Drugs for fungal infections, head lice, hyperhidrosis, hair growth and pigmentation - Sweatman

Question 1

what is the unique, significnat adverse effect of ketoconazole use that were the subject of a recent FDA article?

Answer 1

Adrenal insufficiency - ketoconazoles ability to disrupt steroid synthesis

Question 2

what are 2 common adverse effects shared by all azoles

Answer 2

Hepatotoxicity

Drug-drug interactions via CYP interactions

Question 3

what are 3 BBW associated with Itraconazole use? Why does it carry these?

Answer 3

Heart Failure
Ventricular dysfunction
Co-administration with drugs (CYP)
Itraconazole produces negative inotropic effects on the heart

Question 4

Are azoles safe in pregnancy?

Answer 4

no

Question 5

Are azoles safe in breast feeding?

Answer 5

no - potential of the drug to pass to infant

Question 6

which azoles produce QT prolongation?

Answer 6

Fluconazole, Psoaconazole, Voriconazole

Question 7

Which azole are you worried about visual disturbances due to optic neuritis?

Answer 7

Voriconazole

Question 8

Which azole are you worried about photosensitization of skin?

Answer 8

Voriconazole

Question 9

which azole must be administered with a full meal for adequate bioavailability?

Answer 9

Posaconazole

Question 10

This is a potential test question
You have a pt that has a fungal infection and renal failure - what azole can you not give, or at least need to dose adjust?

Answer 10

Fluconazole

most azoles are extensively hepatically metabolized, but fluconazole is metabolized and eliinated renally

Question 11

which azoles have access to CSF?

Answer 11

Fluconazole and Voriconazole

Question 12

What is the MOA of Griseofulvin?

Answer 12

binds microtubules, disrupts the mitotic spindle - thus inhibits fungal growth

Question 13

what is the effect of Griseofulvin on CYP?

Answer 13

it is a CYP3A4 inducer (azoles are inhibitors)

Question 14

is Griseofulvin safe in pregnancy?

Answer 14

no

Question 15

What drug allergy in a pt would make you not want to give Griseofulvin?

Answer 15

Penicillin allergy

commonality in structure with Beta lactams

Question 16

What is the MOA of Terbinafine and Naftifine (allylamines)?

Answer 16

inhibit squalene epoxidase, a step in ergosterol synthesis

Question 17

is terbinafine safe in pregnancy?

Answer 17

yes

Question 18

what precautions do you need to take with Terbinafine?

Answer 18

CBCs and LFTs

Question 19

what is an important point about the allylamines and azoles in combination therapy?

Answer 19

both classes work to block ergosterol incorporation into fungal cell walls - there is no gain in combining the two classes

Question 20

what is the route of delivery for Ciclopirox and Amorolfine?

Answer 20

TOPICAL ONLY

Question 21

for review only, what is the MOA of azoles? what enzyme do they inhibit?

Answer 21

inhibit the cytochrome P450 enzyme sterol 14 demethylase

blocks production of ergosterol

Question 22

for review only, what is the MOA of capsofungin (and Echinocandin)

Answer 22

inhibits 1,3-B-glucan synthase

results in disruption of cell wall integrity

Question 23

for review only, what is the MOA of amphotericin B?

Answer 23

binds ergosterol and creates pores in the fungal cell membrane

Question 24

what is the general mechanism used to treat hyperhidrosis?

Answer 24

anti-cholinergics

Question 25

from the CNS, what causes activation of Eccrine (thermoregulatory) sweat glands?

Answer 25

sympathetic innervation with Ach as neurotransmitter, rather than customary NE (the nerves innervating eccrine, or thermoregulatory, sweat glands are sympathetic cholinergic nerves, this is unique)

Question 26

so an M2 student has sweaty armpits in anticipation of being pimped by Sweatman in class (eh, eh?) what is the post-synaptic neuro-effector receptor responsible for the sweating?

Answer 26

Muscarinic M2 | the nerves innervating eccrine, or thermoregulatory, sweat glands are sympathetic cholinergic nerves, this is unique

Question 27

what are the affects of cholinergic agonists or AchE inhibitors? what is the pneumonic?

