Pharmacology 2

Question 1

Drug excretion

Answer 1

 More important
 Urine, via kidney. Unaltered drugs or water soluble metabolites  Faeces. Unabsorbed, unaltered drugs by oral administration
 Less important
 Bile
 Sweat
 Skin

Question 2

Renal drug elimination depends on

Answer 2

• Blood flow to kidneys
• GFR
• Urine flow rate and pH which indirectly alter passive reabsoption + active tubular secretion

Question 3

Faeces

Answer 3

Metabolised drug excreted by the liver into bile before eliminated in faeces
Unabsorbed drug from small intestine eliminated in faeces

Question 4

Excretion vs Elimination

Answer 4

Excretion refers to the removal of metabolic waste produced in the body.
Elimination refers to the removal of indigestible material.
Most of the body’s activities produce metabolic wastes that
must be removed.

Question 5

Onset, peak and duration

Answer 5

 Onset
- The time taken for the drug to elicit a therapeutic response
 Peak
- Time taken for the drug to reach its maximum therapeutic response
 Duration
- The time for which the drug concentration in the body is enough to elicit a therapeutic response

Question 6

Half-life

Answer 6

 The time taken for half of the original amount of a drug administered to be removed by the body.
 It is a measure of the rate at which medicines are removed from the body.

Question 7

1st order kinetics

Answer 7

 For most drugs, most of the time, the proportion of a drug that is removed from the blood circulation reduces at a constant rate.
 The period of time required for the concentration of drug in the body to be reduced by one half is called the Half-Life or T1/2.
- e.g. gentamicin

Question 8

Zero order kinetics

Answer 8

 In Zero Order Kinetics the mechanism to process the drug becomes saturated because there is too much drug for the number of enzymes, binding sites etc to deal with. Thus, a specific constant amount of the drug is dealt with in given period of time.
 There are fewer drugs that are processed by Zero Order Kinetics, at normal therapeutic doses, than by First Order Kinetics. Examples of drugs that are include: phenytoin, aspirin, warfarin and alcohol; this is why bottles of alcohol have units printed on them because the body can remove 1 unit of alcohol in 1 hour.

Question 9

Therapeutic window

Answer 9

• The dose range of a drug that provides safe and effective therapy with minimal adverse effects

Question 10

Therapeutic drug monitoring

Answer 10

 Concentration of a drug in the blood plasma is easily sampled via venepuncture
 Plasma drug concentrations are used in routine clinical situations to optimise doses of medicines
 This is called therapeutic drug monitoring

Question 11

Types of drug target

Answer 11

 Enzymes
- Cyclooxygenases, e.g. aspirin
 Transporter systems
- Cardiac glycosides, e.g. digoxin
 Receptors
- 4 super families
 Other, non-specific actions
-Emollients, antacids

Question 12

Protein binding

Answer 12

 Drugs usually transported or exert their effect by binding to proteins.
 Protein targets include:
 Receptors
 Ion channels
 Enzymes
 Carrier proteins
 Except antitumour drugs that bind to DNA

Question 13

Drug receptor complex

Answer 13

• A drug-receptor complex forms when a drug (ligand) binds to a specific macromolecule (receptor), initiating a biological response.
• These interactions are often reversible, and the magnitude of the response is proportional to the number of occupied receptors
• Most receptors have naturally occurring molecules that bind to them - Endogenous (occurs naturally, made inside the patient)
• Molecules can be designed to bind to the same receptor - Exogenous (Introduced from outside the patient)
• Endorphins (endogenous), Morphine (exogenous)- bind to opioid Mu receptors to relieve pain

Question 14

Lock and key hypotesis

Answer 14

• The shape of the drug complements the shape of the receptor
  Chemical specicifity
   Affinity
  The ‘strength’ of the binding between the drug and the receptor

Question 15

Receptor superfamilies

Answer 15

• Membrane
• Ligand gated ion channels
• GPCR
• Integral tyrosine kinase linked receptors
• Intracellular
• Nuclear receptors

Question 16

Ligand-gated ion channels (ionotropic receptors)

Answer 16

• Ligand binds to receptor causes either hyperpolarisation or depolarisation leading to cellular effect
• Example= ACh (agonist= pilocarpine, antagonist= atropine/solifenacin)
• Miliseconds

Question 17

G-Protein Coupled Receptors (GPCRs)

Answer 17

• A signaling molecule binds to the GPCR. The GPCR changes shape. The GPCR activates a G protein. The G protein activates second messengers. The second messengers trigger a series of events that change cell function (adrenoreceptors= salbutamol)
• Seconds

Question 18

Kinase-linked receptors

Answer 18

• Tyrosine kinase receptors (RTKs) are transmembrane proteins that, upon ligand binding, activate their intracellular tyrosine kinase domain, leading to a cascade of protein phosphorylation events that transmit signals to the cell nucleus, regulating processes like growth, differentiation, and metabolism
• Brumetanib is an example

Question 19

Nuclear receptors

Answer 19

• Nuclear receptors are ligand-activated transcription factors that, upon binding to specific ligands (like hormones), translocate to the nucleus, bind to DNA response elements, and regulate gene expression, influencing various biological processes
• Oestrogen, thyroid hormone

Question 20

Effect of adrenoreceptors in different tissues

Answer 20

Question 21

Agonists, antagonists and partials

Answer 21

• ** Agonists: are drugs that bind to their target receptor and produce
  the desired response.
   Partial agonists: bind to the target and activate them but produce a response that is less than that which we would expect from a full agonist
   Antagonists:** have affinity for the receptor and bind to it but have no efficacy

Question 23

Antagonists

Answer 23

 Competitive: drugs that bind to the chemical target and prevent
activation by the normal target agent. e.g. naloxone at Mu opioid receptor
 Non-competitive: drugs that do not necessarily bind to the chemical target but at some other point in the chain of events to block target activation. e.g. ketamine at NMDA receptors
 Irreversible: drug binds to the receptor so strongly that it permanently deactivates the receptor. e.g. aspirin at COX

 Chemical: the agonist and the antagonist bind together rather than
either binding to a receptor. The agonist is thus, deactivated. Ca + doxycycline
 Physiological: bind to a different receptor for another physiological action that counteracts the first drug.
 e.g. histamine binds to H1 & H2 receptors and causes vasodilation; adrenaline binds to α1 adrenergic receptors in vessels resulting in vasoconstriction.

Question 24

Other terms

Answer 24

 Efficacy: maximal response a drug produces determines its efficacy
 Potency: if two drugs produce the same response but one does this at a lower dose it has greater potency
 Up regulation: if deprived of stimulation by an agonist the number of receptors increases
 Down regulation: continuous exposure to an agonist causes the number of receptors to decrease
* Specificity- Ability of a drug to combine with a particular type of receptor
* Affinity-The closeness of the fit between the drug & receptor.

Question 25

Synergistic effects

Answer 25

 Effect of 2 drugs combined may be greater than those drugs being given separately  Alcohol & antihistamines, antidepressants, barbiturates, narcotics  Not always undesirable. Drugs may be combined to create an interaction that will have beneficial effects (e.g. vasodilators & diuretics to control high BP)

Question 26

6 Rights

Answer 26

 Right drug  Right dose  Right time  Right route  Right patient  Right documentation

Question 27

Factors for individual variation

Answer 27

* Age * Gender * Pregnancy * Liver disease * Kidney disease * Other diseases * Other medications * Patient compliance....