Flashcards
Pharmacology:
ADME:
Factors affecting Absorption?
Absorption
Distribution
Metabolism
Excretion
Factors:
Bioavailability (AUC)
Gastric motility
pH partition/ionisation
Pharmacology:
Factors affecting Distribution?
Drug specific binding affects volume of distribution
Blood protein binding affinity for albumin for example
Pharmacology:
Factors affecting metabolism?
Enzyme induction e.g. Warfarin and Phenytoin - increased risk of bleeding Decreased INR
Enzyme inhibition e.g. Warfarin and Metronidazole - decreased metabolism of morphine increase
Increased INR
Pharmacology:
INR - what does it indicate
Indication of the time it takes for the blood to clot
Higher the INR = the longer it will take the blood to clot
Pharmacology:
Importance of grapefruit juice?
CYP3A4 inhibitor
Protein binding effects
Pharmacology:
Define
Druggability/ligandability
Efficacy
Druggability/ligandability - ability of protein target to bind drug/small molecule
Efficacy - ability of a drug to elicit its effect
Pharmacology:
Receptor activation steps
Binding of ligand
Conformational change within the protein
Causes action dependent on receptor
- signal transduction via secondary messengers (e.g. GPCR)
- Ligand-gated ion channel = opening of channel
Pharmacology:
Receptor classes
Ligand gated ion channels - Nicotinic Acetylcholine recptor
GPCRs - Beta-adrenoceptors
Kinase-linked receptors - Growth factor e.g. IGF receptor
Cytosolic/nuclear receptors - steroid receptors
Pharmacology:
Intrinsic activity definition?
Calculation?
Intrinsic activity – ability of a drug to produce a maximum functional response
Intrinsic Activity = Emax of partial agonist ÷ Emax of full agonist
Pharmacology:
Competitive inhibition?
Non-competitive inhibition?
Competitive inhibition = antagonist binds to the same site with higher affinity to
Non-competitive inhibition = Antagonist binds to allosteric binding site to reduce affinity of substrate
Pharmacology:
Cholinergic receptor subtypes:
Agonist and Antagonist for each? (not acetylcholine)
mAChR - muscarinic cholinergic receptor:
Agonist: Muscarinic
Antagonist: Atropine
nAChR - nicotinic cholinergic receptor:
Agonist: Nicotine
Antagonist: Curare
Pharmacology:
Irreversible antagonist? Receptor reserve? Allosteric modulation? Inverse Agonist? Tolerance? Desensitisation?
Irreversible antagonist: covalent bonding inactivation
Receptor reserve: agonist only requires small fraction of receptors to elicit maximal reponse
Allosteric modulation: binding at site other than active site modulates receptor affinity for ligands
Inverse agonist: binding produces opposite response
Tolerance: reduction in agonistic effect due to repeated stimulation
Desensitisation: result of tolerance, receptor uncoupling, degradation and internalisation
Pharmacology:
Enzymes as drug targets:
Statins?
ACEi?
Parkinson’s treatment?
Statins: HMG co reductase - rate limiting step in cholesterol synthesis
e.g. Atorvastatin
ACEi: angiotensin converting enzyme inhibition (RAAS manipulation)
e.g. enalapril
Parkinson’s treatment: Target MAO (monoamine oxidase) to prevent dopamine degradation
COMT/DDC inhibition prevent L-DOPA degradation
Pharmacology:
Transporters as targets: Diuretics: ENaC? NKCC? Ca channel blocker? Na Channel blocker? Cl- Channel poteniator?
ENaC - Thiazide diuretics
Na K Cl symporter - Furosemide (loop diuretic)
Ca antagonist: Amlodipine
Na antagonist: Lidocaine
Cl- modulator: Benzodiazepines increase Cl-
Pharmacology:
Pumps as targets:
Na/K ATPase
K/H ATPase proton pump
Na/K ATPase - Digoxin
PPI - Omeprazole (irreversible antagonism)
Pharmacology:
Routes of administration:
Intrathecal?
Intra-articular?
Intravitreal?
Intrathecal – through the theca of the spinal sheath into the subarachnoid space
Intra-articular – injection into a joint capsule e.g. knee in arthritis
Intravitreal – into the eye (vitreous fluid) e.g. Avastin in wet macula degeneration
Pharmacology:
Passage across membranes:? (5)
Example for each?
Diffusion - Ion channel Passive diffusion - Steroids Active transport - P-gp (drug remover transporter) Pinocytosis Facilitated diffusion - glucose
Pharmacology:
Passive diffusion = water or lipid/fat soluble?
Facilitated diffusion = water or lipid/fat soluble?
Passive diffusion molecule must be lipid soluble
Facilitated diffusion molecule must be small and water soluble
Pharmacology:
Drug ionisation: Dependent on what?
Which form is water soluble/fat soluble?
- Strength of ionisable group
- pH of solution drug is in
PKa
Ionised form = water soluble
Unionised form = lipid soluble
Pharmacology:
Best absorption for weak acids and bases?
Weak acid = Stomach as low pH so less of the drug will be ionised form
Weak base = intestine higher pH so less drug will be ionised form
Pharmacology:
Enteric coating?
Modified release tablets?
Enteric coating: protection against low pH
Modified release tablets: slow release
Pharmacology:
Parasympathetic Nervous System which Rest/Flight? Short/long pre? Short/long post? Nerve transmitters? Receptors?
Sympathetic Nervous System which Rest/Flight? Short/long pre? Short/long post? Nerve transmitters? Receptors?
Parasympathetic: Rest and Digest
- Long preganglionic
- Short postganglionic
- ACh at every step
- Pre = nicotinic AChRs
- Post = muscarinic AChRs
Sympathetic: Fight or flight
- Short preganglionic
- Long postganglionic
- ACh pre then Adrenergic (NA/AD)
- Pre = nAChRs
- Post = Alpha/Beta and ACh (sweat glands only) adrenergic receptors
Pharmacology:
Dopamine is a precursor to what?
Dopamine –> Noradrenaline –> Adrenaline
Pharmacology:
Adrenergic receptor subtypes and their effects:
Alpha adrenoceptors?
Beta adrenoceptors?
Alpha 1 + 2 (smooth muscle so BP) Alpha 1 contracts
Beta 1 - chronotropic and inotropic effects
Beta 2 - bronchodilation, vasodilation: relaxation of smooth muscle
Beta 3 - bladder
