BP SSA

Question 1

Targets of drug 14-alpha demethylase

Answer 1

Azole antifungal drugs (except for abafungin) inhibit the enzyme lanosterol 14 α-demethylase; the enzyme necessary to convert lanosterol to ergosterol.

Depletion of ergosterol in fungal membrane disrupts the structure and many functions of fungal membrane leading to inhibition of fungal growth

Question 2

Routes of administration for antifungal drugs

Answer 2

topical, creams, ointments, soaps, shampoo. Can also be given systemically to treat severe infections or orally for other such infections

Question 3

Vd -
Clearance -
Half life

Answer 3

Vd - initial dose/T0

Clearance - ke x vd or (0.693/HL)xVd

Half life - 0.693/ke or use the
graph

Question 4

How do you tell using the data how the drug was administered

Answer 4

bioavailability of 1 indicates intravenously, anything less than that is a different form of administration

Question 5

Why is clavulanic acid commonly prescribed with beta lactam antibiotics

Answer 5

while not effective by itself as an antibiotic, when administered with beta lactam antibiotics it can overcome antibiotic resistance in bacteria that secrete β-lactamase, which otherwise inactivates most penicillins.

Question 6

Graded concentration curves and how to quantify the response of a specific drug

Answer 6

which has higher efficacy (up the y axis); which has greatest affinity (Kd/EC50 ) - left and right along the x axis

Question 7

What drugs increase the likelihood of finding candida in the mouth

Answer 7

immunosuppressants and a steroid inhaler

Question 8

Codeine and morphine

Answer 8

Opiod analgesics - given for chronic pain (morphine); weak opiod - codeine
3 receptors - µ (analgesics) δ (peripheral analgesia) and κ (euphorics)
Act on descending inhibitory pathways to stop excitation of transmission of the neurone and inhibit release of neuropeptides

Question 9

Benzodiazepines - why it is fat soluble, side effects, mechanisms of how they inhibit

Answer 9

Act on the GABA-A receptor resulting in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties.

Benzodiazepines work by increasing the efficiency of a natural brain chemical, GABA, to decrease the excitability of neurons.

High volume of distribution means they are lipid soluble and can be stored in the adipose tissues of the body

Side effects - fewer than barbiturates as they do not effect the excitatory system. drowsiness, light-headedness, confusion; sexual fantasies. Interact with alcohol. Development of dependence

Question 10

2 other ways to sedate a patient -

Answer 10

increase dose of anxiolytics, gaseous anaesthetics e.g. NO, IV general anaesthetics

Question 11

Blood and anticoagulants - heparin

Answer 11

family of sulphated mucopolysaccharides found in secretory mast cells. Sulphate group is required for binding to antithrombin III which

inactivates thrombin (direct effect), IX, X, XI and XII (indirect via positive feedback loops).

Inactive orally - administered iv or sc

Short half life <1hr; eliminated by renal excretion. Rapid effect

Question 12

Blood and anticoagulants - warfarin

Answer 12

Inhibits hepatic synthesis of vitamin K1 dependent clotting factors - II, VII, IX and X - inhibits vitamin K reductase

1-2 day lag period; oral drug (rapid absorption)

Question 13

Anaesthetics

Answer 13

Prevent pain for a limited period of time for surgical or other procedures

Question 14

Inhalation Anaesthetics

Answer 14

Depth of anaesthesia determined by conc. in the brain or spinal cord (oil/gas partition coefficient) and vascularisation of the tissue

Absorbed and eliminated by the lungs. Limited hepatic metabolism

Side effects - malignant hyperthermia, hypotension, depressed respiration, depressed glomerular filtration

Question 15

Intravenous Anaesthetics

Answer 15

Act on GABA-A receptor - subunit interface dependent on the drug or NMDA receptor antagonist

Rapid onset and metabolism

Question 16

How do antidepressants work- Tricyclic antidepressants

Answer 16

nhibit 5-HT and NA uptake but block M1 receptors (dry mouth), H1 receptors (sedation and weight gain) and alpha1 receptors (postural hypotension

Question 17

How do antidepressants work- Selective serotonin reuptake inhibitors

Answer 17

selective for 5-HT and NA transporter - fewer side effects

Question 18

How do antidepressants work- Monoamine oxidase inhibitors

Answer 18

stop the break down of 5-HT, NA and DA by blocking monoamine oxidase. Old forms blocked irreversibly; new are reversible and only inhibit MAO-A.

