Anti-Thyroid, Anti-Diabetogenic Drugs Flashcards
(80 cards)
1
Q
Anti-thyroid drugs
mechanisms
A
1. Block Na+/I- symport: Thiocyanate, perchlorate, fluoborate 2. Block thyroid peroxidase: Propylthiouracil, carbimazole 3. Block thiol endopeptidase: KI, Lugol’s iodine 4. Block 5’-deiodinase: PTU, Amiodarone, β 🅱️
2
Q
Na+/I- symport inhibitors and their side effects
A
1. Thiocyanate: Neuropsychiatric symptoms 2. Perchlorate: Aplastic anaemia 3. Fluoborate Not preferred due to toxicity
3
Q
Thyroid peroxidase inhibitors and their side effects
A
1. Propylthiouracil: Short acting but hepatotoxic 2. Carbimazole: Long acting but teratogenic Common S/E: • Agranulocytosis • GIT upset • Allergic dermatitis
4
Q
Propylthiouracil PTU
A
• Short acting thyroid peroxidase inhibitor
• Requires multiple dosing
• S/E hepatotoxic
Uses:
1. DoC in 1st trimester of🤰 for hyperthyroidism and Grave’s disease
2. Preferred in breast feeding
3. DoC in severe thyrotoxicosis/ thyroid storm because it inhibits peripheral T4 ➡️ T3
5
Q
Carbimazole (prodrug of methimazole)
A
Longest acting thyroid peroxidase inhibitor Single dose Teratogenic: • choanal/oesophageal atresia • cutis aplasia Uses: DoC of hyperthyroidism and Grave’s disease overall (preferred in 2nd/3rd trimester of 🤰, but not in breast feeding) They are 10 times more potent than PTU
6
Q
Thiol endopeptidase inhibitors
A
Inhibit T3-T4 release
Fastest anti-thyroid drugs
• Potassium iodide, Lugol’s iodine
Develop tolerance:
1. Inhibit vasculogenesis in thyroid
2. Make thyroid tissue firm and reduce size of thyroid gland
Use: prior to thyroid surgery to reduce complications
7
Q
Side effects of thiol endopeptidase inhibitors
A
- Hypersensitivity: rash, angioedema
- Iodism ➡️ headache
- Dysgeusia ➡️ metallic taste in mouth
The drugs are potassium iodide and Lugol’s iodine
8
Q
5’ de-iodinase inhibitors
A
Block peripheral conversion of T3-T4 Drugs: 1. PTU 2. Amiodarone 3. β-blockers 4. Steroids
9
Q
Radioactive iodine
A
Two isotopes: 1. I-123 Emits γ rays Used in thyroid scan 2. I-131 Emits γ and β rays β-rays are destructive Used in thyroid ablation
10
Q
Uses of I-131
A
- Hyperthyroidism: elderly and arrhythmia patients
- Thyroid cancer except medullary
- Recurrent Grave’s disease:
Worsens ocular symptoms ➡️ steroids given 2 months before - Toxic nodular goitre
11
Q
Side effects of I-131
A
- Permanent hypothyroidism
- 2° cancer
- Hyperparathyroidism
12
Q
Contraindications of I-131
A
- Pregnancy 🤰
- Thyroid peroxidase inhibitor is stopped 4 days before I-131 therapy:
It decreases uptake of I-131
13
Q
Treatment of hypothyroidism
A
1. Levothyroxine: Na+ salt of T4 Long acting In 🤰, dose 🔼 by 30% Oral bioavailability is 80% ➡️ dose 🔽 by 20% in IV 2. Liothyronine: Na+ salt of T3 Short acting 100% bioavailability, so no dose reduction
14
Q
Liothyronine (T3) is more potent than T4 but not recommended as routine therapy
in hypothyroidism
A
Liothyronine (T3) has shorter halflife (24 hours), requires multiple daily doses.
