Pharmacology - Autumn Flashcards
Where are the different types of muscarinic receptors located?
M1 - Neural (memory and Learning) (Gq) M2 - Cardiac (Gi) M3- Exocrine and Smooth muscle (Gq)
Nicotinic and muscarinic. Which is g protein linked and which is ionotropic
Nicotinic - Inotropic FAST Muscarininc - G Protein linked - SLOW
What is special about the autonomic control of arterioles?
No parasympathetic control
Describe the synthesis of Acetylcholine
AcetylCoA + Choline (Choline Acetyltransferase CAT) =Ach + CoA
Describe the breakdown of Ach
Ach (acetylcholinesterase) Choline + Acetate
Describe the synthesis of Noradrenaline
Tyrosine (tyrosine hydroxylase) Dopa (Dopa decarboxylase ) dopamine (Dopa beta Hydroxylase) Noradranline
How is noradrenaline broken down ?
Uptake 1 = Monoamine Oxidase A (MAO-A) Uptake 2 = COMT
Differentiate between pharmacokinetics and pharmacodynamics
Pharmacokinetics = effect of the body on the drug Pharmacodynamics = Effect of the drug on the body
Outline what is meant by non-specific drug action
Produce responses to physiochemical properties e.g. Antacids - basic compound neutralises stomach acid
What is AFFINITY
How willingly a drug binds to a receptor
EFFICACY
the ability of a drug to generate a response
Describe the change in a dose-response curve between an agonist and a second agonist of lower affinity.
Curve moves to the right
Describe the change in a dose-response curve between an agonist and a second partial agonist
Same starting point but only reaches half tissue response Ss
Why does claryrhromycin potentiate warfarin?
They are metabolised by the same pathway
What is INR
International Normalised ratio -prothrombin time ~10secs so physiological INR should be 1
Name another drug class that is an inducer of the liver enzymes for warfarin
Barbiturates
What is the mechanism of action of digoxin?
Blocks the K+ binding site on the external K+/Na+ ATPase
Why might digoxin dosage need to be less for older patients?
Liver/kidney function declines with age. (Digoxin primarily cleared by the kidney) so would be cleared more slowly.
Why might malnutrition affect the efficacy of warfarin
warfarin is 90% plasma bound. If malnourished there is a decrease in plasma protein. Heavily bound drugs are very sensitive to changes in plasma protein levels.
What are the 4 types of ion channels that control contraction of the heart muscle?
If = funny channel (Na Channel) Ca(t)= Transient. Opens first Ca(l)= Long lasting. K channels repolarisation.
Name 3 organs that are largely under parasympathetic control
Lungs, Eyes, Heart (at rest)
What effect does the the following receptors have on the vasculature? Alpha 1 adrenoreceptor Beta 2 adrenoreceptor
Alpha 1 adrenoreceptor - constricts Beta 2 adrenoreceptor - dilates
Out of the 4 types of receptors how many are membrane bound and which if any is not ?
3 are membrane bound. Only Type 4 (Intracellular steroid type receptors) are intracellular
Name a cardiac glycoside and outline its mechanism of action
Digoxin - Binds the K+ binding site of the K+/Na+ pump. Slows down the exchange therefore increasing the intracellular Ca2+ and increases contractility. = inc. contractility of the heart
Give an example of a competitive antagonist
Atropine -Competitive muscarinic cholinoceptor antagonist
Explain enterohepatic cycling
The drug or metabolites get excreted into the gut from the liver. But they are reabsorbed and returned to the liver via enterohepatic circulation. Can lead to drug persistence
What is bioavailability
The proportion of a drug that is available within the body to exert its pharmacological effect (after it leaves the liver and enter the systemic circulation)
Explain first order kinetics
elimitation of a drug is at a rate that is proportional to the concentration of a drug remaining in the body. (Log concentration vs time = straight line )
Explain zero order kinetics and give an example of a drug cleared this way
A constant amount of drug is cleared per unit of time (eg alcohol) (Concn vs time = straight line)
List 5 mechanisms of drug tolerance
- Pharmacokinetic factors - Metabolism increases
- Loss of Receptors - membrane endocytosis
- Change in receptors - Conformational change
- Exhaustion of mediator stores - eg amphetamines
- Physiological adaptation - “homeostatic response”
What does parenteral mean
Everything but the GI tract
How would you describe the shape of a log dose-response curve?
