DRUGS 🤯🤕

Question 1

Oestrogen

Answer 1

Builds endometrium

• Produced by follicles
• Negative feedback on GnRH, LH & FSH secretion
• Tamoxifen competes w estrogen for its R
  Allowing ER dimerisation but preventing co-activators from binding to the dimer on the ERE DNA element

Question 2

Progestin

Answer 2

Stabilises endometrium

• Produced by follicles
• Helps implantation of fertilised ovum
• Negative feedback on GnRH & LH secretion (to prevent ovulation)

Side effects:
- irregular menstrual or vaginal bleeding
- inhibition of luteinising hormone secretion
- reduction in androgen-dependent acne
- prevention of sperm entry into uterus

Question 3

Inhibin

Answer 3

Inhibits FSH secretion to prevent another follicle from forming

Released by corpus luteum (dead follicle that has released egg already)

Question 4

FSH

Answer 4

Stimulates follicle maturation in ovaries

Produced in anterior pituitary

Question 5

LH

Answer 5

Stimulates release of ovum
Produced in anterior pituitary

Question 6

GnRH

Answer 6

Stimulates FSH & LH secretion by anterior pituitary

Produced in hypothalamus

Question 7

Progestin only pill

Answer 7

• Creates a mucus plug in the cervix to prevent further sperm penetration
• Prevents LH surge → essentially prevents future ovulation but cannot stop already released egg from being fertilised
• Oestrogens should not be given without progestins to women with uterus
• Oestrogens cause hyperproliferation of endometrium = endometrial cancer
• Side effect of progestin only = irregular menstrual bleeding and high failure rate if improperly used

Question 8

Combined pill

Answer 8

With estrogen:
Estrogen inhibits FSH
Preventing follicle maturation

Question 9

Hormone replacement for menopause/emergency contraception

Answer 9

pretty much same action as two pills but since higher doses they can be used for hormone replacement therapy or for emergency contraceptive

Question 10

Mifepristone

Answer 10

Pregnancy Termination (antiprogestin)

Question 11

Levonorgestrel

Answer 11

‘Morning after’/emergency pill

Progestin competitive inhibitor)
High progestin dose

Prevents LH surge - prevents/delays ovulation

(Only work if taken 2 days before LH surge)
Doesn’t affect foetus

Question 12

Ulipristal

Answer 12

Morning after’ pill

Progestin competitive inhibitor

High progestin dose

Inhibits progesterone binding to receptor (exact mechanism unknown)

Prevents/delays ovulation

Question 13

Letrozole & Anastrozole

Answer 13

P450 Aromatase Inhibitors

Block androgen binding to aromatase active site (more specifically blocks conversion of testosterone to oestradiol and conversion of androstenedione to oestrone).

Reduces oestrogen synthesis

Question 14

Tamoxifen

Answer 14

Oestrogen receptor inhibition

Tamoxifen is metabolised to 4-hydroxytamoxifen by liver (CYP2D6/CYP3A4), entering the cell.

Binds to oestrogen receptor allowing receptor dimerisation but preventing further binding of co-activators, preventing

gene transcription (more specifically oestrogen response elements) in cells

Lack of conformational change of oestrogen receptor results in no gene transcription

Question 15

Alprostadil

Answer 15

(PGE pathway)

Increases PGE1

Injectable into the corpus cavernosa?
Painful (as PGE is an inflammatory molecule).

Question 16

Papaverine

Answer 16

PDE pathway

Unknown - Proposed to inhibit phosphodiesterase 5

Causes vasodilation

Only used if alprostadil is contraindicated
No localised pain

Question 17

Phentolamine

Answer 17

Adrenergic nerve inhibitor

Competitive antagonism of alpha-1 adrenoreceptors

Causes vasodilation

Inhibits the action of adrenergic nerve stimulation which is smooth muscle contraction (think SNS → fight or flight so vasoconstriction in non-essential organs)
By inhibiting this vasoconstriction it promotes vasodilation

Question 18

Levitra - Vardenafil
Viagra - Sildenafil
Cialis Tadalafil
=Lower dose & longer duration of action

Think ‘fils’ fill the corpus cavernosum with blood through vasodilation

Answer 18

PDE5 inhibitors

Take pill 1-2h before intercourse
Still needs stimulation from NANC nerves
prevents degradation of cGMP to 5’-GMP to allow endogenous NO to be more effective

Metabolised/inactivated by P450 3A4

QUICK NOTE HOW SMOKING DISRUPTS DRUG FUNCTION:
Damages Endothelial cell resulting in release of vasoconstrictors, harden blood vessels, decreasing penile blood flow,
Increases RADICALS (superoxide & peroxy nitrite) that decrease NOS activity
Increased SNS (sympathetic nervous system) tone

Question 19

Finasteride
Dutasteride
- Better and more consistent therapy than finasteride
Ideally drug of choice

Answer 19

Inhibits 5AR (5-alpha-reductase) and decreases DHT (5-alpha-dihydrotestosterone

Reduces prostate size and reduces pressure of bladder and urethra

Used for benign prostatic hyperplasia (enlarged prostate)

Finasteride can also be used for androgenic alopecia (male pattern balding).