Contraindicated in cardiac patients as it poses greater risk of cardiotoxicity. More expensive
than levothyroxine. Difficulty in monitoring its adequacy by routine lab tests
15
Q
Uses of levothyroxine
A
Via oral route: 1. Replacement in hypothyroidism OD 30 min before breakfast 🍳 on empty stomach 2. Thyroid cancer: to 🔽 TSH 3. Thyroid nodules: if TSH 🔼 Via IV route: 4. Myxedema coma: Dose calculated based on lean body mass
16
Q
Side effects of levothyroxine
A
- 🔼 atrial fibrillation, so 🔽 dose in patients with arrhythmia
- Osteoporosis
- Hyperglycaemia
- Asthenia
17
Q
Uses of liothyronine
A
- Treatment of myxedema coma
- Preparation of thyroid cancer
- Patients for I-131 therapy
18
Q
Receptors of the pancreas for glucose metabolism
A
GLP-1-R
GLUT-2-R
19
Q
Absorption of disaccharides into circulation
A
It is converted into glucose by α-glucosidase and then absorbed into circulation
20
Q
GLP-1 receptor is stimulated by what mechanism
A
- Glucose ➡️ Intestinal epithelial cells
- 🔼 release of GLP-1 (Incretin)
- Reaches plasma
- GLP-1 metabolised in plasma by DPP-4 ➡️ GLP-1-short acting
- Both stimulates GLP-1-R receptor
21
Q
Action of GLP-1-short acting (and its precursor)
A
- Act on GLP-1-R (+)
- Inhibits motility of stomach
➡️ delays gastric emptying
➡️ induces satiety
➡️ blunt’s post prandial hyperglycemia
22
Q
Action of GLP-1-Receptor of pancreas
A
- Releases insulin ➡️ bring GLUT-4 out on cell membrane
- Releases amylin ➡️
negative motility of stomach ➡️
delays gastric emptying ➡️
blunts post-prandial hyperglycemia
23
Q
Insulin secretion by GLUT-2 Receptor
A
- Post prandial hyperglycemia
- Sensed by GLUT-2-R on β-islet cells
- Glucose enters β-cells through GLUT-2
- ATP generated based on inner glucose level
- ATP sensitive K+ channels are blocked
- 🔼 Ca2+ in cell
- Insulin release
24
Q
α-glucosidase inhibitors
examples and uses
A
Pseudocarbohydrates FDA approved only for DM-type II
1. Acarbose
2. Voglibose
3. Miglitol-max absorption
Source: bacteria
Use: prandial and post prandial hyperglycemia
Taken after 1st bite of food
25
α-glucosidase inhibitors
| side effects
1. Flatulence due to excess disaccharide digestion by 🦠
2. Diarrhea (osmotic)
3. 🔽 absorption of other drugs ➡️ other drugs should be taken 2hr before or after this
The drugs are Acarbose, Voglibose, Miglitol
26
α-glucosidase inhibitors
| CI
1. Renal failure
2. IBD
3. Gastroparesis
The drugs are Acarbose, Voglibose, Miglitol
27
GLP-1 releasing drugs
| types and common features
```
Two types:
1. GLP-1-R agonist
2. DPP-4 receptor
Use: T2 DM
S/E:
1. Pancreatitis: by its overstimulation
2. 🤢, 🤮: delayed gastric emptying
3. Weight loss
```
28
GLP-1 agonist drugs
| types, examples and their dosing intervals
```
1. Exendin-4 (from Gila monster) and its derivatives:
• Exenatide - BD
• Lixisenatide - OD
2. Synthetic:
• Liraglutide - OD
• Albiglutide
• Dulaglutide
• Semaglutide
Last 3 are long acting, given weekly once
```
29
GLP-1 agonist
| route, use, CI
```
Subcutaneous route
Recently oral semaglutide
Use:
T2 DM maintained
Monotherapy or not
CI:
1. Renal failure:
• Exenatide: S/E: renal failure
• Lixisenatide: renal excretion
2. MEN-II
3. Medullary Thyroid Cancer
```
30
GLP-1 agonist
| side effects
1. Pancreatitis
2. 🤢,🤮: 🔽 with Albiglutide
3. Weight loss:
2° use of Liraglutide for obesity
4. 🔼 risk of diabetic retinopathy:
with semaglutide
31
Teduglutide
```
GLP-2 agonist
Use:
short bowel syndrome to 🔼 absorption
Mechanism:
🔼 proliferation of intestinal epithelial cells
S/E:
1. Colon cancer
2. Flu like symptoms
3. GIT upset
```
32
DPP-4 inhibitor drugs
```
Gliptans
1. Sita 👱🏽♀️
2. Saxa: CHF
3. Alo
4. Lina 👩🏽🦰: not CI in renal failure
5. Vilda 🧑🏻🦰: Hepatitis
Like linagliptan
```
33
DPP-4 inhibitors
| route, use and contraindications
Orally for T2 DM maintenance as monotherapy or not
| CI: renal failure except linagliptin excreted by liver.