Sigmoid
What are the 2 ways a drug moves around the body ?
Bulf flow transfer (as a bolus)
Diffusional transfer (molecules diffusing)
In which part of the kidney are lipid soluble drugs reabsorbed?
In the proximal and distal tubules
What are the 3 types of Phase 1 metabolism reactions?
Oxidation (mainly this for phase 1)
Reduction
Hydrolysis
What is the primary purpose of Phase 1 Reactions?
Introduce an accessible functional group into the molecule
What is the primary purpose of Phase 2 meabolic reactions
Adds a large polar endogenous molecule - allows excretion
What group do CYP450 enzymes have at the active site?
A porphyrin ring and (Fe3+) iron
What 4 factors influence drug distribution:
- Regional blood flow
- Extracellular binding (plasma protein binding)
- Capillary permeability
- Localisation in tissues
Where does active secretion of a acids and bases take place?
In the proximal tubule
Which three products are generated by a CYP 450 reaction
NADP+
oxidised drug
water
List 4 common Phase 1 oxidative metabolism reactions
Hydroxylation
N-demethylation
O-demethylation
N-oxidation (not a CYP450 reaction)
Which enzyme catalyses N-oxidation
Flavin Containing Monooxygenase (FMO)
What is the cause of fish odour syndrome
Deficiencey of Flavin Containing Monooxygenase (FMO3) so can’t metabolise trimethylamine so excrete it in sweat and breath.
What catalyses hydrolysis reactions?
Esterases
Amidases
What are the characteristics of the products of Phase 2 metabolism reactions?
The conjugate that is formed is almost always inactive
It is less lipid soluble
It is more polar
It is easier to excrete
What are the 6 Phase 2 metabolism reactions?
- *G**lucoronidation - Most common
- *A**cetylation
- *M**ethylation
- *S**ulphation
- *A**minoacid conjugation
- *G**lutathione conjugation
Glucoronidation - What is it? What is the conjugating agent ? The catalyst? and what properties do the compounds generated have?
Glucoronidation = The addition of a sugar to a foreign compound
Catalyst = glucuronyl transferase
Conjugating agent = UDPGA
Products are polar and often high molecular weight
Very basically outline the properties of the andrenergic receptors
alpha1- Vasoconstriction
Alpha2- presynaptic negative feedback
B1- Tachycardia
B2 - Relaxation of smooth muscle(_Bronchodilatio, uterine smooth muscle relaxation in threatened pre-term labour) (suppress inflammatory mediators)
Give two examples of directly acting cholinomimetic drugs
1) Choline esters (bethanechol)
2) Alkaloids (pilocarpine)
Both drugs have very similar structures to acetylcholine
What is pilocarpine? What are it’s main uses and side effects?
A non-selective muscarinic agonist with good lipid solubility. Particularly useful in ophthalmology as a local treatment for glaucoma
Side effects: blurred vision, sweating, gastrointestinal disturbance and pain, hypotension, respiratory distress
What is bethanechol? What are it’s main uses and side effects?
A selective M3 acetylcholine receptor agonist. Mainly used to assist bladder emptying and to enhance gastric motility.
Side effects: sweating, impaired vision, nausea, bradycardia, hypotension, respiratory difficulty
What anticholinesterase drugs are used to treat Alzheimer’s disease?
Donepezil
Rivastigmine
Galantamine
Memantine (NMDA receprtor blobcker)
Why are excipients added to a drug formulation?
To alter bioavailability of a drug
To improve the flavour of the drug
To reduce the rate at which the drug is released into the blood
Give two examples of nicotinic receptor antagonists.
Hexamethonium
Trimetaphan
Give examples of muscarinic receptor antagonists. (3)
Atropine
Hyoscine
Tropicamide
Give examples of directly acting SNS agonists and the receptor they selectively bind?
Adrenaline (non-selective)
Phenylephrine (α1)
Clonidine (α2)
Dobutamine (β1)
Salbutamol (β2)
Higher concentrations of drugs will start to lose selectivity and effect other receptors
When does ingestion of tyramine cause problems?
When taking MAO inhibitors tyramine competes with MAO which is required for the breakdown of NA
Causes hypertensive crisis