Can lead to hypertensive crisis (cheese effect)

Question 19

Antidepressants and dry mouth?

Answer 19

TCAs block M1 receptors which lead to dry mouth

Question 20

Local anaesthetics

Answer 20

Block electrical signalling in neurones by blocking voltage gated Na+ channels

Interact with alpha subunit in ionised form

General structure - basic side chain ensures that molecules are ionised at physiological pH, aromatic group determines lipid solubility, duration of action is limited by the hydrolysis of the ester/amide bond and by the lipid solubility of the agent.

Esters are metabolised in the plasma by esterases (shorter half life)

Amides are metabolised in the liver by CYP - longer half life

Injected as a hydrochloride salt in acid solution

Use dependent block - anaesthetic gains access to and has higher affinity for channels more readily when open or inactive

Works better on small myelinated fibres e.g. C fibres

Question 21

Difference in amide and ester with local anaesthetics

Answer 21

Duration of action is limited by the hydrolysis of the ester/amide bond
Ester group - allergic reactions

Question 22

ovary hormones

Answer 22

GRH - gonadotrophin releasing hormone
FSH - follicle stimulating hormone
LH - lutensing hormone
Oestrogen - sensitises LH releasing cells, proliferation of the endometrium, inhibits FSH so regulates the cycle
Progesterone - renders the endometrium suitable for implanting the fertilised ovum, inhibits further release of GRH, FSH and LH

DIAGRAM FROM LECTURES

Question 23

What affects volume of distribution

Answer 23

Membrane permeability
Blood perfusion
Lipid solubility
pH-pKa
Plasma protein binding
Tissue binding

Question 24

What most affects drug clearance from body:

Answer 24

Physiochemical properties of the compound e.g. volatile gases are eliminated by exhalation; water soluble unchanged in the urine
Elimination mechanisms e.g. enzymes can become saturated at doses outside the therapeutic dose
Exposure to chemicals

Question 25

Give the formula
a. Volume of distribution (Vd)

b. Half life
c. Clearance

Answer 25

Total amount of drug in the body (dose) / drug blood plasma concentration (conc at zero)

0.693/Ke

CL = Ke x Vd

Question 26

What is the mechanism of action for ibuprofen?

Answer 26

Ibuprofen is an NSAID which is anti-inflammatory, anti-pyretic and analgesic . Phospholipase A2 converts phospholipdis in the plasma in the plasma membrane to arachnoid acid. Ibuprofen Prevents cyclooxygenase from catalysing the conversion of arachidonic acid into prostaglandin, this alleviates inflammation as no pro inflammatory mediators produced at the end of cascade. It interacts with both COX 1(GI tract) and COX 2 (inflammatory cells). COX 1 is predominantly in the GI tract and can cause gut bleeding due to interactions with ibuprofen. COX 2 has larger functional group so easier for ibuprofen to interact with it.

Question 27

You are prescribing to a 68-year-old male, what other factors should you take in to account before prescribing ibuprofen?

Answer 27

Medical history- more likely to experience drug reaction if they’ve had one before

Disease- GI tract bleeding, cardiovascular disease

Current medication- drug interaction e.g. avoid taking if on anticoagulants. Elderlely have decreased activty of drug metabolsing enzymes so there is more variability in the half life of drugs

Allergies - facial swelling etc.

Renal function- decreased GFR with age, drug remains in the body for longer

Question 28

What are other classes of drugs which can be given to control pain

Answer 28

Opioids

- Sedatives

Question 29

What is the describe the difference between the mechanisms of action for the other classes of drugs and ibuprofen

Answer 29

Opiod analgesics - given for chronic pain (morphine); weak opiod - codeine
3 receptors - µ (analgesics) δ (peripheral analgesia) and κ (euphorics)
Act on descending inhibitory pathways to stop excitation of transmission of the neurone and inhibit release of neuropeptides which is different to NSAIDs as they inhibit inflammation.
Opioid receptors are linked through G-proteins to inhibit adenylate cyclase

Sedatives- benzodiazapines are positive allosteric modualtors.
Benzodiazepines act by binding to a specific regulatory site on the GABAA receptor
BDZ binding enhances neuronal inhibitory effect of GABA
GABA and BDZ bind to independent sites of the same receptor-Cl-ion channel complex
BDZ do not open the Cl- ion channel by themselves, they increase the affinity of the receptor for GABA