34
DPP-4 inhibitors
| side effects
```
1. Pancreatitis:
max with Sita 👱🏽♀️
2. Hypersensitivity (rare):
• SJS
• Angioedema
3. Block CD-26 (structurally similar) ➡️ 🔼 risk of infections
4. Saxa: CHF
5. Vilda 🧑🏻🦰: hepatitis
```
35
Amylin analogue
| mechanism, side effects
```
Pramlintide
Mechanism:
1. Delays gastric emptying ➡️ slow absorption of glucose
2. Satiety
3. 🔽 glucagon release
S/E:
1. 🤢, 🤮
2. Weight loss
```
36
Amylin analogue
| use
Pramlintide
Post prandial hyperglycemia
In T1 and T2 DM, it can be used along with insulin
📝 :
1. Dose of insulin 🔽 by 50%
2. Amylin has acidic pH of 4
So should not be combined with insulin in same 💉 (crystallization of insulin)
37
Oral hypoglycemic agents OHA
| mechanisms
```
1. 🔼 insulin release:
Inhibit ATP sensitive K+ channel
2. 🔽 insulin resistance:
Act on insulin receptor
3. 🔽 hepatic glucose production
📝: these can be used only for T2 except 3. which can be used for both
```
38
SGLT-2 receptor inhibitors
Mechanism:
Reduce glucose reabsorption
Use: T2 DM
39
Common S/E for GLP-1 related drugs, insulin, OHA
Hypoglycemia
| Insulin > OHA > GLP-1 related drugs
40
Insulin classification
```
1. Short acting:
• Fast - Glulisine, lispro, aspart
• Slow - regular insulin
2. Intermediate acting:
• NPH, Lente insulin
4. Long acting: regular insulin +
• SFA = Detemir
• Arg + Gly = Glargine
• HA = Degludec (longest acting)
```
41
Short acting insulin
```
1. Fast acting:
• Glulisine, Lispro, Aspart
• monomeric insulin: broken down into monomers immediately
2. Slow acting:
• regular insulin (neutral pH)
```
42
Intermediate acting insulin
| - NPH / Isophane
* Regular insulin + zinc protamine in PO4 buffer
* Also called NPH (Neural Protamine Hagedorn) or Isophane
* The only insulin with turbid solution - cloudy/milky appearance
43
Detemir and Glargine, 2 long acting insulins
```
1. Detemir:
• Regular insulin + saturated FA
• 🔼 albumin binding
2. Glargine:
• + 2 arginine + 1 glycine
• acidic pH
• crystallizes when injected
```
44
Degludec longest acting insulin
* Regular insulin + Hexadecanoic acid
* 🔼 albumin binding
* When injected forms multiple hexamers
45
Insulin timings ⏱
```
• For post prandial hyperglycemia:-
1. Fast acting:
Taken 20 min before food
2. Slow acting:
Taken 60 min before food
• Subcutaneously for maintenance of DM:-
3. Intermediate:
BD dosing
4. Long acting:
OD dosing
```
46
Insulin combinations in syringe 💉
One for post prandial hyperglycemia and one got maintenance of DM
1. Same 💉:
NPH + short acting drugs
Short acting drugs are withdrawn first
2. Different 💉:
Other insulin
Eg., Glargine will crystallize when with a short acting insulin in same 💉 ➡️ white cloudy 🌫 precipitate
47
Insulin
| sites of subcutaneous administration
Abdomen M/C except periumbilical (lipodystrophy)
Ant. thigh/ upper buttock/ upper arm
Rate:
Maximum in abdomen except Glargine (depends on disintegration of crystals)
48
DoC for diabetic ketoacidosis and hyperkalemia
DoC is regular insulin
49
Lente insulin
```
Insulin + Zn
It precipitates into:
1. Amorphous powder:
Short acting ➡️ semilente
2. Crystals:
Long acting ➡️ ultralente
Combined both (30:70 resp.) to form intermediate acting lente insulin