Question 20

Alfuzosin & Tamsulosin

Answer 20

Alpha-1A selective (specific for prostate gland and bladder neck)
Less cardiac side effects
Less effective against benign prostatic hyperplasia but also less hypotension

Reduces degree of smooth muscle contraction in prostate to reduce pressure on urethra and increase urinary flow.

Specific for alpha-1 and won’t induce tachycardia via alpha-2 receptors

Question 21

Prazosin & Terazosin

Answer 21

Less receptor selectivity
More effective in BPH treatment but dose titration is needed to minimise hypotensive effects
Reduces degree of smooth muscle contraction in prostate to reduce pressure on urethra and increase urinary flow.

Specific for alpha-1 and won’t induce tachycardia via alpha-2 receptors

Question 22

Thalidomide

Answer 22

R enantiomer: sedative

S enantiomer: teratogenic

Used for morning sickness due to sedative effects of R enantiomer, but S enantiomer caused birth defects

Question 23

Pilocarpine

Answer 23

Muscarinic ACH agonist
SLUDGE BBB

Question 24

Carbachol

Answer 24

Muscarinic ACH agonist
SLUDGE BBB

Question 25

Atropine

Answer 25

Anticholinergic/competitive reversible muscarinic antagonist Anti-sludge BBB

Question 26

Muscarine

Answer 26

Agonist of muscarinic acetylcholine R SLUDGE BBB

Question 27

Scopolamine

Answer 27

Anticholinergics or Competitive reversible muscarinic antagonist Anti-sludge BBB

Question 28

Acetylcholine

Answer 28

Agonist of nicotinic and muscarinic acetylcholine receptor. SLUDGE BBB

Question 29

Adrenaline

Answer 29

Physiological antagonist of acetylcholine - binds to adrenergic receptors, causing opposite effects.

Question 30

Pyridostigmine

Answer 30

Acetylcholinesterase inhibitor ‘stigmines’ - increases acetylcholine concentrations. SLUDGE-BBB

Question 31

Class I: Antidysrhythmics Sodium Channel Block (e.g. lignocaine)

Answer 31

Block voltage gated sodium channels by preferentially binding to inactivated state, reducing sodium influx and membrane depolarisation.

Question 32

Class II Beta adrenoceptor antagonism (Beta blockers)

Answer 32

Blocks beta 1 and beta 2 receptors Block sympathetic activity, decreasing cAMP

Question 33

Class III: Potassium channel block

Answer 33

Prolong cardiac action potential, increasing refractory period of sodium channels, preventing reentrant tachycardia and suppressing ectopic activity. Prolonged plateau phase

Question 34

Class IV: Calcium channel block (e.g. verapamil and diltiazem)

Answer 34

Calcium channel antagonists Slow conduction in the SA and AV nodes, reduced calcium entry, also reduces the after-depolarisation. Calcium antagonists will also reduce contractile force Shortened plateau phase

Question 35

Adenosine

Answer 35

Acts on adenosine receptors Makes pacemakers less excitable Opening of K+ channels and hyperpolarization Used for tachycardia

Question 36

Atropine

Answer 36

Competitive antagonist of muscarinic receptors. Removes the parasympathetic brake on the heart rate Used for sinus bradycardia

Question 37

Isoprenaline

Answer 37

Beta agonist sympathomimetic produces a positive inotropic and chronotropic effect Treatment of heart block or bradycardia with haemodynamic compromise

Question 38

Adrenaline

Answer 38

Non-specific agonist for adrenergic receptors. Produces a positive ionotropic and chronotropic effect. Used for cardiac arrest

Question 39

Ivabradine

Answer 39

New drug: Coronary heart disease Chronic heart failure

Question 40

Benzodiazepines(BNZ)

Answer 40

Antiepileptic drugs Binds to alpha 1 (VTA) → reduction of GABA release → Increase GABA release

Question 41

Barbiturates

Answer 41

Similar to BNZ + inducer of P450s

Question 42

Valproate

Answer 42

Is a T-type calcium channel blocker (which is why it is helpful to treat absences, since they are caused by abnormalities in these channels.

Question 43

Calcium channel blockers (e.g. valproate and ethosuximide)

Answer 43

Block T-type channels contributing to rhythmic discharges in thalamus involved in absence seizures.

Question 44

Morphine

Answer 44

Opioid: Full agonist of opioid receptor Via µ opioid receptors (which work as G protein-coupled receptors which inhibit adenylate cyclase activity, open K+ channels and inhibit the opening of Ca2+ channels in nerve endings), opioids inhibit the release of neurotransmitters like substance P from nerve terminals, leading to suppression of asc/desc pain pathway signalling. Kappa receptors can exert additional effect on spinal cord.