Answer 27

``` DUMBBELS Diarrhea Urination Miosis/muscle weakness Bronchorrhea Bradycardia Emesis Lacrimation Salivation/sweating ```

Question 28

what is first line treatment for hyperhidrosis (i.e. early stages)

Answer 28

start with general antiperspirants, such as aluminum chloride

Question 29

what is second line treatment for hyperhidrosis (i.e. no response to antiperspirants)?

Answer 29

botulinum toxin

Question 30

what is the treatment modality (3rd line) used for hyperhidrosis if there is no response to botulinum toxin?

Answer 30

systemic anticholinergics | or surgery with sympathectomy

Question 31

what is the MOA of Aluminum Chloride

Answer 31

short-term occlusion of eccrine and apocrine sweat gland ducts

Question 32

What is the MOA of botulinum toxin

Answer 32

cleaves SNARE proteins, prevents fusion of vesicle containing Ach and the presynaptic membrane - prevents Ach release into the cleft

Question 33

what is a rare but impt BBW associated wiht Botulinum Toxin

Answer 33

systemic botulism is rare, but reported

Question 34

for systemic anti-muscarinic therapy used for the treatment of hyperhidrosis, what type of drugs and what drug names do we want to choose, and why

Answer 34

we want to choose drugs that cannot cross the BBB, so as to not cause anti-muscarinic sedation and delirium need quaternary ammonium compounds glycopyrrolate, propantheline

Question 35

what drugs can you use to diminish the central emotionally impacted sympathetic causation of sweating

Answer 35

propranolol (beta blocker) or clonidine (a2 agonist)

Question 36

what are the two general divisions of head lice treatment types?

Answer 36

chemical and physical

Question 37

in general, what is the effect of chemical methods to treat head lice

Answer 37

result in paralysis of louse and result in its demise from dehydration

Question 38

in general, what is the effect of physical methods to treat head lice

Answer 38

suffocation of the little shits

Question 39

Malathion - MOA and what does it treat?

Answer 39

AchE inhibitor | Chemical method to treat head lice

Question 40

What should you admin in the event that Malathion is ingested (instead of applied topically, as indicated)

Answer 40

use atropine | muscarinic antagonist to help reduce the Ach overstimulation caused by Malathion

Question 41

Permethrin - MOA and what does it treat?

Answer 41

blocks volt gated Na channels - slows and stops nervous system activity chemical method to treat head lice (also first line for scabies)

Question 42

Ivermectin - MOA and what does it treat?

Answer 42

binds glutamate receptors gating chloride - leads to hyperpolarization of cell also may act as agonist for GABA used to treat head lice, and is a broad spectrum antiparasitic agent

Question 43

In broad generalities, what is your approach to treatment of head lice? what all do you need to eradicate and how many treatments?

Answer 43

more than one treatment may be necessary in order to eradicate all adult and nit louse

Question 44

What is the mechanism of resistance by lice to the chemical agents?

Answer 44

typical mechanisms common to other drugs decreased concentration at target, increased rate of inactivation / removal, point mutations in targets i.e. knock down resistance from point mutations in targets like the volt gate sodium channel (permethrin target)

Question 45

What is dimethicone? what is it used to treat? what is its MOA?

Answer 45

a mechanical (physical) methd of lice treatment it is a silicon based polymer that lubricates hair and aids in removal of lice and nits and causes suffocation of lice

Question 46

what is Air Alle, what is it used to treat?

Answer 46

mechanical treatment of hair lice, application of heat causes dehydration of louse leads to death

Question 47

what drug treats hair conditions by inhibiting 5-alpha dihydrotestosterone production?

Answer 47

Finasteride (propecia)

Question 48

what drug used for the treatment of hair conditions requires activation by UV light

Answer 48

Methoxsalen

Question 49

What drugs block the production of melanin when used to treat hair conditions?

Answer 49

hydroquinone, Tretinoin

Question 50

what is the danger of the practice of scalp cooling? (used to prevent alpecia following CTX)

Answer 50

preservation of scalp micrometastases

Question 51

what is the MOA of minoxidil?

Answer 51

it is a potent oral vasodilator - mechanism of topical application leading to hypertrichosis is unknown

Question 52

you are thinking about prescribing Finasteride (propecia) to somebody with alopecia; what herbal supplement do you need to ask them if they are taking, because it acts by a similar mechanism as finasteride

Answer 52

Saw Palmetto - used for BPH

Question 53

what is a potential, debilitating side effect of Finasteride or saw palmetto?

Answer 53

sexual dysfunction / infertility

Question 54

what is Eflornithine used to treat?

Answer 54

topical drug to reduce unwanted female facial hair growth

Question 55

What is the MOA of Eflornithine used to treat unwanted female facial hair

Answer 55

inhibits ornithine decarboxylase - a mandatory step in polyamine production - causes decreased cell division and differentiation

Question 56

what else, besides unwanted female facial hair growth, can Eflornithine be used to treat?

Answer 56

given IV, is trypanostatic - employed in tx of sleeping sickness

Question 57

what 3 drug regimen is used in the treatment of melasma, or facial skin darkening caused by hormonal changes, prgnancy, OCs or HRT?

Answer 57

Fluocinolone, Hydroquinone, Tretinoin

Question 58

what is the MOA of Fluocinolone? (part of 3 drug regimen to treat melasma)

Answer 58

anti-inflammatory corticosteroid

Question 59

what is the MOA of Hydroquinone? (part of 3 drug regimen for melasma)

Answer 59

inhibits melanin formation, blocking melanocyte enzymatic oxidation of tyrosine to DOPA

Question 60

what is the MOA of tretinoin? (part of 3 drug regimen for melasma?)

Answer 60

modulates skin growth and pigmentation | it is a retinoid, so it just does retinoid things

Question 61

when on the 3 drug regimen for melasma Fluocinolone, Hydroquinone, Tretinoin, what do pts need to be cautioned about

Answer 61

increased sensitivity to UV, protection is necessary

Question 62

What is the MOA of Methoxsalen? used to treat a number of different skin conditions

Answer 62

activated by exposure to UV light | conjugation and cross-linking of DNA - cell death

Question 63

in cases of CTX induced alopecia, regrowth often occurs, via stem cells located where in the hair follicle

Answer 63

stem cells located in the bulge

Question 64

what is the mechanism of CTX induced hair loss

Answer 64

apoptotic cell death, a result of dec BCL2, and inc Bax and p53