```
50
Afrezza insulin
```
Inhalational insulin
Fast acting
Use: post-prandial hyperglycemia
Available as color coded cartridges,
BGY containing
4,8,12 units of insulin
```
51
Afrezza insulin
| side effects and CI
```
S/E:
1. M/C cough
2. 🔼 risk of 🫁 cancer
CI:
1. Bronchial asthma/COPD
2. Smokers 🚬
```
52
Insulin
| side effects
```
1. Hypoglycemia: M/C except Alfrezza
🔼 in short acting so max on regular insulin
🔽 in long acting
2. Lipodystrophy
3. Lipohypertrophy:
Due to HSL ➡️ 🔽 lipolysis
4. Hypokalemia
```
53
Sulfonylureas and Meglitinides
| Properties
Both are oral hypoglycemic agents, 🔼 insulin release
Sulfonylureas are more potent and longer acting
Both are metabolised by liver and excreted by kidney
54
Sulfonylureas and Meglitinides
| uses
Sulfonylurea:
1. Maintaining type 2 DM
2. Maximum 🔽 in HbA1C
> than biguanides
55
Sulfonylureas and Meglitinides
| side effects
Common S/E:
Hypoglycemia and weight gain
Higher in sulfonylureas (preferred in thin patients)
(HSL 🅱️)
56
Sulfonylureas and Meglitinides
| contraindications
Sulfonylureas:
CI in renal and liver failure
Meglitinides:
Metabolised by liver and excreted by kidney
Can be used in renal and liver failure with dose adjustment
57
Sulfonylureas
| first generation drugs
```
Not preferred due to low potency
1. Acetohexamide
2. Tolbutamide: hepatotoxic
3. Chlorpropamide:
S/E: SIADH hyponatremia
Disulfiram like reaction
```
58
Sulfonylureas
| second generation drugs
```
1. Glyburide/ Glibenclamide:
concentrated in β-islet cells
2. Glimepiride
3. Gliclazide
4. Glipizide: lesser risk of hypoglycemia
```
59
Glyburide
| Glibenclamide
Most potent sulfonylurea
Concentrated in β cells ➡️ longer acting than t1/2
S/E:
1. Potent inhibitor of cardiac ATP sensitive K+ channels
➡️ blunt myocardial response to ischemia
2. Disulfiram like reaction
60
Glipizide
Less potent and short acting 2nd generation sulfonylurea
Lesser risk of hypoglycemia
Preferred in patients of renal failure and elderly patients
61
Mechanism of thiazolidinediones
```
1. Stimulates PPAR-γ (nuclear receptor)
➡️ transcription factor 🔼
➡️ insulin resistance 🔽
2. Adipocyte proliferation 🔼
3. GLUT-4 production 🔼
```
62
Examples of OHA which 🔽 insulin resistance
```
Thiazolidinediones
1. Pioglitazone: black box warning 🕋
2. Rosiglitazone:
banned, MI and bladder cancer
3. Troglitazone:
banned, hepatotoxic
```
63
Pioglitazone
```
Thiazolidinedione available in India with a black box warning 🕋
Also stimulates PPAR-α ➡️
🔼 LPL ➡️:
1. 🔽 TAG, VLDL, chylomicron
2. 🔼 HDL
S/E: bladder cancer
Use: T2 DM
```
64
Thiazolidinedione
| common S/E
1. Stimulates epithelial Na+ channels ➡️ Na+/water retention, edema, CHF, weight gain
2. Macular edema
3. 🔼 risk of bone fracture in females
65
OHAs which 🔽 hepatic glucose production
Biguanides
1. Metformin
2. Phenformin: banned due to severe lactic acidosis
66
Biguanides
| mechanism
```
1. Stimulate AMP kinase:
• gluconeogenesis 🔽 ➡️ hepatic glucose production 🔽
• 🔽 insulin resistance
• 🔼 lipid oxidation ➡️ 🔽 LDL
2. Block gastric emptying ➡️ 🔼 satiety
```
67
Metformin
| Uses
```
1. DoC for Rx and prophylaxis of DM
🔽 microvascular complications
2. Polycystic Ovarian Syndrome
3. AIDS related metabolic syndrome
4. Non- alcoholic fatty liver disease
5. Antipsychotic induced weight gain
```
68
Metformin
| side effects
1. 🔽 Ca2+ induced vitamin B12 absorption
2. 🤢, 🤮
3. Weight loss
4. Lactic acidosis
69
Metformin
| contraindications
🔼 risk of lactic acidosis in
1. Elderly
2. Chronic alcoholics
3. Renal/liver failure
4. CHF
5. Severe lung disease
70
SGLT-2 inhibitors
| examples and basic features
-gliflozins
1. Canagliflozin
2. Dapa-
3. Empa-
4. Ertu-
Oral drugs
Use:
polytherapy only for DM with metformin/ DPP 🅱️
71
SGLT-2 inhibitors
| S/E common
```
1. 🔼 glucose in urine:
M/C - UTI
by M/C Candida (➡️ vaginal pruritis in females)
2. 🔼 Na+ in using:
🔼 water loss
• diuretic effect
• hypotension
• dehydration
```
72
SGLT-2 inhibitors
| rare side effects
```
1. Urosepsis:
M/C cause: E. coli
2. Fourier gangrene
3. Osteoporosis ➡️ 🦴 fracture
4. Pancreatitis
5. DKA with euglycemia
6. Canagliflozin: 🔼 risk of limb amputation
7. Dapagliflozin: 🔼 risk of bladder and breast cancer
```
73
Beneficial effects of SGLT-2 inhibitors
1. 🔼 CVS mortality (🔽 bp) like GLP1 agonist
| 2. Weight loss
74
Anti diabetic action of colesevelam
Use: T2 DM
Mechanism: bile acid binding resins 🔼 🔽 glucose absorption
75
Anti diabetic action of bromocriptine
D2 agonist
Use: T2 DM
Mechanism:
🔽 in hypothalamic drive for hyperglycemia
76
Dual PPAR agonist as anti diabetic drugs
```
Stimulates PPAR α, γ
α: 🔽 TAG
γ: 🔽 glucose
Drugs:
1. Saroglitazar
2. Ragaglitazar
```
77
Iodides should be initiated after thioamide therapy or avoided if treatment with
radioactive iodine seems likely
Iodide therapy will increase the intraglandular stores of iodine. It delays the onset of action
of thioamide therapy. Increased intraglandular iodine stores will inhibit the uptake of
radioactive iodine into the gland. So the therapy will be ineffective
78
Amiodarone produces both hypo and hyperthyroidism.
Amiodarone has structural similarity with thyroid hormone and high iodine content. The
iodine content accumulated in thyroid will inhibit thyroid synthesis and release resulting in
hypothyroidism.
Amiodarone causes autoimmune thyroiditis and releases excess thyroid hormone into circulation. Iodine content can increase the thyroid hormone synthesis and release.
79
Meglitinide analogs are useful for controlling postprandial hyperglycemia
Meglitinide analogs (Repaglinide and Nateglinide) have rapid onset of action and the peak effect is observed within 1 hour of ingestion. Hence if taken just before a meal, they effectively suppress postprandial hyperglycemia
80
Non selective beta blockers should be avoided in diabetics.
Beta-adrenoceptor-blocking drugs may impair the sympathetically mediated release of glucose from the liver in response to hypoglycaemia and also reduce the adrenergically mediated symptoms of hypoglycaemia (except sweating). Insulin hypoglycaemia may thus be more prolonged and/or less noticeable.
Ideally, a patient with diabetes needing a b-adrenoceptor blocker should be given a b1-selective member, e.g. bisoprolol only and non selective beta blocker has to be avoided
